Enhancement of Bone Tissue Regeneration with Multi-Functional Nanoparticles by Coordination of Immune, Osteogenic, and Angiogenic Responses.

Inorganic nanoparticles are promising materials for bone tissue engineering due to their chemical resemblance to the native bone structure. However, most studies are unable to capture the entirety of the defective environment, providing limited bone regenerative abilities. Hence, this study aims to develop a multifunctional nanoparticle to collectively control the defective bone niche, including immune, angiogenic, and osteogenic systems. The nanoparticles, self-assembled by biomimetic mineralization and tannic acid (TA)-mediated metal-polyphenol network (MPN), are released sustainably after the incorporation within a gelatin cryogel. The released nanoparticles display a reduction in M1 macrophages by means of reactive oxygen species (ROS) elimination. Consequently, osteoclast maturation is also reduced, which is observed by the minimal formation of multinucleated cells (0.4%). Furthermore, the proportion of M2 macrophages, osteogenic differentiation, and angiogenic potential are consistently increased by the effects of magnesium from the nanoparticles. This orchestrated control of multiple systems influences the in vivo vascularized bone regeneration in which 80% of the critical-sized bone defect is regenerated with new bones with mature lamellar structure and arteriole-scale micro-vessels. Altogether, this study emphasizes the importance of the coordinated modulation of immune, osteogenic, and angiogenic systems at the bone defect site for robust bone regeneration.

Cell-homing and immunomodulatory composite hydrogels for effective wound healing with neovascularization.

Wound healing in cases of excessive inflammation poses a significant challenge due to compromised neovascularization. Here, we propose a multi-functional composite hydrogel engineered to overcome such conditions through recruitment and activation of macrophages with adapted degradation of the hydrogel. The composite hydrogel (G-TSrP) is created by combining gelatin methacryloyl (GelMA) and nanoparticles (TSrP) composed of tannic acid (TA) and Sr2+. These nanoparticles are prepared using a one-step mineralization process assisted by metal-phenolic network formation. G-TSrP exhibits the ability to eliminate reactive oxygen species and direct polarization of macrophages toward M2 phenotype. It has been observed that the liberation of TA and Sr2+ from G-TSrP actively facilitate the recruitment and up-regulation of the expression of extracellular matrix remodeling genes of macrophages, and thereby, coordinate in vivo adapted degradation of the G-TSrP. Most significantly, G-TSrP accelerates angiogenesis despite the TA's inhibitory properties, which are counteracted by the released Sr2+. Moreover, G-TSrP enhances wound closure under inflammation and promotes normal tissue formation with strong vessel growth. Genetic analysis confirms macrophage-mediated wound healing by the composite hydrogel. Collectively, these findings pave the way for the development of biomaterials that promote wound healing by creating regenerative environment.

Delayed escape behavior requires claustral activity.

Animals are known to exhibit innate and learned forms of defensive behaviors, but it is unclear whether animals can escape through methods other than these forms. In this study, we develop the delayed escape task, in which male rats temporarily hold the information required for future escape, and we demonstrate that this task, in which the subject extrapolates from past experience without direct experience of its behavioral outcome, does not fall into either of the two forms of behavior. During the holding period, a subset of neurons in the rostral-to-striatum claustrum (rsCla), only when pooled together, sustain enhanced population activity without ongoing sensory stimuli. Transient inhibition of rsCla neurons during the initial part of the holding period produces prolonged inhibition of the enhanced activity. The transient inhibition also attenuates the delayed escape behavior. Our data suggest that the rsCla activity bridges escape-inducing stimuli to the delayed onset of escape.

Potential Migration and Health Risks of Heavy Metals and Metalloids in Take-Out Food Containers in South Korea.

The consumption of take-out food has increased worldwide; consequently, people are increasingly being exposed to chemicals from food containers. However, research on the migration of metals from containers to food is limited, and therefore, information required to determine the health risks is lacking. Herein, the amount of transfer of nine metals and metalloids (Pb, Sb, Cd, Ge, Co, Mn, Sn, As, and Hg) from food containers to food in South Korea was assessed from take-out food containers classified into paper and plastic container groups. The sample containers were eluted over time by either warming with 4% acetic acid at 70 °C or cooling with 4% acetic acid at 100 °C /deionized water at 25 °C. It was analyzed using an inductively coupled plasma mass spectrometer and a direct mercury analyzer. The reliability of the quantitative results was verified by calculating the linearity, limit of detection, and limit of quantification. We found that the amount of metals and metalloids (Pb, Sb, Cd, and Co) eluting over time was highly significant in the plastic group. Regardless of the food simulant and elution time, the amount of Sb transferred from the food containers to food was substantially higher in the plastic (average concentration: 0.488-1.194 µg/L) than in the paper group (average concentration: 0.001-0.03 µg/L). Fortunately, all food containers were distributed at levels safe for human health (hazard index: 0.000-64.756%). However, caution is needed when warm food is added to food containers. Overall, our results provide baseline data for the management and use of take-out containers.

Formulating Electron Beam-Induced Covalent Linkages for Stable and High-Energy-Density Silicon Microparticle Anode.

High-capacity silicon (Si) materials hold a position at the forefront of advanced lithium-ion batteries. The inherent potential offers considerable advantages for substantially increasing the energy density in batteries, capable of maximizing the benefit by changing the paradigm from nano- to micron-sized Si particles. Nevertheless, intrinsic structural instability remains a significant barrier to its practical application, especially for larger Si particles. Here, a covalently interconnected system is reported employing Si microparticles (5 µm) and a highly elastic gel polymer electrolyte (GPE) through electron beam irradiation. The integrated system mitigates the substantial volumetric expansion of pure Si, enhancing overall stability, while accelerating charge carrier kinetics due to the high ionic conductivity. Through the cost-effective but practical approach of electron beam technology, the resulting 500 mAh-pouch cell showed exceptional stability and high gravimetric/volumetric energy densities of 413 Wh kg-1, 1022 Wh L-1, highlighting the feasibility even in current battery production lines.

Fabrication of Versatile Janus Microparticles through Geometry and Surface Chemistry Control.

Amphiphilic Janus particles typically comprise two distinct hemispheres with spatially dispersed physicochemical properties. The anisotropic structure and physicochemical properties of Janus particles can be exploited for various applications. However, their preparation typically requires complex and sophisticated processes and expensive equipment to control the formation of different structures and chemical compositions. Herein, a simple synthetic approach for the facile fabrication of versatile Janus particles with efficient control of the Janus ratio and wettability based on particle fixation at a three-phase interface and photopolymerization is reported. Agarose gel and surfactant are used to control the surface-coated boundaries of the Janus particles through the equilibrium of a floating microparticle at the fluid interface. poly(propylene glycol) diacrylate or poly(N-isopropylacrylamide) coating on polystyrene-based microparticles allows easy control of the chemical functionality of the particle surfaces. Depending on the particle morphology and wettability, the interfacial behavior between two immiscible liquids can be adjusted, which allows the stabilization of Pickering emulsions that encapsulate independent oil droplets in water or vice versa. This facile approach has the potential to enable more efficient mass production of Janus particles and their use in various applications, such as biomedical and environmental engineering.

Cross-sectional and skeletal anatomy of long-tailed gorals (Naemorhedus caudatus) using imaging evaluations.

BACKGROUND: Accurate diagnosis of diseases in animals is crucial for their treatment, and imaging evaluations such as radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) are important tools for this purpose. However, a cross-sectional anatomical atlas of normal skeletal and internal organs of long-tailed gorals (Naemorhedus caudatus) has not yet been prepared for diagnosing their diseases. OBJECTIVES: The objective of this study was to create an anatomical atlas of gorals using CT and MRI, which are imaging techniques that have not been extensively studied in this type of wild animal in Korea. METHODS: The researchers used CT and MRI to create an anatomical atlas of gorals, and selected 37 cross-sections from the head, thoracic, lumbar, and sacrum parts of gorals to produce an average cross-sectional anatomy atlas. RESULTS: This study successfully created an anatomical atlas of gorals using CT and MRI. CONCLUSIONS: The atlas provides valuable information for the diagnosis of diseases in gorals, which can improve their treatment and welfare. The study highlights the importance of developing cross-sectional anatomical atlases of gorals to diagnose and treat their diseases effectively.

Design and Optimization of Composite Cathodes for Solid-State Batteries Using Hybrid Carbon Networks with Facile Electronic and Ionic Percolation Pathways.

Solid-state batteries (SSBs) have emerged as a promising alternative to conventional liquid electrolyte batteries due to their potential for higher energy density and improved safety. However, achieving high performance in SSBs is difficult because of inadequate contact and interfacial reactions that generate high interfacial resistance, as well as inadequate solid-solid contact between electrodes. These chronic issues are associated with inhomogeneous ion and electron transport networks owing to imperfect solid-solid interfacial contact. This study developed an optimal interfacial engineering strategy to facilitate an ion-electron transport network by designing an active material (NCM622) uniformly filled with a thin layer of a solid electrolyte (garnet-type Li6.25Ga0.25La3Zr2O12) and conductive additives. The optimal composite electrode architecture enhanced the high capacity, high rate capability, and long-term cycle stability, even at room temperature, owing to the percolating network for facile ionic conduction that assured a homogeneous reaction. In addition to mitigating the mechanical degradation of the cathode electrode, it also reduced the crosstalk effects on the anode-solid electrolyte interface. Effectively optimizing the selection and use of conductive additives in composite electrodes offers a promising approach to addressing key performance-limiting factors in SSBs, including interfacial resistance and solid-solid contact issues. This study underscores the critical importance of cathode architecture design for achieving high-performance SSBs by ensuring that the interfaces are intact with solid electrolytes at both the cathode and anode interfaces while promoting uniform reactions. This study provides valuable insights into the development of SSBs with improved performance, which could have significant implications for a wide range of applications.

Molecular Characteristics of Catalytic Nitrogen Removal from Coal Tar Pitch over γ-Alumina-Supported NiMo and CoMo Catalysts.

The removal of nitrogen from coal tar pitch (CTP) through the hydrodenitrogenation (HDN) of CTP and its molecular behavior were evaluated in the presence of NiMo/γ-alumina and CoMo/γ-alumina catalysts. Fourier transform ion cyclotron resonance mass spectrometry with atmospheric pressure photoionization was used to analyze the complicated chemical classes and species of CTP and the treated products at the molecular level. Nitrogen species were qualitatively analyzed before and after hydrotreatment. A single-stage hydrotreatment with an HDN catalyst resulted in a high sulfur removal performance (85.6-94.7%) but a low nitrogen removal performance (26.8-29.2%). Based on relative abundance analyses of nitrogen and binary nitrogen species, CcHh-NnSs was the most challenging species to remove during HDN treatment. Furthermore, prior hydrodesulfurization was combined with HDN treatment, and the dual hydrotreatments yielded a significantly improved nitrogen removal performance (46.4-48.7%).

Role of Gasdermin E in the Biogenesis of Apoptotic Cell-Derived Exosomes.

The gasdermins are a family of pore-forming proteins that has recently been suggested to play a central role in pyroptosis. In this study, we describe the novel roles of gasdermins in the biogenesis of apoptotic cell-derived exosomes. In apoptotic human HeLa and HEK293 cells, GSDMA, GSDMC, GSDMD, and GSDME increased the release of apoptotic exosomes. GSDMB and DFNB59, in contrast, negatively affected the release of apoptotic exosomes. GSDME at its full-length and cleaved forms was localized in the exosomes and exosomal membrane. Full-length and cleaved forms of GSDME are suggested to increase Ca2+ influx to the cytosol through endosomal pores and thus increase the biogenesis of apoptotic exosomes. In addition, the GSDME-mediated biogenesis of apoptotic exosomes depended on the ESCRT-III complex and endosomal recruitment of Ca2+-dependent proteins, that is, annexins A2 and A7, the PEF domain family proteins sorcin and grancalcin, and the Bro1 domain protein HD-PTP. Therefore, we propose that the biogenesis of apoptotic exosomes begins when gasdermin-mediated endosomal pores increase cytosolic Ca2+, continues through the recruitment of annexin-sorcin/grancalcin-HD-PTP, and is completed when the ESCRT-III complex synthesizes intraluminal vesicles in the multivesicular bodies of dying cells. Finally, we found that GSDME-bearing tumors released apoptotic exosomes to induce inflammatory responses in the in vivo mouse 4T1 orthotropic model of BALB/c breast cancer. The data indicate that the switch from apoptosis to pyroptosis could drive the transfer of mass signals to nearby or distant living cells and tissues by way of extracellular vesicles, and that gasdermins play critical roles in that process.

TR score: A noninvasive model to predict histological stages in patients with primary biliary cholangitis.

Introduction: The aim of this study was to develop a noninvasive prediction model for histological stages in PBC that is simple, easy to implement, and highly accurate. Methods: A total of 114 patients with PBC were included in this study. Demographic, laboratory data and histological assessments were collected. The independent predictors of histological stages were selected to establish a noninvasive serological model. The scores of 22 noninvasive models were calculated and compared with the established model. Results: This study included 99 females (86.8%) and 15 males (13.2%). The number of patients in Scheuer's stage 1, 2, 3 and 4 was 33 (29.0%), 34 (29.8%), 16 (14.0%), and 31 (27.2%), respectively. TBA and RDW are independent predictors of PBC histological stages. The above indexes were used to establish a noninvasive model-TR score. When predicting early histological change (S1) or liver fibrosis and cirrhosis (S3-S4), the AUROC of TR score were 0.887 (95% CI, 0.809-0.965) and 0.893 (95% CI, 0.816-0.969), higher than all of the other 22 models included in this study. When predicting cirrhosis (S4), its AUROC is still as high as 0.921 (95% CI, 0.837-1.000). Conclusion: TR score is an easy, cheap and stable noninvasive model, without complex calculation formulas and tools, and shows good accuracy in diagnosing the histological stages of PBC.

Itch and Janus Kinase Inhibitors.

Itch is a common skin symptom, with complex aetiology and pathogenesis. It is mediated by 2 pathways, the histaminergic and non-histaminergic pathways. Chronic itch is understood to be processed by the latter and is difficult to treat with traditional pruritus therapies. The Janus kinase and signal transducer and activator of transcription pathway is a signalling mechanism that regulates gene expression through various cytokines. Janus kinase inhibitors, which have been tested and used for several autoimmune diseases, have also been shown to be effective for itch through clinical trials and case reports. Janus kinase inhibitors could be a good choice for pruritus in atopic dermatitis, psoriasis, and other diseases, such as prurigo nodularis and lichen planus, with rapid itch relief compared with conventional treatments. The most common adverse effects reported include nasopharyngitis, acne, and elevated blood creatine phosphokinase levels. Janus kinase inhibitors are currently prescribed with warnings about a potential increase in malignancies and cardiovascular diseases and usage in people of older ages. This review aims to provide knowledge about itch and the Janus kinase and signal transducer and activator of transcription pathway and to analyse the current evidence for itch relief by Janus kinase inhibitors.

RADIOGRAPHIC MEASUREMENT OF VERTEBRAL HEART SCALE IN KOREAN WILD RACCOON DOGS (NYCTEREUTES PROCYONOIDES KOREENSIS).

Raccoon dogs (Nyctereutes procyonoides koreensis), which belong to the Canidae family, are the second most injured wildlife animals rescued by the Gangwon Wildlife Medical Rescue Center. Various imaging evaluation methods including echocardiography have been developed, but thoracic radiography remains essential for the diagnosis and management of heart disease in dogs. In particular, vertebral heart scale (VHS) measurement is usually used to evaluate the dimensions of the heart silhouette on thoracic radiographs and can measure cardiomegaly more objectively. The VHS of 50 raccoon dogs without cardiac diseases were measured using thoracic radiography in right lateral (RL) and ventrodorsal (VD) recumbent positions. The VHS in the RL view of 50 raccoon dogs was 9.03 ± 0.52 vertebrae (v), which was slightly smaller than the VHS measured in the VD view of 46 raccoon dogs (9.79 ± 0.84 v). In addition, the thoracic morphology of raccoon dogs was determined to be intermediate (thoracic depth-to-width ratio, 0.75-1.25), and thoracic morphology, gender, and weight were not significantly correlated with VHS. The VHS of raccoon dogs in this study will help veterinarians diagnose potential cardiac diseases in raccoon dogs.

Blockchain Technology for Electronic Health Records.

Compared with traditional paper-based medical records, electronic health records (EHRs) are widely used because of their efficiency, security, and reducing data redundancy. However, EHRs still manifest poor interoperability and privacy issues are unresolved. As a distributed ledger protocol composed of encrypted blocks of data organized in chains, blockchain represents a potential tool to solve the shortcomings of EHRs in terms of interoperability and privacy. In this paper, we define EHRs and blockchain technology and introduce several classic schemes based on blockchain technology to strengthen EHR interoperability and privacy protection. We then review ongoing challenges in the areas of data management efficiency, fairness of access, and trust in the systems. In this commentary, we suggest ongoing research needs for health informatics, data sciences, and ethics to establish EHRs based on blockchain technology. Blockchain-based EHR schemes must address the potential inequality of healthcare resources, the huge carbon footprint of computational needs, and potential distrust of health providers and patients that may ensue with wider use of blockchain technology.

Allergic Sensitization Pattern in the Korean Dermatologic Patients.

BACKGROUND: Avoiding causative allergens is important for controlling the clinical course of allergic diseases. Allergen sensitization is influenced by many factors including the environment and lifestyle. The socioeconomic development, climate, and lifestyle changes have increased the prevalence of allergic diseases worldwide. However, there is little information about changes in the trend of the common allergens over time. OBJECTIVE: This study was aimed at identifying the trends of the common allergens in Korea over a 10-year period based on the results of the multiple allergosorbent test chemiluminescent assay (MAST-CLA). METHODS: We retrospectively reviewed the medical records of 5,760 patients aged ≥18 years who visited the Dermatology Department at a tertiary hospital over a period of 10 years. The serum total immunoglobulin (Ig) E and specific IgE levels to 41 allergens were determined using MAST-CLA, along with the clinical diagnosis, duration of illness, white blood cell count and eosinophil percentage. RESULTS: Dermatophagoides farinae, Dermatophagoides pteronyssinus, and house dust were the most prevalent allergens during the 10 years period, but the percentage of higher class responses has decreased in recent years. The number of patients sensitized to house dust (p<0.001), dogs (p=0.005), and cats (p<0.001) increased while that of patients sensitized to cockroaches (p<0.001) and storage mites (p<0.001) decreased over time. There were no significant changes in the total number of sensitizing allergens over time. CONCLUSION: The common allergens have changed over time. Based on the findings of this study, physicians and patients should consider changing their strategies for disease prevention and management.

Effects of CALR-Mutant Type and Burden on the Phenotype of Myeloproliferative Neoplasms.

Somatic CALR mutations occur in approximately 70% of patients with JAK2 V617F-negative essential thrombocythemia (ET) and primary myelofibrosis (PMF). We evaluated the effects of the CALR mutant type and burden on the phenotype of CALR-mutated myeloproliferative neoplasms (MPN). Of the 510 patients with suspected or diagnosed MPN, all 49 patients detected with CALR mutations were diagnosed with ET (n = 32) or PMF (n = 17). The CALR mutant burden was significantly higher in PMF than in ET (45% vs. 34%), and type 1-like and type 2-like mutations were detected in 49% and 51% patients, respectively. Patients with MPN and type 2-like mutation showed a significantly higher median platelet count than those with type 1-like mutation. Particularly, patients with ET and type 2-like mutation had no thrombotic events, despite higher platelet counts. The effect of CALR mutant burden differed depending on the mutant type. A higher mutant burden tended to be associated with a cytopenic phenotype (i.e., lower hemoglobin levels and platelet counts) in patients with the type 1-like mutation and a proliferative hematological phenotype (i.e., higher platelet and neutrophil counts) in patients with the type 2-like mutation. This study suggests that the disease phenotype of MPN may be altered through CALR mutant burden and mutant type.

Update on Extracellular Vesicle-Based Vaccines and Therapeutics to Combat COVID-19.

The COVID-19 pandemic has had a deep impact on people worldwide since late 2019 when SARS-CoV-2 was first identified in Wuhan, China. In addition to its effect on public health, it has affected humans in various aspects of life, including social, economic, cultural, and political. It is also true that researchers have made vigorous efforts to overcome COVID-19 throughout the world, but they still have a long way to go. Accordingly, innumerable therapeutics and vaccine candidates have been studied for their efficacies and have been tried clinically in a very short span of time. For example, the versatility of extracellular vesicles, which are membrane-bound particles released from all types of cells, have recently been highlighted in terms of their effectiveness, biocompatibility, and safety in the fight against COVID-19. Thus, here, we tried to explain the use of extracellular vesicles as therapeutics and for the development of vaccines against COVID-19. Along with the mechanisms and a comprehensive background of their application in trapping the coronavirus or controlling the cytokine storm, we also discuss the obstacles to the clinical use of extracellular vesicles and how these could be resolved in the future.

Temperature and chemical effects on the interfacial energy between a Ga-In-Sn eutectic liquid alloy and nanoscopic asperities.

The interfacial energies between a eutectic Ga-In-Sn liquid alloy and single nanoscopic asperities of SiO x , Au, and PtSi have been determined in the temperature range between room temperature and 90 °C by atomic force spectroscopy. For all asperities used here, we find that the interfacial tension of the eutectic Ga-In-Sn liquid alloy is smaller than its free surface energy by a factor of two (for SiO x ) to eight (for PtSi). Any significant oxide growth upon heating studied was not detected here, and the measured interfacial energies strongly depend on the chemistry of the asperities. We also observe a weak increase of the interfacial energy as a function of the temperature, which can be explained by the reactivity between SiO x and Ga and the occurrence of chemical segregation at the liquid alloy surface.

The impact and role of hepatic hydrothorax in the prognosis of patients with decompensated cirrhosis: A retrospective propensity score-matched study.

Background and aims: Hepatic Hydrothorax (HH) is one of the complications in patients with decompensated cirrhosis and its impact and role in the prognosis of patients with decompensated cirrhosis are not yet clear. Thus, this study aimed to determine the role of HH in patients with decompensated cirrhosis and the long-term impact on their mortality. Materials and methods: A retrospective study analyzed 624 patients with ascites without pleural effusion in decompensated cirrhosis and 113 patients with HH. Propensity scores were calculated based on eight variables, and the HH and non-HH groups were matched in a 1:1 ratio. The effect and role of HH on the prognosis of patients with decompensated cirrhosis was analyzed using the Kaplan-Meier method and Cox proportional hazards regression model. Results: A total of 737 patients were included. Out of 113 HH patients, 106 could be matched to 106 non-HH patients. After matching, baseline characteristics were well-balanced. The multifactorial Cox proportional hazards model indicated that hepatic encephalopathy and HH were independent risk factors affecting prognostic survival in patients with decompensated cirrhosis (P < 0.01), with risk ratios and 95% confidence intervals (CI) of 2.073 (95% CI: 1.229-3.494, P < 0.01) and 4.724 (95% CI: 3.287-6.789, P < 0.01), respectively. Prognostic survival was significantly worse in the HH group compared to patients in the non-HH group, with mortality rates of 17.9, 30.1, and 59.4% at 6 months, 1 year, and 2 years in the HH group, compared to 0.9, 3.8, and 5.6% in the non-HH group, respectively. The estimated median survival time was 21 (95% CI: 18-25) months in the HH group and 49 (95% CI: 46-52) months in the non-HH group (P < 0.001). Conclusion: Hepatic hydrothorax is significantly associated with higher mortality in patients with decompensated cirrhosis and is a highly negligible independent decompensated event affecting their prognosis.