Additive-Driven Nanoscale Architecture of Solid Electrolyte Interphase Revealed by Cryogenic Transmission Electron Microscopy.

In Li metal batteries (LMBs), which boast the highest theoretical capacity, the chemical structure of the solid electrolyte interphase (SEI) serves as the key component that governs the growth of reactive Li. Various types of additives have been developed for electrolyte optimization, representing one of the most effective strategies to enhance the SEI properties for stable Li plating. However, as advanced electrolyte systems become more chemically complicated, the use of additives is empirically optimized. Indeed, their role in SEI formation and the resulting cycle life of LMBs are not well-understood. In this study, we employed cryogenic transmission electron microscopy combined with Raman spectroscopy, theoretical studies including molecular dynamics (MD) simulations and density functional theory (DFT) calculations, and electrochemical measurements to explore the nanoscale architecture of SEI modified by the most representative additives, lithium nitrate (LiNO3) and vinylene carbonate (VC), applied in a localized high-concentration electrolyte. We found that LiNO3 and VC play distinct roles in forming the SEI, governing the solvation structure, and influencing the kinetics of electrochemical reduction. Their collaboration leads to the desired SEI, ensuring prolonged cycle performance for LMBs. Moreover, we propose mechanisms for different Li growth and cycling behaviors that are determined by the physicochemical properties of SEI, such as uniformity, elasticity, and ionic conductivity. Our findings provide critical insights into the appropriate use of additives, particularly regarding their chemical compatibility.

Deterministic Orientation Control of Ferroelectric HfO2 Thin Film Growth by a Topotactic Phase Transition of an Oxide Electrode.

The scale-free ferroelectricity with superior Si compatibility of HfO2 has reawakened the feasibility of scaled-down nonvolatile devices and beyond the complementary metal-oxide-semiconductor (CMOS) architecture based on ferroelectric materials. However, despite the rapid development, fundamental understanding, and control of the metastable ferroelectric phase in terms of oxygen ion movement of HfO2 remain ambiguous. In this study, we have deterministically controlled the orientation of a single-crystalline ferroelectric phase HfO2 thin film via oxygen ion movement. We induced a topotactic phase transition of the metal electrode accompanied by the stabilization of the differently oriented ferroelectric phase HfO2 through the migration of oxygen ions between the oxygen-reactive metal electrode and the HfO2 layer. By stabilizing different polarization directions of HfO2 through oxygen ion migration, we can gain a profound understanding of the oxygen ion-relevant unclear phenomena of ferroelectric HfO2.

Structure Effects of Ligands in Gold-Ligand Complexes for Controlled Formation of Gold Nanoclusters.

Metal nanoclusters (NCs) are a special class of nanoparticles composed of a precise number of metal atoms and ligands. Because the proportion of ligands to metal atoms is high in metal NCs, the ligand type determines the physical properties of metal NCs. Furthermore, ligands presumably govern the entire formation process of the metal NCs. However, their roles in the synthesis, especially as factors in the uniformity of metal NCs, are not understood. It is because the synthetic procedure of metal NCs is highly convoluted. The synthesis is initiated by the formation of various metal-ligand complexes, which have different numbers of atoms and ligands, resulting in different coordinations of metal. Moreover, these complexes, as actual precursors to metal NCs, undergo sequential transformations into a series of intermediate NCs before the formation of the desired NCs. Thus, to resolve the complicated synthesis of metal NCs and achieve their uniformity, it is important to investigate the reactivity of the complexes. Herein, we utilize a combination of mass spectrometry, density functional theory, and electrochemical measurements to understand the ligand effects on the reactivity of AuI-thiolate complexes toward the reductive formation of Au NCs. We discover that the stability of the complexes can be increased by either van der Waals interactions induced by the long carbon chain of ligands or by non-thiol functional groups in the ligands, which additionally coordinate with AuI in the complexes. Such structural effects of thiol ligands determine the reduction reactivity of the complexes and the amount of NaBH4 required for the controlled synthesis of the Au NCs.

Statin administration or blocking PCSK9 alleviates airway hyperresponsiveness and lung fibrosis in high-fat diet-induced obese mice.

BACKGROUND: Obesity is associated with airway hyperresponsiveness and lung fibrosis, which may reduce the effectiveness of standard asthma treatment in individuals suffering from both conditions. Statins and proprotein convertase subtilisin/kexin-9 inhibitors not only reduce serum cholesterol, free fatty acids but also diminish renin-angiotensin system activity and exhibit anti-inflammatory effects. These mechanisms may play a role in mitigating lung pathologies associated with obesity. METHODS: Male C57BL/6 mice were induced to develop obesity through high-fat diet for 16 weeks. Conditional TGF-ß1 transgenic mice were fed a normal diet. These mice were given either atorvastatin or proprotein convertase subtilisin/kexin-9 inhibitor (alirocumab), and the impact on airway hyperresponsiveness and lung pathologies was assessed. RESULTS: High-fat diet-induced obesity enhanced airway hyperresponsiveness, lung fibrosis, macrophages in bronchoalveolar lavage fluid, and pro-inflammatory mediators in the lung. These lipid-lowering agents attenuated airway hyperresponsiveness, macrophages in BALF, lung fibrosis, serum leptin, free fatty acids, TGF-ß1, IL-1ß, IL-6, and IL-17a in the lung. Furthermore, the increased RAS, NLRP3 inflammasome, and cholecystokinin in lung tissue of obese mice were reduced with statin or alirocumab. These agents also suppressed the pro-inflammatory immune responses and lung fibrosis in TGF-ß1 over-expressed transgenic mice with normal diet. CONCLUSIONS: Lipid-lowering treatment has the potential to alleviate obesity-induced airway hyperresponsiveness and lung fibrosis by inhibiting the NLRP3 inflammasome, RAS and cholecystokinin activity.

Controlling Surface Structure and Primary Particle Size to Enhance Performance and Reduce Gas Evolution in Lithium- and Manganese-Rich Layered Oxide Cathodes.

Practical application of lithium- and manganese-rich layered oxide cathodes has been hindered despite their high performance and low cost owing to high gas evolution accompanying capacity loss even in a conservative voltage window. Here, we control the surface structure and primary particle size of lithium- and manganese-rich layered oxide cathodes not only to enhance the electrochemical performance but also to reduce gas evolution. Sulfur-coated Fm3̅m/R3̅m double reduced surface layers and Mo doping dramatically reduce gas evolution, which entails the improvement of electrochemical performance. With the optimization, we prove that it is competitive enough to conventional high-nickel cathodes in the aspects of gas evolution as well as electrochemical performance in the conservative voltage window of 2.5-4.4 V. Our findings provide invaluable insights on the improvement of electrochemical performance and gas evolution properties in lithium- and manganese-rich layered oxide cathodes.

Cold-Responsive Hyaluronated Upconversion Nanoplatform for Transdermal Cryo-Photodynamic Cancer Therapy.

Cryotherapy leverages controlled freezing temperature interventions to engender a cascade of tumor-suppressing effects. However, its bottleneck lies in the standalone ineffectiveness. A promising strategy is using nanoparticle therapeutics to augment the efficacy of cryotherapy. Here, a cold-responsive nanoplatform composed of upconversion nanoparticles coated with silica - chlorin e6 - hyaluronic acid (UCNPs@SiO2-Ce6-HA) is designed. This nanoplatform is employed to integrate cryotherapy with photodynamic therapy (PDT) in order to improve skin cancer treatment efficacy in a synergistic manner. The cryotherapy appeared to enhance the upconversion brightness by suppressing the thermal quenching. The low-temperature treatment afforded a 2.45-fold enhancement in the luminescence of UCNPs and a 3.15-fold increase in the photodynamic efficacy of UCNPs@SiO2-Ce6-HA nanoplatforms. Ex vivo tests with porcine skins and the subsequent validation in mouse tumor tissues revealed the effective HA-mediated transdermal delivery of designed nanoplatforms to deep tumor tissues. After transdermal delivery, in vivo photodynamic therapy using the UCNPs@SiO2-Ce6-HA nanoplatforms resulted in the optimized efficacy of 79% in combination with cryotherapy. These findings underscore the Cryo-PDT as a truly promising integrated treatment paradigm and warrant further exploring the synergistic interplay between cryotherapy and PDT with bright upconversion to unlock their full potential in cancer therapy.

Safety, Tolerability, Pharmacokinetics, and pharmacodynamics of YH35324, a novel Long-Acting High-Affinity IgETrap-Fc protein in subjects with Atopy: Results from the First-in-Human study.

BACKGROUND: YH35324, a long-acting IgETrap-Fc fusion protein, is a novel therapeutic agent for immunoglobulin E (IgE)-mediated allergic diseases. This randomized, double-blind, placebo/active-controlled, single ascending dose Phase 1 study assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH35324 in subjects with atopy. METHODS: Eligible subjects were healthy subjects or atopic adults with mild allergic rhinitis, atopic dermatitis, food allergy, or urticaria, and a serum total IgE level of 30-700 IU/mL (Part A) or > 700 IU/mL (Part B). In Part A, 35 subjects in 5 cohorts received YH35324 (0.3, 1, 3, 6, and 9 mg/kg), 8 received omalizumab (300 mg), and 9 received placebo. In Part B, 8 subjects received YH35324 and 8 received omalizumab. RESULTS: Twenty subjects (38.5 %) in Part A (YH35324: 37.1 %, omalizumab: 50.0 %, placebo: 33.3 %) and 10 subjects (62.5 %) in Part B (YH35324: 100 %; omalizumab: 25.0 %) experienced treatment-emergent adverse events (TEAEs). TEAEs were mostly grade 1/2; no serious AEs, AE-related treatment discontinuation, or anaphylaxis were reported. YH35324 exhibited dose-proportional increase in Cmax and AUClast over the dose range of 0.3-9 mg/kg. YH35324 rapidly suppressed serum-free IgE levels to a significant extent (< 25 and < 82.8 ng/mL, both P < 0.05) and with longer duration than omalizumab. CONCLUSION: This study showed that YH35324 has a favorable safety profile and is effective in reducing serum-free IgE levels in subjects with atopic conditions.

Insights into structural defect formation in individual InP/ZnSe/ZnS quantum dots under UV oxidation.

InP/ZnSe/ZnS quantum dots (QDs) stand as promising candidates for advancing QD-organic light-emitting diodes (QLED), but low emission efficiency due to their susceptibility to oxidation impedes applications. Structural defects play important roles in the emission efficiency degradation of QDs, but the formation mechanism of defects in oxidized QDs has been less investigated. Here, we investigated the impact of diverse structural defects formation on individual QDs and propagation during UV-facilitated oxidation using high-resolution (scanning) transmission electron microscopy. UV-facilitated oxidation of the QDs alters shell morphology by the formation of surface oxides, leaving ZnSe surfaces poorly passivated. Further oxidation leads to the formation of structural defects, such as dislocations, and induces strain at the oxide-QD interfaces, facilitating In diffusion from the QD core. These changes in the QD structures result in emission quenching. This study provides insight into the formation of structural defects through photo-oxidation, and their effects on emission properties of QDs.

Covalent-Frameworked 2D Crown Ether with Chemical Multifunctionality.

Here, we present the synthesis and characterization of a novel 2D crystalline framework, named C2O, which mainly consists of carbon and oxygen in a 2:1 molar ratio and features crown ether holes in its skeletal structure. The covalent-frameworked 2D crown ether can be synthesized on a gram-scale and exhibits fine chemical stability in various environments, including acid, base, and different organic solvents. The C2O efficiently activates KI through the strong coordination of K+ with crown ether holes in a rigid framework, which enhances the nucleophilicity of I- and significantly improves its catalytic activity for CO2 fixation with epoxides. The presence of C2O with KI results in remarkable increases in CO2 conversion from 5.7% to 99.9% and from 2.9% to 74.2% for epichlorohydrin and allyl glycidyl ether, respectively. Moreover, C2O possesses both electrophilic and nucleophilic sites at the edge of its framework, allowing for the customization of physicochemical properties by a diverse range of chemical modifications. Specifically, incorporating allyl glycidyl ether (AGE) as an electrophile or ethoxyethylamine (EEA) as a nucleophile into C2O enables the synthesis of C2O-AGE or C2O-EEA, respectively. These modified frameworks exhibit improved conversions of 97.2% and 99.9% for CO2 fixation with allyl glycidyl ether, outperforming unmodified C2O showing a conversion of 74.2%. This newly developed scalable, durable, and customizable covalent framework holds tremendous potential for the design and preparation of outstanding materials with versatile functionalities, rendering them highly attractive for a wide range of applications.

Effects of Multidisciplinary Health Promotion Program Among Children in Community Childcare Center.

In this study, the effects of a 12-month multidisciplinary education program on the health status, dietary quality, and eating habits of children and adolescents attending community childcare centers were investigated. A total of 88 participants aged 7 to 17 years from 7 community childcare centers in Gyeonggi-do were enrolled. The intervention consisted of 12 multidisciplinary education sessions covering topics such as nutrition, exercise, and psychological education. All participants received the same education, and the effectiveness of the program was evaluated by categorizing them into a high participation group (HPG) and a low participation group (LPG) based on their participation rates. After intervention, in physical activities, moderate-intensity exercise was significantly reduced in the LPG, and there was no significant difference in psychological parameters. However, notable differences were observed in nutritional data. After intervention, intakes of calorie, carbohydrate, protein, and fat were significantly increased in both groups, and in particular, the change was found to be greater in HPG. Additionally, dietary fiber intake compared to the 2015 Korean Dietary Reference Intakes was increased in both groups. Daily food intake also increased dietary fiber intake in HPG, and meat and fruit intake was increased in LPG. In the nutrition quotient, there was a significant difference in HPG's pre- and post-scores in the diversity category, and in nutrient adequacy ratio (NAR), the NAR of phosphorus was increased in both groups. The findings of this study suggest that multidisciplinary education implemented at community childcare centers primarily enhanced nutrition-related factors rather than physical activity or psychological aspects. Trial Registration: Clinical Research Information Service Identifier: KCT0002718.

Observing growth and interfacial dynamics of nanocrystalline ice in thin amorphous ice films.

Ice crystals at low temperatures exhibit structural polymorphs including hexagonal ice, cubic ice, or a hetero-crystalline mixture of the two phases. Despite the significant implications of structure-dependent roles of ice, mechanisms behind the growths of each polymorph have been difficult to access quantitatively. Using in-situ cryo-electron microscopy and computational ice-dynamics simulations, we directly observe crystalline ice growth in an amorphous ice film of nanoscale thickness, which exhibits three-dimensional ice nucleation and subsequent two-dimensional ice growth. We reveal that nanoscale ice crystals exhibit polymorph-dependent growth kinetics, while hetero-crystalline ice exhibits anisotropic growth, with accelerated growth occurring at the prismatic planes. Fast-growing facets are associated with low-density interfaces that possess higher surface energy, driving tetrahedral ordering of interfacial H2O molecules and accelerating ice growth. These findings, based on nanoscale observations, improve our understanding on early stages of ice formation and mechanistic roles of the ice interface.

Small, solubilized platinum nanocrystals consist of an ordered core surrounded by mobile surface atoms.

In situ structures of Platinum (Pt) nanoparticles (NPs) can be determined with graphene liquid cell transmission electron microscopy. Atomic-scale three-dimensional structural information about their physiochemical properties in solution is critical for understanding their chemical function. We here analyze eight atomic-resolution maps of small (<3 nm) colloidal Pt NPs. Their structures are composed of an ordered crystalline core surrounded by surface atoms with comparatively high mobility. 3D reconstructions calculated from cumulative doses of 8500 and 17,000 electrons/pixel, respectively, are characterized in terms of loss of atomic densities and atomic displacements. Less than 5% of the total number of atoms are lost due to dissolution or knock-on damage in five of the structures analyzed, whereas 10-16% are lost in the remaining three. Less than 5% of the atomic positions are displaced due to the increased electron irradiation in all structures. The surface dynamics will play a critical role in the diverse catalytic function of Pt NPs and must be considered in efforts to model Pt NP function computationally.

Characterization of Hum j 6, a Major Allergen From Humulus japonicus Pollen, the Primary Cause of Weed Pollinosis in East Asia.

PURPOSE: Humulus japonicus (HJ) is one of the most important causes of weed pollinosis in East Asia. The 10 kDa protein with pI 10 in 2-dimensional gel has been recognized as the representative major allergen of HJ, but its major allergens have not been characterized. This study aimed to characterize the major allergen of HJ. METHODS: A major allergen in Japanese hop was detected by proteome analysis; it was purified to homogeneity and its sequence was obtained by transcriptome analysis. The recombinant proteins were produced in Escherichia coli and Pichia expression systems, and their immunoglobulin E (IgE) reactivities were compared to those of the natural counterpart. We also analyzed post-translational modifications such as glycosylation and phosphorylation. RESULTS: Pectin methylesterase inhibitor, Hum j 6, was found to be the major allergen of HJ, and in silico signal peptide prediction corresponds to a 15.1 kDa protein with a theoretical pI of 8.28. Natural Hum j 6 was recognized by IgE antibodies from 86.4% (19/22) of HJ pollinosis patients, whereas the recombinant proteins did not show strong IgE reactivity. No glycosylation was detected, while at least 15 phosphorylated amino acids, possibly causing the pI and molecular weight shift, were detected by tandem mass spectrometry analysis. CONCLUSIONS: Hum j 6 was identified as the representative major allergen of HJ and seems to be modified significantly after translation. These findings are useful for the development of component-resolved diagnosis and immunotherapy.

Invasive FoxM1 phosphorylated by PLK1 induces the polarization of tumor-associated macrophages to promote immune escape and metastasis, amplified by IFITM1.

BACKGROUND: Understanding the mechanism behind immune cell plasticity in cancer metastasis is crucial for identifying key regulators. Previously we found that mitotic factors regulate epithelial-mesenchymal transition, but how these factors convert to metastatic players in the tumor microenvironment (TME) is not fully understood. METHODS: The clinical importance of mitotic factors was analyzed by heatmap analysis, a KM plot, and immunohistochemistry in lung adenocarcinoma (LUAD) patients. Immunoprecipitation, LC-MS/MS, kinase assay, and site-directed mutagenesis were performed for the interaction and phosphorylation. A tail-vein injection mouse model, Transwell-based 3D culture, microarray analysis, coculture with monocytes, and chromatin immunoprecipitation assays were used to elucidate the function of phosphorylated FoxM1 in metastasis of TME. RESULTS: The phosphorylated FoxM1 at Ser25 by PLK1 acquires the reprogramming ability to stimulate the invasive traits in cancer and influence immune cell plasticity. This invasive form of p-FoxM1 upregulates the expression of IL1A/1B, VEGFA, and IL6 by direct activation, recruiting monocytes and promoting the polarization of M2d-like tumor-associated macrophages (TAMs). Upregulation of PD-L1 in LUAD having phosphomimetic FoxM1 facilitates immune evasion. In invasive LUAD with phosphomimetic FoxM1, IFITM1 is the most highly expressed through the activation of the STING-TBK1-IRF3 signaling, which enhances FoxM1-mediated signaling. Clinically, higher expression of FOXM1, PLK1, and IFITM1 is inversely correlated with the survival rate of advanced LUAD patients, providing a promising therapeutic strategy for the treatment of LUAD. CONCLUSION: FoxM1-based therapy would be a potential therapeutic strategy for LUAD to reduce TAM polarization, immune escape, and metastasis, since FoxM1 functions as a genetic reprogramming factor reinforcing LUAD malignancy in the TME.

Effects of chitinase-1 inhibitor in obesity-induced and -aggravated asthma in a murine model.

AIMS: Despite recent investigations on the role of chitinase in asthma, its role in obesity-induced asthma has not been evaluated. Therefore, we investigated the roles of chitin, chitinase-1, and a chitinase-1 inhibitor (compound X, CPX) in a murine model. MAIN METHODS: We assigned C57BL/6 mice to the ovalbumin (OVA) model or obesity model group. In the OVA model, mice received intraperitoneal OVA twice within a 2-week interval and intranasal OVA for 3 consecutive days. Additionally, chitin was intranasally administered for 3 consecutive days, and CPX was intraperitoneally injected three times over 5 days. In the obesity model, a high-fat diet (HFD) was maintained for 13 weeks, and CPX was intraperitoneally injected eight times over 4 weeks. KEY FINDINGS: In the OVA model, chitin aggravated OVA-induced airway hyper-responsiveness (AHR), increased bronchoalveolar lavage fluid (BALF) cell proliferation, increased fibrosis, and increased the levels of various inflammatory cytokines (including chitinase-1, TGF-ß, TNF-α, IL-1 ß, IL-6, IL-4, and IL-13). CPX treatment significantly ameliorated these effects. In the obesity model, HFD significantly increased AHR, BALF cell proliferation, fibrosis, and the levels of various inflammatory cytokines. Particularly, compared to the control group, the mRNA expression of chitinase, chitinase-like molecules, and other molecules associated with inflammation and the immune system was significantly upregulated in the HFD and HFD/OVA groups. Immunofluorescence analysis also showed increased chitinase-1 expression in these groups. CPX significantly ameliorated all these effects in this model. SIGNIFICANCE: This study showed that CPX can be an effective therapeutic agent in asthma, especially, obesity-induced and -aggravated asthma to protect against the progression to airway remodeling and fibrosis.

Classification of a 3D Film Pattern Image Using the Optimal Height of the Histogram for Quality Inspection.

A 3D film pattern image was recently developed for marketing purposes, and an inspection method is needed to evaluate the quality of the pattern for mass production. However, due to its recent development, there are limited methods to inspect the 3D film pattern. The good pattern in the 3D film has a clear outline and high contrast, while the bad pattern has a blurry outline and low contrast. Due to these characteristics, it is challenging to examine the quality of the 3D film pattern. In this paper, we propose a simple algorithm that classifies the 3D film pattern as either good or bad by using the height of the histograms. Despite its simplicity, the proposed method can accurately and quickly inspect the 3D film pattern. In the experimental results, the proposed method achieved 99.09% classification accuracy with a computation time of 6.64 s, demonstrating better performance than existing algorithms.