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Rationale and Objectives: To determine the relationship between heightened levels of reader performance and reader practice in terms of number of cases read and previous experience. Materials and Methods: A test set of mammograms was developed comprising 50 cases. These cases consisted of 15 abnormals (biopsy proven) and 35 normals (confirmed at subsequent rescreen). Sixty-nine breast image readers reviewed these cases independently and their performance was measured by recording their individual receiver operating characteristic score (area under the curve), sensitivity, and specificity. These measures of performance were then compared to a range of factors relating to the reader such as years of certification and reporting, number of cases read per year, previous experiences, and satisfaction levels. Correlation analyses using Spearman methods were performed along with the Mann-Whitney test to detect differences in performance between specific reader groups. Results: Improved reader performance was found for years certified (P = .004), years of experience (P = .0001), and hours reading per week (P = .003) shown by positive statistical significant relationships with Az values (area under receiver operating characteristic curve). Statistical comparisons of Az values scored for individuals who read varying number of cases per year showed that those individuals whose annual mammographic case load was 5000 or more (P = .03) or between 2000 and 4999 (P = .05), had statistically significantly higher scores than those who read less than 1000 cases per year. Conclusion: The results of this study have shown variations in reader performance relating to parameters of reader practice and experience. Levels of variance are shown and potential acceptance levels for diagnostic efficacy are proposed which may inform policy makers, judicial systems and public debate. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) are critical regulators of the immune system, and altered TLR responses lead to a variety of inflammatory diseases. Interference of intracellular TLR signaling, which is mediated by multiple Toll/interleukin-1 receptor (TIR) domains on all TLRs and TLR adapters, is an effective therapeutic strategy against immune dysregulation. Peptides that inhibit TIR-TIR interactions by fragmenting interface residues have potential as therapeutic decoys. However, a systematic method for discovering TIR-targeting moieties has been elusive, limiting exploration of the vast, unsequenced space of the TIR domain family. A comprehensive parallel screening method is developed to uncover novel TIR-binding peptides derived from previously unexplored surfaces on a wide range of TIR domains. A large peptide library is constructed, named TIR surfacesome, by tiling surface sequences of the large TIR domain family and screening against MAL TIR and MyD88 TIR , TIRs of two major TLR adaptor proteins, resulting in the discovery of hundreds of TIR-binding peptides. The selected peptides inhibited TLR signaling and demonstrated anti-inflammatory effects in macrophages, and therapeutic potential in mouse inflammatory models. This approach may facilitate the development of TLR-targeted therapeutics., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The physicochemical characterization of trivalent ions is limited due to a lack of accurate force fields. By leveraging the latest machine learning force field to model aqueous AlCl 3 , we discover that upon dissolution of Al 3+ , water molecules beyond the second hydration shell are involved in the hydration process. A combination of scissoring of coordinating water is followed by synchronized secondary motion of water in the second solvation shell due to hydrogen bonding. Consequently, the water beyond the second solvation penetrates through the second solvation shell and coordinates to the Al 3+ . Our study reveals a novel microscopic understanding of solvation dynamics for the trivalent ion.

One of the key design factors that regulate the properties of grafted nanoparticles (GNPs) and their self-assembly is the conformation of the grafted polymer. On the curved surface of the GNP core, the conformation of the polymer chain is not uniform in the radial direction. The segment is a non-Gaussian chain in the concentrated polymer brush (CPB) regime near the interface between GNP core and grafted polymer, while it is less constrained in the semidilute polymer brush (SDPB) regime near the surface of GNP. Here, the property of polymer conformation showing crossover behavior at the CPB/SDPB threshold through the coarse-grain molecular dynamics simulation of nanoparticles with explicit grafted chains is explored. Moreover, the self-assembly structure depends on the effective softness, which is defined as a function of the threshold of two regimes estimated from the conformation of the polymer., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Myristica fragrans Houtt. is rich in lignans, neolignans, and diarylnonanoids, with well-documented anti-inflammatory properties. However, there is limited research on the conjugated forms of diarylnonanoids, neolignans, monoterpenes, and others and their anti-inflammatory effects. Our study isolated 33 new compounds ( 2 - 7, 9 - 22 , and 41 - 52 ), including two neolignans, alongside various neolignan-diarylnonanoid, propenylbenzene-diarylnonanoid, 2,3-dimethylbutane-type lignan-diarylnonanoid, and monoterpene-diarylnonanoid conjugates, along with previously reported compounds ( 1 , 8 , and 23 - 40 ). Their chemical structures were determined via spectroscopic analyses. Compounds 2 , 4 , 9 , 11 , 12 , 14 , 17 , and 18 exhibited potent inhibition of NF-κB/AP1 and IRF signaling induced by TLR agonists. Notably, stereoisomers showed distinct behavior, while 10 R ,11 R -isomers induced cytotoxicity, and 10 S ,11 R -isomers produced contrasting effects, especially within group-I compounds., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Many countries consider long-term implications for society.

Development of robust electrocatalysts for the oxygen evolution reaction (OER) underpins the efficient production of green hydrogen via anion exchange membrane water electrolysis (AEMWE). This study elucidates the factors contributing to the degradation of cobalt-based (Co-based) OER catalysts synthesized via electrodeposition, thus establishing strategic approaches to enhance their longevity. Systematic variations in the electroplating process and subsequent heat treatment reveal a delicate balance between catalytic activity and durability, substantiated by comprehensive electrochemical assessments and material analyses. Building upon these findings, the Co-based anode is successfully optimized in the AEMWE single-cell configuration, showcasing an average degradation rate of 0.07 mV h -1 over a continuous operation for 1500 h at a current density of 1 A cm -2 ., (© 2024 Wiley‐VCH GmbH.)

The investigation of bottlebrush copolymer self-assembly in solution involves a comprehensive approach integrating simulation and experimental research, due to their unique physical characteristics. However, the intricate architecture of bottlebrush copolymers and the diverse solvent conditions introduce a wide range of parameter spaces. In this study, we investigated the solution self-assembly behavior of bottlebrush copolymers by combining dissipative particle dynamics (DPD) simulation results and machine learning (ML) including graph convolutional networks (GCNs). The architecture of bottlebrush copolymers is encoded by graphs including connectivity, side chain length, bead types, and interaction parameters of DPD simulation. Using GCN, we accurately predicted the single chain properties of bottlebrush copolymers with over 95% accuracy. Furthermore, phase behavior was precisely predicted using these single chain properties. Shapley additive explanations (SHAP) values of single chain properties to the various self-assembly morphologies were calculated to investigate the correlation between single chain properties and morphologies. In addition, we analyzed single chain properties and phase behavior as a function of DPD interaction parameters, extracting relevant physical properties for vesicle morphology formation. This work paves the way for tailored design in solution of self-assembled nanostructures of bottlebrush copolymers, offering a GCN framework for precise prediction of self-assembly morphologies under various chain architectures and solvent conditions.

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 Au I -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 Au I in the complexes. Such structural effects of thiol ligands determine the reduction reactivity of the complexes and the amount of NaBH 4 required for the controlled synthesis of the Au NCs.

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 (LiNO 3 ) and vinylene carbonate (VC), applied in a localized high-concentration electrolyte. We found that LiNO 3 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.

Overexpression of human CD200 (hCD200) in porcine endothelial cells (PECs) has been reported to suppress xenogeneic immune responses of human macrophages against porcine endothelial cells. The current study aimed to address whether the above-mentioned beneficial effect of hCD200 is mediated by overcoming the molecular incompatibility between porcine CD200 (pCD200) and hCD200 receptor or simply by increasing the expression levels of CD200 without any molecular incompatibility across the two species. We overexpressed hCD200 or pCD200 using lentiviral vectors with V5 marker in porcine endothelial cells and compared their suppressive activity against U937-derived human macrophage-like cells (hMCs) and primary macrophages. In xenogeneic coculture of porcine endothelial cells and human macrophage-like cells or macrophages, hCD200-porcine endothelial cells suppressed phagocytosis and cytotoxicity of human macrophages to a greater extent than pCD200-porcine endothelial cells. Secretion of tumor necrosis factor-α, interleukin-1β, and monocyte chemoattractant protein-1 from human macrophages and expression of M1 phenotypes (inducible nitric oxide synthase, dectin-1, and CD86) were also suppressed by hCD200 to a greater extent than pCD200. Furthermore, in signal transduction downstream of CD200 receptor, hCD200 induced Dok2 phosphorylation and suppressed IκB phosphorylation to a greater extent than pCD200. The above data supported the possibility of a significant molecular incompatibility between pCD200 and human CD200 receptor, suggesting that the beneficial effects of hCD200 overexpression in porcine endothelial cells could be mediated by overcoming the molecular incompatibility across the species barrier rather than by simple overexpression effects of CD200., (© 2024 The Authors. Xenotransplantation published by John Wiley & Sons Ltd.)

The goal of most materials discovery is to discover materials that are superior to those currently known. Fundamentally, this is close to extrapolation, which is a weak point for most machine learning models that learn the probability distribution of data. Herein, we develop reinforcement learning-guided combinatorial chemistry, which is a rule-based molecular designer driven by trained policy for selecting subsequent molecular fragments to get a target molecule. Since our model has the potential to generate all possible molecular structures that can be obtained from combinations of molecular fragments, unknown molecules with superior properties can be discovered. We theoretically and empirically demonstrate that our model is more suitable for discovering better compounds than probability distribution-learning models. In an experiment aimed at discovering molecules that hit seven extreme target properties, our model discovered 1315 of all target-hitting molecules and 7629 of five target-hitting molecules out of 100 000 trials, whereas the probability distribution-learning models failed. Moreover, it has been confirmed that every molecule generated under the binding rules of molecular fragments is 100% chemically valid. To illustrate the performance in actual problems, we also demonstrate that our models work well on two practical applications: discovering protein docking molecules and HIV inhibitors., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The chemical degradation of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-based aqueous energy storage and catalytic systems is pH sensitive. Herein, we voltammetrically monitor the local pH (pH local ) at a Pt ultramicroelectrode (UME) upon electro-oxidation of imidazolium-linker functionalized TEMPO and show that its decrease is associated with the greater acidity of the cationic (oxidized) rather than radical (reduced) form of TEMPO. The protons that drive the decrease in pH arise from hydrolysis of the conjugated imidazolium-linker functional group of 4-[2-( N -methylimidazolium)acetoxy]-2,2,6,6-tetramethylpiperidine-1-oxyl chloride (MIMAcO-T), which was studied in comparison with 4-hydroxyl-TEMPO (4-OH-T). Voltammetric hysteresis is observed during the electrode oxidation of 4-OH-T and MIMAcO-T at a Pt UME in an unbuffered aqueous solution. The hysteresis arises from the pH-dependent formation and dissolution of Pt oxides, which interact with pH local in the vicinity of the UME. We find that electrogenerated MIMAcO-T + significantly influences pH local , whereas 4-OH-T + does not. Finite element analysis reveals that the thermodynamic and kinetic acid-base properties of MIMAcO-T + are much more favorable than those of its reduced counterpart. Imidazolium-linker functionalized TEMPO molecules comprising different linking groups were also investigated. Reduced TEMPO molecules with carbonyl linkers behave as weak acids, whereas those with alkyl ether linkers do not. However, oxidized TEMPO + molecules with alkyl ether linkers exhibit more facile acid-base kinetics than those with carbonyl ones. Density functional theory calculations confirm that OH - adduct formation on the imidazolium-linker functional group of TEMPO is responsible for the difference in the acid-base properties of the reduced and oxidized forms.

We propose and demonstrate an angularly offset multiline (AOML) dispersive silicon nitride optical phased array (OPA) that enables efficient line beam scanning with an expanded field of view (FOV) and plateau envelope. The suggested AOML OPA incorporates multiline OPA units, which were seamlessly integrated with a 45° angular offset through a thermo-optic switch based on a multimode interference coupler, resulting in a wide FOV that combines three consecutive scanning ranges. Simultaneously, a periodic diffraction envelope rendered by the multiline OPA units contributes to reduced peak intensity fluctuation of the main lobe across the large FOV. An expedient polishing enabling the angled facet was diligently accomplished through the implementation of oblique polishing techniques applied to the 90° angle of the chip. For each dispersive OPA unit, we engineered an array of delay lines with progressively adjustable delay lengths, enabling a passive wavelength-tunable beam scanning. Experimental validation of the proposed OPA revealed efficient beam scanning, achieved by wavelength tuning from 1530 to 1600 nm and seamless switching between multiline OPAs, yielding an FOV of 152° with a main lobe intensity fluctuation of 2.8 dB. The measured efficiency of dispersive scanning was estimated at 0.97°/nm, as intended.

Technologies that detect circularly polarized light (CPL), particularly in the UV region, have significant potential for various applications, including bioimaging and optical communication. However, a major challenge in directly sensing CPL arises from the conflicting requirements of planar structures for efficient charge transport and distorted structures for effective interaction with CPL. Here, a novel design of an axially chiral n-type organic semiconductor is presented to surmount the challenge, in which a binaphthyl group results in a high dissymmetry factor at the molecular level, while maintaining excellent electron-transporting characteristics through the naphthalene diimide group. Experimental and computational methods reveal different stacking behaviors in homochiral and heterochiral assemblies, yielding different structures: Nanowires and nanoparticles, respectively. Especially, the homochiral assemblies exhibit effective π-π stacking between naphthalene diimides despite axial chirality. Thus, phototransistors fabricated using enantiomers exhibit a high maximum electron mobility of 0.22 cm 2 V -1 s -1 and a detectivity of 3.9 × 10 12 Jones, alongside the CPL distinguishing ability with a dissymmetry factor of responsivity of 0.05. Furthermore, the material possesses a wide bandgap, contributing to its excellent visible-blind UV-selective detection. These findings highlight the new strategy for compact CPL detectors, coupled with the demonstration of less-explored n-type and UV region phototransistors., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

This study proposes a solid-state two-dimensional beam-steering device based on an electro-optical phased array (EOPA) in thin-film lithium niobate (TFLN) and silicon nitride (SiN) hybrid platforms, thereby eliminating the requirement for the direct etching of TFLN. Electro-optic (EO) phase modulator array comprises cascaded multimode interference couplers with an SiN strip-loaded TFLN configuration, which is designed and fabricated via i-line photolithography. Each EO modulator element with an interaction region length of 1.56 cm consumed a minimum power of 3.2 pJ/π under a half-wave voltage of 3.64 V and had an estimated modulation speed of 1.2 GHz. Subsequently, an SiN dispersive antenna with a waveguide grating was tethered to the modulator array to form an EOPA, facilitating the out-of-plane radiation of highly defined near-infrared beams. A prepared EOPA utilized EO phase control and wavelength tuning near 1550 nm to achieve a field-of-view of 22° × 5° in the horizontal and vertical directions. The proposed hybrid integrated platform can potentially facilitate low-power and high-speed beam steering.

The advanced patterning process is the basis of integration technology to realize the development of next-generation high-speed, low-power consumption devices. Recently, area-selective atomic layer deposition (AS-ALD), which allows the direct deposition of target materials on the desired area using a deposition barrier, has emerged as an alternative patterning process. However, the AS-ALD process remains challenging to use for the improvement of patterning resolution and selectivity. In this study, we report a superlattice-based AS-ALD (SAS-ALD) process using a two-dimensional (2D) MoS 2 -MoSe 2 lateral superlattice as a pre-defining template. We achieved a minimum half pitch size of a sub-10 nm scale for the resulting AS-ALD on the 2D superlattice template by controlling the duration time of chemical vapor deposition (CVD) precursors. SAS-ALD introduces a mechanism that enables selectivity through the adsorption and diffusion processes of ALD precursors, distinctly different from conventional AS-ALD method. This technique facilitates selective deposition even on small pattern sizes and is compatible with the use of highly reactive precursors like trimethyl aluminum. Moreover, it allows for the selective deposition of a variety of materials, including Al 2 O 3 , HfO 2 , Ru, Te, and Sb 2 Se 3 ., (© 2024. The Author(s).)

Background: Cold ischemia-reperfusion injury (IRI) is an unavoidable complication of kidney transplantation. We investigated the role of regulatory T cells (Treg) in cold IRI and whether the interleukin (IL)-2/anti-IL-2 antibody complex (IL-2C) can ameliorate cold IRI., Methods: We developed a cold IRI mouse model using kidney transplantation and analyzed the IL-2C impact on cold IRI in acute, subacute and chronic phases., Results: Treg transfer attenuated cold IRI, while Treg depletion aggravated cold IRI. Next, IL-2C administration prior to IRI mitigated acute renal function decline, renal tissue damage and apoptosis and inhibited infiltration of effector cells into kidneys and pro-inflammatory cytokine expression on day 1 after IRI. On day 7 after IRI, IL-2C promoted renal regeneration and reduced subacute renal damage. Furthermore, on day 28 following IRI, IL-2C inhibited chronic fibrosis. IL-2C decreased reactive oxygen species-mediated injury and improved antioxidant function. When IL-2C was administered following IRI, it also increased renal regeneration with Treg infiltration and suppressed renal fibrosis. In contrast, Treg depletion in the presence of IL-2C eliminated the positive effects of IL-2C on IRI., Conclusion: Tregs protect kidneys from cold IRI and IL-2C inhibited cold IRI by increasing the renal Tregs, suggesting a potential of IL-2C in treating cold IRI., Key Points: Interleukin (IL)-2/anti-IL-2 antibody complex attenuated acute renal injury, facilitated subacute renal regeneration and suppressed chronic renal fibrosis after cold ischemia-reperfusion injury (IRI) by increasing the renal Tregs. IL-2/anti-IL-2 antibody complex decreased reactive oxygen species-mediated injury and improved antioxidant function. This study suggests the therapeutic potential of the IL-2/anti-IL-2 antibody complex in kidney transplantation-associated cold IR., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Here, we present the synthesis and characterization of a novel 2D crystalline framework, named C 2 O , 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 C 2 O 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 CO 2 fixation with epoxides. The presence of C 2 O with KI results in remarkable increases in CO 2 conversion from 5.7% to 99.9% and from 2.9% to 74.2% for epichlorohydrin and allyl glycidyl ether, respectively. Moreover, C 2 O 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 C 2 O enables the synthesis of C 2 O-AGE or C 2 O-EEA , respectively. These modified frameworks exhibit improved conversions of 97.2% and 99.9% for CO 2 fixation with allyl glycidyl ether, outperforming unmodified C 2 O 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.

Block copolymer self-assembly affords diverse nanostructures, spanning from spheres and cylinders to networks, offering meticulous control over properties and functionalities at the nanoscale. However, creating thermodynamically stable network structures with high packing frustration remains a challenge. In this study, we report a methodology to access diverse network structures such as gyroid, diamond, and primitive phases from diblock copolymers using end group and linker chemistry. The stability of the medial packing of polymer chain ends (plumber's nightmare structure) over skeletal aggregation (gyroid) is attributed to the interplay between the strength of the end-end interactions and the initial shape of the curvature. Our study establishes an approach to develop tailored network structures from block copolymers, providing an important platform for using block copolymers in nanotechnology applications.

This study aimed to assess the impact of different resistance training (RT) loads and repetition on muscle damage, intramuscular anabolic signaling, and maximal muscle strength (MMS) in weightlifters. Eighteen male weightlifters were randomly assigned to 8 weeks of supervised RT regimes: high-load, low-repetition (HL), low-load, high-repetition (LH), and combination of HL and LH (COMBI). All groups exhibited a significant increase in skeletal muscle mass (SMM) and growth hormone levels, which ultimately contributed to improvement in MMS as indicated by 1-repetition maximum in the back squat and back muscle strength. Notably, while there were no significant changes in the mTOR protein, the phosphorylation of phosphorylation of p70 ribosomal protein S6 kinase 1 (p70S6K1), eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), and eukaryotic elongation factor 2 (eEF2), which are involved in muscle cell growth, was significantly affected by the different training regimens. More importantly, LH-RT led to a significant reduction in muscle damage markers, creatine kinase (CK) and lactate dehydrogenase (LDH), suggesting reduced recovery time and fatigue. Our results demonstrated that the LH-RT paradigm could be a viable alternative for weightlifters to enhance MMS and muscle hypertrophy similar to HL-RT, while reducing RT-induced muscle damage, ultimately contributing to the enhancement of exercise performance.

Background: Uveitis is an inflammatory eye condition that threatens vision, and effective anti-inflammatory treatments with minimal side effects are necessary to treat uveitis., Purpose: This study aimed to investigate the effects of Lithospermum erythrorhizon Siebold & Zucc. against endotoxin-induced uveitis in rat and mouse models., Methods: Endotoxin-induced uveitis models of rats and mice were used to evaluate the effects of l. erythrorhizon treatment. Clinical inflammation scores and retinal thickness were assessed in the extract of l. erythrorhizon-treated rats. Histopathological examination revealed inflammatory cell infiltration into the ciliary body. Protein concentration, cellular infiltration, and prostaglandin-E2 levels were measured in the aqueous humor of the extract of l. erythrorhizon-treated rats. Protective effects of l. erythrorhizon on the anterior segment of the eye were examined in mice with endotoxin-induced uveitis. Additionally, we investigated the effect of l. erythrorhizon on the expression of pro-inflammatory cytokines [tumor necrosis factor alpha, interleukin-6, and interleukin-8] in lipopolysaccharide-stimulated THP1 human macrophages and examined the involvement of nuclear factor kappaB/activator protein 1 and interferon regulatory factor signaling pathways. Furthermore, three components of l. erythrorhizon were identified and assessed for their inhibitory effects on LPS-induced inflammation in RAW264.7 macrophage cells., Results: Treatment of the extract of l. erythrorhizon significantly reduced clinical inflammation scores and retinal thickening in rats with endotoxin-induced uveitis. Histopathological examination revealed decreased inflammatory cell infiltration into the ciliary body. The extract of l. erythrorhizon effectively reduced the protein concentration, cellular infiltration, and PG-E2 levels in the aqueous humor of rats with endotoxin-induced uveitis. In mice with endotoxin-induced uveitis, the extract of l. erythrorhizon demonstrated a protective effect on the anterior segment of the eye by reducing inflammation and retinal thickening. The extract of l. erythrorhizon suppressed the expression of pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-6, and interleukin-8) in lipopolysaccharide-induced inflammation in THP1 human macrophages, by modulating nuclear factor kappaB/activator protein 1 and interferon regulatory factor signaling pathways. Moreover, shikonin, acetylshikonin, and β, β-dimethylacryloylshikonin showed dose-dependent inhibition of nitric oxide, tumor necrosis factor alpha and interleukin-6 production in RAW264.7 macrophage cells., Conclusion: The extract of l. erythrorhizon is a potential therapeutic agent for uveitis management. Administration of the extract of l. erythrorhizon led to reduced inflammation, retinal thickening, and inflammatory cell infiltration in rat and mouse models of uveitis. The compounds (shikonin, acetylshikonin, and β, β-dimethylacryloylshikonin) identified in this study played crucial roles in mediating the anti-inflammatory effects of l. erythrorhizon. These findings indicate that the extract of l. erythrorhizon and its constituent compounds are promising candidates for further research and development of novel treatment modalities for uveitis., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023. Published by Elsevier GmbH.)

Introduction: Transformation describes a dramatic modification in appearance or character. Philip Morris International (PMI)'s sponsorship-linked marketing of Formula 1 auto racing is illustrative of transformation. The company's flagship cigarette brand, Marlboro has been replaced as the identified partner by their newly developed brand, Mission Winnow. This study examines the tobacco company's marketing objectives for transforming the brand identity of its Formula 1 Ferrari race team partnership., Aims and Methods: We provide a case study, and our method of qualitative enquiry is textual analysis. We review marketing planning documents from Philip Morris, which would normally be proprietary, but are publicly accessible because of litigation. Additionally, we review Mission Winnow's social media posts, over a 3-year span, from the brand's Facebook, Instagram, and Twitter accounts., Results: PMI initiated its Formula 1 sponsorship in 1972. Through Marlboro, the company's sponsorship-linked marketing was largely centered on building brand image and reinforcing Marlboro's brand identity of rugged masculinity, independence, heroism, and adventure. When Mission Winnow replaced Marlboro as the identified brand sponsor in 2018, the company's marketing communication shifted to highlighting transformation, progress, open dialogue, teamwork, innovation, technology, and science., Conclusions: Despite Article 5.3 of the World Health Organization's Framework Convention on Tobacco Control (WHO FCTC) calling for Parties to protect public health policies from the commercial and vested interests of tobacco companies, PMI still seeks to be an important stakeholder in such consultations, including those pertaining to harm reduction. Mission Winnow's sponsorship-linked marketing points to a larger company narrative about trying to gain or reclaim legitimacy and credibility., Implications: PMI's continued sponsorship of Formula 1 is a strategic means of drawing attention to the company's "next-generation products" and communicating their supposed "transformation." The company's sponsorship-linked marketing initiatives point to a need for Parties to enforce Article 13 of the WHO FCTC, which calls for a comprehensive ban on tobacco advertising, promotion, and sponsorship., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Lithium-ion transport is significantly retarded in ionic liquids (ILs). In this work, we performed extensive molecular dynamics simulations to mimic the kinetics of lithium ions in ILs using [N-methyl-N-propylpyrrolidium (pyr[Formula: see text])][bis(trifluoromethanesulfonyl)imide (Ntf[Formula: see text])] with added LiNtf[Formula: see text] salt. And we analyzed their transport, developing a two-state model and comparing it to the machine learning-identified states. The transport of lithium ions involves local shell exchanges of the Ntf[Formula: see text] in the medium. We calculated train size distributions over various time scales. The train size distribution decays as a power law, representing non-Poissonian bursty shell exchanges. We analyzed the non-Poissonian processes of lithium ions transport as a two-state (soft and hard) model. We analytically calculated the transition probability of the two-state model, which fits well to the lifetime autocorrelation functions of LiNtf[Formula: see text] shells. To identify two states, we introduced the graph neutral network incorporating local molecular structure. The results reveal that the shell-soft state mainly contributes to the transport of the lithium ions, and their contribution is more important in low temperatures. Hence, it is the key for enhanced lithium ion transport to increase the fraction of the shell-soft state., (© 2023. The Author(s), under exclusive licence to EDP Sciences, SIF and Springer-Verlag GmbH Germany, part of Springer Nature.)

To construct tissue-like prosthetic materials, soft electroactive hydrogels are the best candidate owing to their physiological mechanical modulus, low electrical resistance and bidirectional stimulating and recording capability of electrophysiological signals from biological tissues 1,2 . Nevertheless, until now, bioelectronic devices for such prostheses have been patch type, which cannot be applied onto rough, narrow or deep tissue surfaces 3-5 . Here we present an injectable tissue prosthesis with instantaneous bidirectional electrical conduction in the neuromuscular system. The soft and injectable prosthesis is composed of a biocompatible hydrogel with unique phenylborate-mediated multiple crosslinking, such as irreversible yet freely rearrangeable biphenyl bonds and reversible coordinate bonds with conductive gold nanoparticles formed in situ by cross-coupling. Closed-loop robot-assisted rehabilitation by injecting this prosthetic material is successfully demonstrated in the early stage of severe muscle injury in rats, and accelerated tissue repair is achieved in the later stage., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To assess the comparability of international ethics principles and practices used in regulating pediatric research as a first step in determining whether reciprocal deference for international ethics review is feasible. Prior studies by the authors focused on other aspects of international health research, such as biobanks and direct-to-participant genomic research. The unique nature of pediatric research and its distinctive regulation by many countries warranted a separate study., Study Design: A representative sample of 21 countries was selected, with geographical, ethnic, cultural, political, and economic diversity. A leading expert on pediatric research ethics and law was selected to summarize the ethics review of pediatric research in each country. To ensure the comparability of the responses, a 5-part summary of pediatric research ethics principles in the US was developed by the investigators and distributed to all country representatives. The international experts were asked to assess and describe whether principles in their country and the US were congruent. Results were obtained and compiled in the spring and summer of 2022., Results: Some of the countries varied in their conceptualization or description of one or more ethical principles for pediatric research, but overall, the countries in the study demonstrated a fundamental concordance., Conclusions: Similar regulation of pediatric research in 21 countries suggests that international reciprocity is a viable strategy., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Highly stable IGZO thin-film transistors derived from atomic layer deposition are crucial for the semiconductor industry. However, unavoidable defect generation during high-temperature annealing results in abnormal positive bias temperature stress (PBTS). Herein, we propose a defect engineering method by controlling the gate insulator (GI) deposition temperature. Applying a GI deposition temperature of 400 °C to the In 0.52 Ga 0.18 Zn 0.30 O active layer effectively suppresses defects even after 600 °C annealing, preserving the amorphous phase of IGZO. The device exhibits a threshold voltage ( V TH ) of 0.05 V, a field-effect mobility of 27.6 cm 2 /Vs, a subthreshold swing of 61 mV/decade, and a hysteresis voltage of 0.01 V, demonstrating highly reliable PBTS and negative bias temperature stress. A power-law fit of the PBTS stability under 2 MV/cm of gate field stress and 120 °C of temperature stress predicts a V TH shift of -0.01 V after 10 years. Moreover, the proposed method ensures reliable uniformity over a large 4 in. area.

Objectives: This article explores the secondary use provisions of the European Health Data Space (EHDS), proposed by the European Commission in May 2022, and offers policy recommendations for South Korea., Methods: The authors analyzed the texts of the EHDS proposal and other documents published by the European Union, as well as surveyed the relevant literature., Results: The EHDS proposal seeks to create new patient rights over electronic health data collected and used for primary care; and establish a data sharing system for the re-use of electronic health data for secondary purposes, including research, the provision of personalized healthcare, and developing healthcare artificial intelligence (AI) applications. These provisions envisage requiring both private and public data holders to share certain types of electronic health data on a mandatory basis with third parties. New government bodies, called health data access bodies, would review data access applications and issue data permits., Conclusions: The overarching aim of the EHDS proposal is to make electronic health data, which are currently held in the hands of a small number of organizations, available for re-use by third parties to stimulate innovation and research. While it will be very challenging for South Korea to adopt a similar scheme and require private entities to share their proprietary data with third parties, the South Korean government should consider making at least health data collected through publicly funded research more readily available for secondary use.

In this study, the shear-induced lamellar alignment of a thin-film ABA triblock copolymer melt was achieved via a non-equilibrium coarse-grained molecular dynamics simulation. The ABA triblock copolymer system displayed a slightly different phase behavior under different shear conditions compared to the AB diblock copolymer system. Unlike previous studies that only considered the wall velocity, the Flory-Huggins parameter was considered in our study as a factor that determines lamellar alignment. Pre-aligned lamellae and randomly mixed polymers were used as the initial states for the shear simulation to compare the shear-induced lamellar alignment on each. The two initial conditions displayed different alignment behaviors; specifically, in the pre-aligned lamellae, a tilted structure was observed when the system was not aligned in the shear direction. To explain the difference between the tilted and realigned structures, the potential energy over the simulation time, polymer dynamics from the Van Hove correlation function, and the directional order parameter were investigated. It was inferred that a tilted structure is induced by the energy barrier of realignment originating from the restricted movement of the local polymer chains. Once they cross the energy barrier, block copolymers tend to align in the shear direction to attain energy stabilization through the polymer flow.

Metal nanoclusters (NCs), an important class of nanoparticles (NPs), are extremely small in size and possess quasi-molecular properties. Due to accurate stoichiometry of constituent atoms and ligands, NCs have strong structure-property relationship. The synthesis of NCs is seemingly similar to that of NPs as both are formed by colloidal phase transitions. However, they are considerably different because of metal-ligand complexes in NC synthesis. Reactive ligands can convert metal salts to complexes, actual precursors to metal NCs. During the complex formation, various metal species occur, having different reactivity and fraction depending on synthetic conditions. It can alter their degree of participation in NC synthesis and the homogeneity of final products. Herein, we investigate the effects of complex formation on the entire NC synthesis. By controlling the fraction of various Au species showing different reactivity, we find that the extent of complex formation alters reduction kinetics and the uniformity of Au NCs. We demonstrate that this concept can be universally applied to synthesize Ag, Pt, Pd, and Rh NCs., (© 2023. The Author(s).)

This study is aimed at investigating the potential molecular features of allergic rhinitis (AR) and identifying gene signatures and related transcription factors using transcriptome analysis and in silico datasets. Transcriptome profiles were obtained using three independent cohorts (GSE101720, GSE19190, and GSE46171) comprising healthy controls (HC) and patients with AR. The pooled dataset ( n = 82) was used to identify the critical signatures of AR compared with HC. Subsequently, key transcription factors were identified by a combined analysis using transcriptome and in silico datasets. Gene ontology: bioprocess (GO: BP) analysis using differentially expressed genes (DEGs) revealed that immune response-related genes were significantly enriched in AR compared with HC. Among them, IL1RL1 , CD274 , and CD44 were significantly higher in AR patients. We also identified key transcription factors between HC and AR using the in silico dataset and found that AR samples frequently express KLF transcription factor 4 ( KLF4 ), which regulates immune response-related genes including IL1RL1 , CD274 , and CD44 in human nasal epithelial cells. Our integrative analysis of transcriptomic regulation provides new insights into AR, which may help in developing precision management for patients with AR., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Youngsic Jeon et al.)

In this study, the crystallization behavior of polyvinylidene fluoride (PVDF) in NMP/DMF solvent at 9 to 67 weight percent (wt%) was analyzed by molecular dynamics (MD) simulation. The PVDF phase did not gradually change with the incremental increase in PVDF wt%, but displayed rapid shifts at 34 and 50 wt% in both solvents. The solvation behavior between the two solvents was quite identical from the similar radial distribution functions. However, PVDFs in DMF solvent showed a higher ratio of β phase crystalline structures than those in NMP solvent. It was found that DMF solvents were more tightly packed near trans state PVDF fluorine compared to NMP solvents. Also, NMP oxygen atoms interacted more favorably with gauche state PVDF hydrogen atoms over DMF oxygen atoms. The evaluation of properties observed in atomic scale interactions, such as trans state inhibition and gauche state preference, can be used as indicators in future solvent research., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Design of bifunctional multimetallic alloy catalysts, which are one of the most promising candidates for water splitting, is a significant issue for the efficient production of renewable energy. Owing to large dimensions of the components and composition of multimetallic alloys, as well as the trade-off behavior in terms of the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) overpotentials for bifunctional catalysts, it is difficult to search for high-performance bifunctional catalysts with multimetallic alloys using conventional trial-and-error experiments. Here, an optimal bifunctional catalyst for water splitting is obtained by combining Pareto active learning and experiments, where 110 experimental data points out of 77946 possible points lead to effective model development. The as-obtained bifunctional catalysts for HER and OER exhibit high performance, which is revealed by model development using Pareto active learning; among the catalysts, an optimal catalyst (Pt 0.15 Pd 0.30 Ru 0.30 Cu 0.25 ) exhibits a water splitting behavior of 1.56 V at a current density of 10 mA cm -2 . This study opens avenues for the efficient exploration of multimetallic alloys, which can be applied in multifunctional catalysts as well as in other applications., (© 2023 Wiley-VCH GmbH.)

Screen printing (SP) has been extensively studied owing to its widespread industrial applications; however, only a few studies have focused on the substrate effect. Herein, we demonstrate that a screen-printed line can undergo a broadening effect or lateral undulation, which is determined by the substrate and printed dimensions. The degree of spreading was systematically investigated by employing 1D and 2D geometrical parameters. Based on the liquidity of the ink, we developed a simple inviscid theory with imposed perturbation to analyze the instability of screen-printed lines. The dispersion relation was derived to estimate the geometry of the laterally undulated lines and compared with the experimental results. The proposed argument is particularly applicable to a regime in which SP inks have greater liquidity. The screen-printed patterns exhibited unique undulated shapes and were utilized as photomasks for the facile fabrication of raccoon-type microchannels.

Background: Ventilator-associated pneumonia (VAP) is a source of morbidity and mortality for trauma patients. Aspiration events are also common because of traumatic brain injury, altered mental status, or facial trauma. In patients requiring mechanical ventilation, early pneumonias (EPs) may be erroneously classified as ventilator associated., Methods: A prospective early bronchoscopy protocol was implemented from January 2020 to January 2022. Trauma patients intubated before arrival or within 48 hours of admission underwent bronchoalveolar lavage (BAL) within 24 hours of intubation. Patients with more than 100,000 colony-forming units on BAL were considered to have EP., Results: A total of 117 patients underwent early BAL. Ninety-three (79.5%) had some growth on BAL with 36 (30.8%) meeting criteria for EP. For the total study population, 29 patients (24.8%) were diagnosed with VAP later in their hospital course, 12 of which had previously been diagnosed with EP. Of EP patients (n = 36), 21 (58.3%) were treated with antibiotics based on clinical signs of infection. Of EP patients who had a later pneumonia diagnosed by BAL (n = 12), seven (58.3%) grew the same organism from their initial BAL. When these patients were excluded from VAP calculation, the rate was reduced by 27.6%. Patients with EP had a higher rate of smoking history (41.7% vs. 19.8%, p < 0.001) compared with patients without EP. There was no difference in median hospital length of stay, intensive care unit length of stay, ventilator days, or mortality between the two cohorts., Conclusion: Early pneumonia is common in trauma patients intubated within the first 48 hours of admission and screening with early BAL identifies patients with aspiration or pretraumatic indicators of pneumonia. Accounting for these patients with early BAL significantly reduces reported VAP rates., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2022 American Association for the Surgery of Trauma.)

Unit-cell-thick MoS 2 is a promising electrocatalyst for the hydrogen evolution reaction (HER) owing to its tunable catalytic activity, which is determined based on the energetics and molecular interactions of different types of HER active sites. Kinetic responses of MoS 2 active sites, including the reaction onset, diffusion of the electrolyte and H 2 bubbles, and continuation of these processes, are important factors affecting the catalytic activity of MoS 2 . Investigating these factors requires a direct real-time analysis of the HER occurring on spatially independent active sites. Herein, the H 2 evolution and electrolyte diffusion on the surface of MoS 2 are observed in real time by in situ electrochemical liquid-phase transmission electron microscopy (LPTEM). Time-dependent LPTEM observations reveal that different types of active sites are sequentially activated under the same conditions. Furthermore, the electrolyte flow to these sites is influenced by the reduction potential and site geometry, which affects the bubble detachment and overall HER activity of MoS 2 ., (© 2022 Wiley-VCH GmbH.)

Benefiting from the demixing of substances in the two-phase region, a smart polymer laminate film system that exhibits direction-controlled phase separation behavior was developed in this study. Here, nanoemulsion films (NEFs) in which liquid nanodrops were uniformly confined in a polymer laminate film through the layer-by-layer deposition of oppositely charged emulsion nanodrops and polyelectrolytes were fabricated. Upon reaching a critical temperature, the NEFs exhibited a micropore-guided demixing phenomenon. A simulation study based on coarse-grained molecular dynamics revealed that the perpendicular diffusion of oil droplets through the micropores generated in the polyelectrolyte layer is crucial for determining the coarsening kinetics and phase separation level, which is consistent with the experimental results. Considering the substantial advantages of this unique and tunable two-dimensional demixing behavior, the viability of using the as-proposed NEF system for providing an efficient route for the development of smart drug delivery patches was demonstrated.

In East Asia, the dried root of Lithospermum erythrorhizon has been utilized as an anti-inflammatory, antipyretic, detoxifying, and anti-inflammatory agent. Recently, we reported that L. erythrorhizon protects against allergic rhinitis; however, the component within L. erythrorhizon that exerts antiallergic activity remains unknown. The purpose of the current study was to isolate and characterize the antiallergic active components in an ethanolic extract of L. erythrorhizon roots. We examined the antiallergic effects of L. erythrorhizon reflux ethanol extracts in an ovalbumin (OVA)-induced allergic rhinitis mouse model, and compared the chemical compounds extracted using the hot reflux and cold extraction methods. Chromatographic separation identified two novel anthraquinones, erythrin A and B, one newly discovered compound from the Lithospermum genus, N1″,N3″-dicoumaroylspermidine, and nineteen other recognized compounds. Their chemical structures were elucidated by single (1D) and 2D analysis of nuclear magnetic resonance (NMR) spectroscopic data, as well as high resolution mass spectrometry. Among the identified compounds, N,N'-dicoumaroylspermidine strongly inhibited the release of β-hexosaminidase, as well as the production of IL-3, IL-4, and IL-13 by IgE-sensitized and BSA-stimulated RBL-2H3 cells. Using the OVA-induced allergic rhinitis mouse model, we showed that N,N'-dicoumaroylspermidine reduced the production of serum OVA-specific IgE and the number of inflammatory cells in nasal lavage fluid. N,N'-dicoumaroylspermidine isolated from L. erythrorhizon exhibits antiallergic properties, making it potentially effective for allergic rhinitis.