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Basal cell hyperplasia is commonly observed in nasal polyp epithelium of eosinophilic chronic rhinosinusitis (eCRS). We examined the function and mechanisms of basal cell hyperplasia in the pathophysiology of eCRS.

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The purpose of the present study is to investigate changes in the kynurenine pathway after intracerebral hemorrhage (ICH) and its effects on ICH-induced injury. The exposure of a primary rat microglial culture to thrombin increased the mRNA level of kynurenine 3-monooxygenase (KMO), and this increase was attenuated by a p38 MAPK inhibitor. Thrombin also increased the protein level of KMO. In the cultured medium, the ratio of quinolinic acid (QUIN), an N-methyl-d-aspartate receptor (NMDAR) agonist, to kynurenic acid (KYNA), its antagonist, increased. The increase in the QUIN/KYNA ratio was blocked by Ro61-8048, a KMO inhibitor. The mRNA expression of KMO increased in an in vivomurine ICH model. Immunohistochemical staining showed that increased KMO co-localized with neurons, microglia, and astrocytes. The QUIN/KYNA ratio increased after ICH but was blocked by Ro61-8048 or clodronate, a microglia toxin. Ro61-8048 ameliorated brain edema; however, this effect was masked by MK-801, an NMDAR antagonist. Ro61-8048 protected against neuron loss in the perihematomal region and repaired neurological deficits assessed using the corner turn and pole tests. In conclusion, thrombin-induced changes in KMO in microglia mainly and intermediary metabolites of the kynurenine pathway appear to play crucial roles in neuronal injury after ICH.

In titanium dioxide (TiO2), oxygen vacancies- and cation interstitials-related functionalities have widely been studied in various fields, such as catalysis, sensors, and electronic devices. Anatase Nb-doped TiO2, a promising transparent conducting oxide material, shows a reversible metal–insulator transition by annealing in an oxidizing and reducing atmosphere. Theoretical and experimental studies have proposed that interstitial oxygen is key to this behavior. However, the chemical state of interstitial oxygen and its impact on the crystal lattice, which governs the electrical conduction mechanism, have not been elusive for over a decade. Herein, we reveal that superoxo-type (M–OO–) interstitial oxygen hinders electrical conductivity. Polarized X-ray absorption spectroscopy is combined with multimodal experiments, such as X-ray diffraction, Raman spectroscopy, and electrical transport measurements. The results show that the superoxo-type interstitial oxygens introduced in the vicinity of the dopant Nb ions trap conduction electrons. Furthermore, the interstitial oxygens induce off-centered [NbO6] and rutile-like [TiO6] octahedral distortions, potentially reducing carrier mobility. This study showcases the potential for expanding the oxygen-related functionalities of oxide materials from transparent conductors to battery materials, catalysts, and oxygen conductors.

The Creutz–Taube ion, [(NH3)5RuII(μ-pz)RuIII(NH3)5]5+(pz = pyrazine) is a prominent example of multinuclear Ru systems, which exists in a mixed-valence state. Previous research efforts to interrogate the properties of this complex uncovered important knowledge regarding intramolecular charge transfer between strongly interacting metal centers. In this work, the Ru coordination with pyrazine was extended into two dimensions to create a [Ru(pz)2Cl2]n(Ru-pz) metal–organic framework (MOF). Both solvothermal and solvent-free synthetic methodologies were explored to optimize crystallinity and phase-purity. The detailed structural analysis using single-crystal and powder X-ray diffraction techniques, as well as X-ray absorption spectroscopy and total X-ray scattering confirmed the layered framework structure. In addition, an isostructural Os analogue could also be obtained. The spectroscopic and electrochemical properties of the resultant materials were assessed, which confirmed the existence of mixed-valence states and electronic delocalization between metal centers. This phenomenon facilitated electron propagation in solid-state with conductivity values of some samples reaching the semiconductor range of 10–7–10–4S/cm. These findings expand the well-established chemistry of discrete mixed-valent Ru complexes into the field of MOFs providing useful insights for further development of these systems.

In rational drug discovery, both free energy of binding and the binding half-life (koff) are important factors in determining the efficacy of drugs. Numerous computational methods have been developed to predict these important properties, many of which rely on molecular dynamics (MD) simulations. While binding free-energy methods (thermodynamic equilibrium predictions) have been well validated and have demonstrated the ability to drive daily synthesis decisions in a commercial drug discovery setting, the prediction of koff(kinetics predictions) has had limited validation, and predictive methods have largely not been deployed in drug discovery settings. We developed ModBind, a novel method for MD simulation-based koffpredictions. ModBind demonstrated similar accuracy to current state-of-the-art free-energy prediction methods. Additionally, ModBind performs ∼100 times faster than most available MD simulation-based free-energy or koffmethods, allowing for widespread use by the molecular modeling community. While most free-energy methods rely on relative free-energy changes and are primarily useful for optimization of a congeneric series, our method requires no structural similarity between ligands, making ModBind an absolute predictor of koff. ModBind is thus a tool that can be used in virtual screening of diverse ligands, making it distinct from relative free-energy methods. We also discuss conditions that enable approximate prediction of ligand efficacy using ModBind and the limitations of this approach.

This study addresses a critical gap in the existing literature on carbon dioxide and ionic liquid (IL) mixtures, where fragmented and incomplete data, particularly for flow properties, hinder practical applications. Therefore, this work aimed to establish a robust and efficient method for predicting the density of the CO2–IL mixtures across diverse operating conditions and IL families using novel validation techniques. Both linear and symbolic regression models provided relevant insights but failed to accurately capture the IL–CO2interactions in a mixture that determine the molar volume of CO2at infinite dilution when solubilized by a given IL. Therefore, more mathematically flexible artificial neural networks (ANN) were trained based on three different sets of features: (1) IL critical properties, (2) IL structural descriptors, and (3) a selective combination of (1) and (2). While all models showed relative deviations consistently below 3% for the testing data, combining critical and structural data significantly improved accuracy (R2= 0.986, testing data set). A postprocessing outlier-handling method enhanced model performance, removing a minimal fraction (below 0.2%) of unphysical data points. Furthermore, molecular dynamics simulations validated the robust generalization of all ANN models, with the combined model exhibiting remarkable accuracy over operating conditions outside the training ranges for ILs in the training set and even for ILs that are not included in this data set. This computational approach provides a significantly faster and broader alternative to other thermodynamical tools, establishing a solid method for future machine learning (ML)-based property prediction augmented by external validation from cross-comparison tests and statistical thermodynamics models.

With the help of isotherm equations, how solubility changes with solubilizer concentration (“solubility isotherm”) can reveal the underlying interactions. However, despite their success in elucidating the mechanisms of hydrotropy (via the cooperative (sigmoidal) isotherm) and synergistic solvation (via the quadratic (bell-shaped) isotherm), these simple statistical thermodynamic isotherm equations alone are insufficient for more complex isotherms that combine their features. Here, we show (i) how simple isotherms can be combined via the isotherm multiplicativity rule founded on the excess number relationship (i.e., solubilizer concentration dependence of the solubilizer excess number around a solute) and (ii) how (i) leads to successful modeling of complex solubility isotherms, capturing that cooperative solute–solubilizer association, in turn, induces the exclusion of solubilizers from the already crowded solute’s locality at higher concentrations. Moreover, we will demonstrate that both the cooperative and quadratic solubility isotherms can be derived directly from the excess number relationship, establishing it not only as the basis for the multiplicativity rule but also as the fundamental relationship for simple and complex solubility isotherms.

Intratumoral administration is a widely used method for oncolytic virotherapy, as it enables immediate access of virus particles to the target tumor and potentially lead to the suppression of untreated distant tumors via in situvaccination. However, because the injection volume and concentration of the virus solution are physically limited, the dose level cannot be increased. Additionally, efficacy in distant tumors needs improvement to prolong patient survival. Here, we demonstrate the benefit of oxaliplatin, with detailed mechanisms revealed through transcriptome analysis, which may provide a solution for the crucial deficiencies of oncolytic virotherapy. In virus-injected tumors, oxaliplatin improved virus retention through suppression of type I interferons. In distant virus-naive tumors, oxaliplatin induced alterations in the intratumoral macrophage characteristics, leading to the chemotaxis and recruitment of activated T cells and subsequently inducing an inflammatory state in the non-injected tumors. Our findings can be a trigger to change the therapeutic paradigm of oncolytic virotherapy for patients with systemic metastases.

Interleukin-23 inhibition is effective in treating ulcerative colitis. Guselkumab is a dual-acting, human IgG1, interleukin-23p19 subunit inhibitor that potently neutralises interleukin-23 and can bind to CD64. We aimed to evaluate the efficacy and safety of guselkumab as induction and maintenance therapy in patients with ulcerative colitis.

This study aimed to compare the in-vitro behavior of four Hyaluronic acid (HA) gels when exposed to two different hyaluronidase (HSE) formulations.

This article thoroughly investigates the relationship between the lateral misalignment and the receiver coil current in the dynamic wireless power transfer (DWPT) system. Based on this analysis, a control configuration is proposed to automatically reduce the lateral misalignment between the transmitter and receiver coils, thereby enhancing the DWPT efficiency. The control configuration includes a lateral position estimator, which utilizes the fusion of the inertial measurement unit and the current sensor. This algorithm enables estimating the lateral misalignment of the vehicle at the same rate as the motor drives. Furthermore, the lateral misalignment is controlled by the front steering mechanism. The proposed method has been successfully evaluated using a DWPT system and an electric vehicle developed by our research group. The test results show that the energy transmission efficiency was expected to be increased by 6.6 % in comparison with the human driving at the second transmitter coil.

Dynamic wireless power transfer using repeater coils is studied as a cost-effective method that allows a single inverter to supply power to multiple transmitter coils. However, this method has a zone where the receiver coil positions on a transmitter coil called a dead zone. In the dead zone, the transfer efficiency and received power are significantly reduced. This is caused by matching the series resonance frequencies of each closed-loop circuit with the operating frequency of the inverter. Therefore, this article proposes the operating frequency control of the inverter to improve the power factor, which increases the efficiency and received power. The angle difference between the inverter output voltage and current is measured, and the operating frequency is controlled using a proportional–integral controller so that the angle difference becomes 0. From the experimental results, it was confirmed that the efficiency is 0.90 and the received power increases by $\text{1.33} \,\text{kW}$ when the operating frequency in the dead zone is not fixed compared to when it was fixed. In addition, the settling time of the operating frequency and angle difference was compared between the hill climbing algorithm and the proportional–integral controller. The settling time decreased by $\text{2.9} \,\text{ms}$.

Cold atmospheric plasma (CAP) irradiation exhibits a sterilizing effect without causing thermal denaturation or leaving behind residual toxicants. CAP also has potential applications in various fields, including agriculture, leading to research efforts in recent years. This study investigated the effects of CAP on the seed germination rate of spinach (Spinacia oleracea), which typically has a low seed germination rate. Our results confirmed that irradiation with N2-CAP and Air-CAP significantly enhanced the germination rate of spinach seeds. Notably, we discovered that CAP irradiation promoted germination even in spinach seeds coated with a fungicide (thiuram) and a disinfectant (Captan), which are commonly used. Additionally, we examined whether the interval between CAP irradiation and the subsequent germination-induction treatment influenced the germination efficiency. We found that the germination-promoting effect of CAP on spinach seeds persisted for at least 30 days, demonstrating the high utility and practicality of CAP in the agricultural sector.Graphical AbstractCold atmospheric plasma irradiation has sustained effects on improving the germination rate of spinach seeds coated with thiuram and Captan.

While epidemiological and experimental studies have demonstrated kidney-protective effects of estrogen and female sex in adulthood, some epidemiological data showed deterioration of kidney function during puberty when estrogen production increases. However, molecular mechanisms explaining these conflicting phenomena remain unknown. Here, we showed that the pubertal sex hormone surge in female mice increases susceptibility to kidney ischemia reperfusion injury partly via downregulation of insulin-like growth factor 1 receptor (IGF-1R) expression in proximal tubules. Adult mice ovariectomized pre-pubertally (at postnatal day 21) showed strong tolerance to kidney ischemia, which was partly reversed by the administration of 17β-estradiol, while adult mice ovariectomized post-pubertally (at 8 weeks of age) were vulnerable to kidney ischemia. Kidney tubular IGF-1R protein expression decreased during postnatal growth but was highly expressed in adult mice ovariectomized pre-pubertally and in infant mice, which might be partly explained by different expression of an E3 ligase (MDM2) of IGF-1R. Mice deficient of Igf-1r in proximal tubules (iIGF-1RKO mice) during postnatal kidney growth showed increased susceptibility to ischemic injury. RNA-seq and western blotting analysis using proximal tubular cells from pre-pubertally ovariectomized iIGF-1RKO and control mice revealed altered expression of cell cycle-associated molecules such as cyclin D1. These results suggest that Igf-1r deletion during postnatal growth renders proximal tubular cells susceptible to ischemia possibly via altered cell cycle regulation. Thus, our findings provide evidence that exposure to pubertal sex hormones leads to increased susceptibility to kidney ischemia, which is partly mediated by modulation of IGF-1R signaling.

This study evaluated the concordance between blush on CT and angiography based on pelvic regions in patients with pelvic fractures. The location of active bleeding often differs between CT and angiography, indicating that bleeding may change intermittently and at various sites.

A modern field-programmable gate array (FPGA) card can be equipped with high-bandwidth memory and high-bandwidth optical interconnection networks. This paper presents an in-network stable radix sorter on an eight-FPGA cluster. Each custom Stratix10 MX2100 FPGA card has up to 819-Gbps memory bandwidth (${51.2}\;{\rm Gbps} \times {16}\;{\rm channels}$) and up to 800-Gbps network bandwidth (${25}\;{\rm Gbps} \times {32}\;{\rm channels}$) with eight custom embedded optical modules. Our radix sorter for a 32-bit key range consists of eight 4-bit counting sorts optimized to in-network processing. Each counting sort needs only one memory read/write access for improving its throughput. We demonstrated a sorting throughput of 37.2 GB/s and an energy efficiency of 9.2 MB/J for 32-bit key range and 16-GiB data size using eight memory channels with 409.6 Gbps memory bandwidth per FPGA. It can scale up to 256 FPGAs with a sorting throughput of 983 GB/s for a 32-bit key range and 512-GiB data size.

Obesity and overweight, fundamental components of the metabolic syndrome, predispose individuals to lifestyle-related diseases. The extent to which adopting healthy lifestyles can reduce obesity risk, even in those with a high genetic risk, remains uncertain. Our aim was to assess the extent to which lifestyle modifications can improve outcomes in individuals with a high polygenic score (PGS) for obesity. We quantified the genetic risk of obesity using PGSs. Four datasets from the Tohoku Medical Megabank Community-Based Cohort (TMM CommCohort) were employed in the study. One dataset (n= 9958) was used to select the best model for calculating PGS. The remaining datasets (total n= 69,341) were used in a meta-analysis to validate the model and to evaluate associated risks. The odds ratio (OR) for obesity risk in the intermediate (11th–90th percentiles in the dataset) and high PGS categories (91st–100th) was 2.27 [95% confidence intervals: 2.12–2.44] and 4.83 [4.45–5.25], respectively, compared to that in the low PGS category (1st–10th). Trend analysis showed that an increase in leisure-time physical activity was significantly associated with reduced obesity risk across all genetic risk categories, representing an OR of 0.9 [0.87–0.94] even among individuals in the high PGS category. Similarly, sodium intake displayed a positive association with obesity across all genetic risk categories, yielding an OR of 1.24 [1.17–1.31] in the high PGS category. The risk of obesity was linked to the adoption of healthy lifestyles, even in individuals with high PGS. Our results may provide perspectives for integrating PGSs into preventive medicine.

Artificial intelligence (AI) is a promising new technology that has the potential of diagnosing allergic conjunctival diseases (ACDs). However, its development is slowed by the absence of a tailored image database and explainable AI models. Thus, the purpose of this study was to develop an explainable AI model that can not only diagnose ACDs but also present the basis for the diagnosis.

Controlling the nucleation, growth, and dissolution of Li is crucial for the high cycling stability in rechargeable Li metal batteries. The overpotential for Li nucleation (ηnc) on Li alloys such as Li–Au is generally lower than that on metal current collectors (CCs) with very limited Li solubility like Cu. However, the alloying process of CC and its impact on the Li nucleation kinetics remain unclear. Herein, we experimentally investigate the Li nucleation mechanism on Li–Au alloys using scanning electron microscopy with multiple detectors to distinguish the atomic number and topography contrast. Nonequilibrium processes near the Au CC film/lithium phosphorus oxynitride (LiPON) glass electrolyte interface were observed. Local dissolution of Li occurs concurrently with the Li plating process. This phenomenon indicates that Li nucleates as a metastable phase in Li–Au alloy CC films during Li plating due to the substantially lower interfacial energy of Li with the alloy phase. This low interfacial energy also leads to a low ηnc. Moreover, the local Li redissolution process results in a nonrandom spatial distribution of Li growth sites. Consequently, the alloy layer acts as a buffer, facilitating a more uniform distribution of the reaction sites.

The synthesis, structure, and circularly polarized phosphorescence (CPP) properties of axially chiral cyclometalated binuclear platinum(II) complexes were described. A series of optically pure binuclear platinum(II) complexes were synthesized in five steps from commercially available (R)- or (S)-1,1′-bi-2-naphthol (BINOL) as starting materials. Their three-dimensional molecular structures and square-planar coordination geometries were elucidated from X-ray diffraction and 2D NMR analysis. The complexes were found to exhibit red- to near-infrared photoluminescence in solution and in the solid state. Furthermore, dilute DMSO solutions of the enantiopure samples showed red CPP with relatively high luminescence dissymmetry factor (glum) values. Density functional theory (DFT) calculations were conducted to examine their three-dimensional molecular conformations and photophysical properties.

Revision hip and knee total joint arthroplasty (TJA) carries a high burden of postoperative complications, including surgical site infections (SSI), venous thromboembolism (VTE), reoperation, and readmission, which negatively affect postoperative outcomes and patient satisfaction. Socioeconomic area-level composite indices such as the area deprivation index (ADI) are increasingly important measures of social determinants of health (SDoH). This study aims to determine the potential association between ADI and SSI, VTE, reoperation, and readmission occurrence 90 days following revision TJA.