Influence of Oxygen Vacancies Introduced via Acceptor (Gadolinium) Doping to the Pseudocapacitive Properties of Nano-Sized Cerium Oxide.

The voluntary introduction of defects can be considered an effective strategy for enhancing the electrochemical properties of metal oxide electrodes. In this study, the enhanced pseudocapacitive properties of an acceptor (Gd) doped cerium oxide nanoparticle-a sustainable metal oxide with low environmental and human toxicity-are investigated in depth using ex situ X-ray photoemission spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS). Interestingly, with 15 at% Gd doping (15GDC), the specific capacitance of the nanoparticles measured at 1 A g-1 enhanced to 547.8 F g-1, which is fivefold higher than undoped CeO2 (98.7 F g-1 at 1 A g-1). The rate-dependent capacitance is also improved for 15GDC, which showed a 31.0% decrease in the specific capacitance upon a tenfold increase in the current density, while CeO2 showed a 49.9% decrease. The enhanced electrochemical properties are studied in depth via ex situ XPS and EIS analysis, which revealed that the oxygen vacancies at the surface of the nanoparticles played important roles in enhancing both the specific capacitance and the high-rate performance of 15GDC by acting as the active site for pseudocapacitive redox reaction and allowing fast diffusion of oxygen ions at the surface of 15GDC nanoparticles.

Inhibition of Toll-like Receptors Alters Macrophage Cholesterol Efflux and Foam Cell Formation.

Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins interact with toll-like receptors (TLR), causing an increased inflammatory response and altered cholesterol homeostasis. We aimed to determine the effects of TLR antagonists on cholesterol efflux and foam cell formation in human macrophages. Stimulated monocytes were treated with TLR antagonists (MIP2), and the cholesterol efflux transporter expression and foam cell formation were analyzed. The administration of MIP2 attenuated the foam cell formation induced by lipopolysaccharides (LPS) and oxidized low-density lipoproteins (ox-LDL) in stimulated THP-1 cells (p < 0.001). The expression of ATP-binding cassette transporters A (ABCA)-1, ABCG-1, scavenger receptor (SR)-B1, liver X receptor (LXR)-α, and peroxisome proliferator-activated receptor (PPAR)-γ mRNA and proteins were increased (p < 0.001) following MIP2 administration. A concentration-dependent decrease in the phosphorylation of p65, p38, and JNK was also observed following MIP2 administration. Moreover, an inhibition of p65 phosphorylation enhanced the expression of ABCA1, ABCG1, SR-B1, and LXR-α. TLR inhibition promoted the cholesterol efflux pathway by increasing the expression of ABCA-1, ABCG-1, and SR-B1, thereby reducing foam cell formation. Our results suggest a potential role of the p65/NF-kB/LXR-α/ABCA1 axis in TLR-mediated cholesterol homeostasis.

Efficacy of live and inactivated recombinant Newcastle disease virus vaccines expressing clade 2.3.4.4b H5 hemagglutinin against H5N1 highly pathogenic avian influenza in SPF chickens, Broilers, and domestic ducks.

A Newcastle disease virus (NDV)-vectored vaccine expressing clade 2.3.4.4b H5 Hemagglutinin was developed and assessed for efficacy against H5N1 highly pathogenic avian influenza (HPAI) in specific pathogen-free (SPF) chickens, broilers, and domestic ducks. In SPF chickens, the live recombinant NDV-vectored vaccine, rK148/22-H5, achieved complete survival against HPAI and NDV challenges and significantly reduced viral shedding. Notably, the live rK148/22-H5 vaccine conferred good clinical protection in broilers despite the presence of maternally derived antibodies. Good clinical protection was observed in domestic ducks, with decreased viral shedding. It demonstrated complete survival and reduced cloacal viral shedding when used as an inactivated vaccine from SPF chickens. The rK148/22-H5 vaccine is potentially a viable and supportive option for biosecurity measure, effectively protecting in chickens against the deadly clade 2.3.4.4b H5 HPAI and NDV infections. Furthermore, it aligns with the strategy of Differentiating Infected from Vaccinated Animals (DIVA).

Multiscale Control of Nanofiber-Composite Hydrogel for Complex 3D Cell Culture by Extracellular Matrix Composition and Nanofiber Alignment.

In order to manipulate the complex behavior of cells in a 3-dimensional (3D) environment, it is important to provide the microenvironment that can accurately portray the complexity of highly anisotropic tissue structures. However, it is technically challenging to generate a complex microenvironment using conventional biomaterials that are mostly isotropic with limited bioactivity. In this study, the gelatin-hyaluronic acid hydrogel incorporated with aqueous-dispersible, short nanofibers capable of in situ alignment is developed to emulate the native heterogeneous extracellular matrix consisting of fibrous and non-fibrous components. The gelatin nanofibers containing magnetic nanoparticles, which could be aligned by external magnetic field, are dispersed and embedded in gelatin-hyaluronic acid hydrogel encapsulated with dermal fibroblasts. The aligned nanofibers via magnetic field could be safely integrated into the hydrogel, and the process could be repeated to generate larger 3D hydrogels with variable nanofiber alignments. The aligned nanofibers in the hydrogel can more effectively guide the anisotropic morphology (e.g., elongation) of dermal fibroblasts than random nanofibers, whereas myofibroblastic differentiation is more prominent in random nanofibers. At a given nanofiber configuration, the hydrogel composition having intermediate hyaluronic acid content induces myofibroblastic differentiation. These results indicate that modulating the degree of nanofiber alignment and the hyaluronic acid content of the hydrogel are crucial factors that critically influence the fibroblast phenotypes. The nanofiber-composite hydrogel capable of directional nanofiber alignment and tunable material composition can effectively induce a wide array of phenotypic plasticity in 3D cell culture.

A Novel Zwitterion Incorporated Nano-Crystalline Ceramic and Polymer for Bacterial Resistant Dental CAD-CAM Block.

OBJECTIVES: To create bacteria-resistant dental CAD-CAM blocks with a biofilm-resistant effect by incorporating Nano-crystalline ceramic and polymer (NCP) with 2-methacryloyloxyethyl phosphorylcholine (MPC) and sulfobetaine methacrylate (SBMA) and at an equimolar ratio, referred to as MS. METHODS: Experimental groups comprised NCP blocks containing zwitterions at 0.15wt% (MS015) and 0.45wt% (MS045). NCP blocks without MS served as control (CTRL). Flexural strength, surface hardness, water sorption and solubility, photometric properties, and cytotoxicity were assessed for all samples. Additionally, the resistance to single and multi-species bacterial adhesion was investigated. RESULTS: MS045 showed significant reduction in flexural strength (P < 0.01) compared to both CTRL and MS015. Both MS015 and MS045 showed significantly increased water sorption and significant reduction in water solubility compared to CTRL. Light transmission remained consistent across all MS content levels, but the irradiance value decreased by 12% in the MS045 group compared to the MS015 group. Notably, compared to the CTRL group, the MS015 group exhibited enhanced resistance to adhesion by Porphyromonas gingivalis and a multi-species salivary biofilm, with biofilm thickness and biomass reduced by 45% and 56%, respectively. CONCLUSIONS: NCP containing 0.15% MS can effectively reduce adhesion of multiple species of bacteria while maintaining physical and mechanical properties. CLINICAL SIGNIFICANCE: NCP integrating zwitterions is clinically advantageous in resisting bacterial adhesion at internal and external margins of milled indirect restoration.

Site-specific mutagenesis screening in KRASG12D mutant library to uncover resistance mechanisms to KRASG12D inhibitors.

KRAS plays a crucial role in regulating cell survival and proliferation and is one of the most commonly mutated oncogenes in human cancers. The novel KRASG12D inhibitor, MRTX1133, demonstrates promising antitumor efficacy in vitro and in vivo. However, the development of acquired resistance in treated patients presents a considerable challenge to sustained therapeutic effectiveness. In response to this challenge, we conducted site-specific mutagenesis screening to identify potential secondary mutations that could induce resistance to MRTX1133. We screened a range of KRASG12D variants harboring potential secondary mutations, and 44 representative variants were selected for in-depth validation of the pooled screening outcomes. We identified eight variants (G12D with V9E, V9W, V9Q, G13P, T58Y, R68G, Y96W, and Q99L) that exhibited substantial resistance, with V9W showing notable resistance, and downstream signaling analyses and structural modeling were conducted. We observed that secondary mutations in KRASG12D can lead to acquired resistance to MRTX1133 and BI-2865, a novel pan-KRAS inhibitor, in human cancer cell lines. This evidence is critical for devising new strategies to counteract resistance mechanisms and, ultimately, enhance treatment outcomes in patients with KRASG12D-mutant cancers.

Genomic epidemiology of highly pathogenic avian influenza A (H5N1) virus in wild birds in South Korea during 2021-2022: Changes in viral epidemic patterns.

Clade 2.3.4.4b highly pathogenic avian influenza A (HPAI) viruses have been detected in wild birds worldwide, causing recurrent outbreaks since 2016. During the winter of 2021-2022, we detected one H5N8 and forty-three H5N1 clade 2.3.4.4b HPAI viruses from wild birds in South Korea. Phylogenetic analysis revealed that HA gene of H5N1 viruses was divided into two genetically distinct groups (N1.G1 and N1.G2). Bayesian phylodynamic analysis demonstrated that wild birds play a vital role in viral transmission and long-term maintenance. We identified five genotypes (N1.G1.1, N1.G2, N1.G2.1, N1.G2.2, and N1.G2.2.1) having distinct gene segment constellations most probably produced by reassortments with low-pathogenic avian influenza viruses. Our results suggest that clade 2.3.4.4b persists in wild birds for a long time, causing continuous outbreaks, compared with previous clades of H5 HPAI viruses. Our study emphasizes the need for enhancing control measures in response to the changing viral epidemiology.

Sex Differences in the Impact of Dynapenic Abdominal Obesity on Mild Cognitive Impairment among Korean Elderly in the Community.

Abdominal obesity (AO) and dynapenia (DP) are associated with cognitive decline, and the relationship between dynapenic abdominal obesity (DAO), a combination of DP and AO, and mild cognitive impairment (MCI) has been confirmed. This study aims to determine whether this relationship exhibits potential sex differences. The relationship between MCI and DAO was confirmed in 1309 community elderly individuals aged 65 years or older who were not diagnosed with dementia. The MCI was defined as a Korean mini-mental state examination (K-MMSE) score of 18-23 points. Multiple logistic regression analyses were conducted, categorizing participants into groups: a control group without AO or DP, an AO group, a DP group, and a DAO group. The study results showed that in women, both DP and DAO were significantly associated with MCI not only in the unadjusted Model 1 but also in Model 2, which adjusted for general characteristics and health behaviors, and Model 3, which additionally adjusted for chronic diseases and disease-related characteristics. In men, DP was associated with MCI in the unadjusted Model 1. The findings highlight sex differences in the impact of the DAO on MCI. These differences should be considered when studying the factors related to MCI in old age.

Detection of multiple recombinations of avian coronavirus in South Korea by whole-genome analysis.

Infectious bronchitis virus (IBV), an avian coronavirus, has caused considerable damage to the poultry industry. In Korea, indigenous KM91-like and newly introduced QX-like lineages belonging to the GI-19 lineage have been prevalent despite constant vaccination. In this study, complete genome sequences of 23 IBV isolates in Korea from 2010 to 2020 were obtained using next-generation sequencing, and their phylogenetic relationship and recombination events were analyzed. Phylogenetic analysis based on the S1 gene showed that all isolates belonged to the GI-19 lineage and were divided into five subgroups (KM91-like, K40/09-like, and QX-like II to IV). Among the 23 isolates, 14 recombinants were found, including frequent recombination between KM91-like and QX-like strains. In addition, it was observed that other lineages, such as GI-1, GI-13, and GI-16, were involved in recombination. Most recombination breakpoints were detected in the ORF1ab gene, particularly nsp3. However, when considering the size of each genome, recombination occurred more frequently in the 3a, E and 5a genes. Taken together, genetic recombination frequently occurred throughout the entire genome between various IBV strains in Korea, including live attenuated vaccine strain. Our study suggests the necessity of further research on the contribution of recombination of genomes outside the spike region to the biological characteristics of IBV.

Phloretin Inhibits the Proliferation of Breast Cancer Cells Through the Down-regulation of Estrogen Receptor α.

BACKGROUND/AIM: Phloretin is a natural flavonoid compound found in some plants, such as apples and pears, as well as in the bark of apple trees. Phloretin has been shown to have inhibitory effects on glucose transporters in cells and can potentially inhibit the growth of cancer cells. However, the mechanism by which phloretin regulates the expression of estrogen receptor alpha (ERα), a key transcription factor in breast cancer, is still unclear. This study investigated how phloretin affects the growth of ERα positive human breast cancer cells. MATERIALS AND METHODS: The growth of breast cancer cell lines, including MCF7 and T47D, was examined using cell proliferation and colony formation assays. Western blotting and semi-quantitative RT-PCR were used to examine protein and mRNA levels, respectively. Localization of cellular proteins was analyzed using subcellular fractionation. Transient transfection and reported gene assays were used to elucidate the impact of phloretin on cell proliferation and ERα transactivation. RESULTS: Phloretin decreased ERα expression at the mRNA and protein levels in MCF7 and T47D cells. It also inhibited the binding of ERα to the estrogen response element present in the promoter of target genes. Moreover, treatment with phloretin inhibited the expression of cyclin D1 and breast cancer marker gene pS2, which are known ERα target genes. Consequently, it inhibited the growth of ERα-positive human breast cancer cells. Furthermore, inhibition of breast cancer growth by phloretin was found to be mediated through both the ERα and ERK1/ERK2 pathways. CONCLUSION: Phloretin, a dihydrochalcone extracted from natural sources, exhibits the ability to regulate ERα function and suppress breast cancer cell proliferation.

Flexible, Biodegradable, and Wireless Magnetoelectric Paper for Simple In Situ Personalization of Bioelectric Implants.

Bioelectronic implants delivering electrical stimulation offer an attractive alternative to traditional pharmaceuticals in electrotherapy. However, achieving simple, rapid, and cost-effective personalization of these implants for customized treatment in unique clinical and physical scenarios presents a substantial challenge. This challenge is further compounded by the need to ensure safety and minimal invasiveness, requiring essential attributes such as flexibility, biocompatibility, lightness, biodegradability, and wireless stimulation capability. Here, a flexible, biodegradable bioelectronic paper with homogeneously distributed wireless stimulation functionality for simple personalization of bioelectronic implants is introduced. The bioelectronic paper synergistically combines i) lead-free magnetoelectric nanoparticles (MENs) that facilitate electrical stimulation in response to external magnetic field and ii) flexible and biodegradable nanofibers (NFs) that enable localization of MENs for high-selectivity stimulation, oxygen/nutrient permeation, cell orientation modulation, and biodegradation rate control. The effectiveness of wireless electrical stimulation in vitro through enhanced neuronal differentiation of neuron-like PC12 cells and the controllability of their microstructural orientation are shown. Also, scalability, design flexibility, and rapid customizability of the bioelectronic paper are shown by creating various 3D macrostructures using simple paper crafting techniques such as cutting and folding. This platform holds promise for simple and rapid personalization of temporary bioelectronic implants for minimally invasive wireless stimulation therapies.

Encoding of multi-modal emotional information via personalized skin-integrated wireless facial interface.

Human affects such as emotions, moods, feelings are increasingly being considered as key parameter to enhance the interaction of human with diverse machines and systems. However, their intrinsically abstract and ambiguous nature make it challenging to accurately extract and exploit the emotional information. Here, we develop a multi-modal human emotion recognition system which can efficiently utilize comprehensive emotional information by combining verbal and non-verbal expression data. This system is composed of personalized skin-integrated facial interface (PSiFI) system that is self-powered, facile, stretchable, transparent, featuring a first bidirectional triboelectric strain and vibration sensor enabling us to sense and combine the verbal and non-verbal expression data for the first time. It is fully integrated with a data processing circuit for wireless data transfer allowing real-time emotion recognition to be performed. With the help of machine learning, various human emotion recognition tasks are done accurately in real time even while wearing mask and demonstrated digital concierge application in VR environment.

High-Performance Optoelectronic Gas Sensing Based on All-Inorganic Mixed-Halide Perovskite Nanocrystals with Halide Engineering.

Gas sensors are of great interest to portable and miniaturized sensing technologies with applications ranging from air quality monitoring to explosive detection and medical diagnostics, but the existing chemiresistive NO2 sensors still suffer from issues such as poor sensitivity, high operating temperature, and slow recovery. Herein, a high-performance NO2 sensors based on all-inorganic perovskite nanocrystals (PNCs) is reported, achieving room temperature operation with ultra-fast response and recovery time. After tailoring the halide composition, superior sensitivity of ≈67 at 8 ppm NO2 is obtained in CsPbI2 Br PNC sensors with a detection level down to 2 ppb, which outperforms other nanomaterial-based NO2 sensors. Furthermore, the remarkable optoelectronic properties of such PNCs enable dual-mode operation, i.e., chemiresistive and chemioptical sensing, presenting a new and versatile platform for advancing high-performance, point-of-care NO2 detection technologies.

Three distinct ORF1a recombinants of the SARS-CoV-2 Delta variant of concern.

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergency of various lineages through mutations and recombination. In the Delta lineage, we identified recombination events in the ORF1a gene, which divided the Delta sublineages into three different genotypes (Delta R1-R3). The regional distributions of Delta R1 and Delta R2 were not correlated, indicating that recombination occurred early in the Delta outbreak. The impact of the ORF1a gene on SARS-CoV-2 transmission remains unclear; however, our findings suggest that recombination may have contributed to the evolution and global spread of the Delta lineage.

Digital Mechanical Metamaterial: Encoding Mechanical Information with Graphical Stiffness Pattern for Adaptive Soft Machines.

Inspired by the adaptive features exhibited by biological organisms like the octopus, soft machines that can tune their shape and mechanical properties have shown great potential in applications involving unstructured and continuously changing environments. However, current soft machines are far from achieving the same level of adaptability as their biological counterparts, hampered by limited real-time tunability and severely deficient reprogrammable space of properties and functionalities. As a steppingstone toward fully adaptive soft robots and smart interactive machines, an encodable multifunctional material that uses graphical stiffness patterns is introduced here to in situ program versatile mechanical capabilities without requiring additional infrastructure. Through independently switching the digital binary stiffness states (soft or rigid) of individual constituent units of a simple auxetic structure with elliptical voids, in situ and gradational tunability is demonstrated here in various mechanical qualities such as shape-shifting and -memory, stress-strain response, and Poisson's ratio under compressive load as well as application-oriented functionalities such as tunable and reusable energy absorption and pressure delivery. This digitally programmable material is expected to pave the way toward multienvironment soft robots and interactive machines.

Highly Compressible 3D-Printed Soft Magnetoelastic Sensors for Human-Machine Interfaces.

Incorporating perception into robots or objects holds great potential to revolutionize daily human life. To achieve this, critical factors include the design of an integrable three-dimensional (3D) soft sensor with self-powering capability, a wide working range, and tuneable functionalities. Here, we introduce a highly compressible 3D-printed soft magnetoelastic sensor with a wide strain sensing range. Inspired by the lattice metamaterial, which offers a highly porous structure with tuneable mechanical properties, we realized a remarkably compliant 3D self-powering sensor. Using magnetoelastic composite materials and 3D printing combined with sacrificial molding, a broad design space for constituent materials and structures is investigated, allowing for tuneable mechanical properties and sensor performances. These sensors are successfully integrated with two robotic systems as the robot operation and perception units, enabling robot control and recognition of diverse physical interactions with a user. Overall, we believe that this work represents a cornerstone for compliant 3D self-powered soft sensors, giving impetus to the development of advanced human-machine interfaces.

Comparative Risk of Type 2 Diabetes after Gastrectomy and Endoscopic Resection for Gastric Cancer: A Nationwide Cohort Study.

BACKGROUND: Patients with gastric cancer (GC) experience 2 characteristic treatment modalities (gastrectomy or endoscopic resection), which may induce heterogeneity in the risk of post-cancer treatment type 2 diabetes (T2D). We investigated differences in the risk for T2D development in survivors of GC according to the 2 treatment methods. STUDY DESIGN: This retrospective nationwide population-based cohort study included 14,646 patients with GC who underwent gastrectomy (n = 12,918) or endoscopic resection (n = 1,728). We enrolled patients who survived for at least 5 years after gastrectomy or endoscopic resection, had no history of diabetes, and had not received adjuvant chemotherapy. T2D risk was evaluated using Cox regression for the gastrectomy group and compared to that of the endoscopic resection group. Because of the competing risks of incident T2D and death, a competing risk regression was performed. RESULTS: After a median follow-up duration of 8.1 years, the incidence rates of T2D in the endoscopic resection group and gastrectomy group were 7.58 and 6.98 per 1,000 person-years, respectively. Patients undergoing gastrectomy showed a significantly higher risk for developing T2D than patients undergoing endoscopic resection (hazard ratio [HR], 1.37; 95% CI 1.18 to 1.58; p < 0.0001). In subgroup analyses, gastrectomy was associated with increased T2D risk in female patients (HR, 1.72; 95% CI 1.22 to 2.43; p = 0.030 for interaction). CONCLUSIONS: Among GC survivors, patients undergoing gastrectomy showed a 37% increased risk of T2D development compared to patients undergoing endoscopic resection. Subgroup analyses showed that T2D risk increased by up to 72% in female patients. These results provide insights for establishing screening and preventive strategies for GC survivors to prevent T2D according to different treatment modalities.

A soft, self-sensing tensile valve for perceptive soft robots.

Soft inflatable robots are a promising paradigm for applications that benefit from their inherent safety and adaptability. However, for perception, complex connections of rigid electronics both in hardware and software remain the mainstay. Although recent efforts have created soft analogs of individual rigid components, the integration of sensing and control systems is challenging to achieve without compromising the complete softness, form factor, or capabilities. Here, we report a soft self-sensing tensile valve that integrates the functional capabilities of sensors and control valves to directly transform applied tensile strain into distinctive steady-state output pressure states using only a single, constant pressure source. By harnessing a unique mechanism, "helical pinching", we derive physical sharing of both sensing and control valve structures, achieving all-in-one integration in a compact form factor. We demonstrate programmability and applicability of our platform, illustrating a pathway towards fully soft, electronics-free, untethered, and autonomous robotic systems.