Evaluation of Treatment of Methicillin-Resistant Staphylococcus aureus Biofilms with Intermittent Electrochemically-Generated H2O2 or HOCl.

Chronic wound infections can be difficult to treat and may lead to impaired healing and worsened patient outcomes. Novel treatment strategies are needed. This study evaluated effects of intermittently produced H2O2 and HOCl, generated via an electrochemical bandage (e-bandage), against methicillin-resistant Staphylococcus aureus biofilms in an agar membrane biofilm model. By changing the working electrode potential, the e-bandage generated either HOCl (1.5 VAg/AgCl) or H2O2 (-0.6 VAg/AgCl). The degree of biocidal activity of intermittent treatment with HOCl and H2O2 correlated with HOCl treatment time; HOCl treatment durations of 0, 1.5, 3, 4.5, and 6 hours (with the rest of the 6 hour total treatment time devoted to H2O2 generation) resulted in mean biofilm reductions of 1.36±0.2, 2.22±0.16, 3.46±0.38, 4.63±0.74 and 7.66±0.5 log CFU/cm2, respectively vs. non-polarized controls, respectively. However, application of H2O2 immediately after HOCl treatment was detrimental to biofilm removal. For example, 3-hours HOCl treatment followed by 3-hours H2O2 resulted in a 1.90±0.84 log CFU/cm2 lower mean biofilm reduction than 3-hours HOCl treatment followed by 3-hours non-polarization. HOCl generated over 3-hours exhibited biocidal activity for at least 7.5-hours after e-bandage operation ceased; 3-hours of HOCl generation followed by 7.5-hours of non-polarization resulted in a biofilm cell reduction of 7.92±0.12 log CFU/cm2 vs. non polarized controls. Finally, intermittent treatment with HOCl (i.e., interspersed with periods of e-bandage non-polarization) for various intervals showed similar effects (approximately 6 log CFU/cm2 reduction vs. non-polarized control) to continuous treatment with HOCl for 3-hours, followed by 3-hours of non-polarization. These findings suggest that timing and sequencing of HOCl and H2O2 treatments are crucial for maximizing biofilm control.

Self-Powering Gas Sensing System Enabled by Double-Layer Triboelectric Nanogenerators Based on Poly(2-vinylpyridine)@BaTiO3 Core-Shell Hybrids with Superior Dispersibility and Uniformity.

Current core-shell hybrids used in diverse energy-related applications possess limited dispersibility and film uniformity that govern their overall performances. Herein, we showcase superdispersible core-shell hybrids (P2VP@BaTiO3) composed of a poly(2-vinylpyridine) (P2VP) (5-20 wt %) and a barium titanate oxide (BaTiO3), maximizing dielectric constants by forming the high-quality uniform films. The P2VP@BaTiO3-based triboelectric nanogenerators (TENGs), especially the 10 wt % P2VP (P2VP10@BaTiO3)-based one, deliver significantly enhanced output performances compared to physically mixed P2VP/BaTiO3 counterparts. The P2VP10@BaTiO3-based double-layer TENG exhibits not only an excellent transferred charge density of 281.7 µC m-2 with a power density of 27.2 W m-2 but also extraordinary device stability (∼100% sustainability of the maximum output voltage for 54,000 cycles and ∼68.7% voltage retention even at 99% humidity). Notably, introducing the MoS2/SiO2/Ni-mesh layer into this double-layer TENG enables ultrahigh charge density of up to 1228 µC m-2, which is the top value reported for the TENGs so far. Furthermore, we also demonstrate a near-field communication-based sensing system for monitoring CO2 gas using our developed self-powered generator with enhanced output performance and robustness.

DUAL ACTION ELECTROCHEMICAL BANDAGE OPERATED by a PROGRAMMABLE MULTIMODAL WEARABLE POTENTIOSTAT.

Electrochemical bandages (e-bandages) can be applied to biofilm-infected wounds to generate reactive oxygen species, such as hypochlorous acid (HOCl) or hydrogen peroxide (H 2 O 2 ). The e-bandage-generated HOCl or H 2 O 2 kills biofilms in vitro and in infected wounds on mice. The HOCl-generating e-bandage is more active against biofilms in vitro , although this distinction is less apparent in vivo . The H 2 O 2 -generating e-bandage, more than the HOCl-generating e-bandage, is associated with improved healing of infected wounds. A strategy in which H 2 O 2 and HOCl are generated alternately-for dual action-was explored. The goal was to develop a programmable multimodal wearable potentiostat (PMWP) that could be programmed to generate HOCl or H 2 O 2 , as needed. An ultralow-power microcontroller unit managed operation of the PMWP. The system was operated with a 260-mAh capacity coin battery and weighed 4.6 grams, making it suitable for small animal experiments or human use. The overall cost of a single wearable potentiostat was $6.50 (USD). The device was verified using established electrochemical systems and functioned comparably to a commercial potentiostat. To determine antimicrobial effectiveness, PMWP-controlled e-bandages were tested against clinical isolates of four prevalent chronic wound bacterial pathogens, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter baumannii , and Enterococcus faecium , and one fungal pathogen of emerging concern, Candida auris . PMWP-controlled e-bandages exhibited broad-spectrum activity against biofilms of all study isolates tested when programmed to deliver HOCl followed by H 2 O 2 . These results show that the PMWP operates effectively and is suitable for animal testing.

High-Precision Tailored Polymer Molecular Weights for Specific Photovoltaic Applications through Ultrasound-Induced Simultaneous Physical and Chemical Events.

It is highly challenging to reproducibly prepare semiconducting polymers with targeted molecular weight tailored for next-generation photovoltaic applications. Once such an easily accessible methodology is established, which can not only contribute to overcome the current limitation of the statistically determined nature of semiconducting polymers, but also facilitate rapid incorporation into the broad synthetic chemists' toolbox. Here, we describe a simple yet robust ultrasonication-assisted Stille polymerization for accessing semiconducting polymers with high-precision tailored molecular weights (from low to ultrahigh molecular weight ranges) while mitigating their interbatch variations. We propose that ultrasound-induced simultaneous physical and chemical events enable precise control of the semiconducting polymers' molecular weights with high reproducibility to satisfy all the optical/electrical and morphological demands of diverse types of high-performance semiconducting polymer-based devices; as demonstrated in in-depth experimental screenings in applications of both organic and perovskite photovoltaics. We believe that this methodology provides a fast development of new and existing semiconducting polymers with the highest-level performances possible on various photovoltaic devices.

Three-in-One Strategy Enables Single-Component Organic Solar Cells with Record Efficiency and High Stability.

Single-component organic solar cells (SCOSCs) with covalently bonding donor and acceptor are becoming increasingly attractive because of their superior stability over traditional multicomponent blend organic solar cells (OSCs). Nevertheless, the efficiency of SCOSCs is far behind the state-of-the-art multicomponent OSCs. Herein, by combination of the advantages of three-component and single-component devices, this work reports an innovative three-in-one strategy to boost the performance of SCOSCs. In this three-in-one strategy, three independent components (PM6, D18, and PYIT) are covalently linked together to create a new single-component active layer based on ternary conjugated block copolymer (TCBC) PM6-D18-b-PYIT by a facile polymerization. Precisely manipulating the component ratios in the polymer chains of PM6-D18-b-PYIT is able to broaden light utilization, promote charge dynamics, optimize, and stabilize film morphology, contributing to the simultaneously enhanced efficiency and stability of the SCOSCs. Ultimately, the PM6-D18-b-PYIT-based device exhibits a power conversion efficiency (PCE) of 14.89%, which is the highest efficiency of the reported SCOSCs. Thanks to the aggregation restriction of each component and chain entanglement in the three-in-one system, the PM6-D18-b-PYIT-based SCOSC displays significantly higher stability than the corresponding two-component (PM6-D18:PYIT) and three-component (PM6:D18:PYIT). These results demonstrate that the three-in-one strategy is facile and promising for developing SCOSCs with superior efficiency and stability.

Multifunctional Acrylic Polymers with Enhanced Adhesive Property Serving as Excellent Edge Encapsulant for Stable Optoelectronic Devices.

Pendant groups in acrylic adhesive polymers (Ads) have a profound influence on adhesive and cohesive properties and additionally on encapsulant application. However, a systematic investigation to assess the impact of the pendant groups' length and bulkiness is rare, and there is not even a single report on applying Ads as interfacial adhesion promotors and encapsulation materials simultaneously. Herein, we have developed a series of multifunctional methacrylic polymers, namely, R-co-Ads, with varying pendant length and bulkiness (R = methyl (C1), ethyl (C2), propyl (C3), butyl (C4), pentyl (C5), hexyl (C6), isobutyl (iC4), and 2-ethylhexyl (2EH)). The adhesion-related experimental results reveal that R-co-Ads have high transparency, strong adhesion strength to the various contact surfaces, and a fast cure speed. In particular, C1-co-Ad shows a superior adhesion performance with an improved cross-cut index of 4B and a shear bonding strength of 1.56 MPa. We also have adopted C1-co-Ad for encapsulation of various emerging optoelectronic applications (e.g., perovskite solar cell-, charge transport-, and conductivity-related characteristics), demonstrating its excellent edge encapsulant served to improve the device stability against ambient air conditions. Our study establishes the structure-adhesion-surface relationships, advancing the better design of adhesives and encapsulants for various research fields.

Octafluoronaphthalene as a thermal-annealing-free volatile solid additive enables high-performance organic solar cells.

A thermal annealing-free solid additive octafluoronaphthalene was developed for high-performance organic solar cells. In an additive-modified device, an impressive power conversion efficiency of 18.59% from 17.27% was achieved with simultaneously enhanced current density from 26.86 to 27.53 mA cm-2 and fill factor from 74.34% to 78.85%.

Emergence and Prevalence of an African Swine Fever Virus Variant in Wild Boar Populations in South Korea from 2019 to 2022.

African swine fever (ASF), a viral disease caused by the African swine fever virus (ASFV), is associated with high mortality rates in domestic pigs and wild boars. ASF has been spreading since its discovery in wild boars in Korea in October 2019. Genomic analyses have provided insights into the genetic diversity of the ASFV isolated from various regions, enabling a better understanding of the virus origin and transmission patterns. We conducted a genome analysis to evaluate the diversity and mutations of ASFV spreading among wild boars in Korea during 2019-2022. We compared the genomes of ASFV strains isolated from Korean wild boars and publicly available ASFV genomes. Genomic analysis revealed several single-nucleotide polymorphisms within multigene families (MGFs) 360-1La and 360-4L in Korean ASFV. MGF 360-1La and 360-4L variations were not observed in other ASFV strains, including those of genotype II. Finally, we partially analyzed MGFs 360-1La and 360-4L in ASFV-positive samples between 2019 and 2022, confirming the geographical distribution of the variants. Our findings can help identify new genetic markers for epidemiological ASFV analysis and provide essential information for effective disease management.

Complete genome analysis of the African swine fever virus isolated from a wild boar responsible for the first viral outbreak in Korea, 2019.

African swine fever (ASF), a highly contagious and severe hemorrhagic viral disease in swine, is emerging as a major threat not only in Korea but also worldwide. The first confirmed case of ASF in Korea was reported in 2019. Despite the occurrence of ASF in Korea, only a few studies have genetically characterized the causative ASF virus (ASFV). In this study, we aimed to genetically characterize the ASFV responsible for the 2019 outbreak in Korea. The genome of the ASFV isolated during the first outbreak in Korea was analyzed. The Korea/YC1/2019 strain has 188,950 base pairs, with a GC content of 38.4%. The complete genome sequence was compared with other ASFV genomes annotated in the NCBI database. The Korea/YC1/2019 strain shared the highest similarity with Georgia 2007, Belgium 2018/1, and ASFV-wbBS01 strains. This study expands our knowledge of the genetic diversity of ASFV, providing valuable information for epidemiology, diagnostics, therapies, and vaccine development.

Design of PD-1-decorated nanocages targeting tumor-draining lymph node for promoting T cell activation.

Targeted delivery of immunomodulatory molecules to the lymph nodes is an attractive means of improving the efficacy of anti-cancer immunotherapy. In this study, to improve the efficacy of PD-1 blockade-based therapy, nanocages were designed by surface engineering to decorate a programmed cell death protein 1 (PD-1) that is capable of binding against programmed death-ligand 1 (PD-L1) and -ligand 2 (PD-L2). This nanocage-mediated multivalent interaction remarkably increases the binding affinity and improves the antagonistic activity compared to free soluble PD-1. In addition, with the desirable nanocage size for optimal tumor-draining lymph node (TDLN) targeting (approximately 20 nm), rapid draining and increased accumulation into the TDLNs were observed. Moreover, the interference of the PD-1/PD-L axis with ultra-high affinity in the tumor microenvironment (effector phase) and the TDLNs (cognitive phase) significantly enhances the dendritic cell-mediated tumor-specific T cell activation. This characteristic successfully inhibited tumor growth and induced complete tumor eradication in some mice. Thus, the delivery of immunomodulatory molecules with nanocages can be a highly efficient strategy to achieve stronger anti-tumor immunity.

Overcoming therapeutic efficiency limitations against TRAIL-resistant tumors using re-sensitizing agent-loaded trimeric TRAIL-presenting nanocages.

Tumor-specific apoptosis-inducing ligands have attracted considerable attention in cancer therapy. But, the evasion of apoptosis by tumors can cause acquired resistance to the therapy. TNF-related apoptosis-inducing ligand (TRAIL) has been investigated as an ideal antitumor agent owing to its inherent tumor cell-specific apoptotic activity. However, there are several barriers to its wider application, including the inability for stable formation of the trimeric structure, poor stability and pharmacokinetics, and differences in the sensitivity of different tumor types. Especially, almost 70% of tumor cells have acquired resistance to TRAIL, leading to failure of TRAIL-based therapeutics in clinical trials. To overcome therapeutic efficiency limitations against TRAIL-resistant tumors, we exploited the characteristic of a naturally derived nanocage that not only delivers TRAIL in its native-like trimeric structure, but also delivers a drug (doxorubicin [DOX]) that re-sensitizes TRAIL-resistant tumor cells. These TRAIL-presenting nanocages (TTPNs) showed high loading efficiency, pH-dependent release profiles, and effective intracellular delivery of the re-sensitizing agent DOX. As a result, DOX-TTPNs efficiently re-sensitized TRAIL-resistant tumor cells to TRAIL-mediated apoptosis in vitro by regulating levels of the TRAIL receptor, DR5, and anti- and pro-apoptotic proteins involved in extrinsic and intrinsic apoptosis pathways. We further demonstrated the antitumor efficacy of DOX-TTPNs in vivo, showing that even at a very low dose, the incorporated DOX successfully re-sensitized tumors to the apoptotic effects of TRAIL, underscoring the potential of this platform as an antitumor agent. Given that other homotrimeric TNF superfamily ligands and immunotherapeutic agents can be substituted for TRAIL ligand and re-sensitizing drugs on the surface and in the inner cavity of the nanocage, respectively, this platform is potentially suitable for development of a broad range of anticancer or immunotherapeutic combinations.

Corrigendum: 2018 Korean Society for the Study of Obesity Guideline for the Management of Obesity in Korea.

[This corrects the article on p. 40 in vol. 28, PMID: 31089578.].

2018 Korean Society for the Study of Obesity Guideline for the Management of Obesity in Korea.

Obesity increases the risks of diabetes, hypertension, and cardiovascular diseases, ultimately contributing to mortality. Korean Society for the Study of Obesity (KSSO) was established to improve the management of obesity through research and education; to that end, the Committee of Clinical Practice Guidelines of KSSO reviews systemic evidence using expert panels to develop clinical guidelines. The clinical practice guidelines for obesity were revised in 2018 using National Health Insurance Service Health checkup data from 2006 to 2015. Following these guidelines, we added a category, class III obesity, which includes individuals with body mass index (BMI) ≥35 kg/m2. Agreeing with the International Federation for the Surgery of Obesity and Metabolic Disorders, Asian Pacific Chapter consensus, we determined that bariatric surgery is indicated for Korean patients with BMI ≥35 kg/m2 and for Korean patients with BMI ≥30 kg/m2 who have comorbidities. The new guidelines focus on guiding clinicians and patients to manage obesity more effectively. Our recommendations and treatment algorithms can serve as a guide for the evaluation, prevention, and management of overweight and obesity.

Renal medullary carcinomas depend upon SMARCB1 loss and are sensitive to proteasome inhibition.

Renal medullary carcinoma (RMC) is a rare and deadly kidney cancer in patients of African descent with sickle cell trait. We have developed faithful patient-derived RMC models and using whole-genome sequencing, we identified loss-of-function intronic fusion events in one SMARCB1 allele with concurrent loss of the other allele. Biochemical and functional characterization of these models revealed that RMC requires the loss of SMARCB1 for survival. Through integration of RNAi and CRISPR-Cas9 loss-of-function genetic screens and a small-molecule screen, we found that the ubiquitin-proteasome system (UPS) was essential in RMC. Inhibition of the UPS caused a G2/M arrest due to constitutive accumulation of cyclin B1. These observations extend across cancers that harbor SMARCB1 loss, which also require expression of the E2 ubiquitin-conjugating enzyme, UBE2C. Our studies identify a synthetic lethal relationship between SMARCB1-deficient cancers and reliance on the UPS which provides the foundation for a mechanism-informed clinical trial with proteasome inhibitors.

Transfer-free synthesis of multilayer graphene using a single-step process in an evaporator and formation confirmation by laser mode-locking.

Multilayer graphene is synthesized by a simplified process employing an evaporator in which a target substrate is deposited with a Ni catalyst layer before being heated to grow graphene directly. Carbon atoms adsorbed onto the surface of the Ni source as impurities from the atmosphere are incorporated into the catalyst layer during the deposition, and diffuse toward the catalyst/substrate interface, where they crystallize as graphene with a thickness of less than 2 nm. The need for a transfer process and external carbon supply is eliminated. The graphene is characterized by conventional analysis approaches, including nano-scale visualization and Raman spectroscopy, and utilizing photonics, graphene-functionalized passive laser mode-locking is demonstrated to confirm the successful synthesis of the graphene layer, resulting in an operating center wavelength of 1569.4 nm, a pulse duration of 1.35 ps, and a repetition rate of 31.6 MHz.

Active contours driven by the salient edge energy model.

In this brief, we present a new indicator, i.e., salient edge energy, for guiding a given contour robustly and precisely toward the object boundary. Specifically, we define the salient edge energy by exploiting the higher order statistics on the diffusion space, and incorporate it into a variational level set formulation with the local region-based segmentation energy for solving the problem of curve evolution. In contrast to most previous methods, the proposed salient edge energy allows the curve to find only significant local minima relevant to the object boundary even in the noisy and cluttered background. Moreover, the segmentation performance derived from our new energy is less sensitive to the size of local windows compared with other recently developed methods, owing to the ability of our energy function to suppress diverse clutters. The proposed method has been tested on various images, and experimental results show that the salient edge energy effectively drives the active contour both qualitatively and quantitatively compared to various state-of-the-art methods.

Direct growth and patterning of multilayer graphene onto a targeted substrate without an external carbon source.

Using only a simple tube furnace, we demonstrate the synthesis of patterned graphene directly on a designed substrate without the need for an external carbon source. Carbon atoms are absorbed onto Ni evaporator sources as impurities, and incorporated into catalyst layers during the deposition. Heat treatment conditions were optimized so that the atoms diffused out along the grain boundaries to form nanocrystals at the catalyst-substrate interfaces. Graphene patterns were obtained under patterned catalysts, which restricted graphene formation to within patterned areas. The resultant multilayer graphene was characterized by Raman spectroscopy and transmission electron microscopy to verify the high crystallinity and two-dimensional nanomorphology. Finally, a metal-semiconductor diode with a catalyst-graphene contact structure were fabricated and characterized to assess the semiconducting properties of the graphene sheets with respect to the display of asymmetric current-voltage behavior.

Ultrafast optical nonlinearity of multi-layered graphene synthesized by the interface growth process.

We propose a novel photonic application as well as an optical tool to verify the crystallinity of interface-grown graphene demonstrating passive mode-locked lasers. The interface growth process enables the formation of multi-layered graphene at an interface of substrate and catalyst, therefore directly onto the targeted substrate without a transfer process. The synthesized graphene is characterized using Raman spectroscopy and x-ray photoelectron spectroscopy before ultrashort pulse formation to confirm the validity of the process for high-speed photonic applications of graphene. The resultant pulses have a repetition rate, pulse duration, RF extinction ratio of 14.01 MHz, 1.0 ps, and ∼35 dB, respectively.

Saliency detection via textural contrast.

We present a new approach for visual saliency detection from various natural images. It is inspired by our careful observation that the human visual system (HVS) responds sensitively and quickly to high textural contrast, derived from the discriminative directional pattern from its surroundings as well as the noticeable luminance difference, for understanding a given scene. By formulating such textural contrast within a multiscale framework, we construct a more reliable saliency map even without color information when compared to most previous approaches still suffering from the complex and cluttered background. The proposed method has been extensively tested on a wide range of natural images, and experimental results show that the proposed scheme is effective in detecting visual saliency compared to various state-of-the-art methods.

Detecting shadows from a single image.

We present a novel (to our best knowledge) optical recognition technique for detecting shadows from a single image. Most prior approaches definitely depend on explicit physical computational models, but physics-based approaches have the critical problem that they may fail severely even with slight perturbations. Unlike traditional approaches, our method does not rely on any explicit physical models. This breakthrough originates from a discovery of a new modeling mechanism, derived from a biological vision principle, the so-called retinex theory, which is well suited for single-image shadow detection. Experimental results demonstrate that the proposed method outperforms the previous optical recognition techniques and gives robust results even in real-world complex scenes.