Probiotic Potential of Bacillus Subtilis Strain I3: Antagonistic Activity Against Chalkbrood Pathogen and Pesticide Degradation for Enhancing Honeybee Health.

To explore the potential of probiotic candidates beneficial for honeybee health through the modulation of the gut microbiome, bee gut microbes were isolated from bumblebee (Bombus terrestris) and honeybee (Apis mellifera) using diverse media and cultural conditions. A total of 77 bee gut bacteria, classified under the phyla Proteobacteria, Firmicutes, and Actinobacteria, were identified. The antagonistic activity of the isolates against Ascosphaera apis, a fungal pathogen responsible for chalkbrood disease in honeybee larvae, was investigated. The highest growth inhibition percentage against A. apis was demonstrated by Bacillus subtilis strain I3 among the bacterial strains. The presence of antimicrobial peptide genes in the I3 strain was detected using PCR amplification of gene fragments encoding surfactin and fengycin utilizing specific primers. The export of antimicrobial peptides by the I3 strain into growth medium was verified using liquid chromatography coupled with mass spectroscopy. Furthermore, the strain's capabilities for degrading pesticides, used for controlling varroa mites, and its spent growth medium antioxidant activity were substantiated. The survival rate of honeybees infected with (A) apis was investigated after feeding larvae with only medium (fructose + glucose + yeast extract + royal jelly), (B) subtilis I3 strain, A. apis with medium and I3 strain + A. apis with medium. Honeybees receiving the I3 strain + A. apis exhibited a 50% reduction in mortality rate due to I3 strain supplementation under experimental conditions, compared to the control group. In silico molecular docking revealed that fengycin hydrolase from I3 strain effectively interacted with tau-fluvalinate, suggesting its potential in bee health and environmental protection. Further studies are needed to confirm the effects of the I3 strain in different populations of honey bees across several regions to account for genetic and environmental variations.

New Pimarane Diterpenoids Isolated from EtOAc-Extract of Apiospora arundinis Culture Medium Show Antibenign Prostatic Hyperplasia Potential.

Three new pimarane diterpenoids, libertellenones U-W (1-3), together with libertellenone C (4) and myrocin A (5) were isolated from an EtOAc-extract of Apiospora arundinis culture medium. The chemical structures of the new compounds were elucidated using MS, NMR, and CD spectroscopic data. Benign prostatic hyperplasia (BPH), the abnormal and pathological proliferation of epithelial and stromal cells in prostatic tissues, is a common disease in middle-aged and elderly men. In this study, the anti-BPH effects of myrocin A (5) were evaluated using BPH-1 and WPMY-1 cells. Treatment with myrocin A (5) exerted antiproliferative effects in BPH-1 and dihydrotestosterone (DHT)-stimulated WPMY-1 cells. In BPH, treatment with myrocin A (5) significantly suppressed the mRNA levels of androgen receptor (AR) and its downstream targets nuclear receptor coactivator 1 (NCOA1), proliferating cell nuclear antigen (PCNA) and kallikrein-related peptidase 3 (KLK3). Additionally, DHT-stimulated WPMY-1 cells demonstrated an upregulated mRNA levels of AR, NCOA1, PCNA, and KLK3. However, treatment with myrocin A (5) resulted in suppression of the mRNA levels. Moreover, myrocin A (5) docked computationally into the binding site of the androgen receptor (-5.5 kcal/mol).

Cost-effectiveness of the 20-valent pneumococcal conjugate vaccine versus the 23-valent pneumococcal polysaccharide vaccine for older adults in South Korea.

BACKGROUND: Despite the demonstrated immunogenicity and safety of the 20-valent pneumococcal conjugate vaccine (PCV20) in older adults, the cost-effectiveness of the PCV20 was not examined compared to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in South Korea. Therefore, this study aimed to evaluate the cost-effectiveness of PCV20 compared with PPSV23 in adults aged 65 years and older in South Korea. METHODS: We constructed a Markov model that included susceptible states, invasive pneumococcal disease (IPD), non-bacteremic pneumonia (NBP), and death. The population was categorized by disease risk status (low risk, moderate risk, and high risk) and age group (65-74/75-84/85-99 years) at model entry. The annual incidence and mortality of IPD and NBP associated with PCV20 and PPSV23 were estimated based on serotype coverage, vaccine coverage, and vaccine effectiveness. The disease costs and utilities were obtained from previous studies. The incremental cost-effectiveness ratio (ICER) was used to evaluate cost-effectiveness within the threshold of 16,824 USD per quality-adjusted life-year (QALY). RESULTS: Among the total population (n = 8,843,072), PCV20 prevented 1941 and 50,575 cases of IPDs and NBPs, respectively, and 898 and 8593 deaths due to IPDs and NBPs compared to PPSV23. The total medical cost per person was 12.11 USD higher in PCV20, with a gain of 0.0053 LYs and 0.0045 QALYs per person. The ICER for PCV20 and PPSV23 was 2270 USD/LY and 2677 USD/QALY. CONCLUSIONS: In South Korea, PCV20 is a cost-effective option compared with PPSV23 for adults aged 65 years and older. These cost-effectiveness results provide evidence for decision-making regarding the approval and National Immunization Program implementation of PCV20.

Assessing potential impact of gut microbiome disruptions on the environmental stress resilience of indoor-reared Bombus terrestris.

Bumblebees are crucial for both natural ecosystems and agriculture, but their decline in distribution and abundance over the past decade is alarming. The global importance of bumblebees in natural ecosystems and agricultural food production cannot be overstated. However, the reported decline over the past decade has led to a surge of interest in understanding and addressing bumblebee population decline. Hence, we aimed to detect disruptions in the gut microbiome of male and worker bumblebees reared indoor and outdoor to assess potential resilience to environmental stress. Using the Illumina MiSeq platform for 16s rRNA amplicon sequencing, we analyzed the gut microbiome of male and worker bees that were raised indoors (designated as the IM and IW group) and those that were raised outdoors (also designated as the OM and OW group). Our results show presence of core bacteria Neisseriaceae, Orbaceae, Lactobacillaceae and Bifidobacteriaceae from indoor reared worker bees. However, a higher abundance of Bifidobacterium and absence of Fructobacillus from indoor reared worker bees was also observed. Indoor-reared male bees had lower diversity and fewer observed OTUs compared to outdoor-reared male bees. Additionally, the relative abundance of Actinobacteriota, Bacteroidota, and Firmicutes was significantly lower in indoor-reared males, while Proteobacteria was significantly increased. Despite this, we did not observe any dysbiosis in the gut microbiota of indoor-reared bumblebees when comparing the role of the gut symbionts among the groups. These results suggest that indoor-reared Bombus terrestris may be resilient to environmental stress when used as outdoor pollinators.

Severity of myxomatous mitral valve disease in dogs may be predicted using neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratio.

OBJECTIVE: To investigate the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in dogs with myxomatous mitral valve disease (MMVD). ANIMALS: 106 dogs with MMVD and 22 healthy dogs were included in the study. PROCEDURES: CBC data were obtained retrospectively, and NLR, MLR, and PLR were compared between dogs with MMVD and healthy dogs. The ratios were also analyzed according to MMVD severity. RESULTS: NLR and MLR were significantly higher in dogs with MMVD C and D (NLR of 4.99 [3.69-7.27]; MLR of 0.56 [0.36-0.74]) than in healthy dogs (NLR: 3.05 [1.82-3.37], P < .001; MLR: 0.21 [0.14-0.32], P < .001), MMVD stage B1 (NLR: 3.15 [2.15-3.86], P < .001; MLR: 0.26 [0.20-0.36], P < .001), and MMVD stage B2 dogs (NLR: 3.22 [2.45-3.85], P < .001; MLR: 0.30 [0.19-0.37], P < .001). The area under the receiver operating characteristic curves of the NLR and MLR to distinguish dogs with MMVD C and D from those with MMVD B were 0.84 and 0.89, respectively. The optimal cutoff value for NLR was 4.296 (sensitivity, 68%; specificity, 83.95%), and the MLR value was 0.322 (sensitivity, 96%; specificity, 66.67%). NLR and MLR were significantly decreased after treatment in dogs with congestive heart failure (CHF). CLINICAL RELEVANCE: NLR and MLR can be used as adjunctive indicators of CHF in dogs.

Impact of π-Expanded Boron-Carbonyl Hybrid Acceptors on TADF Properties: Controlling Local Triplet Excited States and Unusual Emission Tuning.

Three donor-acceptor-type thermally activated delayed fluorescence (TADF) emitters (PXZBAO (1), PXZBTO (2), and PXZBPO (3)) comprising a phenoxazine (PXZ) donor and differently π-expanded boron-carbonyl (BCO) hybrid acceptor units are proposed. The emitters exhibit red (1) to orange (3) emissions with an increase in the π-expansion in the BCO acceptors. The control of the strength of local aromaticity for the BCO unit and the corresponding LUMO level is attributed to inducing the unusual emission color shifts. The photoluminescence quantum yield and delayed fluorescence lifetime of the emitters are also adjusted by the π-expansion. Notably, although 1 possesses a 3nπ* state in the acceptor unit as a local triplet excited state (3LE, T2), the T2 states of 2 and 3 mainly comprise a 3ππ* state in the acceptor. Consequently, all of the emitters exhibit strong spin-orbit coupling between their T2 and excited singlet (S1) states, leading to a fast reverse intersystem crossing with rate constants of ∼106 s-1. By employing the emitters as dopants, we realize efficient red-to-orange TADF-OLEDs. Maximum external quantum efficiencies of 17.7% for the yellowish-orange (3), 15.5% for the orange (2), and 13.9% for the red (1) devices are achieved, and the values are very close to the theoretical limit predicted from the optical simulation.

Comparisons of musculoskeletal injuries among three different modalities of Taekwondo (Kyorugi, Poomsae, and Shibum): a one-year follow-up prospective epidemiologic study.

The purpose of the study was to report the injury rates and characteristics (body location, type, mechanism, and severity) of musculoskeletal injuries in Kyorugi, Poomsae, and Shibum. A total of 137 Korean collegiate Taekwondo players - Kyorugi (n = 44), Poomsae (n = 46), and Shibum (n = 47) - were prospectively studied in 2019. Injury rates per 1,000 athlete-exposures (AEs) and time-exposures (TEs) during training and competition were calculated. Additionally, body location, type, mechanism, and severity of injury were analysed. The highest injury rate was recorded in Poomsae (172.0/1,000 AEs and 79.5/1,000 TEs) followed by Kyorugi (47.1/1,000 AEs and 25.9/1,000 TEs) and Shibum (57.5/1,000 AEs and 17.0/1,000 TEs). The frequently injured body location was the thigh (Kyorugi = 17%; Poomsae = 25%; Shibum = 18%). The common injury types were muscle cramps/spasms in Kyorugi (33%) and Poomsae (59%), and sprain in Shibum (41%). The common injury mechanisms were gradual onset in Kyorugi (40%) and Shibum (49%), and non-contact trauma in Poomsae (91%). Regarding the severity, the number of days from the injury onset to recovery > 1 week were higher in the order of Kyorugi (78%), Shibum (54%), and Poomsae (28%). Our data provide preliminary evidence that different injury prevention strategies should be applied to each modality of Taekwondo.

A systematic review of economic evaluations of tyrosine kinase inhibitors for non-small cell lung cancer (NSCLC).

INTRODUCTION: Although tyrosine kinase inhibitors (TKIs) have improved the efficacy of treatment for non-small cell lung cancer (NSCLC), the accessibility of TKIs is limited due to high costs. Despite the critical role of the cost-effectiveness of TKIs on decision-making, no systematic reviews have compared the cost-effectiveness of comparable TKIs. Therefore, we systemically reviewed the economic evaluation studies on various TKIs for NSCLC. AREAS COVERED: We searched PubMed and the Cochran Library to identify the published economic evaluation studies of TKIs in NSCLC patients that were published by January 2022. All of the included studies (n = 38) evaluated the cost-effectiveness of epidermal growth factor receptor (EGFR)-TKIs (n = 29) or anaplastic lymphocyte kinase (ALK)-TKIs (n = 9). The cost-effectiveness results were reported as the incremental cost-effectiveness ratio per quality-adjusted life-year, except for three studies. EXPERT OPINION: We found that the economic evaluation studies of the first and second generation of EGFR-TKIs and ALK-TKIs varied by the country and study settings, such as comparator and input parameters. In 12 studies, osimertinib (EGFR-TKI) was not cost-effective compared to other first/second EGFR-TKIs, regardless of the study settings. More evidence can be provided about cost-effectiveness of the third-generation TKIs in future research.

Odorless Glutathione Microneedle Patches for Skin Whitening.

Glutathione is a natural anti-aging substance that prevents the oxidation of protein thiols from reactive oxygen species. In the pharmaceutical industry, reduced glutathione (GSH) has been widely used for skin whitening due to its ability to inhibit tyrosinase. However, its poor permeability and foul odor limit its use in skin applications. Herein, we report a GSH-loaded dissolving microneedle (MN) patch prepared with hyaluronic acid (HA) that enables enhanced permeation across the skin and reduces the foul odor of GSH. HA was selected to prepare odorless GSH solutions and used for MN fabrications as a carrier of GSH. GSH-loaded MN (GSH-MN) arrays prepared from MN-forming solution containing up to 10% GSH showed good pattern uniformity and appropriate mechanical properties for insertion into the skin. The GSH-MNs with a loading capacity of 17.4% dissolve within 10 min following insertion into porcine skin and release the loaded GSH without being oxidized. This new approach combines functional biopolymers to reduce the characteristic GSH odor and advanced transdermal delivery based on MN technology to enhance skin permeation without pain. We believe this technique could expand the application of GSH in many cosmeceutical fields.

Gold Nanoparticles on Polymer-Wrapped Carbon Nanotubes: An Efficient and Selective Catalyst for the Electroreduction of CO2.

Multiple approaches will be needed to reduce the atmospheric CO2 levels, which have been linked to the undesirable effects of global climate change. The electroreduction of CO2 driven by renewable energy is one approach to reduce CO2 emissions while producing chemical building blocks, but current electrocatalysts exhibit low activity and selectivity. Here, we report the structural and electrochemical characterization of a promising catalyst for the electroreduction of CO2 to CO: Au nanoparticles supported on polymer-wrapped multiwall carbon nanotubes. This catalyst exhibits high selectivity for CO over H2 : 80-92 % CO, as well as high activity: partial current density for CO as high as 160 mA cm-2 . The observed high activity, originating from a high electrochemically active surface area (23 m2 g-1 Au), in combination with the low loading (0.17 mg cm-2 ) of the highly dispersed Au nanoparticles underscores the promise of this catalyst for efficient electroreduction of CO2 .

Early Stage Anodic Instability of Glassy Carbon Electrodes in Propylene Carbonate Solvent Containing Lithium Hexafluorophosphate.

Irreversible changes to the morphology of glassy carbon (GC) electrodes at potentials between 3.5 and 4.5 V vs Li/Li+ in propylene carbonate (PC) solvent containing lithium hexafluorophosphate (LiPF6) are reported. Analysis of cyclic voltammetry (CV) experiments in the range of 3.0 to 6.0 V shows that the capacitance of the electrochemical double-layer increased irreversibly beginning at potentials as low as 3.5 V. These changes resulted from nonfaradaic interactions, and were not due to oxidative electrochemical decomposition of the electrode and electrolyte, anion intercalation, nor caused by the presence of water, a common impurity in organic electrolyte solutions. Atomic force microscopy (AFM) images revealed that increasing the potential of a bare GC surface from 3.0 to 4.5 V resulted in a 6× increase in roughness, in good agreement with the changes in double-layer capacitance. Treating the GC surface via exposure to trichloromethylsilane vapors resulted in a stable double-layer capacitance between 3.0 and 4.5 V, and this treatment also correlated with less roughening. These results inform future efforts aimed at controlling surface composition and morphology of carbon electrodes.

Growth and Deposition of Au Nanoclusters on Polymer-wrapped Graphene and Their Oxygen Reduction Activity.

The development of a non-Pt electrocatalyst with a high performance for the oxygen reduction reaction (ORR) is one of the central issues in polymer electrolyte fuel cells science. Au-nanoparticles (Au-NPs) with a diameter of <2 nm are one of the promising substitutes of Pt-NPs; however, it is still a challenge to synthesize such a small-sized Au-NPs with a narrow diameter distribution on a carbon support without using capping agents. We here describe a facile method to deposit uniform Au-NPs (diameter = 1.6 nm and 3.3 nm) on the stacked-graphene (<10 layers) coated with poly[2,2'-(2,6-pyridine)-5,5'-bibenzimidazole] without using any capping agents. The obtained Au-NPs exhibit an excellent ORR activity with the onset potential at -0.11 V and -0.09 V (vs. Ag/AgCl) for 1.6 nm and 3.3 nm, respectively. On the other hand, inhomogeneous Au-NPs with 4.6 nm in average diameter shows the onset potential at -0.15 V (vs. Ag/AgCl).

Facile Enhancement in CO-Tolerance of a Polymer-Coated Pt Electrocatalyst Supported on Carbon Black: Comparison between Vulcan and Ketjenblack.

The CO poisoning and low durability of the anode platinum electrocatalyst in the direct methanol fuel cell (DMFC) are the two crucial obstacles of the wide commercialization of the DMFC. In this study, we synthesized two different electrocatalysts using VulcanXC-72R (VC) and Ketjenblack (KB) as the carbon supporting material for the methanol oxidation reaction (MOR) and long-term durability test, in which the carbon supporting materials were wrapped by poly[2,2'-(2,6-pyridine)-5,5'-bibenzimidazole] (PyPBI) before the platinum deposition and the fabricated electrocatalysts were coated by the poly(vinylphosphonic acid) (PVPA) via the base-acid reaction. We have found that the as-prepared KB/PyPBI/Pt/PVPA shows a higher durability (7% loss in ECSA) under the potential cycling from 1.0 to 1.5 V vs. RHE compared to that of the VC/PyPBI/Pt/PVPA, which showed a 20% loss in ECSA after 10 000 cycle-durability test. Meanwhile, the KB/PyPBI/Pt/PVPA shows a higher CO tolerance before and after the durability test compared to that of the VC/PyPBI/Pt/PVPA, especially under very high methanol concentration (4 M and 8 M), which is close to the practical application of the DMFC. The observed higher CO tolerance is due to the higher amount of the PVPA (14.6 wt %) in the KB/PyPBI/Pt/PVPA caused by the higher specific surface area of the KB (1232 m(2)/g) compared to the VC (235 m(2)/g).

Graphene oxide and laponite composite films with high oxygen-barrier properties.

The design and fabrication of oxygen barrier films is important for both fundamental and industrial applications. We prepared three different thin films composed of graphene oxide (GO) and laponite (LN), a typical low cost inorganic clay, with the GO/LN volume ratios of 1.9/0.1, 1.7/0.3 and 1.5/0.5 together with a double layer film of the GO and LN. We found that the films with GO/LN = 1.9/0.1 and the double layers exhibited high oxygen barrier and oxygen transmission rate values that reached 0.55 and 0.37 cm(3) per m(2) per atm per day, respectively, which were much lower than those of the films prepared from the pure GO, only LN and GO/LN = 1.7/0.3 and 1.5/0.5. This study is important for the design and fabrication of a film from GO-based all inorganic nanomaterials for applications in gas-barrier membranes.

Palladium-Based Anion-Exchange Membrane Fuel Cell Using KOH-Doped Polybenzimidazole as the Electrolyte.

The development of a low-cost and high-performance fuel cell is a strong social demand. Anion-exchange membrane fuel cells (AEMFCs) have recently emerged as an alternative technology to conventional fuel cells that use a proton-exchange membrane as they enable the use of cheaper metals than platinum. An AEMFC exhibiting a maximum power density of 241 mW cm-2 based on a palladium-based electrocatalyst has been developed. The polybenzimidazole-wrapped carbon nanotubes were used to anchor the palladium nanoparticles, and the material was doped using KOH to form an ideal triple-phase boundary structure around the palladium. The observed maximum power density is the highest among previously reported AEMFCs using palladium as the metal catalyst.