Polyphenol-Enabled 2D Nanopatch for Enhanced Nasal Mucoadhesion and Immune Activation.

The advancement of effective nasal mucoadhesive delivery faces challenges due to rapid mucociliary clearance (MCC). Conventional studies have employed mucoadhesive materials, mainly forming spherical nanoparticles, but these offer limited adhesion to the nasal mucosa. This study hypothesizes that a 2D nanoscale structure utilizing adhesive polyphenols can provide a superior strategy for countering MCC, aligning with the planar mucosal layers. We explore the use of tannic acid (TA), a polyphenolic molecule known for its adhesive properties and ability to form complexes with biomolecules. Our study introduces an unprecedented 2D nanopatch, assembled through the interaction of TA with green fluorescent protein (GFP), and cell-penetrating peptide (CPP). This 2D nanopatch demonstrates robust adhesion to nasal mucosa and significantly enhances immunoglobulin A secretions, suggesting its potential for enhancing nasal vaccine delivery. The promise of a polyphenol-enabled adhesive 2D nanopatch signifies a pivotal shift from conventional spherical nanoparticles, opening new pathways for delivery strategies through respiratory mucoadhesion.

The Role of Receptor Activator of Nuclear Factor-κB Ligand/Osteoprotegerin Ratio in Synovial Fluid as a Potential Marker for Periprosthetic Osteolysis Following Total Ankle Arthroplasty.

Background: Periprosthetic osteolysis is a prevalent complication following total ankle arthroplasty (TAA), implicating various cytokines in osteoclastogenesis as pivotal in this process. This study aimed to evaluate the relationship between osteolysis and the concentrations of osteoclastogenesis-related cytokines in synovial fluid and investigate its clinical value following TAA. Methods: Synovial fluid samples from 23 ankles that underwent revision surgery for osteolysis following TAA were analyzed as the osteolysis group. As a control group, we included synovial fluid samples obtained from 23 ankles during primary TAA for osteoarthritis. The receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in these samples was quantified using sandwich enzyme-linked immunosorbent assay techniques, and a bead-based multiplex immunoassay facilitated the detection of specific osteoclastogenesis-related cytokines. Results: RANKL levels averaged 487.9 pg/mL in 14 of 23 patients in the osteolysis group, with no detection in the control group's synovial fluid. Conversely, a significant reduction in OPG levels was observed in the osteolysis group (p = 0.002), resulting in a markedly higher mean RANKL/OPG ratio (0.23) relative to controls (p = 0.020). Moreover, the osteolysis group had increased concentrations of various osteoclastogenesis-related cytokines (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, IL-8, IP-10, and monocyte chemotactic protein-1) in the synovial fluid relative to the control group. Conclusions: Our results demonstrated that periprosthetic osteolysis was associated with osteoclastogenesis activation through an elevated RANKL/OPG ratio following TAA. We assume that RANKL and other osteoclastogenesis-related cytokines in the synovial fluid have clinical value as a potential marker for the development and progression of osteolysis following TAA.

An investigation of antioxidative and anti-inflammatory effects of Taraxacum coreanum (white dandelion) in lactating Holstein dairy cows.

Objective: The aim of this investigation was to examine the impact of Taraxacum coreanum (known as dandelion) (TC) and TC mixtures with milk thistle (MT) or Aspergillus oryzae (AO) as feed additives on the immune response, milk quality, and milk production in Holstein cows over 6 weeks of administration. Materials and Methods: Thirty-two healthy Holstein dairy cows were provided 30 kg of total mixed ration (TMR) with no TC, 90 gm TC, 54 gm TC + 36 gm MT, or 54 gm TC + 36 gm AO 40% groups. The feed additives were supplied daily in two equal portions (per 45 gm) by topdressing the TMR for 6 weeks. Milk and blood samples were collected weekly. Results: In the TC-treated cows (TC, TC + MT, and TC + AO groups), significantly lower peripheral blood white blood cell (WBC) counts at 6 weeks and milk somatic cell counts (SCCs) at 4-6 weeks of administration were observed. Concentrations of serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) were notably elevated in cows treated with TC for 4-6 weeks, while levels of proinflammatory cytokines concentrations of tumor necrosis factor-alpha (TNF-α) and chemokine (IL-8) were significantly reduced in TC-treated cows after 3-6 weeks of administration. Conclusion: These results suggested that TC or a TC mixture with other medicinal herbs supplementations enhanced the serum antioxidative activities and, consequently, might suppress the adverse immune response due to lower serum TNF-α and IL-8 release supported by lower WBC and SCC counts.

High-Efficiency Interdigitated Electrode-Based Droplet Merger for Enabling Error-Free Droplet Microfluidic Systems.

Merging two droplets into a droplet to add and mix two contents is one of the common droplet microfluidic functions with droplet generation and sorting, performing broad ranges of biological and chemical assays in droplets. However, traditional droplet-merging techniques often encounter unsynchronized droplets, causing overmerging or mis-merging, and unwanted merging outside of the desired zone. This is more severe when the incoming droplets to be merged are polydisperse in their sizes, often observed in assays that require long-term incubation, elevated-temperature, and/or multiple droplet processing steps. Here, we developed an interdigitated electrode (IDE)-based droplet merger consisting of a droplet autosynchronizing channel and a merging channel. The autosynchronizing channel provides >95% merging efficiency even when 20% polydispersity in the droplet size exists. The highly localized and enhanced dielectrophoretic force generated by the IDEs on the channel bottom allows droplet merging at an extremely low voltage (4.5 V) and only locally at the IDE region. A systematic evaluation of how various design and operation parameters of the IDE merger, such as IDE finger dimensions, dielectric coating layer thickness, droplet size, and droplet flow speed impact the performance was conducted. The optimized device showed consistent performance even when operating for up to 100 h consecutively at high throughput (100 droplets/s). The presented technology has been integrated into a droplet microfluidics workflow to test the lytic activities of bacteriophage on bacterial host cells with 100% merging efficiency. We expect this function to be integrated into droplet microfluidic systems performing broad ranges of high-throughput chemical and biological assays.

Investigating neuromodulatory effect of transauricular vagus nerve stimulation on resting-state electroencephalography.

Purpose: The purpose of this study was to investigate the neuromodulatory effects of transauricular vagus nerve stimulation (taVNS) and determine optimal taVNS duration to induce the meaningful neuromodulatroty effects using resting-state electroencephalography (EEG). Method: Fifteen participants participated in this study and taVNS was applied to the cymba conchae for a duration of 40 min. Resting-state EEG was measured before and during taVNS application. EEG power spectral density (PSD) and brain network indices (clustering coefficient and path length) were calculated across five frequency bands (delta, theta, alpha, beta and gamma), respectively, to assess the neuromodulatory effect of taVNS. Moreover, we divided the whole brain region into the five regions of interest (frontal, central, left temporal, right temporal, and occipital) to confirm the neuromodulation effect on each specific brain region. Result: Our results demonstrated a significant increase in EEG frequency powers across all five frequency bands during taVNS. Furthermore, significant changes in network indices were observed in the theta and gamma bands compared to the pre-taVNS measurements. These effects were particularly pronounced after approximately 10 min of stimulation, with a more dominant impact observed after approximately 20-30 min of taVNS application. Conclusion: The findings of this study indicate that taVNS can effectively modulate the brain activity, thereby exerting significant effects on brain characteristics. Moreover, taVNS duration of approximately 20-30 min was considered appropriate for inducing a stable and efficient neuromodulatory effects. Consequently, these findings have the potential to contribute to research aimed at enhancing cognitive and motor functions through the modulation of EEG using taVNS. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00361-8.

Draft genome for Pseudomonas alkylphenolica IMGN1, isolated from soil.

Biocontrol using organisms like Pseudomonas alkylphenolica offers a viable alternative to chemical pesticides, enhancing plant growth and reducing environmental impact. This study details the genome of Pseudomonas alkylphenolica IMGN1, a strain known for promoting plant growth, advancing our understanding of biocontrol mechanisms.

Complete genome sequence of Bacillus paramobilis sp. strain IMGN7 from soil.

Here, we report the complete genome sequence of Bacillus paramobilis sp. strain IMGN7, which was isolated from soil in South Korea. Its complete genome size is 5.28 Mbp. This genome will provide various insights for further studies about their function as biocontrol agents, such as bioremediation and antibiosis.

Draft genome sequence of bacterium Bacillus proteolyticus strain IMGN4 from soil.

Here, we present the draft genome of Bacillus proteolyticus IMGN4, the gram-positive, soil-dwelling bacterium discovered in mountain Maemi, Republic of Korea in May 2019. The assembly resulted in 7 contigs, comprising a total of 6,063,502 base pairs and have 6,115 coding sequences.

Effectiveness and safety of motion-style acupuncture treatment using traction for inpatients with acute low back pain caused by a traffic accident: A randomized controlled trial.

BACKGROUND: Musculoskeletal symptoms, such as neck pain and low back pain (LBP) are common after a traffic accident (TA). While motion-style acupuncture treatment (MSAT) is effective in relieving pain, MSAT using traction (T-MSAT) has rarely been studied, and evidence for its efficacy and safety is lacking. To address this gap, this study aimed to assess the effectiveness and safety of T-MSAT for pain and functional disturbances in patients with acute LBP caused by a TA. METHODS: This two-armed, parallel, assessor blinded randomized controlled trial, conducted at Jaseng Hospital of Korean Medicine, included 100 patients with acute LBP occurring within 1 week of a TA. The participants were randomly allocated (1:1 ratio) to receive either combined T-MSAT and integrative Korean medicine treatment (IKMT) or only conventional IKMT, applied for 3 consecutive days after admission. The primary outcome was the difference between numerical rating scale (NRS) scores for LBP at baseline and after treatment completion on day 4 after admission. RESULTS: At the primary endpoint, the difference in NRS scores for LBP between the T-MSAT and control groups was 0.94 (95% confidence interval [CI] 0.40-1.48). The T-MSAT group showed a significantly lower NRS score for LBP than the control group. Differences in visual analogue scale (VAS) scores between the T-MSAT and control groups were significant at baseline and discharge. The area under the curve of the VAS score showed a significant difference (-46.86 [95% CI -85.13 to -8.59]), indicating faster pain reduction in the T-MSAT group than in the control group. Recovery (30% pain reduction) was achieved more rapidly in the T-MSAT group than in the control group (log-rank test P = .005). Meanwhile, the NRS, VAS, Oswestry disability index, and quality of life scores at discharge or at the 12-week follow-up showed no significant difference. The rates of mild adverse events (AEs) were comparable between the groups. No severe AEs were reported, and none of the AEs were associated with the clinical trial. CONCLUSIONS: T-MSAT combined with IKMT is a safe treatment that can effectively and quickly reduce initial pain in patients with LBP.

Impact of Long-Term Supplementation with Probiotics on Gut Microbiota and Growth Performance in Post-Weaned Piglets.

This study aimed to investigate effects of long-term probiotic supplementation on gut microbiota and growth performance in health weaned piglets. The non-probiotic group (N-PrB) was fed only a basal diet, while the probiotic group (PrB) was fed a basal diet + probiotic combination (E. faecium 1.6 × 108 CFU/g, B. subtilis 2.0 × 108 CFU/g, S. cerevisiae 3.0 × 108 CFU/g). The probiotics combination was provided to the PrB, mixing with the basal diet in 5 kg/ton. As a result, the PrB exhibited significantly improved weight gain compared to the N-PrB (p = 0.00991). In the gut microbiome analysis, the PrB exhibited a significant increasing tendency of α-diversity compared to those of the N-PrB (p < 0.01). In the bacterial relative abundance changes in bacteria comprising the gut microbiota, Ruminococcaceae (p = 0.00281) and Prevotella (p = 0.00687) tended to significantly increase in the PrB, but decreased in the N-PrB. The Eubaterium coprostanoligenes group exhibited an increasing tendency in both groups, but tended to increase more significantly in the PrB compared to the N-PrB (p = 0.00681). Muribaculaceae tended to significantly increase in the N-PrB, but decreased in the PrB (p = 0.002779). In this study, significant differences on the gut microbiome were found according to the probiotics supplementation in the weaned piglets and these gut microbiome changes appeared to improve the growth performance.

Accelerating metal nanoparticle exsolution by exploiting tolerance factor of perovskite stannate.

The octahedral symmetry in ionic crystals can play a critical role in atomic nucleation and migration during solid-solid phase transformation. Similarly, octahedron distortion, which is characterized by Goldschmidt tolerance factor, strongly influences the exsolution kinetics in the perovskite lattice framework during high-temperature annealing. However, a fundamental study on manipulating the exsolution process by octahedron distortion is still lacking. In this study, we accelerate Ni metal exsolution on the surface of perovskite stannates by increasing the [BO6] octahedron distortion in the lattices. Decreasing the A-site ionic radius (rBa2+ = 161 pm → rSr2+ = 144 pm → rCa2+ = 134 pm) increased the density of exsolved Ni nanoparticles by up to 640% (i.e., 47 particles µm-2 of Ba(Sn, Ni)O3 → 304 particles µm-2 of Ca(Sn, Ni)O3) after the identical exsolution process. Based on the theoretical calculation and experimental characterization, the decrease in crystal symmetry by octahedral distortion promoted the Ni exsolution owing to the boosted Ni migration by weakening the bond strength and generating domain boundaries. The findings highlight the importance of octahedral distortion to control atomic migration through the perovskite lattice framework and provide a strategy to tailor the density of uniformly populated nanoparticles in nanocomposite oxides for multifunctional material design.

Exploring Neuroprotective Effects of Topical Brimonidine in Experimental Diabetic Retinopathy.

BACKGROUND/AIM: Diabetic retinopathy is a leading cause of blindness worldwide, characterized by neurovascular dysfunction. This study aimed to investigate the impact of brimonidine, a selective adrenoceptor agonist, on diabetic retinal neurodegeneration, recognizing the critical role of neurodegeneration in diabetic retinopathy. MATERIALS AND METHODS: Streptozotocin-induced diabetes was established in adult male Sprague-Dawley rats to mimic diabetic retinopathy. Rats, except non-diabetic control rats, received topical applications of 0.15% brimonidine tartrate (treatment group) or balanced salt solution (diabetic control group) twice daily following diabetes induction. Each group comprised six randomly assigned animals. Retinal samples were analyzed using immunofluorescence staining, apoptosis assay, and western blot. RESULTS: Topical brimonidine treatment reduced apoptosis of retinal ganglion cells at 8 weeks after induction of diabetes (p<0.05). Glial activation induced by diabetes was reduced by brimonidine treatment. Immunoblot and immunofluorescence assay revealed that the decrease in phospho- protein kinase B (AKT) level resulting from diabetes was also attenuated by brimonidine (p<0.05). Furthermore, brimonidine alleviated the decrease in anti-apoptotic proteins [BCL2 apoptosis regulator (BCL2) and BCL-xl] induced by diabetes (p<0.05). Elevation of phospho-p38 mitogen-activated protein kinase (p38MAPK) and p53 in diabetic rats were reduced by brimonidine (p<0.05). Additionally, brimonidine treatment attenuated the upregulation of the pro-apoptotic molecule BCL-2 associated X in retinas of diabetic rats (p<0.05). CONCLUSION: These findings suggest that topical brimonidine treatment may protect retinal ganglion cells in experimental diabetes by modulating the AKT pathway and reducing pro-apoptotic p38MAPK levels. This presents a potential neuroprotective approach in diabetes, offering the advantage of localized treatment without the added burden of oral medication.

Parallel Analysis of Exosomes and Cytokines in Aqueous Humor Samples to Evaluate Biomarkers for Glaucoma.

Recent emerging studies have demonstrated numerous critical roles of exosomes in cell-to-cell signaling. We investigated exosomes in the aqueous humor of glaucoma patients and controls and compared their characteristics with other biomarkers such as cytokines. Glaucoma patients exhibited higher exosome particle counts and smaller sizes compared to controls. Higher exosome density was correlated with more severe visual field loss. Conversely, concentrations of aqueous humor cytokines, particularly PD-L1, were primarily associated with intraocular pressure, and none of the cytokines showed a significant association with visual field damage. This may reflect the characteristics of exosomes, which are advantageous for crossing various biological barriers. Exosomes may contain more information about glaucoma functional damage occurring in the retina or optic nerve head. This highlights the potential importance of exosomes as signaling mediators distinct from other existing molecules.

Spatiotemporal Control of Inflammatory Lytic Cell Death Through Optogenetic Induction of RIPK3 Oligomerization.

Necroptosis is a programmed lytic cell death involving active cytokine production and plasma membrane rupture through distinct signaling cascades. However, it remains challenging to delineate this inflammatory cell death pathway at specific signaling nodes with spatiotemporal accuracy. To address this challenge, we developed an optogenetic system, termed Light-activatable Receptor-Interacting Protein Kinase 3 or La-RIPK3, to enable ligand-free, optical induction of RIPK3 oligomerization. La-RIPK3 activation dissects RIPK3-centric lytic cell death through the induction of RIPK3-containing necrosome, which mediates cytokine production and plasma membrane rupture. Bulk RNA-Seq analysis reveals that RIPK3 oligomerization results in partially overlapped gene expression compared to pharmacological induction of necroptosis. Additionally, La-RIPK3 activates separated groups of genes regulated by RIPK3 kinase-dependent and -independent processes. Using patterned light stimulation delivered by a spatial light modulator, we demonstrate precise spatiotemporal control of necroptosis in La-RIPK3-transduced HT-29 cells. Optogenetic control of proinflammatory lytic cell death could lead to the development of innovative experimental strategies to finetune the immune landscape for disease intervention.

Investigating chiral morphogenesis of gold using generative cellular automata.

Homochirality is an important feature in biological systems and occurs even in inorganic nanoparticles. However, the mechanism of chirality formation and the key steps during growth are not fully understood. Here we identify two distinguishable pathways from achiral to chiral morphologies in gold nanoparticles by training an artificial neural network of cellular automata according to experimental results. We find that the chirality is initially determined by the nature of the asymmetric growth along the boundaries of enantiomeric high-index planes. The deep learning-based interpretation of chiral morphogenesis provides a theoretical understanding but also allows us to predict an unprecedented crossover pathway and the resulting morphology.

Spin angular momentum-encoded single-photon emitters in a chiral nanoparticle-coupled WSe2 monolayer.

Spin angular momentum (SAM)-encoded single-photon emitters, also known as circularly polarized single photons, are basic building blocks for the advancement of chiral quantum optics and cryptography. Despite substantial efforts such as coupling quantum emitters to grating-like optical metasurfaces and applying intense magnetic fields, it remains challenging to generate circularly polarized single photons from a subwavelength-scale nanostructure in the absence of a magnetic field. Here, we demonstrate single-photon emitters encoded with SAM in a strained WSe2 monolayer coupled with chiral plasmonic gold nanoparticles. Single-photon emissions were observed at the nanoparticle position, exhibiting photon antibunching behavior with a g(2)(0) value of ~0.3 and circular polarization properties with a slight preference for left-circular polarization. Specifically, the measured Stokes parameters confirmed strong circular polarization characteristics, in contrast to emitters coupled with achiral gold nanocubes. Therefore, this work provides potential insights to make SAM-encoded single-photon emitters and understand the interaction of plasmonic dipoles and single photons, facilitating the development of chiral quantum optics.

Three-Dimensional Analysis of Bone Remodeling After Closed Treatment for Mandibular Condylar Head Fracture.

Closed treatment of mandibular condylar fractures has been used for its indications based on the fracture site, fracture status, and patient age. Posttreatment mandibular condyle size is associated with mandibular function; however, a few studies have reported bone remodeling patterns and volume changes in the condyle and glenoid fossa after mandibular condylar head fractures (CHFs). Therefore, volumetric changes in the mandibular condyle and glenoid fossa were analyzed in the present study, and bone remodeling patterns were evaluated after mandibular CHFs. The present study included 16 condyles from 12 patients who received closed treatment for CHF. After reconstruction of a 3-dimensional skull model, including the mandible, using computed tomography data taken immediately after injury and 6 months after treatment, volume changes in the mandibular condyle and glenoid fossa were analyzed. The condylar volume increased by 0.32±0.66 cm3 during the 6-month healing period without statistical significance (P=0.093). Regarding the glenoid fossa, the fossa showed a statistically significant volume increase of 0.41±0.59 cm3 (P=0.021), and 12 glenoid fossae (75%) showed downward bone apposition; however, no change or only mild bone resorption was observed in 4 glenoid fossae (25%). The results of this study indicated that the volume changes in the mandibular condyle after closed treatment of a mandibular CHF are not significant, and the glenoid fossa adapts to the displaced mandibular condyle through downward growth accompanied by volume increase.

Effect of Dynamic Binaural Beats on Sleep Quality: A Proof-of-Concept Study with Questionnaire and Biosignals.

Binaural beat (BB) has been investigated as a potential modality to enhance sleep quality. In this study, we introduce a new form of BB, referred to as dynamic BB (DBB), which incorporates dynamically changing carrier frequency differences between the left and right ears. Specifically, the carrier frequency of the right ear varied between 100 and 103 Hz over a period, while the left ear remained fixed at 100 Hz, yielding a frequency difference range of 0 to 3 Hz. The objective of this study was to examine the effect of DBB on sleep quality. Ten healthy participants were included in a cross-over design, where they experienced both DBB and a SHAM (absence of sound) condition across two consecutive nights, with polysomnography evaluation. DBB was administrated during pre-sleep initiation, sleep onset, and transition from rapid-eye-movement (REM) to non-REM stage. DBB significantly reduced sleep latency compared to the SHAM condition. Electrocardiogram analysis revealed that exposure to DBB led to diminished heart rate variability during the pre-sleep initiation and sleep onset periods, accompanied by a decrease in low frequency power of heart rate during the sleep onset period. DBB might be effective in improving the sleep quality, suggesting its possible application in insomnia treatments.