Probiotic LB101 alleviates dry eye in mice by suppressing matrix metalloproteinase-9 expression through the regulation of gut microbiota-involved NF-κB signaling.

Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic LB101 (Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175 [4:1] mix) against DE, we investigated its effect on tear amount and inflammatory marker expression levels in mice with unilateral exorbital lacrimal gland excision/atropine-benzalkonium chloride application (EB) or fecal microbiota transplantation from mice with EB (eFMT). Oral gavage of LB101 increased EB-suppressed tear amount and decreased EB-induced blinking number. Furthermore, LB101 decreased EB-induced TNF-α, IL-1ß, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva, while EB-suppressed IL-10 and occludin expression increased. LB101 also decreased EB-induced TNF-α and IL-1ß expression and NF-κB+CD11c+ cell population in the colon. eFMT also decreased tear amount and increased blinking number in the transplanted mice. eFMT increased TNF-α, IL-1ß, and MMP-9 expression and TNF-α+ and NF-κB+CD11c+ cell populations in the conjunctiva and TNF-α and IL-1ß expression and NF-κB+CD11c+ cell populations in the colon. Oral gavage of LB101 increased eFMT-suppressed tear amount and decreased eFMT-induced blinking number. Furthermore, LB101 decreased TNF-α, IL-1ß, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva and TNF-α and IL-1ß expression and NF-κB+CD11c+ cell population in the colon, while eFMT-suppressed IL-10 and occludin expression decreased. Furthermore, LB101 increased eFMT-suppressed Muribaculaceae, Prevotellaceae, and Lactobacillaceae populations in the gut microbiota, while eFMT-induced Bacteroidaceae population decreased. These findings suggest that DE may cause gut dysbiosis, which may be a risk factor for DE, and LB101 may alleviate DE with gut inflammation by suppressing the expression of MMP-9 and proinflammatory cytokines TNF-α and IL-1ß with the regulation of gut microbiota-involved NF-κB signaling.

The Probiotic Properties and Safety of Limosilactobacillus mucosae NK41 and Bifidobacterium longum NK46.

Probiotics should possess specific properties to exert beneficial effects, and their safety must be ensured for human consumption. The purpose of this study was to evaluate the probiotic properties and safety of Limosilactobacillus mucosae NK41 and Bifidobacterium longum NK46 isolated from human feces in vitro. Both strains exhibited high resistance to simulated gastrointestinal fluid. Furthermore, probiotic-related cell surface characteristics including auto-aggregation and cell surface hydrophobicity were assessed by measuring the absorbance at a wavelength of 600 nm, which demonstrated good auto-aggregation ability and affinity for xylene, indicating their effective adhesion to Caco-2 cells. In addition, hemolytic, gelatinase, and ß-glucuronidase activities were found to be negative in both strains. The susceptibility to nine commonly used antibiotics was assessed using the broth macrodilution method, which demonstrated that both strains were susceptible to all tested antibiotics. Furthermore, L. mucosae NK41 and B. longum NK46 produced significantly higher levels of L-lactate (71.8 ± 0.7% and 97.8 ± 0.4%) than D-lactate (28.2 ± 0.7% and 2.2 ± 0.4%, respectively). Using PCR amplification to investigate genes associated with virulence factors, we found that neither strain harbored any virulence genes. These findings suggest that L. mucosae NK41 and B. longum NK46 have the potential to be used as probiotics and are considered safe for human consumption.

Tetradentate Pt(II) Complexes with Bulky Carbazole Moieties for High-Efficiency and Narrow-Emitting Blue Organic Light-Emitting Devices.

Blue tetradentate Pt(II) complexes, Pt-tBuCz and Pt-dipCz, are synthesized by introducing carbazoles with bulky substituents for improving the rigidity and inhibiting intermolecular interactions of phosphorescent emitter. tert-Butyl and 2,6-diisopropylphenyl groups are substituted as the blocking groups at 3 position of the carbazole in Pt-tBuCz and Pt-dipCz, respectively. These new phosphorescent emitters exhibit a narrow full width at half maximum (FWHM) and a high horizontal emitting dipole orientation ratio. Pt-dipCz demonstrates a small FWHM of 24 nm, a high emitting dipole orientation ratio of 81%, and a high photoluminescence quantum yield value of 94%. As a result, the Pt-tBuCz and Pt-dipCz devices exhibited external quantum efficiencies (EQEs) of 23.7% and 25.0% with small FWHMs of 25 and 22 nm, respectively. For the Pt-dipCz device, the small FWHM and high EQE of >20% are maintained even at a doping concentration of 20 wt%. Furthermore, phosphor-sensitized organic light-emitting diodes fabricated using Pt-dipCz as a sensitizer achieved a high EQE of 31.4% with an FWHM of 18 nm. This result indicates that the 2,6-diisopropylphenyl group is a effective blocking group for Pt(II) complexes to develop highly efficient, color stable, doping concentration resistant, and efficiently sensitizing blue phosphors.

IL-6 expression-suppressing Lactobacillus reuteri strains alleviate gut microbiota-induced anxiety and depression in mice.

Fecal microbiota transplantation from patients with depression/inflammatory bowel disease (PDI) causes depression with gut inflammation in mice. Here, we investigated the effects of six Lactobacillus reuteri strains on brain-derived neurotropic factor (BDNF), serotonin, and interleukin (IL)-6 expression in neuronal or macrophage cells and PDI fecal microbiota-cultured microbiota (PcM)-induced depression in mice. Of these strains, L6 most potently increased BDNF and serotonin levels in corticosterone-stimulated SH-SY5Y and PC12 cells, followed by L3. L6 most potently decreased IL-6 expression in lipopolysaccharide (LPS)-stimulated macrophages. When L1 (weakest in vitro), L3, and L6 were orally administered in mice with PcM-induced depression, L6 most potently suppressed depression-like behaviors and hippocampal TNF-α and IL-6 expression and increased hippocampal serotonin, BDNF, 5HT7, GABAARα1, and GABABR1b expression, followed by L3 and L1. L6 also suppressed TNF-α and IL-6 expression in the colon. BDNF or serotonin levels in corticosterone-stimulated neuronal cells were negatively correlated with depression-related biomarkers in PcM-transplanted mice, while IL-6 levels in LPS-stimulated macrophage were positively correlated. These findings suggest that IL-6 expression-suppressing and BDNF/serotonin expression-inducing LBPs in vitro, particularly L6, may alleviate gut microbiota-involved depression with colitis in vivo.

Lactobacillus plantarum and Bifidobacterium longum Alleviate Liver Injury and Fibrosis in Mice by Regulating NF-κB and AMPK Signaling.

In a preliminary study, live biotherapeutic products (LBPs) Lactobacillus plantarum LC27 and Bifidobacterium longum LC67 inhibited the secretion of alanine transaminase (ALT) and aspartate transaminase (AST) in LPS-stimulated HepG2 cells, while Escherichia coli K1 (Ec) increased ALT and ALT secretion. Therefore, we examined the effects of LC27 and LC67 on LPS-induced liver injury and fibrosis in mice and the correlation between their biomarkers in cell and animal experiments. Orally administered LC27 or LC67 significantly decreased blood ALT, AST, γ-glutamyl transferase (γGTP), TNF-α, triglyceride (TG), total cholesterol (TCh), total bile acid, and LPS levels, liver TNF-α, toll-like receptor-4 gene (Tlr4), α-smooth muscle actin (αSMA), and collagen-1 expression and αSMA+GFAP+ and NF-κB+F4/80+ cell populations, and colonic Tlr4, TNF-α, and IL-6 expression and NF-κB-positive cell population in LPS-treated mice. Furthermore, they increased AMPKa phosphorylation in the liver and colon. However, Ec increased the expression of TNF-α and IL-6 in blood, liver, and colon. The suppression of LPS-stimulated ALT and AST secretion in HepG2 cells by LBPs was positively correlated with their ameliorating effects on LPS-induced blood γGTP, ALT, and AST levels and liver αSMA and collagen-1 expression in mice. Based on these findings, LC27 and LC67 may improve liver injury and fibrosis by regulating NF-κB and AMPK signaling pathway and a protocol that can assay the inhibitory activity of LBPs on LPS-induced ALT and AST secretion in HepG2 may be useful for guessing their antihepatitic effects in the in vivo experiments.

Effects of Green Network Management of Urban Street Trees on Airborne Particulate Matter (PM2.5) Concentration.

Street trees are crucial for air pollutant reduction in urban areas. Herein, we used computational fluid dynamics (CFD) simulation to identify changes in airborne particulate matter (PM2.5) concentration based on wind characteristics (direction and velocity) and the green network of street trees. The green network was assessed based on composition of the green area of street trees in the central reserve area and between the motor and pedestrian roads. The PM2.5 concentration varied according to the presence or absence of major reserve planting and the planting structure of the street trees, but not according to the wind direction or velocity. The concentration was lower when the wind direction was 45° (than when the wind direction was 0°), whereas it showed a more significant decrease as the wind velocity increased. Despite variation at each measurement site, the PM2.5 reduction was generally higher when the central reserve and street trees had a multi-planting structure. Hence, to ensure an effective reduction in the PM2.5 concentration on motor roads and reduce its negative impact on pedestrians, both arbors and shrubs should be planted in the central reserve area. The study results will serve as reference for managing the green area network and linear green infrastructure in terms of improving the atmospheric environment.

Ultrathin Covalent Organic Framework Anchored on Graphene for Enhanced Organic Pollutant Removal.

Covalent organic frameworks (COFs) are of great potential as adsorbents owing to their tailorable functionalities, low density and high porosity. However, their intrinsically stacked two-dimensional (2D) structure limits the full use of their complete surface for sorption, especially the internal pores. The construction of ultrathin COFs could increase the exposure of active sites to the targeted molecules in a pollutant environment. Herein, an ultrathin COF with a uniform thickness of ca. 2 nm is prepared employing graphene as the surface template. The resulting hybrid aerogel with an ultralow density (7.1 mg cm-3 ) exhibits the ability to remove organic dye molecules of different sizes with high efficiency. The three-dimensional (3D) macroporous structure and well-exposed adsorption sites permit rapid diffusion of solution and efficient adsorption of organic pollutants, thereby, greatly contributing to its enhanced uptake capacity. This work highlights the effect of COF layer thickness on adsorption performance.

Effects of Probiotic NVP-1704 on Mental Health and Sleep in Healthy Adults: An 8-Week Randomized, Double-Blind, Placebo-Controlled Trial.

The human gut microbiome is closely linked to mental health and sleep. We aimed to verify the efficacy and safety of probiotic NVP-1704, a mixture of Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98, in improving stress, depression, anxiety, and sleep disturbances, along with the measurement of some blood biomarkers. A total of 156 healthy adults with subclinical symptoms of depression, anxiety, and insomnia were retrospectively registered and randomly assigned to receive either NVP-1704 (n = 78) or a placebo (n = 78) for eight weeks. Participants completed the Stress Response Inventory, Beck's Depression and Anxiety Inventory, Pittsburg Sleep Quality Index, and Insomnia Severity Index at baseline, at four and eight weeks of treatment. Pre- and post-treatment blood tests for biomarkers were conducted. After intervention, gut microbiota composition was quantified by pyrosequencing the bacterial 16S rRNA gene. The NVP-1704 group had a more significant reduction in depressive symptoms at four and eight weeks of treatment, and anxiety symptoms at four weeks compared to the placebo group. Those receiving NVP-1704 also experienced an improvement in sleep quality. NVP-1704 treatment led to a decrease in serum interleukin-6 levels. Furthermore, NVP-1704 increased Bifidobacteriaceae and Lactobacillacea, whereas it decreased Enterobacteriaceae in the gut microbiota composition. Our findings suggest that probiotic NVP-1704 could be beneficial for mental health and sleep.

Rare-earth-platinum alloy nanoparticles in mesoporous zeolite for catalysis.

Platinum is a much used catalyst that, in petrochemical processes, is often alloyed with other metals to improve catalytic activity, selectivity and longevity1-5. Such catalysts are usually prepared in the form of metallic nanoparticles supported on porous solids, and their production involves reducing metal precursor compounds under a H2 flow at high temperatures6. The method works well when using easily reducible late transition metals, but Pt alloy formation with rare-earth elements through the H2 reduction route is almost impossible owing to the low chemical potential of rare-earth element oxides6. Here we use as support a mesoporous zeolite that has pore walls with surface framework defects (called 'silanol nests') and show that the zeolite enables alloy formation between Pt and rare-earth elements. We find that the silanol nests enable the rare-earth elements to exist as single atomic species with a substantially higher chemical potential compared with that of the bulk oxide, making it possible for them to diffuse onto Pt. High-resolution transmission electron microscopy and hydrogen chemisorption measurements indicate that the resultant bimetallic nanoparticles supported on the mesoporous zeolite are intermetallic compounds, which we find to be stable, highly active and selective catalysts for the propane dehydrogenation reaction. When used with late transition metals, the same preparation strategy produces Pt alloy catalysts that incorporate an unusually large amount of the second metal and, in the case of the PtCo alloy, show high catalytic activity and selectivity in the preferential oxidation of carbon monoxide in H2.

Probiotic NVP-1703 Alleviates Allergic Rhinitis by Inducing IL-10 Expression: A Four-week Clinical Trial.

Although several recent studies reported that probiotics might be beneficial for allergic rhinitis (AR), the effect of probiotics on AR is not consistent and have not been reproduced between studies. We aimed to determine the efficacy and safety of probiotic NVP-1703, a mixture of Bifidobacterium longum and Lactobacillus plantarum, in subjects with perennial AR. Adult subjects with perennial AR received either NVP-1703 (n = 47) or placebo (n = 48) for four weeks. Total nasal symptom scores (TNSS), rhinitis control assessment test (RCAT), blood eosinophil count, allergen-specific IgE, and immunological parameters in serum and urine were compared at baseline and after four weeks. TNSS changes from baseline at weeks 1, 3, and 4 were significant between the NVP-1703 and placebo groups (p = 0.033, 0.031, and 0.029, respectively). RCAT score showed significant differences between the NVP-1703 and placebo groups (p = 0.049) at week 4. Dermatophagoides farinae-specific IgE levels and serum IL-10 levels were significantly different between the NVP-1703 and placebo groups (p = 0.033 and p = 0.047, respectively). IL-10/IL-4 and IL-10/IL-13 ratios were different between the NVP-1703 and placebo groups at week 4 (p = 0.046 and 0.018, respectively). NVP-1703 treatment reduced urinary prostaglandin F2α and leukotriene E4 levels (p > 0.05). Therefore, NVP-1703 can be treatment option for perennial AR.

Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 Alleviate Escherichia coli-Induced depression and Gut Dysbiosis in Mice.

Lactobacillus reuteri NK33 (NK33) and Bifidobacterium adolescentis NK98 (NK98) alleviate immobilization stress-induced depression. To understand the gut microbiota-mediated mechanisms of NK33 and NK98 against depression, we examined their effects on Escherichia coli K1 (K1)-induced depression and gut dysbiosis in mice. NK33, NK98, and their mixtures (1:1, 4:1, and 9:1) mitigated K1-induced depression and colitis. NK33 and NK98 additively or synergistically increased BDNF+/NeuN+ cell population and suppressed NF-κB action in the hippocampus. They alleviated gut dysbiosis by reducing the Proteobacteria population and increasing the Clostridia population. These results suggest that NK33 and NK98 may alleviate depression and colitis by ameliorating gut dysbiosis.

Capacitively Coupled Arrays of Multiplexed Flexible Silicon Transistors for Long-Term Cardiac Electrophysiology.

Advanced capabilities in electrical recording are essential for the treatment of heart-rhythm diseases. The most advanced technologies use flexible integrated electronics; however, the penetration of biological fluids into the underlying electronics and any ensuing electrochemical reactions pose significant safety risks. Here, we show that an ultrathin, leakage-free, biocompatible dielectric layer can completely seal an underlying layer of flexible electronics while allowing for electrophysiological measurements through capacitive coupling between tissue and the electronics, and thus without the need for direct metal contact. The resulting current-leakage levels and operational lifetimes are, respectively, four orders of magnitude smaller and between two and three orders of magnitude longer than those of any other flexible-electronics technology. Systematic electrophysiological studies with normal, paced and arrhythmic conditions in Langendorff hearts highlight the capabilities of the capacitive-coupling approach. Our technology provides a realistic pathway towards the broad applicability of biocompatible, flexible electronic implants.

The Rhizome Mixture of Anemarrhena asphodeloides and Coptis chinensis Attenuates Mesalazine-Resistant Colitis in Mice.

We investigated the effect of DWac on the gut microbiota composition in mice with 2,3,6-trinitrobenzenesulfonic acid- (TNBS-) induced colitis. Treatment with DWac restored TNBS-disturbed gut microbiota composition and attenuated TNBS-induced colitis. Moreover, we examined the effect of DWac in mice with mesalazine-resistant colitis (MRC). Intrarectal injection of TNBS in MRC mice caused severe colitis, as well as colon shortening, edema, and increased myeloperoxidase activity. Treatment with mesalazine (30 mg/kg) did not attenuate TNBS-induced colitis in MRC mice, whereas treatment with DWac (30 mg/kg) significantly attenuated TNBS-induced colitis. Moreover, treatment with the mixture of mesalazine (15 mg/kg) and DWac (15 mg/kg) additively attenuated colitis in MRC mice. Treatment with DWac and its mixture with mesalazine inhibited TNBS-induced activation of NF-κB and expression of M1 macrophage markers but increased TNBS-suppressed expression of M2 macrophage markers. Furthermore, these inhibited TNBS-induced T-bet, RORγt, TNF-α, and IL-17 expression but increased TNBS-suppressed Foxp3 and IL-10 expression. However, Th2 cell differentiation and GATA3 and IL-5 expression were not affected. These findings suggest that DWac can ameliorate MRC by increasing the polarization of M2 macrophage and correcting the disturbance of gut microbiota and Th1/Th17/Treg, as well as additively attenuating MRC along with mesalazine.

The Efficacy and Safety of Lidocaine-Containing Hyaluronic Acid Dermal Filler for Treatment of Nasolabial Folds: A Multicenter, Randomized Clinical Study.

BACKGROUND: The use of injectable hyaluronic acid-based gel is well established in aesthetic facial procedures especially on the nasolabial fold (NLF). OBJECTIVE: To compare the efficacy and safety of PP-501-A-Lidocaine dermal filler with RestylaneLidocaine(®) when administered to the NLF. METHODS: Sixty-six subjects seeking correction of NLFs, with moderate or severe wrinkle severity, were recruited for this multicenter, randomized, patient and evaluator-blind, matched pairs, and active-controlled design clinical study. PP-501-A-Lidocaine and RestylaneLidocaine(®) were injected into the deep layer of the dermis and/or subcutis of the NLF. The first validity evaluation variable was the average wrinkle severity rating scale (WSRS), as scored by independent blinded evaluators at week 24. The second validity evaluation variable including the global aesthetic improvement scale (GAIS), the WSRS, and adverse event reporting at weeks 8, 16, and 24 were also performed. RESULTS: The mean improvement in the WSRS from baseline was 1.58 ± 0.68 for the PP-501-A-Lidocaine and 1.51 ± 0.66 for the RestylaneLidocaine(®) at week 24. The average value at week 8 after the final application was 1.62 ± 0.78 and 1.60 ± 0.75 in parts subject to PP-501-A-Lidocaine and RestylaneLidocaine(®), respectively, and 1.58 ± 0.70 and 1.57 ± 0.68 at week 16, respectively. Both improvement and duration of the treatment effect were similar between the two groups. GAIS data rated by the treating investigator and participants showed no statistically significant differences. Both fillers were well tolerated and adverse reactions were mild and transient in most cases. CONCLUSION: PP-501-A-Lidocaine showed an equivalent efficacy and safety observed after 6 months of follow-up compared to RestylaneLidocaine(®). LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266.

Phytochrome and blue light-mediated stomatal opening in the orchid, paphiopedilum.

Guard cells of the orchid genus, Paphiopedilum have been reported to lack developed chloroplasts and detectable chlorophyll a autofluorescence. Paphiopedilum stomata lack a photosynthesis-dependent opening response but have a blue light-specific opening. The present study found that low fluence rate green and red light elicited stomatal opening in Paphiopedilum and this opening was reversed by far red light, indicating the presence of a phytochrome-mediated opening response. Phytochrome-dependent, red light-stimulated opening was largest under low fluence rates and decreased to near zero as fluence rate increased. A recently discovered green light reversibility of blue light-specific stomatal opening was used to probe the properties of the blue light response in Paphiopedilum stomata. Blue light-stimulated opening was completely reversed by green light in the presence of far red light. Red light enhanced the blue light response of Paphiopedilum guard cells when given as a pretreatment or together with blue light. Analysis of guard cell pigments showed that guard cells have small amounts of chlorophyll a and b, zeaxanthin, violaxanthin, antheraxanthin and lutein. Zeaxanthin content increased in response to blue light or ascorbate and declined in the dark or under illumination in the presence of dithiothreitol, indicating the presence of an active xanthophyll cycle. Thus Paphiopedilum stomata possess both a blue light-mediated opening response with characteristics similar to species with normal chloroplast development and a novel phytochrome-mediated opening response.