ATAD5 functions as a regulatory platform for Ub-PCNA deubiquitination.

Ubiquitination status of proliferating cell nuclear antigen (PCNA) is crucial for regulating DNA lesion bypass. After the resolution of fork stalling, PCNA is subsequently deubiquitinated, but the underlying mechanism remains undefined. We found that the N-terminal domain of ATAD5 (ATAD5-N), the largest subunit of the PCNA-unloading complex, functions as a scaffold for Ub-PCNA deubiquitination. ATAD5 recognizes DNA-loaded Ub-PCNA through distinct DNA-binding and PCNA-binding motifs. Furthermore, ATAD5 forms a heterotrimeric complex with UAF1-USP1 deubiquitinase, facilitating the deubiquitination of DNA-loaded Ub-PCNA. ATAD5 also enhances the Ub-PCNA deubiquitination by USP7 and USP11 through specific interactions. ATAD5 promotes the distinct deubiquitination process of UAF1-USP1, USP7, and USP11 for poly-Ub-PCNA. Additionally, ATAD5 mutants deficient in UAF1-binding had increased sensitivity to DNA-damaging agents. Our results ultimately reveal that ATAD5 and USPs cooperate to efficiently deubiquitinate Ub-PCNA prior to its release from the DNA in order to safely deactivate the DNA repair process.

Synthesis of Mesoporous Silica Sol with Low Refractive Properties for Increasing Transmittance.

Currently, coating with anti-reflective materials is an attractive approach to improve the quality of screen-based displays. In this study, mesoporous silica particles were systematically synthesized as a function of surfactant (i.e., CTAC-cetyltrimethylammonium chloride) concentration to serve as main coating fillers possessing low refractive indices. Precisely changing the amount of the CTAC surfactant, silica sol with an average diameter of 50 nm exhibits distinctively different specific surface areas, pore size, and pore volume. Prior to the preparation of final coating solutions containing these silica particle fillers, the percentage of solid content was optimized on a glass slide. The use of 50 wt% solid content exhibited the highest transmittance of light. Among various content levels of silica sol, the use of 3.5 wt% of silica particles in the solid content displayed the highest transmittance (i.e., best anti-reflectiveness). Under the almost identical coating layers prepared with the fixed amount of silica particles possessing different surface areas, pore size, and pore volume, it appears that the largest pore volume played the most important role in improving the anti-reflective properties. Experimentally understanding the key feature of low-refractive filler materials under the optimized conditions could provide a clear view to develop highly effective anti-reflective materials for various display applications.

CLCC1 promotes hepatic neutral lipid flux and nuclear pore complex assembly.

Imbalances in lipid storage and secretion lead to the accumulation of hepatocyte lipid droplets (LDs) (i.e., hepatic steatosis). Our understanding of the mechanisms that govern the channeling of hepatocyte neutral lipids towards cytosolic LDs or secreted lipoproteins remains incomplete. Here, we performed a series of CRISPR-Cas9 screens under different metabolic states to uncover mechanisms of hepatic neutral lipid flux. Clustering of chemical-genetic interactions identified CLIC-like chloride channel 1 (CLCC1) as a critical regulator of neutral lipid storage and secretion. Loss of CLCC1 resulted in the buildup of large LDs in hepatoma cells and knockout in mice caused liver steatosis. Remarkably, the LDs are in the lumen of the ER and exhibit properties of lipoproteins, indicating a profound shift in neutral lipid flux. Finally, remote homology searches identified a domain in CLCC1 that is homologous to yeast Brl1p and Brr6p, factors that promote the fusion of the inner and outer nuclear envelopes during nuclear pore complex assembly. Loss of CLCC1 lead to extensive nuclear membrane herniations, consistent with impaired nuclear pore complex assembly. Thus, we identify CLCC1 as the human Brl1p/Brr6p homolog and propose that CLCC1-mediated membrane remodeling promotes hepatic neutral lipid flux and nuclear pore complex assembly.

Wnt pathway inhibition with the porcupine inhibitor LGK974 decreases trabecular bone but not fibrosis in a murine model with fibrotic bone.

G protein-coupled receptors (GPCRs) mediate a wide spectrum of physiological functions, including the development, remodeling, and repair of the skeleton. Fibrous dysplasia (FD) of the bone is characterized by fibrotic, expansile bone lesions caused by activating mutations in GNAS. There are no effective therapies for FD. We previously showed that ColI(2.3)+/Rs1+ mice, in which Gs-GPCR signaling was hyper-activated in osteoblastic cell lineages using an engineered receptor strategy, developed a fibrotic bone phenotype with trabecularization that could be reversed by normalizing Gs-GPCR signaling, suggesting that targeting the Gs-GPCR or components of the downstream signaling pathway could serve as a promising therapeutic strategy for FD. The Wnt signaling pathway has been implicated in the pathogenesis of FD-like bone, but the specific Wnts and which cells produce them remain largely unknown. Single-cell RNA sequencing on long-bone stromal cells of 9-wk-old male ColI(2.3)+/Rs1+ mice and littermate controls showed that fibroblastic stromal cells in ColI(2.3)+/Rs1+ mice were expanded. Multiple Wnt ligands were up- or downregulated in different cellular populations, including in non-osteoblastic cells. Treatment with the porcupine inhibitor LGK974, which blocks Wnt signaling broadly, induced partial resorption of the trabecular bone in the femurs of ColI(2.3)+/Rs1+ mice, but no significant changes in the craniofacial skeleton. Bone fibrosis remained evident after treatment. Notably, LGK974 caused significant bone loss in control mice. These results provide new insights into the role of Wnt and Gs-signaling in fibrosis and bone formation in a mouse model of Gs-GPCR pathway overactivation.

In Vitro Effects of Weissella cibaria CMU and CMS1 on Receptor Activator of NF-κB Ligand (RANKL)-Induced Osteoclast Differentiation.

Excessive osteoclast activity can promote periodontitis-associated bone destruction. The inhibitory mechanisms of Weissella cibaria strains CMU and CMS1 against periodontitis have not yet been fully elucidated. In this study, we aimed to investigate whether heat-killed (HK) W. cibaria CMU and CMS1 or their respective cell-free supernatants (CFSs) inhibit osteoclast differentiation and bone resorption in response to receptor activator of nuclear factor kappa-B ligand (RANKL)-treated RAW 264.7 cells. TRAP (tartrate-resistant acid phosphatase) staining and bone resorption assays revealed that both HK bacteria and CFSs significantly suppressed the number of TRAP-positive cells, TRAP activity, and bone pit formation compared to the RANKL-treated control (p < 0.05). HK bacteria dose-dependently inhibited osteoclastogenesis while selectively regulating certain genes in CFSs (p < 0.05). We found that disrupting the direct interaction between HK bacteria and RAW 264.7 cells abolished the inhibitory effect of HK bacteria on the expression of osteoclastogenesis-associated proteins (c-Fos, nuclear factor of activated T cells c1 (NFATc1), and cathepsin K). These results suggest that dead bacteria suppress osteoclast differentiation more effectively than the metabolites and may serve as beneficial agents in preventing periodontitis by inhibiting osteoclast differentiation via direct interaction with cells.

Photonic control of ligand nanospacing in self-assembly regulates stem cell fate.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of "closely nanospaced" ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with "closely nanospaced" ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of "distantly nanospaced" ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

The Facile Synthesis and Application of Mesoporous Silica Nanoparticles with a Vinyl Functional Group for Plastic Recycling.

Due to growing concerns about environmental pollution from plastic waste, plastic recycling research is gaining momentum. Traditional methods, such as incorporating inorganic particles, increasing cross-linking density with peroxides, and blending with silicone monomers, often improve mechanical properties but reduce flexibility for specific performance requirements. This study focuses on synthesizing silica nanoparticles with vinyl functional groups and evaluating their mechanical performance when used in recycled plastics. Silica precursors, namely sodium silicate and vinyltrimethoxysilane (VTMS), combined with a surfactant, were employed to create pores, increasing silica's surface area. The early-stage introduction of vinyl functional groups prevented the typical post-synthesis reduction in surface area. Porous silica was produced in varying quantities of VTMS, and the synthesized porous silica nanomaterials were incorporated into recycled polyethylene to induce cross-linking. Despite a decrease in surface area with increasing VTMS content, a significant surface area of 883 m2/g was achieved. In conclusion, porous silica with the right amount of vinyl content exhibited improved mechanical performance, including increased tensile strength, compared to conventional porous silica. This study shows that synthesized porous silica with integrated vinyl functional groups effectively enhances the performance of recycled plastics.

Use of Baclofen as a Treatment for Nocturnal Calf Cramps in Individuals With Lumbar Spinal Stenosis: A Prospective Randomized Study.

OBJECTIVE: This study aimed to compare the efficacy and safety of baclofen and gabapentin in reducing leg pain from nocturnal calf cramps in lumbar spinal stenosis patients. DESIGN: In a randomized clinical trial, the patients with lumbar spinal stenosis who commonly experienced nocturnal calf cramps were included. Patients were randomly assigned to either the baclofen or gabapentin group. Overall leg pain intensity, nocturnal calf cramp frequency and severity, sleep disturbances and functional disability were assessed at baseline and after 4 and 12 wks. RESULTS: Thirty-six patients completed the 3-mo study. Both gabapentin and baclofen groups showed a significant reduction in overall leg pain, calf cramp frequency and intensity, and insomnia severity index scores from baseline to the endpoint. However, there were no significant differences between the two groups in terms of symptom reduction at different time points. The baclofen group also demonstrated a significant decrease in Oswestry Disability Index scores ( P < 0.001), while the gabapentin group did not ( P = 0.344). No adverse effects were reported in either group. CONCLUSIONS: Baclofen seems to be as effective and as safe as gabapentin in treating nocturnal calf cramps in lumbar spinal stenosis patients and even shows superiority in enhancing functional outcomes.

Organic Matrix Derived from Host-Microbe Interplay Contributes to Pathological Renal Biomineralization.

Matrix stones are a rare form of kidney stones. They feature a high percentage of hydrogel-like organic matter, and their formation is closely associated with urinary tract infections. Herein, comprehensive materials and biochemical approaches were taken to map the organic-inorganic interface and gather insights into the host-microbe interplay in pathological renal biomineralization. Surgically extracted soft and slimy matrix stones were examined using micro-X-ray computed tomography and various microspectroscopy techniques. Higher-mineral-density laminae were positive for calcium-bound Alizarin red. Lower-mineral-density laminae revealed periodic acid-Schiff-positive organic filamentous networks of varied thickness. These organic filamentous networks, which featured a high polysaccharide content, were enriched with zinc, carbon, and sulfur elements. Neutrophil extracellular traps (NETs) along with immune response-related proteins, including calprotectin, myeloperoxidase, CD63, and CD86, also were identified in the filamentous networks. Expressions of NETs and upregulation of polysaccharide-rich mucin secretion are proposed as a part of the host immune defense to "trap" pathogens. These host-microbe derived organic matrices can facilitate heterogeneous nucleation and precipitation of inorganic particulates, resulting in macroscale aggregates known as "matrix stones". These insights into the plausible aggregation of constituents through host-microbe interplay underscore the unique "double-edged sword" effect of the host immune response to pathogens and the resulting renal biominerals.

Evaluation of Paraspinal Muscle Degeneration on Pain Relief after Percutaneous Epidural Adhesiolysis in Patients with Degenerative Lumbar Spinal Disease.

Background and Objectives: The analgesic effectiveness of epidural adhesiolysis may be influenced by morphological changes in the paraspinal muscles, particularly in elderly patients. The objective of this study was to assess whether the cross-sectional area or fatty infiltration of the paraspinal muscles impacts the treatment outcomes of epidural adhesiolysis. Materials and Methods: The analysis included a total of 183 patients with degenerative lumbar disease who underwent epidural adhesiolysis. Good analgesia was defined as a reduction in pain score of ≥30% at the 6-month follow up. We measured the cross-sectional area and fatty infiltration rate of the paraspinal muscles and divided the study population into age groups (≥65 years and <65 years). Variables were compared between the good and poor analgesia groups. Results: The results revealed that elderly patients experienced poorer analgesic outcomes as the rate of fatty infiltration in the paraspinal muscles increased (p = 0.029), predominantly in female patients. However, there was no correlation between the cross-sectional area and the analgesic outcome in patients younger than or older than 65 years (p = 0.397 and p = 0.349, respectively). Multivariable logistic regression analysis indicated that baseline pain scores < 7 (Odds Ratio (OR) = 4.039, 95% Confidence Interval (CI) = 1.594-10.233, p = 0.003), spondylolisthesis (OR = 4.074, 95% CI = 1.144-14.511, p = 0.030), and ≥ 50% fatty infiltration of the paraspinal muscles (OR = 6.576, 95% CI = 1.300-33.268, p = 0.023) were significantly associated with poor outcomes after adhesiolysis in elderly patients. Conclusions: Fatty degeneration of paraspinal muscles is correlated with inferior analgesic outcomes following epidural adhesiolysis in elderly patients, but not in young and middle-aged patients. The cross-sectional area of the paraspinal muscles is not associated with pain relief after the procedure.

In Vitro Preventive Effect and Mechanism of Action of Weissella cibaria CMU against Streptococcus mutans Biofilm Formation and Periodontal Pathogens.

In this study, we evaluated the in vitro anti-biofilm, antibacterial, and anti-inflammatory activity of Weissella cibaria CMU (CMU), an oral probiotic, against periodontopathogens. Compared to other oral probiotics, CMU showed a superior inhibitory effect on the biofilm formation and growth of Streptococcus mutans on orthodontic wires and artificial teeth (p < 0.05). CMU exerted potent antibacterial effects against S. mutans and Porphyromonas gingivalis according to a line test. In human gingival fibroblasts (HGFs) stimulated by P. gingivalis, Fusobacterium nucleatum, or Prevotella intermedia, CMU suppressed the gene expression of pro-inflammatory cytokines [interleukin (IL)-6, IL-1ß, IL-8, and tumor necrosis factor-α] in a dose-dependent manner (p < 0.05). CMU restored the production of the tissue inhibitor of metalloproteinase-1 following its inhibition by P. gingivalis, and it suppressed the expression of matrix metalloproteinase (MMP)-1 and -3 induced by periodontopathogens (p < 0.05). Moreover, CMU needed direct contact with HGFs to exert their anti-inflammatory function, indicating that they act directly on gingival cells to modulate local inflammation. Our preclinical study provides evidence for the potential benefits of topical CMU treatments in preventing the development of caries and periodontitis caused by the dysbiosis of the dental plaque microbiome.

Subgrouping patients with zoster-associated pain according to sensory symptom profiles: A cluster analysis.

Background and goal of study: Patients with zoster-associated pain exhibit a variety of sensory symptoms and forms of pain and complain of different pain patterns. The purpose of this study is to subgroup patients with zoster-associated pain who visited a hospital using painDETECT sensory symptom scores, analyze their respective characteristics and pain-related data, and compare similarities and differences among the groups. Materials and methods: The characteristics of 1,050 patients complaining of zoster-associated pain and pain-related data were reviewed retrospectively. To identify subgroups of patients with zoster-associated pain according to sensory symptom profiles, a hierarchical cluster analysis was performed based on the responses to a painDETECT questionnaire. Demographics and pain-related data were compared among all subgroups. Results and discussion: Patients with zoster-associated pain were classified into 5 subgroups according to the distribution of sensory profiles, with each subgroup exhibiting distinct differences in the expression of sensory symptoms. Patients in cluster 1 complained of burning sensations, allodynia, and thermal sensitivity, but felt numbness less strongly. Cluster 2 and 3 patients complained of burning sensations and electric shock-like pain, respectively. Cluster 4 patients complained of most sensory symptoms at similar intensities and reported relatively strong prickling pain. Cluster 5 patients suffered from both burning and shock-like pains. Patient ages and the prevalence of cardiovascular disease were significantly lower in cluster 1. Patients in clusters 1 and 4 reported longer pain duration compared with those in clusters 2 and 3. However, no significant differences were found with respect to sex, body mass index, diabetes mellitus, mental health problems, and sleep disturbance. Pain scores, distribution of dermatomes and gabapentinoid use were also similar among the groups. Conclusions: Five different subgroups of patients with zoster-associated pain were identified on the basis of sensory symptoms. A subgroup of younger patients with longer pain duration showed specific and distinct symptoms, such as burning sensations and allodynia. Unlike patients with acute or subacute pain, patients with chronic pain were associated with diverse sensory symptom profiles.

Facile Mesoporous Hollow Silica Synthesis for Formaldehyde Adsorption.

Formaldehyde emitted from household products is classified as a hazardous substance that can adversely affect human health. Recently, various studies related to adsorption materials for reducing formaldehyde have been widely reported. In this study, mesoporous and mesoporous hollow silicas with amine functional groups introduced were utilized as adsorption materials for formaldehyde. Formaldehyde adsorption characteristics of mesoporous and mesoporous hollow silicas having well-developed pores were compared based on their synthesis methods-with or without a calcination process. Mesoporous hollow silica synthesized through a non-calcination process had the best formaldehyde adsorption characteristics, followed by mesoporous hollow silica synthesized through a calcination process and mesoporous silica. This is because a hollow structure has better adsorption properties than mesoporous silica due to large internal pores. The specific surface area of mesoporous hollow silica synthesized without a calcination process was also higher than that synthesized with a calcination process, leading to a better adsorption performance. This research suggests a facile synthetic method of mesoporous hollow silica and confirms its noticeable potential as a support for the adsorption of harmful gases.

Amine-Impregnated Dendritic Mesoporous Silica for the Adsorption of Formaldehyde.

To adsorb and remove formaldehyde, which is a harmful volatile organic chemical (VOC) detected indoors, an alkylamine was introduced into the substrate as a formaldehyde adsorbent. In this study, Tetraethylenepentaamine (TEPA) was introduced into the mesoporous silica using the amine impregnation method. Since the impregnated alkylamine can block the pores of the silica substrate, the pore size and pore volume are very important factors for its use as a substrate for an adsorbent. Focusing on the substrate's pore properties, Santa Barbara Amorphous-15 (SBA-15) was chosen as a conventional one-dimensional pore-structured mesoporous silica, and dendritic mesoporous silica (DMS) as a three-dimensional pore-structured mesoporous silica. To 1 g each of silica substrate DMS and SBA-15, 0, 0.5, 1.5, and 2.5 g of TEPA were introduced. A fixed concentration and amount of formaldehyde gas was flowed through the adsorbent and then the adsorbent was changed to the 2,4-Dinitrophenylhydrazine (2,4-DNPH) cartridge to adsorb the remaining formaldehyde. According to the methods recommended by the World Health Organization (WHO) and National Institute for Occupational Safety & Health (NIOSH), the formaldehyde captured by 2,4-DNPH was analyzed using high-performance liquid chromatography (HPLC). A comparison of DMS and SBA-15 in the amine impregnation method shows that not only surface area, but also large pore size and high pore volume, contribute to the formaldehyde adsorption ability.

Regulation of BRCA1 stability through the tandem UBX domains of isoleucyl-tRNA synthetase 1.

Aminoacyl-tRNA synthetases (ARSs) have evolved to acquire various additional domains. These domains allow ARSs to communicate with other cellular proteins in order to promote non-translational functions. Vertebrate cytoplasmic isoleucyl-tRNA synthetases (IARS1s) have an uncharacterized unique domain, UNE-I. Here, we present the crystal structure of the chicken IARS1 UNE-I complexed with glutamyl-tRNA synthetase 1 (EARS1). UNE-I consists of tandem ubiquitin regulatory X (UBX) domains that interact with a distinct hairpin loop on EARS1 and protect its neighboring proteins in the multi-synthetase complex from degradation. Phosphomimetic mutation of the two serine residues in the hairpin loop releases IARS1 from the complex. IARS1 interacts with BRCA1 in the nucleus, regulates its stability by inhibiting ubiquitylation via the UBX domains, and controls DNA repair function.

Contact ratio and adaptations in the maxillary and mandibular dentoalveolar joints in rats and human clinical analogs.

Spatial maps of function-based contact areas and resulting mechanical strains in bones of intact fibrous joints in preclinical small-scale animal models are limited. Functional imaging in situ on intact dentoalveolar fibrous joints (DAJs) in hemimandibles and hemimaxillae harvested from 10 male Sprague-Dawley rats (N = 5 at 12 weeks, N = 5 at 20 weeks) was performed in this study. Physical features including bone volume fraction (BVF), bone pore diameter and pore density, and cementum fraction (CF) of the molars in the maxillary and mandibular joints were evaluated. Biomechanical testing in situ provided estimates of joint stiffness, changes in periodontal ligament spaces (PDL-space) between the molar and bony socket, and thereby localization of contact area in the respective joints. Contact area localization revealed mechanically stressed interradicular and apical regions in the joints. These anatomy-specific contact stresses in maxillary and mandibular joints were correlated with the physical features and resulting strains in interradicular and bony socket compartments. The mandibular joint spaces, in general, were higher than maxillary, and this trend was consistent with age (younger loaded: Mn - 134 ± 55 µm, Mx - 110 ± 47 µm; older loaded: Mn - 122 ± 49 µm, Mx - 105 ± 48 µm). However, a significant decrease (P < 0.05) in mandibular and maxillary joint spaces with age (younger unloaded: Mn - 147 ± 51 µm; Mx - 125 ± 42 µm; older unloaded: Mn - 134 ± 46 µm; Mx - 116 ± 44 µm) was observed. The bone volume fraction (BVF) of mandibular interradicular bone (IR bone) increased significantly with age (P < 0.05) with the percent porosity of coronal mandibular bone lower than its maxillary counterpart. The contact ratio (contact area to total surface area) of maxillary teeth was significantly greater (P < 0.05) than mandibular teeth; both maxillary interradicular and apical contact ratios (IR bone: 41%, 56%; Apical bone: 4%, 12%) increased with age, and were higher than the mandibular (IR bone: 19%, 44%; Apical bone: 1%, 4%) counterpart. Resulting higher but uniform strains in maxillary bone contrasted with lower but higher variance in mandibular strains at a younger age. Anatomy-specific colocalization of physical properties and functional strains in bone provided insights into form-guided adaptive dominance of the maxilla compared to material property-guided adaptive dominance of the mandible. These age-related trends from the preclinical animal model paralleled with age- and tooth position-specific variabilities in mandibular craniofacial bones of adolescent and adult patients following orthodontic treatment.

Photoswitchable Microgels for Dynamic Macrophage Modulation.

Dynamic manipulation of supramolecular self-assembled structures is achieved irreversibly or under non-physiological conditions, thereby limiting their biomedical, environmental, and catalysis applicability. In this study, microgels composed of azobenzene derivatives stacked via π-cation and π-π interactions are developed that are electrostatically stabilized with Arg-Gly-Asp (RGD)-bearing anionic polymers. Lateral swelling of RGD-bearing microgels occurs via cis-azobenzene formation mediated by near-infrared-light-upconverted ultraviolet light, which disrupts intermolecular interactions on the visible-light-absorbing upconversion-nanoparticle-coated materials. Real-time imaging and molecular dynamics simulations demonstrate the deswelling of RGD-bearing microgels via visible-light-mediated trans-azobenzene formation. Near-infrared light can induce in situ swelling of RGD-bearing microgels to increase RGD availability and trigger release of loaded interleukin-4, which facilitates the adhesion structure assembly linked with pro-regenerative polarization of host macrophages. In contrast, visible light can induce deswelling of RGD-bearing microgels to decrease RGD availability that suppresses macrophage adhesion that yields pro-inflammatory polarization. These microgels exhibit high stability and non-toxicity. Versatile use of ligands and protein delivery can offer cytocompatible and photoswitchable manipulability of diverse host cells.

Therapeutic Efficacy of Weissella cibaria CMU and CMS1 on Allergic Inflammation Exacerbated by Diesel Exhaust Particulate Matter in a Murine Asthma Model.

Background and Objectives: Diesel exhaust particulate matter (DEPM) is an air pollutant that is associated with asthma. In this study, the therapeutic efficacy of Weissella cibaria strains CMU (Chonnam Medical University) and CMS (Chonnam Medical School) 1, together with the drug Synatura, an anti-tussive expectorant, was investigated in a murine asthma model exacerbated by DEPM. Materials and Methods: BALB/c mice were sensitized with ovalbumin (OVA) before intranasal challenge with OVA and DEPM. W. cibaria CMU, CMS1, and Synatura were administered orally for 21 days. Results: Neither Synatura nor W. cibaria strains affected spleen, liver, or lung weights. W. cibaria strains CMU and CMS1 significantly reduced the levels of interleukin (IL)-4, OVA-specific immunoglobulin E (IgE), and total lung collagen in bronchoalveolar lavage fluid (BALF), similar to those with Synatura, regardless of the oral dose concentration (p < 0.05). In addition, the W. cibaria CMU strain significantly alleviated IL-1ß, IL-6, IL-12, monocyte chemotactic protein-1, and tumor necrosis factor-α in BALF, whereas the CMS1 strain significantly alleviated IL-10 and IL-12 in BALF (p < 0.05); however, Synatura did not show any statistical efficacy against them (p > 0.05). All concentrations of W. cibaria CMU and low concentrations of W. cibaria CMS1 significantly reduced lung bronchiolar changes and inflammatory cell infiltration. Conclusions: In conclusion, W. cibaria CMU in asthmatic mice showed better efficacy than W. cibaria CMS1 in improving asthma exacerbated by DEPM exposure, as well as better results than pharmaceuticals.

Toxicological and safety evaluations of Weissella cibaria strain CMU in animal toxicity and genotoxicity.

Weissella cibaria belongs to the Lactobacillaceae family and has been isolated from traditional fermented foods and saliva of children with good oral health. Previous investigations have shown that W. cibaria CMU (Chonnam Medical University) is expected to be safe based on results of in silico and in vitro analyses. However, there is a lack of studies assessing its safety in vivo. A toxicological safety evaluation of W. cibaria CMU was performed using an acute oral safety study in rats, a 14-day oral range finding study, a subsequent 13-week oral toxicity study in rats and a genetic toxicity battery (in vitro bacterial reverse mutation, in vitro chromosome aberration in Chinese Hamster Ovary cells and in vivo micronucleus study in mice). The results of the studies in rats showed that the acute lethal dose of W. cibaria CMU is > 5000 mg/kg body weight (bw)/day (1.8 × 109 CFU/kg bw/day) and the 14-day or 13-week no observed adverse effect level (NOAEL) is 5000 mg/kg bw/day (1.8 × 109 CFU/kg bw/day), the highest dose administered. W. cibaria CMU was non-mutagenic in the bacterial reverse mutation test and non-clastogenic or aneugenic in vitro and in vivo. In conclusion, the toxicological studies performed demonstrated W. cibaria CMU to be a safe strain to consume. This study is the first study examining the potential of a W. cibaria strain to cause genetic toxicity and subchronic toxicity in rats according to the Organization for Economic Cooperation and Development guidelines.

Facile Synthesis of Mesoporous Silica at Room Temperature for CO2 Adsorption.

Although mesoporous silica materials have been widely investigated for many applications, most silica materials are made by calcination processes. We successfully developed a convenient method to synthesize mesoporous materials at room temperature. Although the silica materials made by the two different methods, which are the calcination process and the room-temperature process, have similar specific surface areas, the silica materials produced with the room-temperature process have a significantly larger pore volume. This larger pore volume has the potential to attach to functional groups that can be applied to various industrial fields such as CO2 adsorption. This mesoporous silica with a larger pore volume was analyzed by TEM, FT-IR, low angle X-ray diffraction, N2-adsorption analysis, and CO2 adsorption experiments in comparison with the mesoporous silica synthesized with the traditional calcination method.