Enhancement of denitrification by sulfur-based carrier in sequencing batch reactor (SBR) for advanced wastewater treatment.

This study was to enhance the nitrogen removal efficiency in the sequencing batch reactor (SBR) process by adding sulfur-based carriers. The nitrogen removal efficiency of the control group was compared with that of the experimental group through a two-series operation of SBR1 without carrier and SBR2 with the carrier under the condition of no external carbon source. A total nitrogen (T-N) removal efficiency of 6.6%, 72.6%, and 79.9% was observed in SBR1, SBR2 (5%), and (10%), respectively. The T-N removal efficiency was improved in the system with carriers, which showed an increase in the removal efficiency of approximately 91.7%. The results suggest that the inclusion of the carrier led to an elevation in the sulfur ratio, implying an augmented surface area for sulfur-based denitrifying microorganisms. Additionally, CaCO3 contributed essential alkalinity for sulfur denitrification, thereby preventing a decline in pH. Regardless of the carrier, the efficiency of organic matter removal surpassed 89%, indicating that the sulfur-based carrier did not adversely affect the biological reaction associated with organic matter. Therefore, autotrophic denitrification was successfully performed using a sulfur carrier in the SBR process without an external carbon source, improving the nitrogen removal efficiency.

Development and application of novel peptide-formulated nanoparticles for treatment of atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin condition that is characterized by skin inflammation, itching, and redness. Although various treatments can alleviate symptoms, they often come with side effects, highlighting the need for new treatments. Here, we discovered a new peptide-based therapy using the intra-dermal delivery technology (IDDT) platform developed by Remedi Co., Ltd (REMEDI). The platform screens and identifies peptides derived from proteins in the human body that possess cell-penetrating peptide (CPP) properties. We screened over 1000-peptides and identified several derived from the Speckled protein (SP) family that have excellent CPP properties and have anti-inflammatory effects. We assessed these peptides for their potential as a treatment for atopic dermatitis. Among them, the RMSP1 peptide showed the most potent anti-inflammatory effects by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription 3 (STAT3) signaling pathways while possessing CPP properties. To further improve efficacy and stability, we developed a palmitoylated version called Pal-RMSP1. Formulation studies using liposomes (Pal-RMSP1 LP) and micelles (Pal-RMSP1 DP) demonstrated improved anti-inflammatory effects in vitro and enhanced therapeutic effects in vivo. Our study indicates that nano-formulated Pal-RMSP1 could have the potential to become a new treatment option for atopic dermatitis.

Fabrication of transparent cellulose nanofibril composite film with smooth surface and ultraviolet blocking ability using hydrophilic lignin.

Ecofriendly multifunctional films with only biomass-based components have gathered significant interest from researchers as next-generation materials. Following this trend, a TEMPO-oxidized cellulose nanofibril (TOCNF) film containing hydrophilic lignin (CL) was fabricated. To produce the lignin, peracetic acid oxidation was carried out, leading to the introduction of carboxyl groups into the lignin structure. By adding hydrophilic lignin, various characteristics (e.g., surface smoothness, UV protection, antimicrobial activity, and barrier properties) of the TOCNF film were enhanced. In particular, the shrinkage of CNF was successfully prevented by the addition of CL, which is attributed to the lower surface roughness (Ra) from 18.93 nm to 4.99 nm. As a result, the smooth surface of the TOCNF/CL film was shown compared to neat TOCNF film and TOCNF/Kraft lignin composite film. In addition, the TOCNF/CL film showed a superior UV blocking ability of 99.9 % with high transparency of 78.4 %, which is higher than that of CNF-lignin composite films in other research. Also, water vapor transmission rate was reduced after adding CL to TOCNF film. Consequently, the developed TOCNF/CL film can be potentially utilized in various applications, such as food packaging.

Production of single-component cellulose-based hydrogel and its utilization as adsorbent for aqueous contaminants.

The growing concern for the environment has resulted in renewed interest in bio-based resources. This study aims to produce a hydrogel adsorbent from cellulose and examine its adsorption performance. In pursuit of this goal, we report a simple one-pot synthesis of cellulose acetate sulfate (CAS), followed by the formation of CAS hydrogels and their subsequent adsorption performances. The CAS includes both hydrophilic and hydrophobic functional groups, enable the formation of a single-component hydrogel through intermolecular interactions in deionized water. The thermal reversibility of CAS hydrogels makes them easily processable into various shapes. The durability of the CAS hydrogel adsorbents can be improved by introducing divalent cations (e.g., Ca2+), which create ionically crosslinked hydrogels. The ionically a crosslinked CAS hydrogel adsorbent exhibits a maximum adsorption capacity of 245 mg/g for methylene blue (MB) at 23 °C and a pH of 7. The adsorption behavior of MB on the CAS hydrogel follows both the pseudo-second-order model and the Langmuir adsorption isotherm model. Furthermore, the CAS hydrogel adsorbent maintains a 70 % removal ratio after five cycles. The simplicity of synthesis and hydrogel formation opens up new possibilities for producing and utilizing cellulose-based hydrogels as adsorbents for aqueous contaminants.

Exposure dose and temperature of chlorine on deterioration of thin-film composite membranes for reverse osmosis and nanofiltration.

In this study, the effect of chlorine, which is used as a chemical cleaning agent or disinfection agent on membrane deterioration, was analyzed under various conditions during the membrane process. Reverse osmosis (RO: ESPA2-LD and RE4040-BE) and nanofiltration (NF: NE4040-70) membranes made of polyamide (PA) thin film composite (TFC) were used for evaluation. Chlorine exposure was performed at doses ranging from 1000 ppm h to 10,000 ppm h using 10 ppm and 100 ppm, and temperatures from 10 °C to 30 °C. Raw water containing NaCl, MgSO4, and dextrose was used to compare the filtration performance after exposure to each of the conditions studied. Reduction in removal performance and enhancement in permeability were observed as chlorine exposure increased. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and scanning electron microscope (SEM) were employed to determine the surface characteristics of the decomposed membranes. ATR-FTIR was used to compare the intensity of the peaks related to the TFC membrane. Based on the analysis, the state of membrane degradation was elucidated. SEM was used to confirm visual degradation of the membrane surface. Permeability and correlation analyses were performed on CnT as an index for determining membrane lifetime in order to investigate the power coefficient. The relative influence of the exposure concentration and time on membrane degradation was explored by comparing the power efficiency according to the exposure dose and temperature.

Neurog1-Derived Peptides RMNE1 and DualPep-Shine Penetrate the Skin and Inhibit Melanin Synthesis by Regulating MITF Transcription.

Anti-pigmentation peptides have been developed as alternative skin-lightening agents to replace conventional chemicals that have adverse effects on the skin. However, the maximum size of these peptides is often limited by their low skin and cell penetration. To address this issue, we used our intra-dermal delivery technology (IDDT) platform to identify peptides with hypo-pigmenting and high cell-penetrating activity. Using our cell-penetrating peptides (CPPs) from the IDDT platform, we identified RMNE1 and its derivative RMNE3, "DualPep-Shine", which showed levels of α-Melanocyte stimulating hormone (α-MSH)-induced melanin inhibition comparable to the conventional tyrosinase inhibitor, Kojic acid. In addition, DualPep-Shine was delivered into the nucleus and regulated the gene expression levels of melanogenic enzymes by inhibiting the promoter activity of microphthalmia-associated transcription factor-M (MITF-M). Using a 3D human skin model, we found that DualPep-Shine penetrated the lower region of the epidermis and reduced the melanin content in a dose-dependent manner. Furthermore, DualPep-Shine showed high safety with little immunogenicity, indicating its potential as a novel cosmeceutical ingredient and anti-pigmentation therapeutic agent.

Physicochemical characteristics of lignin-g-PMMA/PLA blend via atom transfer radical polymerization depending on the structural difference of organosolv lignin.

Lignin has different structural characteristics depending on the extraction conditions. In this study, three types of ethanol organosolv lignin (EOL) were produced under different extraction conditions involving the reaction temperature (140, 160, 180 °C), sulfuric acid concentration (0.5, 1, 1.5 %), and ethanol concentration (40, 60, 80 %) to compare the difference in properties when mixed with polylactic acid (PLA) matrix after atom transfer radical polymerization (ATRP). ATRP of EOL was conducted to improve its compatibility with PLA using methyl methacrylate (MMA) as a monomer. The molecular weight of each EOL increased significantly, and the glass transition temperature (Tg) decreased from approximately 150 to 110 °C. The EOL-g-PMMA copolymer exhibited a melting point (Tm), whereas EOL did not, implying that the thermoplasticity increased. The EOL-g-PMMA/PLA blend and film were prepared with 10 % of the copolymer in the PLA matrix. The tensile strength and strain of the blend were higher than those of unmodified organosolv lignin as the compatibility increased, and the UV transmittance was lower than that of neat PLA because of the UV protecting properties of EOL moiety.

Two distinct receptor-binding domains of human glycyl-tRNA synthetase 1 displayed on extracellular vesicles activate M1 polarization and phagocytic bridging of macrophages to cancer cells.

Macrophages play important roles in cancer microenvironment. Human cytosolic glycyl-tRNA synthetase (GARS1) was previously shown to be secreted via extracellular vesicles (EVs) from macrophages to trigger cancer cell death. However, the effects of GARS1-containing EVs (GARS1-EVs) on macrophages as well as on cancer cells and the working mechanisms of GARS1 in cancer microenvironment are not yet understood. Here we show that GARS1-EVs induce M1 polarization and facilitate phagocytosis of macrophages. GARS1-EVs triggers M1 polarization of macrophage via the specific interaction of the extracellular cadherin subdomains 1-4 of the cadherin EGF LAG seven-pass G-type receptor 2 (CELSR2) with the N-terminal WHEP domain containing peptide region of GARS1, and activates the RAF-MEK-ERK pathway for M1 type cytokine production and phagocytosis. Besides, GARS1 interacted with cadherin 6 (CDH6) of cancer cells via its C-terminal tRNA-binding domain to induce cancer cell death. In vivo model, GARS1-EVs showed potent suppressive activity against tumor initiation via M1 type macrophages. GARS1 displayed on macrophage-secreted extracellular vesicles suppressed tumor growth in dual mode, namely through pro-apoptotic effect on cancer cells and M1 polarization effect on macrophages. Collectively, these results elucidate the unique tumor suppressive activity and mechanism of GARS1-EVs by activating M1 macrophage via CELSR2 as well as by direct killing of cancer cells via CDH6.

Solitary osteolytic skull metastasis as the only recurrence of advanced gastric cancer: a case report and literature review.

Bone metastases from gastric cancer are very rare, and skull metastases develop in only 11.2% among patients who develop bone metastases from gastric cancer. We report a case of solitary osteolytic skull metastasis as the only recurrence of advanced gastric cancer. A 67-year-old man was referred to us with a two-month history of headache and progressive scalp swelling in the left parietal region. A right hemiparesis developed a week before admission. Thirteen months previously, he had undergone radical total gastrectomy with Roux-en-Y reconstruction. Pathological analysis indicated well-differentiated adenocarcinoma of the gastric cardia (stage IIIA: pT3N2M0). Brain magnetic resonance imaging showed a large skull metastasis in the left parietal region (approximately 65 × 54 mm). An extensive search did not reveal any other tumors. Gross total tumor resection was performed, and the biopsy revealed an adenocarcinoma, suggesting metastasis of the gastric cancer.

Skeletal Muscle Regeneration by the Exosomes of Adipose Tissue-Derived Mesenchymal Stem Cells.

Profound skeletal muscle loss can lead to severe disability and cosmetic deformities. Mesenchymal stem cell (MSC)-derived exosomes have shown potential as an effective therapeutic tool for tissue regeneration. This study aimed to determine the regenerative capacity of MSC-derived exosomes for skeletal muscle regeneration. Exosomes were isolated from human adipose tissue-derived MSCs (AD-MSCs). The effects of MSC-derived exosomes on satellite cells were investigated using cell viability, relevant genes, and protein analyses. Moreover, NOD-SCID mice were used and randomly assigned to the healthy control (n = 4), muscle defect (n = 6), and muscle defect + exosome (n = 6) groups. Muscle defects were created using a biopsy punch on the quadriceps of the hind limb. Four weeks after the surgery, the quadriceps muscles were harvested, weighed, and histologically analyzed. MSC-derived exosome treatment increased the proliferation and expression of myocyte-related genes, and immunofluorescence analysis for myogenin revealed a similar trend. Histologically, MSC-derived exosome-treated mice showed relatively preserved shapes and sizes of the muscle bundles. Immunohistochemical staining revealed greater expression of myogenin and myoblast determination protein 1 in the MSC-derived exosome-treated group. These results indicate that exosomes extracted from AD-MSCs have the therapeutic potential for skeletal muscle regeneration.

Evaluation of Xylooligosaccharides Production for a Specific Degree of Polymerization by Liquid Hot Water Treatment of Tropical Hardwood.

Eucalyptus pellita is known as attractive biomass, and it has been utilized for eucalyptus oil, furniture, and pulp and paper production that causes a significant amount of byproducts. Liquid hot water treatment depending on combined severity factor (CSF) was subjected to isolate hemicellulose fraction from E. pellita and to produce xylooligosaccharides (XOS). The xylan extraction ratio based on the initial xylan content of the feedstock was maximized up to 77.6% at 170 °C for 50 min condition (CSF: 1.0), which had accounted for XOS purity of 76.5% based on the total sugar content of the liquid hydrolysate. In this condition, the sum of xylobiose, xylotriose, and xylotetraose which has a low degree of polymerization (DP) of 2 to 4 was determined as 80.6% of the total XOS. The highest XOS production score established using parameters including the xylan extraction ratio, XOS purity, and low DP XOS ratio was 5.7 at CSF 1.0 condition. XOS production score evaluated using the CSF is expected to be used as a productivity indicator of XOS in the industry (R-squared value: 0.92).

Thermal Properties of Ethanol Organosolv Lignin Depending on Its Structure.

In general, lignin exhibits unpredictable and nonuniform thermal properties due to the structural variations caused by the extraction processes. Therefore, a systematic understanding of the correlation between the extraction conditions, structural characteristics, and properties is indispensable for the commercial utilization of lignin. In this study, the effect of extraction conditions on the structural characteristics of ethanol organosolv lignin (EOL) was investigated by response surface methodology. The structural characteristics of EOL (molecular weight, hydroxyl content, and intramolecular coupling structure) were significantly affected by the extraction conditions (temperature, sulfuric acid concentration, and ethanol concentration). In addition, the correlation between the structural characteristics and thermal properties of the extracted EOLs was estimated. The relevant correlations between the structural characteristics and thermal properties were determined. In particular, EOLs that had a low molecular weight, high phenolic hydroxyl content, and low aryl-ether linkage content exhibited prominent thermal properties in terms of their initial decomposition rate and a high glass transition temperature, T g. Correspondingly, EOL-PLA blends prepared using three EOL types exhibited improved thermal properties (starting point of thermal decomposition and maximum decomposition temperature) compared to neat PLA and had thermal decomposition behaviors coincident with the thermal properties of the constituent EOLs.

Peracetic acid-induced kraft lignin solubilization and its characterization for selective production of macromolecular biopolymers.

This study was conducted to investigate the degradation characteristics of kraft lignin (KL) during peracetic acid (PAA) treatment, and to produce potentially valuable polymers of low molecular weight lignin by controlling the reaction conditions. For the peracetic acid treatment, acetic acid (AA) and hydrogen peroxide (HP) were directly mixed at ratios of 4:1, 1:1, and 1:4 (v/v) and employed as reaction media. After PAA treatment of kraft lignin at 80 °C, complete dissolution of the lignin and reduction in the molecular weight were observed. When the PAA reaction was performed at high HP concentration (1:4, v/v), the aromatic lignin skeleton opened and converted to a structure containing large amounts of carboxyl groups. On the other hand, the treatment at high AA concentration (4:1, v/v) decomposed lignin while maintaining its aromatic structure. Hence, we demonstrated that the selective production of lignin-derived polymers can be controlled depending on PAA and HP concentrations.

Endogenous TLR2 ligand embedded in the catalytic region of human cysteinyl-tRNA synthetase 1.

BACKGROUND: The generation of antigen-specific cytotoxic T lymphocyte (CTL) responses is required for successful cancer vaccine therapy. In this regard, ligands of Toll-like receptors (TLRs) have been suggested to activate adaptive immune responses by modulating the function of antigen-presenting cells (APCs). Despite their therapeutic potential, the development of TLR ligands for immunotherapy is often hampered due to rapid systemic toxicity. Regarding the safety concerns of currently available TLR ligands, finding a new TLR agonist with potent efficacy and safety is needed. METHODS: A unique structural domain (UNE-C1) was identified as a novel TLR2/6 in the catalytic region of human cysteinyl-tRNA synthetase 1 (CARS1) using comprehensive approaches, including RNA sequencing, the human embryonic kidney (HEK)-TLR Blue system, pull-down, and ELISA. The potency of its immunoadjuvant properties was analyzed by assessing antigen-specific antibody and CTL responses. In addition, the efficacy of tumor growth inhibition and the presence of the tumor-infiltrating leukocytes were evaluated using E.G7-OVA and TC-1 mouse models. The combined effect of UNE-C1 with an immune checkpoint inhibitor, anti-CTLA-4 antibody, was also evaluated in vivo. The safety of UNE-C1 immunization was determined by monitoring splenomegaly and cytokine production in the blood. RESULTS: Here, we report that CARS1 can be secreted from cancer cells to activate immune responses via specific interactions with TLR2/6 of APCs. A unique domain (UNE-C1) inserted into the catalytic region of CARS1 was determined to activate dendritic cells, leading to the stimulation of robust humoral and cellular immune responses in vivo. UNE-C1 also showed synergistic efficacy with cancer antigens and checkpoint inhibitors against different cancer models in vivo. Further, the safety assessment of UNE-C1 showed lower systemic cytokine levels than other known TLR agonists. CONCLUSIONS: We identified the endogenous TLR2/6 activating domain from human cysteinyl-tRNA synthetase CARS1. This novel TLR2/6 ligand showed potent immune-stimulating activity with little toxicity. Thus, the UNE-C1 domain can be developed as an effective immunoadjuvant with checkpoint inhibitors or cancer antigens to boost antitumor immunity.

Extracellular vesicles derived from macrophages display glycyl-tRNA synthetase 1 and exhibit anti-cancer activity.

Glycyl-tRNA synthetase 1 (GARS1), a cytosolic enzyme secreted from macrophages, promotes apoptosis in cancer cells. However, the mechanism underlying GARS1 secretion has not been elucidated. Here, we report that GARS1 is secreted through unique extracellular vesicles (EVs) with a hydrodynamic diameter of 20-58 nm (mean diameter: 36.9 nm) and a buoyant density of 1.13-1.17 g/ml. GARS1 was anchored to the surface of these EVs through palmitoylated C390 residue. Proteomic analysis identified 164 proteins that were uniquely enriched in the GARS1-containing EVs (GARS1-EVs). Among the identified factors, insulin-like growth factor II receptor, and vimentin also contributed to the anti-cancer activity of GARS1-EVs. This study identified the unique secretory vesicles containing GARS1 and various intracellular factors that are involved in the immunological defence response against tumorigenesis.

Correlations between the Status of the Umbilical Cord and Neonatal Health Status.

PURPOSE: This study aimed to identify correlations between the status of the umbilical cord and neonatal health status. METHODS: In total, 172 newborns were enrolled who were admitted to the newborn nursery with a gestational age of 35 weeks or older and a body weight of 2 kg or above. Data were collected on the basic personal information of the newborns, the diameter and soft tissue status of the umbilical cord, and neonatal health status after birth. Analyses were performed using t-test, analysis of variance, x 2 test, and Fisher exact test. RESULTS: Umbilical cord diameter exhibited a statistically significant difference by sex (t=2.71, p=.007). A thin umbilical cord diameter was associated with a 1-minute Apgar score less than 8 points (t=2.47, p=.015) and with being transferred to the intensive care unit (t=2.45, p=.015). Poor soft tissue status of the umbilical cord was associated with a 1-minute Apgar score of less than 8 points (x 2=16.68, p<.001) and with oxygen being supplied (x 2=4.81, p=.028). CONCLUSION: Assessing the umbilical cord diameter and status in newborns is an important tool for evaluating neonatal health status after birth, and this point also underscores the importance of professionals' careful observations in the newborn nursery.

Glucose-dependent control of leucine metabolism by leucyl-tRNA synthetase 1.

Despite the importance of glucose and amino acids for energy metabolism, interactions between the two nutrients are not well understood. We provide evidence for a role of leucyl-tRNA synthetase 1 (LARS1) in glucose-dependent control of leucine usage. Upon glucose starvation, LARS1 was phosphorylated by Unc-51 like autophagy activating kinase 1 (ULK1) at the residues crucial for leucine binding. The phosphorylated LARS1 showed decreased leucine binding, which may inhibit protein synthesis and help save energy. Leucine that is not used for anabolic processes may be available for catabolic pathway energy generation. The LARS1-mediated changes in leucine utilization might help support cell survival under glucose deprivation. Thus, depending on glucose availability, LARS1 may help regulate whether leucine is used for protein synthesis or energy production.

Selective deconstruction of hemicellulose and lignin with producing derivatives by sequential pretreatment process for biorefining concept.

For improving the economic efficiency of the biorefining concept, selective decomposition and separation of biomass components is indispensable. In this respect, a sequential pretreatment process consisting of liquid hot water treatment and diluted peracetic acid (PAA) treatment was proposed for total utilization of lignocellulosic woody biomass. During the liquid hot water treatment, hemicellulose can be decomposed efficiently without significant loss of cellulose and lignin, implying the possibility for xylooligomer production by thermochemical treatment. In the PAA treatment, lignin was successfully degraded and liquefied using a 50% diluted PAA solvent, suggesting the possibility of dicarboxylic acid production. After the sequential process proposed in this study, the cellulose accessibility to the enzyme could be maximized by inducing selective deconstruction of hemicellulose and lignin.

Exosomal secretion of truncated cytosolic lysyl-tRNA synthetase induces inflammation during cell starvation.

Previous work by Kim, et al. (2017) unveiled that lysyl-tRNA synthetase (KRS) is secreted through a mechanism involving syntenin-containing exosomes. They described how KRS, commonly known as part of the translational machinery in the cytoplasm, is secreted into the extracellular space where it induces inflammation. First, KRS secretion is triggered by starvation conditions. The increase in caspase-8 levels during starvation is responsible for proteolysis and generation of the N-terminal truncated form of KRS, and this event is required for KRS dissociation from the multi-synthetase complex (MSC). N-terminal cleavage of KRS eventually leads to a conformational change that allows its interaction with the C-terminal PDZ binding motif of syntenin and subsequent exosome biogenesis. The KRS-syntenin complex translocates to multivesicular bodies (MVBs) that originate from endosomes involved with intraluminal vesicle (ILVs). MVBs are transporters for the secretion of cellular contents into the extracellular space. Syntenin localizes intraluminal vesicles within endosomal membranes. The KRS-syntenin complex transfers on to intraluminal vesicles in MVBs. MVBs are translocated to the plasma membrane for ILV secretion mediated by Rab family proteins. Once KRS exosomes are secreted, their membranes are eventually ruptured by proteases and KRS is released from the exosomes where it can act as an inflammatory cytokine in the extracellular space. Secreted KRS triggers macrophage/neutrophil migration and induces inflammation.

Caspase-8 controls the secretion of inflammatory lysyl-tRNA synthetase in exosomes from cancer cells.

Aminoacyl-tRNA synthetases (ARSs), enzymes that normally control protein synthesis, can be secreted and have different activities in the extracellular space, but the mechanism of their secretion is not understood. This study describes the secretion route of the ARS lysyl-tRNA synthetase (KRS) and how this process is regulated by caspase activity, which has been implicated in the unconventional secretion of other proteins. We show that KRS is secreted from colorectal carcinoma cells within the lumen of exosomes that can trigger an inflammatory response. Caspase-8 cleaved the N-terminal of KRS, thus exposing a PDZ-binding motif located in the C terminus of KRS. Syntenin bound to the exposed PDZ-binding motif of KRS and facilitated the exosomic secretion of KRS dissociated from the multi-tRNA synthetase complex. KRS-containing exosomes released by cancer cells induced macrophage migration, and their secretion of TNF-α and cleaved KRS made a significant contribution to these activities, which suggests a novel mechanism by which caspase-8 may promote inflammation.