Specific targeting of cancer vaccines to antigen-presenting cells via an endogenous TLR2/6 ligand derived from cysteinyl-tRNA synthetase 1.

Cancer vaccines have been developed as a promising way to boost cancer immunity. However, their clinical potency is often limited due to the imprecise delivery of tumor antigens. To overcome this problem, we conjugated an endogenous Toll-like receptor (TLR)2/6 ligand, UNE-C1, to human papilloma virus type 16 (HPV-16)-derived peptide antigen, E7, and found that the UNE-C1-conjugated cancer vaccine (UCV) showed significantly enhanced antitumor activity in vivo compared with the noncovalent combination of UNE-C1 and E7. The combination of UCV with PD-1 blockades further augmented its therapeutic efficacy. Specifically, the conjugation of UNE-C1 to E7 enhanced its retention in inguinal draining lymph nodes, the specific delivery to dendritic cells and E7 antigen-specific T cell responses, and antitumor efficacy in vivo compared with the noncovalent combination of the two peptides. These findings suggest the potential of UNE-C1 derived from human cysteinyl-tRNA synthetase 1 as a unique vehicle for the specific delivery of cancer antigens to antigen-presenting cells via TLR2/6 for the improvement of cancer vaccines.

Single-Component Cellulose Acetate Sulfate Hydrogels for Direct Ink Writing 3D Printing.

Hydrogels, typically favored for 3D printing due to their viscoelasticity, are now trending toward ecofriendly alternatives amid growing environmental concerns. In this study, we crafted cellulose-based hydrogels, specifically employing cellulose acetate sulfate (CAS). By keeping the acetyl group substitution degree (DSacetyl = 1.8) and CAS molecular weight constant, we varied rheological properties by adjusting sulfate group substitution (DSsulfate = 0.4, 0.7, and 1.0) and CAS concentration (2-5 wt %). Rheological characterizations, including shear-thinning, yield stress, and thixotropy, were performed to identify optimal conditions for formulating CAS hydrogel ink in direct ink writing for 3D printing under selected experimental conditions. Based on rheological findings, CAS hydrogels with DSsulfate 0.7 and concentration of 4 wt % was used for 3D printing, with subsequent evaluation of printing metrics. Additionally, the effect of ionic cross-linking using Ca2+ ions on the structural integrity of 3D-printed structures was evaluated, demonstrating effective preservation through reinforced polymer networks. The shrinking and swelling behaviors of the 3D-printed structures were also significantly affected by this ionic cross-linking. Building on these findings, this work could broaden the range of cellulose derivatives available for the preparation of cellulose-based hydrogels for 3D printing.

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.

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.

Quantum rectangular MinRank attack on multi-layer UOV signature schemes.

Recent rank-based attacks have reduced the security of Rainbow, which is one of the multi-layer UOV signatures, below the NIST security requirements by speeding up iterative kernel-finding operations using classical mathematics techniques. If quantum algorithms are applied to perform these iterative operations, the rank-based attacks may be more threatening to multi-layer UOV, including Rainbow. In this paper, we propose a quantum rectangular MinRank attack called the Q-rMinRank attack, the first quantum approach to key recovery attacks on multi-layer UOV signatures. Our attack is a general model applicable to multi-layer UOV signature schemes, and in this paper, we provide examples of its application to Rainbow and the Korean TTA standard, HiMQ. We design two quantum oracle circuits to find the kernel in consideration of the depth-width trade-off of quantum circuits. One is to reduce the width of the quantum circuits using qubits as a minimum, and the other is to reduce the depth using parallelization instead of using a lot of qubits. By designing quantum circuits to find kernels with fewer quantum resources and complexity by adding mathematical techniques, we achieve quadratic speedup for the MinRank attack to recover the private keys of multi-layer UOV signatures. We also estimate quantum resources for the designed quantum circuits and analyze quantum complexity based on them. The width-optimized circuit recovers the private keys of Rainbow parameter set V with only 1089 logical qubits. The depth-optimized circuit recovers the private keys of Rainbow parameter set V with a quantum complexity of 2 174 , which is lower than the complexity of 2 221 recovering the secret key of AES-192, which provides the same security level as parameter set III.

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.

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.

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.

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.