Cell-Penetrating Peptide Like Anti-Programmed Cell Death-Ligand 1 Peptide Conjugate-Based Self-Assembled Nanoparticles for Immunogenic Photodynamic Therapy.

The tumor-specific efficacy of the most current anticancer therapeutic agents, including antibody-drug conjugates (ADCs), oligonucleotides, and photosensitizers, is constrained by limitations such as poor cell penetration and low drug delivery. In this study, we addressed these challenges by developing, a positively charged, amphiphilic Chlorin e6 (Ce6)-conjugated, cell-penetrating anti-PD-L1 peptide nanomedicine (CPPD1) with enhanced cell and tissue permeability. The CPPD1 molecule, a bioconjugate of a hydrophobic photosensitizer and strongly positively charged programmed cell death-ligand 1 (PD-L1) binding cell-penetrating peptide (CPP), is capable of self-assembling into nanoparticles with an average size of 199 nm in aqueous solution without the need for any carriers.

Effects of Graphene Quantum Dots on Renal Fibrosis Through Alleviating Oxidative Stress and Restoring Mitochondrial Membrane Potential.

Podocyte injury and proteinuria in glomerular disease are critical indicators of acute kidney injury progression to chronic kidney disease. Renal mitochondrial dysfunction, mediated by intracellular calcium levels and oxidative stress, is a major contributor to podocyte complications. Despite various strategies targeting mitochondria to improve kidney function, effective treatments remain lacking.

Effective Spiral Laser Path for Minimizing Local Heating and Anisotropic Microstructures in Powder Bed Fusion Additive Manufacturing.

Heat accumulation due to repetitive simple laser processing paths during building up a three-dimensional structure is a well-known issue that needs to be settled to reduce the excessively high residual stress and thermal deformation in a powder bed fusion (PBF) additive manufacturing process. Because of the dependency of laser path on the thermal dispersion, it is essential to analyze the heat accumulation phenomenon during laser processing. A computational fluid dynamics (CFD) analysis based on the volume of fraction method is used to optimize the laser path for minimizing the local heating up in the PBF process.

Meta-structure of amorphous-inspired 65.1Co28.2Cr5.3Mo lattices augmented by artificial intelligence.

Unlabelled: A hatching-distance-controlled lattice of 65.1Co28.2Cr5.

Crack Control in Additive Manufacturing by Leveraging Process Parameters and Lattice Design.

This study investigates the design of additive manufacturing for controlled crack propagation using process parameters and lattice structures. We examine two lattice types-octet-truss (OT) and diamond (DM)-fabricated via powder bed fusion with Ti-6Al-4V. Lattice structures are designed with varying densities (10%, 30%, and 50%) and process using two different laser energies.

Macropinocytosis-targeted peptide-docetaxel conjugate for bystander pancreatic cancer treatment.

Oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are highly prevalent in pancreatic ductal adenocarcinoma (PDAC) and have garnered attention as potential targets for targeted therapies, such as KRAS inhibitors. However, the limited therapeutic efficacy of KRAS allele-specific inhibitors necessitate an efficient pan-KRAS cancer cell killing strategy. Here, we have examined enhanced macropinocytosis pathway in KRAS mutant cancer cells and report improved intracellular delivery of albumin-based therapeutics.

Discovery of selective LATS inhibitors scaffold hopping: enhancing drug-likeness and kinase selectivity for potential applications in regenerative medicine.

Due to its essential roles in cell proliferation and apoptosis, the precise regulation of the Hippo pathway through LATS presents a viable biological target for developing new drugs for cancer and regenerative diseases. However, currently available probes for selective and highly drug-like inhibition of LATS require further improvement in terms of both activity, selectivity and drug-like properties. Through scaffold hopping aided by docking studies and AI-assisted prediction of metabolic stabilities, we successfully identified an advanced LATS inhibitor demonstrating potent kinase activity, exceptional selectivity against other kinases, and superior oral pharmacokinetic profiles.

Discovery of A-910, a Highly Potent and Orally Bioavailable Dual MerTK/Axl-Selective Tyrosine Kinase Inhibitor.

TAM receptor tyrosine kinases have emerged as promising therapeutic targets for cancer treatment due to their roles in both tumor intrinsic survival mechanisms and suppression of antitumor immunity within the tumor microenvironment. Inhibiting MerTK and Axl selectively is believed to hinder cancer cell survival, reverse the protumor myeloid phenotype, and suppress efferocytosis, thereby eliciting an antitumor immune response. In this study, we present the discovery of , a highly potent and selective dual MerTK/Axl inhibitor, achieved through a structure-based medicinal chemistry campaign.

Coccygodynia in a Long-Term Cancer Survivor Diagnosed with Metastatic Cancer: A Case Report.

: Rectal cancer is considered cured if no recurrence is found during the 5-year follow-up period after treatment. After this period, patients often believe that the cancer is completely eradicated. However, in modern society, where lifespans have become longer, it is important to recognize that metastatic cancer may occur long after the initial treatment has concluded.

[Postoperative Imaging Findings of Colorectal Surgery: A Pictorial Essay].

Postoperative colorectal imaging studies play an important role in the detection of surgical complications and disease recurrence. In this pictorial essay, we briefly describe methods of surgery, imaging findings of their early and late complications, and postsurgical recurrence of cancer and inflammatory bowel disease.

Nano-anticoagulant based on carrier-free low molecular weight heparin and octadecylamine with an albumin shuttling effect.

Low-molecular-weight heparin (LMWH), derived from unfractionated heparin (UFH), has enhanced anticoagulant efficacy, long duration of action, and extended half-life. Patients receiving LMWH for preventive therapies would strongly benefit from its long-term effects, however, achieving this is challenging. Here, we design and evaluate a nanoengineered LMWH and octadecylamine conjugate (LMHO) that can act for a long time while maintaining close to 97 ± 3% of LMWH activity via end-specific conjugation of the reducing end of LMWH.

Synergistic anticancer immunity in metastatic triple-negative breast cancer through an in situ amplifying Peptide-Drug Conjugate.

Despite significant progress in combining cancer immunotherapy with chemotherapy to treat triple negative breast cancer (TNBC), challenges persist due to target depletion and tumor heterogeneity, especially in metastasis. Chemotherapy lacks precise targeting abilities, and targeted therapy is inadequate in addressing the diverse heterogeneity of tumors. To address these challenges, we introduce RGDEVD-DOX as a tumor-specific immunogenic agent, namely TPD1, which targets integrin αvβ3 and gets continuously activated by apoptosis.

NUAK2 Inhibitors, KHKI-01128 and KHKI-01215, Exhibit Potent Anticancer Activity Against SW480 Colorectal Cancer Cells.

Background/aim: NUAK family kinase 2 (NUAK2) is a promising target for cancer therapeutics due to its reported role in protein phosphorylation, a critical process in cancer cell survival, proliferation, invasion, and senescence. This study aimed to identify novel inhibitors that disrupt NUAK2 activity. We have already identified two KRICT Hippo kinase inhibitor (KHKI) compounds, such as KHKI-01128 and KHKI-01215.

Stimulating macropinocytosis of peptide-drug conjugates through DNA-dependent protein kinase inhibition for treating KRAS-mutant cancer.

KRAS-mutant cancers, due to their protein targeting complexity, present significant therapeutic hurdles. The identification of the macropinocytic phenotype in these cancers has emerged as a promising alternative therapeutic target. Our study introduces MPD1, an macropinocytosis-targeting peptide-drug conjugates (PDC), which is developed to treat KRAS mutant cancers.

Immune modulation of the liver metastatic colorectal cancer microenvironment via the oral CAPOX-mediated cGAS-STING pathway.

We evaluated modulation of the immunosuppressive tumor microenvironment in both local and liver metastatic colorectal cancer (LMCC), focusing on tumor-associated macrophages, which are the predominant immunosuppressive cells in LMCC. We developed an orally administered metronomic chemotherapy regimen, oral CAPOX. This regimen combines capecitabine and a nano-micelle encapsulated, lysine-linked deoxycholate and oxaliplatin complex (OPt/LDC-NM).

Machine learning-based response assessment in patients with rectal cancer after neoadjuvant chemoradiotherapy: radiomics analysis for assessing tumor regression grade using T2-weighted magnetic resonance images.

Purpose: This study aimed to assess tumor regression grade (TRG) in patients with rectal cancer after neoadjuvant chemoradiotherapy (NCRT) through a machine learning-based radiomics analysis using baseline T2-weighted magnetic resonance (MR) images.

Materials And Methods: In total, 148 patients with locally advanced rectal cancer(T2-4 or N+) who underwent MR imaging at baseline and after chemoradiotherapy between January 2010 and May 2021 were included. A region of interest for each tumor mass was drawn by a radiologist on oblique axial T2-weighted images, and main features were selected using principal component analysis after dimension reduction among 116 radiomics and three clinical features.

Reliability and Agreement Assessment of Sarcopenia Diagnosis through Comparison of Bioelectrical Impedance Analysis and Dual-Energy X-ray Absorptiometry.

A unified diagnostic criterion has yet to be established for sarcopenia. Therefore, we analyzed the reliability and validity of sarcopenia diagnosis using bioelectrical impedance analysis (BIA) compared with the gold standard, dual-energy X-ray absorptiometry (DEXA), and evaluated the predictive accuracy of BIA for diagnosis. The clinical trial, involving a total of 239 participants, was conducted between December 2018 and September 2019 on healthy volunteers without significant medical histories.

Coordinated ASBT and EGFR Mechanisms for Optimized Liraglutide Nanoformulation Absorption in the GI Tract.

Background: For maintenance therapy in type 2 diabetes, glucagon-like peptide-1 agonist (GLP-1A), which exhibits low cardiovascular risk and high efficacy, is a promising peptide therapeutic. However, developing an oral GLP-1A presents challenges due to the analog's poor cellular permeability and gastrointestinal (GI) stability.

Methods: To mitigate such limitations, an oral nanoformulation of liraglutide (LG) was designed and achieved by combining LG with bile acid derivatives using the nanoprecipitation method.

Pediatric Extracorporeal Membrane Oxygenation in Korea: A Multicenter Retrospective Study on Utilization and Outcomes Spanning Over a Decade.

Background: Over the last decade, extracorporeal membrane oxygenation (ECMO) use in critically ill children has increased and is associated with favorable outcomes. Our study aims to evaluate the current status of pediatric ECMO in Korea, with a specific focus on its volume and changes in survival rates based on diagnostic indications.

Methods: This multicenter study retrospectively analyzed the indications and outcomes of pediatric ECMO over 10 years in patients at 14 hospitals in Korea from January 2012 to December 2021.

Enhanced Energy Absorption of Additive-Manufactured Ti-6Al-4V Parts via Hybrid Lattice Structures.

In this study, we present the energy absorption capabilities achieved through the application of hybrid lattice structures, emphasizing their potential across various industrial sectors. Utilizing Ti-6Al-4V and powder bed fusion (PBF) techniques, we fabricated distinct octet truss, diamond, and diagonal lattice structures, tailoring each to specific densities such as 10, 30, and 50%. Furthermore, through the innovative layering of diverse lattice types, we introduced hybrid lattice structures that effectively overcome the inherent energy absorption limitations of single-lattice structures.