The pan-cancer analysis of LRG1 and its potential role in kidney renal clear cell carcinoma.

Leucine-rich α-2 glycoprotein 1 (LRG1) is a secreted glycoprotein implicated in various diseases, yet its role across multiple cancers remains insufficiently explored. Consequently, we conducted a comprehensive bioinformatics analysis, exploring LRG1 expression patterns, prognostic implications, and potential therapeutic associations in a pan-cancer context. Additionally, we collected gene expression and clinical data from patients with kidney renal clear cell carcinoma (KIRC) from TCGA, conducting gene set enrichment analysis (GSEA) and Cox proportional hazards regression analysis to explore the potential regulatory role of LRG1 in KIRC.

PROTAC based targeted degradation of LRG1 for mitigating corneal neovascularization.

Leucine-rich alpha-2-glycoprotein 1 (LRG1), a secretory glycoprotein associated with angiogenesis, inflammation, fibrosis, and other pivotal pathophysiological processes, is significantly upregulated in corneal neovascularization (CNV), where it drives neovascularization via the TGF-β-Smad signaling pathway, making it a potential therapeutic target for CNV. This study employs proteolysis-targeting chimera (PROTAC) technology, utilizing our newly developed PROTAC agent, TAC-2, to selectively degrade LRG1 in a mouse model of alkali burn-induced CNV. The cellular study revealed that TAC-2 effectively degraded LRG1 in a time- and dose-dependent manner, with a half-maximal degradation concentration (DC50) of 13.

LRG1-Targeted Camptothecin Nanomicelles with Simultaneous Delivery of Olaparib for Enhanced Colorectal Cancer Chemotherapy.

Camptothecin (CPT), an effective topoisomerase I inhibitor used in colorectal cancer chemotherapy, often faces limitations due to severe toxicities. Addressing this, we developed OCE, a nanomedicine featuring the CPT-ET conjugate─comprising a cathepsin B-sensitive linker and CPT linked to the ET peptide targeting leucine-rich alpha-2-glycoprotein 1 (LRG1) and encapsulating Olaparib, a potent poly ADP-ribose polymerase (PARP) inhibitor. OCE aims for precise CPT delivery to colorectal cancer sites overexpressing LRG1, while Olaparib disrupts compromised DNA repair pathways, enhancing DNA damage and promoting increased tumor cell apoptosis.

Engineering Thermoresponsive Enzyme-Polymer Conjugates via Glycan-Selective Polymerization for Recyclable Homogeneous Biocatalysis.

Enzymes are crucial for various technological applications, but their inherent instability and short lifespan pose challenges. This study presents facile immobilized enzyme technology with the development of thermoresponsive enzyme-polymer conjugates (EPCs), using glucose oxidase (GOx) as a model enzyme, to address these limitations. By conjugating heteropolymers to the glycan moieties of GOx through a precise polymerization process, we could modulate the lower critical solution temperature of the EPCs, enhancing enzyme performance without compromising its active site.

Dehydrogenative α,γ-Diphosphinylation of Allylamines Enabled by Photoinduced Cobaloxime Catalysis.

A regioselective radical α,γ-diphosphinylation of allylamines with secondary phosphine oxides by photoinduced cobaloxime catalysis is described. The reaction tolerates a wide range of allylamines and phosphine oxides, affording α-amino diphosphine dioxides in moderate to good yields with hydrogen evolution. The synthesis of new diphosphine monoxide and diphosphine ligands and the promising antitumor activities of products demonstrate the great potential applications of this approach in catalysis and drug discovery.

Targeted degradation of LRG1 to attenuate renal fibrosis.

Leucine-rich α-2 glycoprotein 1 (LRG1), a secreted glycoprotein, has been identified as significantly upregulated in renal fibrosis, potentially exacerbating the condition by enhancing TGF-β-Smad3-dependent signaling pathways. Herein, utilizing our developed LRG1-targeting peptide for LRG1 recruitment and lenalidomide for E3 ubiquitin ligase engagement, we developed an advanced proteolysis targeting chimera, TAC-2, specifically designed for LRG1 degradation. Our cellular degradation assays validated that TAC-2 effectively degraded LRG1 through a proteasome-dependent mechanism, achieving half-maximal degradation at a concentration of 8.

LRG1-Targeted Nintedanib Delivery for Enhanced Renal Fibrosis Mitigation.

Renal fibrosis lacks effective nephroprotective drugs in clinical settings due to poor accumulation of therapeutic agents in damaged kidneys, underscoring the urgent need for advanced renal-targeted delivery systems. Herein, we exploited the significantly increased expression of the leucine-rich α-2 glycoprotein 1 (LRG1) protein during renal fibrosis to develop a novel drug delivery system. Our engineered nanocarrier, DEN, preferentially targets fibrotic kidneys via the decorated ET peptide's high affinity for LRG1.

The Analgesic Efficacy of Ultrasound-guided Quadratus Lumborum Block Transmuscular or Posterior Approach After Hip Surgery: A Systematic Review and Meta-analysis with Trial Sequential Analysis.

Background: No review or meta-analysis exists to elucidate the efficacy and safety of quadratus lumborum block (QLB) on the pain intensity, opioid requirement, and mobilization in patients undergoing hip surgery. This systematic review and meta-analysis of randomized controlled trials were designed to compare QLB with no block or placebo (without other nerve/plexus blocks) for patients undergoing hip surgery.

Methods: Two individual researchers conducted the platform searches on the PubMed, Cochrane Library, and Embase databases from inception to June 12, 2021.

Dual-Antigen-Loaded Hepatitis B Virus Core Antigen Virus-like Particles Stimulate Efficient Immunotherapy Against Melanoma.

Tumor cells are rich in antigens, which provide a reliable antigen library for the design of personalized vaccines. However, an effective tumor vaccine vector that can efficiently deliver antigens to lymphoid organs to stimulate strong CD8 cytotoxic T-lymphocyte immune response is still lacking. Here we designed a dual-antigen delivery system based on hepatitis B virus core antigen virus-like particles (HBc VLPs).

A Graphdiyne Oxide-Based Iron Sponge with Photothermally Enhanced Tumor-Specific Fenton Chemistry.

Fenton reaction-mediated oncotherapy is an emerging strategy which uses iron ions to catalytically convert endogenous hydrogen peroxide into hydroxyl radicals, the most reactive oxygen species found in biology, for efficient cancer therapy. However, Fenton reaction efficiency in tumor tissue is typically limited due to restrictive conditions. One strategy to overcome this obstacle is to increase the temperature specifically at the tumor site.

Anterior cruciate ligament reconstruction with the use of adductor canal block can achieve similar pain control as femoral nerve block.

Purpose: Moderate-to-severe postoperative pain remains a challenge for both patients and surgeons after anterior cruciate ligament reconstruction (ACLR). The purpose of this study was to systematically review the current evidence in the literature to compare adductor canal block (ACB) with femoral nerve block (FNB) in the treatment of ACLR.

Methods: A comprehensive search of the published literature in PubMed, Scopus, EMBASE, and Cochrane Library databases was performed.

Modularly Designed Peptide Nanoprodrug Augments Antitumor Immunity of PD-L1 Checkpoint Blockade by Targeting Indoleamine 2,3-Dioxygenase.

The limited efficacy of single-agent immune checkpoint inhibitors in treating tumors has prompted investigations on their combination partners. Here, a tumor-homing indoleamine 2,3-dioxygenase (IDO) nanoinhibitor is reported to selectively inhibit immunosuppressive IDO pathway in the tumor microenvironment. It is self-assembled from a modularly designed peptide-drug conjugate containing a hydrophilic targeting motif (arginyl-glycyl-aspartic acid; RGD), two protonatable histidines, and an ester bond-linked hydrophobic IDO inhibitor, which exhibits pH-responsive disassembly and esterase-catalyzed drug release.

A Bioinspired Nanoprobe with Multilevel Responsive T -Weighted MR Signal-Amplification Illuminates Ultrasmall Metastases.

Metastasis remains the major cause of death in cancer patients. Thus, there is a need to sensitively detect tumor metastasis, especially ultrasmall metastasis, for early diagnosis and precise treatment of cancer. Herein, an ultrasensitive T -weighted magnetic resonance imaging (MRI) contrast agent, UMFNP-CREKA is reported.

Sulforaphane Mediates Glutathione Depletion via Polymeric Nanoparticles to Restore Cisplatin Chemosensitivity.

Platinum (Pt)-based chemotherapy is a broadly used therapeutic regimen against various cancers. However, the insufficient cellular uptake, deactivation by thiol-containing species and nonspecific distribution of cisplatin (CDDP) result in its low chemosensitivity as well as systemic side effects, which can largely constrain the employment of CDDP in clinical treatment. To circumvent these problems, in this study, polymeric nanoparticles were utilized to codeliver a water-soluble CDDP derivative, poly(γ,l-glutamic acid)-CDDP conjugate, and a naturally occurring compound derived from broccoli, sulforaphane, which can achieve efficient glutathione (GSH) depletion, to improve the accumulation of CDDP in cancer cells.

Effect of Parkinson's disease on primary total joint arthroplasty outcomes: A meta-analysis of matched control studies.

Background: Currently, no meta-analysis exists elucidate the outcomes of total joint arthroplasty (TJA) in patients with Parkinson's disease (PD). The aim of this study was to investigate the outcomes of TJA in patients with PD with respect to complication and revision in comparison to a TJA cohort without PD.

Methods: MEDLINE, Scopus, EMBASE, and Cochrane Library databases were searched with English language restrictions.

Synthesis and Imaging of Biocompatible Graphdiyne Quantum Dots.

Graphdiyne has attracted much interest from researchers for their potential applications in energy storage, catalysis, and biomedical areas. As one of the derivatives of graphdiyne, graphdiyne quantum dots (GDQDs) may possess superior bioactivity due to active acetylene units. However, the biological application of biocompatible GDQDs have not been reported so far.

Engineering Biomimetic Platesomes for pH-Responsive Drug Delivery and Enhanced Antitumor Activity.

Biomimetic camouflage, i.e., using natural cell membranes for drug delivery, has demonstrated advantages over synthetic materials in both pharmacokinetics and biocompatibility, and so represents a promising solution for the development of safe nanomedicine.

Cooperatively Responsive Peptide Nanotherapeutic that Regulates Angiopoietin Receptor Tie2 Activity in Tumor Microenvironment To Prevent Breast Tumor Relapse after Chemotherapy.

Expressed in macrophages and endothelial cells, the receptor for angiopoietin, tyrosine kinase with immunoglobulin and epidermal growth factor homology-2 (Tie2), is required for the reconstruction of blood vessels in tumor recurrence after chemotherapy. Thus, small therapeutic peptides that target and block Tie2 activity are promising as a therapeutic for the prevention of tumor relapse after chemotherapy. However, such small peptides often have low bioavailability, undergo rapid enzymatic degradation, and exhibit a short circulation half-life, making them ineffective in cancer therapy.

An Extendable Star-Like Nanoplatform for Functional and Anatomical Imaging-Guided Photothermal Oncotherapy.

Combining informative imaging methodologies with effective treatments to destroy tumors is of great importance for oncotherapy. Versatile nanotheranostic agents that inherently possess both diagnostic imaging and therapeutic capabilities are highly desirable to meet these requirements. Here, a simple but powerful nanoplatform based on polydopamine-coated gold nanostar (GNS@PDA), which can be easily diversified to achieve various function extensions, is designed to realize functional and anatomical imaging-guided photothermal oncotherapy.