CUSABIO Quarterly Citation Review: 800 New Product Citations in Q2, Total Citations Hit 27,000!

This study genetically modeled ELP1-associated Sonic Hedgehog medulloblastoma (SHH-MB) and found that ELP1 heterozygous mutant mice exhibit genomic instability, mitotic defects, and differentiation stalling in granule neuron precursors (GNPs). Further experiments using orthotopic transplantation and patient-derived xenograft (PDX) models revealed dampened p53 signaling in ELP1-mutant tumors. Pharmacological inhibition of MDM2 significantly prolonged survival in ELP1-mutant SHH-MB mice, identifying MDM2 as a potential therapeutic target for ELP1-associated medulloblastoma.

This study identified a biomarker panel in extracellular vesicles (EVs) derived from non-small cell lung cancer (NSCLC) through proteomic analysis and machine learning. The study found significantly higher levels of CD155 in plasma EVs from NSCLC patients compared to healthy individuals. Using CD155 as a bait protein, CD155+ tumor-derived EVs (TDEVs) were enriched from the plasma of NSCLC patients. Targeted proteomics identified a panel of seven proteins (MVP, GYS1, SERPINA3, HECTD3, SERPING1, TPM4, and APOD) that demonstrated excellent diagnostic performance for NSCLC, achieving an AUC of 1.0 with 100% sensitivity and specificity. These findings highlight the potential of this biomarker panel for the clinical diagnosis of NSCLC.

This study developed a self-assembling lysosome-targeting chimera (LYTAC) nanoparticle platform, NanoCLY, for triple-negative breast cancer (TNBC) therapy. NanoCLY degrades CTGF protein in the tumor microenvironment, inhibits tumor growth and metastasis, and remodels the inflammatory tumor microenvironment. It demonstrated superior antitumor efficacy in vitro and in vivo and showed synergistic effects when combined with chemotherapy. This research provides a new strategy for TNBC treatment and lays the foundation for the application of targeted protein degradation in oncology.

This study investigates the chronic toxicity mechanisms of 6PPD and its oxidation product 6PPD-quinone in zebrafish. Results show that 6PPD accumulates primarily in the liver, while 6PPD-quinone targets the brain. Both compounds impair zebrafish growth, induce hepatic damage, and disrupt locomotor behavior. Transcriptomic analysis reveals disturbances in lipid and carbohydrate metabolic pathways, with downregulation of PPARγ and upregulation of pro-inflammatory cytokines TNF-α and IL-6. Molecular dynamics simulations and surface plasmon resonance experiments further demonstrate direct binding to PPARγ, elucidating the hepatotoxic mechanisms. The study highlights the hepatotoxic risks of 6PPD and 6PPD-quinone to aquatic life, with 6PPD-quinone exhibiting greater toxicity.

This study investigates alterations in nerve growth factor precursor (proNGF) in neuron-derived extracellular vesicles (NDEVs) from individuals with Down syndrome (DS) along the Alzheimer’s disease (AD) continuum. ProNGF levels increased with age and were higher in both asymptomatic and symptomatic DS individuals compared to healthy controls, with the highest levels in symptomatic individuals. ProNGF correlated significantly with cerebrospinal fluid (CSF) p-tau181 and plasma neurofilament light chain (NfL), suggesting its potential as a biomarker for monitoring AD progression in DS.

This study identified PIM1 as a key gene in sepsis through bioinformatics and clinical research, showing a significant positive correlation with coagulation factors. In a sepsis mouse model, the PIM1 inhibitor SMI-4a reduced TF release by inhibiting mTOR phosphorylation, improving coagulopathy and lung injury. Based on these findings, a multifunctional co-delivery system MPDA@SMI-4a@PEI/siPIM1@GM was developed. It targets macrophages, effectively downregulates PIM1 expression, and improves sepsis-induced coagulopathy and acute lung injury, significantly increasing survival rates.

This study investigates the therapeutic potential of targeting USP11 in interstitial lung disease (ILD). It was found that USP11 stabilizes and extends the half-life of the SFTPC protein, particularly the mutant SFTPCI73T, leading to alveolar epithelial dysfunction and pulmonary fibrosis. Using CRISPR/Cas9, researchers introduced the SFTPCI73T mutation into hiPSC-derived alveolar organoids and demonstrated that USP11 depletion significantly mitigates fibrosis caused by this mutation. Furthermore, USP11 inhibitors, such as mitoxantrone, effectively prevent and treat pulmonary fibrosis in both in vitro and in vivo models, offering a new therapeutic target for ILD.

This study develops a two-plex in vivo molecular imaging technique in the second near-infrared window (NIR-II) to simultaneously monitor CD8+ T cells and PD1 levels in tumors. Utilizing non-overlapping fluorescence from indocyanine green (ICG) and PbS/CdS quantum dots (QDs) targeting PD1 and CD8+ T cells respectively, the method enables dynamic monitoring of tumor immunophenotypes. Results reveal heterogeneous distributions of PD1 and CD8+ T cells across tumor types and indicate that low PD1 and high CD8+ T cell levels predict better anti-tumor effects. This non-invasive imaging approach offers a new way to predict immunotherapy efficacy, potentially complementing traditional biopsy-based diagnostics.

This study investigates the effects of a natural small molecule, isoginkgetin (ISOGK), on hypercholesterolemia and atherosclerosis. ISOGK targets ATP citrate lyase (ACLY) to inhibit its enzyme activity, thereby reducing cholesterol and fatty acid synthesis. In animal models of atherosclerosis induced by high cholesterol diets, ISOGK significantly decreased aortic plaque areas and lipid accumulation, and lowered plasma and hepatic cholesterol and triglyceride levels. ISOGK also demonstrated good safety profiles in vivo and in vitro. This research provides a promising basis for developing novel lipid-lowering drugs.

This study reveals how helminths manipulate the host's innate immunity to reshape the gut microbiota and regulate immunoregulation. It was found that during helminth infection, the antimicrobial peptide CRAMP is highly expressed in macrophages, selectively killing gram-negative bacteria to provide ecological niches for lactobacilli expansion, thereby enhancing the host's immunosuppressive response. Additionally, the study discovered that vitamin D can influence this process by regulating CRAMP expression, offering new insights for the treatment of helminth infections and related diseases.