Superassembled Mesoporous Carbon-Fe2O3 Heterochannels for Photothermal-Enhanced Hyaluronidase Sensing.

Developing an activity detection platform for hyaluronidase (HAase) is crucial for diagnosing and treating cancer. However, traditional detection of HAase is based on changes in the flow rate caused by viscosity or requires complex modifications and processing, which limits the detection accuracy and sensitivity. Herein, hyaluronic acid (HA)-modified mesoporous-based heterochannels (mesoporous carbon-doped γ-Fe2O3 nanoparticles/anodized aluminum oxide, MC-γ-Fe2O3/AAO) featuring ordered 3D transport frameworks and a photothermal property were developed for high performance HAase detection. The HA molecules on the surface of the mesoporous layer provide abundant active sites for HAase detection. An improved ionic current was realized after enzymatic hydrolysis reactions between HA and HAase due to enhanced surface charges and more hydrophilicity, leading to highly sensitive and accurate HAase detection. Notably, the detection performance can be further upgraded with the assistance of the photothermal property of γ-Fe2O3. An amplified detection current signal was achieved owing to a synergistic effect between ion currents and photoresponsive currents. A wide linear detection range from 1 to 50 U/mL and a low detection limit of 0.348 U/mL were obtained, achieving a 2% improvement under illumination. Importantly, the heterochannels have also been successfully applied for HAase detection in fetal bovine serum samples, manifesting considerable application prospects. This work provides a new strategy in constructing photoresponsive nanochannels with a photothermal property for a highly efficient biosensing platform.

Real-time monitoring of abnormal mitochondrial viscosity in glioblastoma with a novel mitochondria-targeting fluorescent probe.

Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood-brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness. In vitro experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally, in vitro 3D tumor spheres and in vivo orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.

Transcriptional landscape of intestinal environment in DSS-induced ulcerative colitis mouse model.

Ulcerative colitis (UC) is a chronic inflammatory disease that targets the colon and has seen an increasing prevalence worldwide. In our pursuit of new diagnostic and therapeutic approaches for UC, we undertook a sequencing of colons from UC mouse models. We focused on analyzing their differentially expressed genes (DEGs), enriching pathways, and constructing protein-protein interaction (PPI) and Competing Endogenous RNA (ceRNA) networks. Our analysis highlighted novel DEGs such as Tppp3, Saa3, Cemip, Pappa, and Nr1d1. These DEGs predominantly play roles in pathways like cytokine-mediated signaling, extracellular matrix organization, extracellular structure organization, and external encapsulating structure organization. This suggests that the UC pathogenesis is intricately linked to the interactions between immune and non-immune cells with the extracellular matrix (ECM). To corroborate our findings, we also verified certain DEGs through quantitative real-time PCR. Within the PPI network, nodes like Stat3, Il1b, Mmp3, and Lgals3 emerged as significant and were identified to be involved in the crucial cytokine-mediated signaling pathway, which is central to inflammation. Our ceRNA network analysis further brought to light the role of the Smad7 Long non-coding RNA (lncRNA). Key MicroRNA (miRNAs) in the ceRNA network were pinpointed as mmu-miR-17-5p, mmu-miR-93-5p, mmu-miR-20b-5p, mmu-miR-16-5p, and mmu-miR-106a-5p, while central mRNAs included Egln3, Plagl2, Sema7a, Arrdc3, and Stat3. These insights imply that ceRNA networks are influential in UC progression and could provide further clarity on its pathogenesis. In conclusion, this research deepens our understanding of UC pathogenesis and paves the way for potential new diagnostic and therapeutic methods. Nevertheless, to solidify our findings, additional experiments are essential to confirm the roles and molecular interplay of the identified DEGs in UC.

Sodium humate ameliorates LPS-induced liver injury in mice by inhibiting TLR4/NF-κB and activating NRF2/HO-1 signaling pathways.

BACKGROUND: Acute liver damage is a type of liver disease that has a significant global occurrence and a lack of successful treatment and prevention approaches. Sodium humate (HNa), a natural organic substance, has extensive applications in traditional Chinese medicine due to its antibacterial, anti-diarrheal, and anti-inflammatory characteristics. The purpose of this research was to examine the mitigating impacts of HNa on liver damage induced by lipopolysaccharide (LPS) in mice. METHODS AND RESULTS: A total of 30 female mice were randomly assigned into Con, Mod, L-HNa, M-HNa, and H-HNa groups. Mice in the Con and Mod groups were gavaged with PBS, whereas L-HNa, M-HNa, and H-HNa groups mice were gavaged with 0.1%, 0.3%, and 0.5% HNa, daily. On day 21, Mod, L-HNa, M-HNa, and H-HNa groups mice were challenged with LPS (10 mg/kg). We discovered that pretreatment with HNa improved liver pathological damage and inflammation by inhibiting the toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway, enhancing the polarization of liver M2 macrophages, and reducing the levels of inflammatory cytokines. Our further study found that pretreatment with HNa enhanced the liver ability to combat oxidative stress and reduced hepatocyte apoptosis by activating the nuclear factor erythroid-2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway and enhancing the activities of antioxidant enzymes. CONCLUSIONS: In conclusion, HNa could alleviate LPS-induced liver damage through inhibiting TLR4/NF-κB and activating NRF2/HO-1 signaling pathways. This study is the first to discover the therapeutic effects of HNa on liver damage induced by LPS.

Super-Assembled Multilayered Mesoporous TiO2 Nanorockets for Light-Powered Space-Confined Microfluidic Catalysis.

In the field of sustainable chemistry, it is still a significant challenge to realize efficient light-powered space-confined catalysis and propulsion due to the limited solar absorption efficiency and the low mass and heat transfer efficiency. Here, novel semiconductor TiO2 nanorockets with asymmetric, hollow, mesoporous, and double-layer structures are successfully constructed through a facile interfacial superassembly strategy. The high concentration of defects and unique topological features improve light scattering and reduce the distance for charge migration and directed charge separation, resulting in enhanced light harvesting in the confined nanospace and resulting in enhanced catalysis and self-propulsion. The movement velocity of double-layered nanorockets can reach up to 10.5 µm s-1 under visible light, which is approximately 57 and 119% higher than that of asymmetric single-layered TiO2 and isotropic hollow TiO2 nanospheres, respectively. In addition, the double-layered nanorockets improve the degradation rate of the common pollutant methylene blue under sustainable visible light with a 247% rise of first-order rate constant compared to isotropic hollow TiO2 nanospheres. Furthermore, FEA simulations reveal and confirm the double-layered confined-space enhanced catalysis and self-propulsion mechanism.