Shui Guan

Selenoprotein thioredoxin reductase 1 (TXNRD1) is frequently upregulated in various cancer cells to sustain cellular redox homeostasis, and its inhibition has emerged as a promising anti-cancer strategy. In this study, we identified PK11007, a thiol-modifying compound previously characterized as a p53 reactivator, as a potent inhibitor of TXNRD1. PK11007 irreversibly inhibited recombinant TXNRD1 in a time- and dose-dependent manner. Using differential scanning fluorimetry (DSF) and LC–MS/MS analysis, we confirmed that PK11007 covalently modifies the C-terminal redox motif (Cys497-Sec498) of TXNRD1. In non-small cell lung cancer (NSCLC) H1299 cells, PK11007-induced TXNRD1 inhibition disrupted cellular redox balance, leading to impaired autophagy flux and cell death. Similar autophagy suppression was observed in TXNRD1-knockdown cells, as well as pharmacological inhibition of TXNRD1 by Auranofin (AF) and TXNRD1 inhibitor 1 (TRi-1). Taken together, these findings highlight that oxidative stress contributes to the cytotoxic effects of PK11007 and uncover autophagy disorder as a downstream consequence of TXNRD1 inhibition.

The present study was devoted to the construction of a polysaccharide-based Schiff base composite hydrogel system for pyrroloquinoline quinone (PQQ) delivery. Carboxymethyl chitosan (CMCS), a water-soluble modification of chitosan, has demonstrated considerable potential in advancing innovative drug delivery methods, primarily due to its favorable physicochemical properties and biocompatibility. Oxidized xanthan gum (OXG) has been widely used in the field of biomaterials due to its good biocompatible properties. PQQ was grafted onto CMCS by covalent bonding in the EDC/NHS system to form PQQ-g-CMCS copolymer, which was subsequently crosslinked with OXG by dynamic Schiff base reaction to prepare a composite hydrogel with a dual network structure successfully. The grafting reaction of PQQ with CMCS and the formation of Schiff base bonds were verified by FT-IR, and the porous structure of the hydrogel was confirmed by SEM observation. By in vitro degradation, swelling tests, and rheological as well as mechanical property analysis, the PQQ-g-CMCS/OXG hydrogels exhibited certain biodegradability, rapid swelling properties, enhanced the network densification and long-term release effects. In addition, the cellular assay also proved that the hydrogel has no significant toxicity, providing a new idea for research in the field of biomedicine.

In clinical practice, traditional antioxidant drugs and therapies show limited efficacy against neurodegenerative diseases (NDs) induced by oxidative stress and excessive reactive oxygen species (ROS), underscoring the need for more effective treatments. In this work, we synthesized PCA-g-CMCS with vigorous antioxidant activity via an EDC/NHS-mediated system and confirmed that the graft retained the pH sensitivity of the precursor CMCS, enabling controllable dissolution across varying pH conditions. Subsequently, we prepared the Schiff’s base hydrogel PCA-g-CMCS/OXG by crosslinking PCA-g-CMCS with OXG at room temperature. The hydrogel significantly improved gel-forming performance, with mechanical/rheological properties matching nerve tissue and enhanced release behaviour, enabling prolonged and efficient drug delivery. Moreover, the hydrogel scaffold exhibited excellent biocompatibility and effectively protected nerve cells from H₂O₂-induced oxidative damage, highlighting its potential for neuroprotection. Thus, the PCA-g-CMCS/OXG hydrogel serves as a promising drug-loading platform, offering a potential therapeutic strategy for ROS-related NDs.

Hydrogel scaffolds incorporating conductive fillers have garnered significant interest due to their potential applications in neural tissue repair and regenerative medicine. However, most conductive fillers have adverse effects on the mechanical properties of hydrogel networks. In the present study, a novel polyacrylamide/alginate (PAAm/Alg) assembled with conductive silver nanowires (AgNWs) composite hydrogel was developed through photopolymerization and crosslinking methods. The chemical structure, morphology, mechanical properties, conductivity, porosity, swelling rate, adhesive strength, thermal stability, in vitro biodegradation, and biocompatibility of the prepared hydrogel samples were investigated. The PAAm/Alg‐AgNWs hydrogels exhibited uniform pore structure distribution, high porosity and water absorption, improved mechanical and conductive properties, good thermal stability, and adequate biodegradability. In particular, the 0.4 wt% AgNWs conductive hydrogel exhibited excellent conductivity of 0.618 S/m and a high Young's modulus of 43.6 kPa, along with good electrical durability and stability over ten cyclic loading. Moreover, the abundant hydrophilic groups in the hydrogel make it have good adhesion properties at different interfaces. Compared with the PAAm/Alg hydrogel, the incorporation of AgNWs enhanced the material's roughness, facilitating cell adhesion, viability, and proliferation. These results showed that the AgNWs assembled into the PAAm/Alg polymers endowed the hydrogel with high electrical conductivity, while excellent mechanical strength and biocompatibility, indicating an attractive conductive substrate for further studies on neural tissue repair and regeneration.

Overcoming the limitations of conventional antioxidants in treating oxidative stress-related neurodegenerative diseases (NDs) remains a critical challenge, thus more effective antioxidant strategies need to be studied urgently. To address this, we developed a novel pH-responsive drug-delivery hydrogel, PCA-g-CMCS/OXG, by grafting protocatechuic acid (PCA) onto carboxymethyl chitosan (CMCS) via amide bonds and blending it with oxidized xanthan gum (OXG) to form dynamic imine bonds. The conjugate PCA-g-CMCS achieved an unprecedented grafting efficiency of 785.3 mg g⁻¹ through optimized reactant ratios, pH, and reaction time. And the multifunctional hydrogel PCA-g-CMCS/OXG offers three key advantages: (1) rapid tunable gelation time (10–110 s) and robust mechanical/rheological properties enabling injectable and sprayable applications; (2) self-healing capability and sustained pH-responsive PCA release over 15 d, ensuring long-term therapeutic efficacy; and (3) superior cytoprotection, as the hydrogel exhibited excellent biocompatibility with SH-SY5Y neuronal cells and significantly increased cell viability to 76.60% from H₂O₂-induced oxidative damage (vs. 48.61% for control, p < 0.01). Therefore, the smart Schiff’s base hydrogel is a drug loaded material with great clinical application prospect for the treatment of NDs.

Cerebrospinal fluid (CSF) leakage caused by accidents or diseases resulting from traumatic brain injury, inflammation, tumor erosion and surgery can lead to many complications. In this study, a multifunctional composite double-layer hydrogel was designed by simulating the structure of native dura mater, which was composed of polyacrylic acid (PAA), polyethyleneimine (PEI), sodium alginate (SA), β-cyclodextrin (β-CD) and edaravone (Ed). The PAA/PEI layer had strong wet adhesion characteristics, while the PEI/SA@β-CD/Ed layer exhibited significant antioxidant, drug release and biocompatibility properties. By controlling the concentration of Ca²⁺, the gelation time can be adjusted rapidly within 95-215 s. Specifically, the final PAA/PEI/SA@β-CD/Ed composite hydrogel exhibited a porous network structure with high porosity and low swelling rate, improved tensile strength, sufficient biodegradability, favourable adhesion performance, enhanced DPPH and ABTS radicals scavenging abilities, and sustained Ed release capacity. In addition, the resulting hydrogel also showed excellent biocompatibility and protective effect on H₂O₂-induced oxidative damage in SH-SY5Y cells. These results preliminarily suggested that the PAA/PEI/SA@β-CD/Ed composite hydrogel would appear to be a promising candidate for dural repair.

Scholars have recently used various methods to study the human body’s characteristics, propose improvements, and rely on medical data. This research introduces a new real−time data collection and analysis system comprising two components: a smart mask for data collection and a processing unit for analysis and storage. The medical mask incorporates four sensors: three heat sensors to measure the nose tip and exhaled air temperature from the nostrils and mouth, along with a microphone for audio data. Collected data is instantly transmitted to the processing unit. Temperature readings are labeled and stored for analysis, while audio data is classified into breathing, coughing, and speaking categories using the Support Vector Machine (SVM) algorithm. The SVM’s performance is further optimized using the Lion Algorithm. Evaluation results indicate satisfactory accuracy for temperature data collected from the mask. The SVM achieved 84.3% accuracy for sound data classification, while the Lion algorithm−optimized SVM achieved an even higher accuracy of 93.6%. Future work aims to establish a reliable data collection tool that will serve as the foundation for developing an intelligent human body analysis model called the real human body neural network (rhBNN+).

Macrophages secrete a variety of pro-inflammatory cytokines in response to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) but abnormal release of cytokines unfortunately promotes cytokine storms. Dimethyl fumarate (DMF), an FDA-approved drug for multiple sclerosis (MS) treatment, has been found as an effective therapeutic agent for resolution. In this study, the anti-inflammatory effect of DMF was found to correlate to selenoprotein thioredoxin reductase 1 (TXNRD1). DMF irreversibly modified the Sec⁴⁹⁸ residue and C-terminal catalytic cysteine residues of TXNRD1 in a time- and dose-dependent manner. In LPS-stimulated RAW 264.7 cells, cellular TXNRD activity was increased through up-regulation of the protein level and DMF inhibited TXNRD activity and the nitric oxide (NO) production of RAW 264.7 cells. Meanwhile, the inhibition of TXNRD1 by DMF would contribute to the redox regulation of inflammation and promote the nuclear factor erythroid 2-related factor 2 (NRF2) activation. Notably, inhibition of cellular TXNRD1 by auranofin or TRi-1 showed anti-inflammatory effect in RAW 264.7 cells. This finding demonstrated that targeting TXNRD1 is a potential mechanism of using immunometabolites for dousing inflammation in response to pathogens and highlights the potential of TXNRD1 inhibitors in immune regulation.

Tissue engineering scaffolds provide biological and physiochemical cures to guide tissue recovery, and electrical signals through the electroactive materials possess tremendous potential to modulate the cell fate. In this study, a novel electroactive hydrogel scaffold was fabricated by assembling poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles on a carboxymethyl chitosan/gelatin (CMCS/Gel) composite hydrogel surface via in situ chemical polymerization. The chemical structure, morphology, conductivity, porosity, swelling rate, in vitro biodegradation, and mechanical properties of the prepared hydrogel samples were characterized. The adhesion, proliferation, and differentiation of neural stem cells (NSCs) on conductive hydrogels were investigated. The CMCS/Gel-PEDOT hydrogels exhibited high porosity, excellent water absorption, improved thermal stability, and adequate biodegradability. Importantly, the mechanical properties of the prepared hydrogels were similar to those of brain tissue, with electrical conductivity up to (1.52 ± 0.15) × 10⁻³ S/cm. Compared to the CMCS/Gel hydrogel, the incorporation of PEDOT nanoparticles significantly improved the adhesion of NSCs, and supported long-term cell growth and proliferation in a three-dimensional (3D) microenvironment. In addition, under the differentiation condition, the conductive hydrogel also significantly enhanced neuronal differentiation with the up-regulation of β-tubulin III expression. These results suggest that CMCS/Gel-PEDOT hydrogels may be an attractive conductive substrate for further studies on neural tissue repair and regeneration.