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Significal challenges exist to bacterial infection wound healing. The bacterial infection and inflammation generated by oxidative stress inevitably hinder the process of wound healing. Ag6Cu2 nanoclusters in this study were successfully prepared and displayed excellent physiological stability. Noticeably, Ag6Cu2 nanoclusters exhibited efficient therapeutic potentials for accelerating the process of wound healing, which had good biosafety under the appropriate concentration. The treatment of Ag6Cu2 was able to suppress the bacterial proliferation by destructing the bacterial, resulting in the secondary release of bacterial contents and to exert anti-inflammatory properties via scavenging the overproduction of reactive oxygen species and upregulating the expression of Nrf2 as well as its downstream genes including HO-1 and NQO1. In-vivo studies further validated the efficient therapeutic effects of Ag6Cu2 nanoclusters by inhibiting the activation of the cascade of inflammatory factors and the proliferation of bacteria as a novel agent in a nano scale for accelerating the process of wound healing.

Abstract Chemoresistance is the main obstacle in osteosarcoma (OS) treatment; however, the underlying mechanism remains unclear. In this study, it is discovered that DDRGK domain‐containing protein 1 (DDRGK1) plays a fundamental role in chemoresistance induced in OS. Bioinformatic and tissue analyses indicate that higher expression of DDRGK1 correlates with advanced tumor stage and poor clinical prognosis of OS. Quantitative proteomic analyses suggest that DDRGK1 plays a critical role in mitochondrial oxidative phosphorylation. DDRGK1 knockout trigger the accumulation of reactive oxygen species (ROS) and attenuate the stability of nuclear factor erythroid‐2‐related factor 2 (NRF2), a major antioxidant response element. Furthermore, DDRGK1 inhibits ubiquitin‐proteasome‐mediated degradation of NRF2 via competitive binding to the Kelch‐like ECH‐associated protein 1 (KEAP1) protein, which recruits NRF2 to CULLIN(CUL3). DDRGK1 knockout attenuates NRF2 stability, contributing to ROS accumulation, which promotes apoptosis and enhanced chemosensitivity to doxorubicin (DOX) and etoposide in cancer cells. Indeed, DDRGK1 knockout significantly enhances osteosarcoma chemosensitivity to DOX in vivo. The combination of DDRGK1 knockdown and DOX treatment provides a promising new avenue for the effective treatment of OS.

Apoptosis and extracellular matrix degradation of the nucleus pulposus are the main initiators of intervertebral disc degeneration (IVDD) and can be explained by endoplasmic reticulum (ER) stress. Thus, pharmacological therapy aimed at suppressing this pathway may be a promising approach for the management of intervertebral disc degeneration. In this study, we aimed to explore the protective effects of Sal003 against intervertebral disc degeneration and its underlying mechanisms. Thapsigargin (Tg)-stimulated rat nucleus pulposus cells and a needle puncture-induced intervertebral disc degeneration rat model were used to explore the protective effects of Sal003. Our results showed that Sal003 inhibited apoptosis and extracellular matrix degradation by suppressing the endoplasmic reticulum stress pathway. The therapeutic effects of Sal003 were also observed in the intervertebral disc degeneration rat model, as evidenced by improved degeneration along with decreased apoptosis and extracellular matrix degradation in intervertebral discs. Our results demonstrated Sal003 as a potential treatment for intervertebral disc degeneration.

Low back pain (LBP) caused by intervertebral disc degeneration (IVDD) is accredited to the release of inflammatory cytokines followed by biomechanical and structural deterioration. In our study, we used a plant-derived medicine, curcumenol, to treat IVDD. A cell viability test was carried out to evaluate the possibility of using curcumenol. RNA-seq was used to determine relative pathways involved with curcumenol addition. Using TNFα as a trigger of inflammation, the activation of the NF-κB signaling pathway and expression of the MMP family were determined by qPCR and western blotting. Nucleus pulposus (NP) cells and the rats’ primary NP cells were cultured. The catabolism status was evaluated by an ex vivo model. A lumbar instability mouse model was carried out to show the effects of curcumenol in vivo. In general, RNA-seq revealed that multiple signaling pathways changed with curcumenol addition, especially the TNFα/NF-κB pathway. So, the NP cells and primary NP cells were induced to suffer inflammation with the activated TNFα/NF-κB signaling pathway and increased expression of the MMP family, such as MMP3, MMP9, and MMP13, which would be mitigated by curcumenol. Owing to the protective effects of curcumenol, the height loss and osteophyte formation of the disc could be prevented in the lumbar instability mouse model in vivo.

The welding heat affected zone (HAZ) is a high-risk region of corrosion, and influenced by multi-factors, such as stress, microbe and microstructure. Sulfate reducing bacteria (SRB) enhance the corrosion of the stressed HAZs, especially coarse-grained HAZ (CGHAZ). CGHAZ has least percentage of HAGBs, largest effective grain size, and highest volume fraction of MA island, which leads to the severer corrosion. SRB accelerate the localized corrosion of steel HAZs, and the maximum pitting depths of CGHAZ with and without SRB reach 9.97 and 7.65 μm, respectively. The elastic stress lowers the equilibrium potential and weakens the protective ability of film, which boosts the corrosion process, while SRB further enhance this accelerating effect of the stress on the corrosion.

Objective: MicroRNA-141-3p (miR-141-3p) has been investigated in various kinds of cancers. This research delves into the functions and regulatory mechanisms of miR-141-3p in necrotizing enterocolitis (NEC) of neonates.Methods: NEC tissues were obtained from neonatal mice, and subsequently, expression of miR-141-3p and motor neuron and pancreas homeobox 1 (MNX1) was assayed via RT-qPCR. Moreover, the intestinal histopathological changes and histiocytic apoptosis were observed via hematoxylin and eosin (H&E) and TUNEL staining. The correlative inflammatory factors and oxidative stress markers were evaluated to uncover the influence of miR-141-3p in NEC tissue damage. Further, the relation between MNX1 and miR-141-3p was predicated, and the functions of MNX1 in inflammatory response and cell growth of IEC-6 cells were investigated.Results: Downregulated miR-141-3p and upregulated MNX1 were discovered in NEC tissues. Moreover, miR-141-3p clearly alleviated inflammation response and oxidative stress damage in NEC, which was achieved through regulating inflammatory cytokines (IL-1β, IL-6, and TNF-α) and oxidative stress markers (MPO, MDA, and SOD) expression. MNX1 was forecasted as a target gene of miR-141-3p; meanwhile, MNX1 overexpression overturned the influence of miR-141-3p in the inflammatory response and cell growth process of IEC-6 cells.Conclusion: These explorations reveal that increased expression of miR-141-3p could improve the damage to intestinal tissues in NEC through targeting MNX1. The research might exhibit a neoteric therapeutic strategy for NEC.