Diabetic wound infections, exacerbated by multidrug-resistant pathogens like MRSA, remain a critical challenge due to biofilm persistence and dysregulated oxidative-inflammatory-metabolic crosstalk. In this work, we engineered COG-Z@P200 hydrogel, a chitosan-based hydrogel integrating polydopamine-coated ZIF-8 nanoparticles, to synergize mild photothermal therapy (40–45 °C) with metabolic-immune reprogramming. Upon NIR irradiation, COG-Z@P200 disrupted MRSA through Zn2⁺-mediated membrane destabilization and localized hyperthermia, achieving >99.5% eradication via combined physical puncture and metabolic interference. Multi-omics analyses revealed suppression of glycolysis (eno, gap downregulation), TCA cycle arrested (sucC, sdhA, icd inhibition), and disruption of arginine biosynthesis (arcA, arcC, arcD downregulation), impairing biofilm formation and pathogenicity. Concurrent silencing of quorum sensing and virulence genes (agr, sec, lac, opp, sdrD) further destabilized MRSA, while upregulation of stress-response genes (yidD, nfsA, kdpA) indicated bacterial metabolic paralysis. In diabetic murine models, the hydrogel attenuated oxidative stress (DHE-confirmed ROS reduction), polarized macrophages to pro-healing M2 phenotypes (Arg-1⁺/TNF-α↓), and enhanced angiogenesis (VEGF/CD31↑) alongside aligned collagen deposition. This multifunctional action accelerated wound closure by 48% versus controls, outperforming clinical standards. By converging nanomaterial-enabled bactericidal strategies with host microenvironment recalibration, COG-Z@P200 hydrogel redefined diabetic wound management, offering an antibiotic-free solution against multidrug-resistant infections. Our work established a biomaterial paradigm that concurrently targets pathogen vulnerabilities and restores tissue homeostasis, addressing the multidimensional complexity of chronic wounds.

Background: Combined chemotherapy is often affected by the different physicochemical properties of chemotherapeutic drugs, which should be improved by the reasonable design of co-loaded preparations. Purpose: A kind of simple but practical graphene oxide (GO) wrapped mesoporous silica nanoparticles (MSN) modified with hyaluronic acid (MSN@GO-HA) were developed for the co-delivery of cinnamaldehyde (CA) and doxorubicin (DOX), in order to enhance their combined treatment on tumor cells and reduce their application defects. Methods: The MSN_CA@GO_DOX-HA was constructed by MSN_CA (loading CA via physical diffusion) and GO_DOX-HA (modified with HA and loading DOX via π–π stacking) through the electrostatic adsorption, followed by the physicochemical characterization, serum stability and in vitro release study. Cytotoxicity on different cells was detected, followed by the tumor cell uptake tests. The intracellular reactive oxygen species (ROS) changes, mitochondrial functions and activities of caspase-3/-9 in MCF-7 cells were also evaluated, respectively. Results: The MSN_CA@GO_DOX-HA nanoparticles kept stable in FBS solution and achieved pH-responsive release behavior, which was beneficial to increase the accumulation of CA and DOX in tumor cells to enhance the treatment. MSN_CA@GO_DOX-HA exerted higher cytotoxicity to MCF-7 human breast cancer cells than H9c2 cardiac myocyte cells, which were not only attributed to the active targeting to tumor cells by HA, but also related with the activation of intrinsic apoptotic pathway in MCF-7 cells induced by CA, which was mediated by the specific ROS signal amplification and the interference with mitochondrial function. Moreover, the efficacy of DOX was also enhanced by the above process. Conclusion: The establishment of the MSN_CA@GO_DOX-HA nanoparticles played a role in promoting strengths and restricting shortcomings of CA and DOX, thereby exerting their function and achieving efficient treatment against cancer.

Purpose: The levels of reactive oxygen species (ROS) in tumor cells are much higher than that in normal cells, and rise rapidly under the influence of exogenous or endogenous inducing factors, eventually leading to the apoptosis of tumor cells. Therefore, this study prepared a dual pH/reducing-responsive poly (N-isopropylacrylamide-co-Cinnamaldehyde-co-D-α-tocopheryl polyethylene glycol 1000 succinate, P_ssNCT) nanogels, which employed two exogenous ROS inducers, cinnamaldehyde (CA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), to selectively induce apoptosis by regulating ROS levels in tumor cells. Methods: The P_ssNCT nanogels were prepared by the free radical precipitation polymerization under the crosslink between pH-sensitive hydrazone and reducing-sensitive disulfide bonds, followed by the physicochemical and morphological characteristics investigations. Plasma stability, dual pH/reducing responsive degradation and in vitro release were also assessed. In cell experiments, cytotoxicity in different cells were first detected. The intracellular ROS levels and mitochondrial functions of tumor cells were then evaluated. Moreover, the apoptosis and western-blot assays were employed to verify the association between ROS levels elevation and apoptosis in tumor cells. Results: The nanogels exhibited a round-like hollow structure with the diameter smaller than 200nm. The nanogels were stable in plasma, while showed rapid degradation in acidic and reducing environments, thus achieving significant release of CA and TPGS in these media. Furthermore, the sufficient amplification of ROS signals was induced by the synergistically function of CA and TPGS on mitochondria, which resulted in the opening of the mitochondrial apoptotic pathway and enhanced cytotoxicity on MCF-7 cells. However, nanogels barely affected L929 cells owing to their lower intracellular ROS basal levels. Conclusion: The specific ROS regulation method achieved by these nanogels could be explored to selectively kill tumor cells according to the difference of ROS signals in different kinds of cells.

Hypoxia is a major stressor and a prominent feature of pathological conditions, such as bacterial infections, inflammation, wounds, and cardiovascular defects. In this study, we investigated whether reoxygenation has a protective effect against hypoxia-induced acute injury and burn using the C57BL/6 mouse model. C57BL/6 mice were exposed to hypoxia and treated with both acute and burn injuries and were in hypoxia until wound healing. Next, C57BL/6 mice were exposed to hypoxia for three days and then transferred to normoxic conditions for reoxygenation until wound healing. Finally, skin wound tissue was collected to analyze healing-related markers, such as inflammation, vascularization, and collagen. Hypoxia significantly increased inflammatory cell infiltration and decreased vascular and collagen production, and reoxygenation notably attenuated hypoxia-induced infiltration of inflammatory cells, upregulation of pro-inflammatory cytokine levels (IL-6 and TNF-α) in the wound, and remission of inflammation in the wound. Immunofluorescence analysis showed that reoxygenation increased the expression of the angiogenic factor α-SMA and decreased ROS expression in burn tissues compared to hypoxia-treated animals. Moreover, further analysis by qPCR showed that reoxygenation could alleviate the expression of hypoxic-induced inflammatory markers (IL-6 and TNF), increase angiogenesis (SMA) and collagen synthesis (Col I), and thus promote wound healing. It is suggested that oxygen can be further evaluated in combination with oxygen-releasing materials as a supplementary therapy for patients with chronic hypoxic wounds.

Motor capability recovery after ischemic stroke involves dynamic remodeling processes of neural connectomes in the nervous system. Various neuromodulatory strategies combining direct stimulating interventions with behavioral trainings for motor recovery after ischemic stroke have been developed. However, the effectiveness of these interventions varies widely due to unspecific activation or inhibition of undefined neuronal subtypes. Optogenetics is a functional and structural connection-based approach that can selectively activate or inhibit specific subtype neurons with a higher precision, and it has been widely applied to build up neuronal plasticities of the nervous system, which shows a great potential in restoring motor functions in stroke animal models. Here, we reviewed neurobiological mechanisms of enhanced brain plasticities underlying motor recovery through the optogenetic stimulation after ischemic stroke. Several brain sites and neural circuits that have been previously proven effective for motor function rehabilitation were identified, which would be helpful for a more schematic understanding of effective neuronal connectomes in the motor function recovery after ischemic stroke.

To explore novel antitumor agents with high efficiency and low toxicity, riluzole alkyl derivatives (4a-4i) were synthesized. Their anti-proliferative activities against HeLa, HepG2, SP2/0, and MCF-7 cancer cell lines were assessed by the CCK-8 assay and compared with human normal liver (LO2) cells. Most of them showed potent cytotoxic effects against four human tumor cell lines and low toxic to LO2 cells. In particular, 2-(N-ethylamine)-6-trifluoromethoxy- benzothiazole (4a) showed a IC₅₀ value of 7.76 μmol/L in HeLa cells and was found to be nontoxic to LO2 cells up to 65 μmol/L. Furthermore, flow cytometry indicated that 4a could induce remarkable early apoptosis and G2/M cell cycle arrest in HeLa cells. It also impaired the migration ability of HeLa cells in wound healing assays. Western blot results demonstrated that 4a suppressed Bcl-2 protein expression but increased the level of Bax in HeLa cells, and elevated the Bax/Bcl-2 expression ratio. These new findings suggest that 4a exhibited beneficially anti-cervical cancer effect on HeLa cells by inducing HeLa cell apoptosis.