Developing engineered muscle tissues utilizing standard cell culture plates and mesenchymal stem cell-conditioned medium.

The construction of engineered muscle tissues that resemble the function and microstructure of human muscles holds significant promise for various applications, including disease modeling, regenerative medicine, and biological machines. However, current muscle tissue engineering approaches often rely on complex equipment which may limit their accessibility and practicality. Herein, we present a convenient approach using a standard 24-well cell culture plate to construct a platform to facilitate engineered muscle tissues formation and culture. Using this platform, engineered muscle tissue with differentiation characteristics can be manufactured in large quantities. Additionally, the mesenchymal stem cell conditioned medium was utilized to promote the formation and functionality of the engineered muscle tissues. The resulting tissues comprised a higher cell density and a better differentiation effect in the tissues. Taken together, this study provides a simple, convenient, and effective platform for studying muscle tissue engineering.

Construction of a 12-Gene Prognostic Risk Model and Tumor Immune Microenvironment Analysis Based on the Clear Cell Renal Cell Carcinoma Model.

OBJECTIVES: Accurate survival predictions and early interventional therapy are crucial for people with clear cell renal cell carcinoma (ccRCC). METHODS: In this retrospective study, we identified differentially expressed immune-related (DE-IRGs) and oncogenic (DE-OGs) genes from The Cancer Genome Atlas (TCGA) dataset to construct a prognostic risk model using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. We compared the immunogenomic characterization between the high- and low-risk patients in the TCGA and the PUCH cohort, including the immune cell infiltration level, immune score, immune checkpoint, and T-effector cell- and interferon (IFN)-γ-related gene expression. RESULTS: A prognostic risk model was constructed based on 9 DE-IRGs and 3 DE-OGs and validated in the training and testing TCGA datasets. The high-risk group exhibited significantly poor overall survival compared with the low-risk group in the training (P < 0.0001), testing (P = 0.016), and total (P < 0.0001) datasets. The prognostic risk model provided accurate predictive value for ccRCC prognosis in all datasets. Decision curve analysis revealed that the nomogram showed the best net benefit for the 1-, 3-, and 5-year risk predictions. Immunogenomic analyses of the TCGA and PUCH cohorts showed higher immune cell infiltration levels, immune scores, immune checkpoint, and T-effector cell- and IFN-γ-related cytotoxic gene expression in the high-risk group than in the low-risk group. CONCLUSION: The 12-gene prognostic risk model can reliably predict overall survival outcomes and is strongly associated with the tumor immune microenvironment of ccRCC.

De novo construction of amine-functionalized metal-organic cages as heterogenous catalysts for microflow catalysis.

Microflow catalysis is a cutting-edge approach to advancing chemical synthesis and manufacturing, but the challenge lies in developing efficient and stable multiphase catalysts. Here we showcase incorporating amine-containing metal-organic cages into automated microfluidic reactors through covalent bonds, enabling highly continuous flow catalysis. Two Fe4L4 tetrahedral cages bearing four uncoordinated amines were designed and synthesized. Post-synthetic modifications of the amine groups with 3-isocyanatopropyltriethoxysilane, introducing silane chains immobilized on the inner walls of the microfluidic reactor. The immobilized cages prove highly efficient for the reaction of anthranilamide with aldehydes, showing superior reactivity and recyclability relative to free cages. This superiority arises from the large cavity, facilitating substrate accommodation and conversion, a high mass transfer rate and stable covalent bonds between cage and microreactor. This study exemplifies the synergy of cages with microreactor technology, highlighting the benefits of heterogenous cages and the potential for future automated synthesis processes.

Advanced biomedical and electronic dual-function skin patch created through microfluidic-regulated 3D bioprinting.

Artificial skin involves multidisciplinary efforts, including materials science, biology, medicine, and tissue engineering. Recent studies have aimed at creating skins that are multifunctional, intelligent, and capable of regenerating tissue. In this work, we present a specialized 3D printing ink composed of polyurethane and bioactive glass (PU-BG) and prepare dual-function skin patch by microfluidic-regulated 3D bioprinting (MRBP) technique. The MRBP endows the skin patch with a highly controlled microstructure and superior strength. Besides, an asymmetric tri-layer is further constructed, which promotes cell attachment and growth through a dual transport mechanism based on hydrogen bonds and gradient structure from hydrophilic to superhydrophilic. More importantly, by combining the features of biomedical skin with electronic skin (e-skin), we achieved a biomedical and electronic dual-function skin patch. In vivo experiments have shown that this skin patch can enhance hemostasis, resist bacterial growth, stimulate the regeneration of blood vessels, and accelerate the healing process. Meanwhile, it also mimics the sensory functions of natural skin to realize signal detection, where the sensitivity reached up to 5.87 kPa-1, as well as cyclic stability (over 500 cycles), a wide detection range of 0-150 kPa, high pressure resolution of 0.1 % under the pressure of 100 kPa. This work offers a versatile and effective method for creating dual-function skin patches and provide new insights into wound healing and tissue repair, which have significant implications for clinical applications.

Prognostic and clinicopathological significance of systemic immune-inflammation index in upper tract urothelial carcinoma: a meta-analysis of 3911 patients.

Background: Systemic immune-inflammation index (SII), a novel prognostic indicator, is being more commonly utilized in different types of cancer. This research project involved combining information from previously published studies to examine how pre-treatment SII can predict outcomes in individuals with upper tract urothelial carcinoma (UTUC). Further examination of the correlation between SII and clinical and pathological features in UTUC. Methods: We thoroughly chose pertinent articles from various databases including PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), WanFang database, and Chinese Scientific Journal Database (VIP) until March 10, 2022.The data collected was analyzed using Stata 17.0 software (Stat Corp, College Station, TX). Subsequently, the impact of SII on the survival outcomes of UTUC patients was evaluated by combining HRs with 95% confidence intervals. Results: Six included studies were finally confirmed, including 3911 UTUC patients in seven cohorts. The results showed that high SII before treatment predicted poor overall survival (HR =1.87, 95%CI 1.20-2.92, p=0.005), cancer specific survival (HR=2.70, 95%CI 1.47-4.96, P=0.001), and recurrence-free survival (HR =1.52, 95%CI 1.12-2.07, P=0.007). And the elevated SII may be related to LVI (present vs. absent) (OR=0.83, 95% CI=0.71-0.97, p=0.018), pT stage (pT ≥3 vs. < 3) (OR=1.82, 95% CI=1.21-2.72, p=0.004), and pN stage (N+ vs. N0) (OR=3.27, 95% CI=1.60-6.71, p=0.001). Conclusion: A comprehensive analysis of all included articles in this study showed that higher pretreatment SII was related to poorer survival outcomes and adverse pathological features independently. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022316333.

Hypervalent Iodine Promoted Selective [2 + 2 + 1] Cycloaddition of Aromatic Ketones and Methylamines: A One-Pot Access to 1-Pyrrolines.

Herein, a versatile highly regioselective three-component annulation of simple aromatic ketones and methylamines using a hypervalent iodine reagent for polyarylated 1-pyrrolines has been described in good to excellent yields. Meanwhile, unsymmetrical 1-pyrroline isomers could be realized and synthesized. Such an intriguing one-pot two-step tandem assembly strategy with green conditions and high regioselectivity shows predictable inspiration in related annulation reactions.

Organophotocatalytic access to C-glycosides: multicomponent coupling reactions using glycosyl bromides.

Photochemical multi-component coupling reactions initiated by the activation of glycosyl bromides in the presence of 1,4-bis(diphenylamino)benzene (BDB) as an organic photocatalyst were developed. C-glycosides accompanied by olefin (di)functionalization were obtained. This method allows us to access various C-glycosides with alkene, carbonyl, alcohol, ether, and amide functionalities.

Transforming Cell-Drug Interaction through Granular Hydrogel-Mediated Delivery of Polyplex Nanoparticles for Enhanced Safety and Extended Efficacy in Gene Therapy.

The utilization of hydrogels for DNA/cationic polymer polyplex nanoparticle (polyplex) delivery has significantly advanced gene therapy in tissue regeneration and cancer treatment. However, persistent challenges related to the efficacy and safety of encapsulated polyplexes, stemming from issues such as aggregation, degradation, or difficulties in controlled release during or postintegration with hydrogel scaffolds, necessitate further exploration. Here, we introduce an injectable gene therapy gel achieved by incorporating concentrated polyplexes onto densely packed hydrogel microparticles (HMPs). Polyplexes, when uniformly adhered to the gene therapy gel through reversible electrostatic interactions, can detach from the HMP surface in a controlled manner, contrasting with free polyplexes, and thereby reducing dose-dependent toxicity during transfection. Additionally, the integration of RGD cell adhesion peptides enhances the scaffolding characteristics of the gel, facilitating cell adhesion, migration, and further minimizing toxicity during gene drug administration. Notably, despite the overall transfection efficiency showing average performance, utilizing confocal microscopy to meticulously observe and analyze the cellular states infiltrating into various depths of the gene therapy gel resulted in the groundbreaking discovery of significantly enhanced local transfection efficiency, with primary cell transfection approaching 80%. This phenomenon could be potentially attributed to the granular hydrogel-mediated delivery of polyplex nanoparticles, which revolutionizes the spatial and temporal distribution and thus the "encounter" mode between polyplexes and cells. Moreover, the gene therapy gel's intrinsic injectability and self-healing properties offer ease of administration, making it a highly promising candidate as a novel gene transfection gel dressing with significant potential across various fields, including regenerative medicine and innovative living materials.

TMEM52B Isoforms P18 and P20 Differentially Promote the Oncogenesis and Metastasis of Nasopharyngeal Carcinoma.

Transmembrane protein 52B (TMEM52B), a newly identified tumor-related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B-P18 and TMEM52B-P20, differing in their N-terminals. While both isoforms exhibit similar pro-oncogenic roles and contribute to drug resistance in NPC, TMEM52B-P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B-P18 is confined to the cytoplasm, while TMEM52B-P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane-localized TMEM52B-P20 promotes E-cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B-P18 and TMEM52B-P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis.

Advancing Engineered Plant Living Materials through Tobacco BY-2 Cell Growth and Transfection within Tailored Granular Hydrogel Scaffolds.

In this study, an innovative approach is presented in the field of engineered plant living materials (EPLMs), leveraging a sophisticated interplay between synthetic biology and engineering. We detail a 3D bioprinting technique for the precise spatial patterning and genetic transformation of the tobacco BY-2 cell line within custom-engineered granular hydrogel scaffolds. Our methodology involves the integration of biocompatible hydrogel microparticles (HMPs) primed for 3D bioprinting with Agrobacterium tumefaciens capable of plant cell transfection, serving as the backbone for the simultaneous growth and transformation of tobacco BY-2 cells. This system facilitates the concurrent growth and genetic modification of tobacco BY-2 cells within our specially designed scaffolds. These scaffolds enable the cells to develop into predefined patterns while remaining conducive to the uptake of exogenous DNA. We showcase the versatility of this technology by fabricating EPLMs with unique structural and functional properties, exemplified by EPLMs exhibiting distinct pigmentation patterns. These patterns are achieved through the integration of the betalain biosynthetic pathway into tobacco BY-2 cells. Overall, our study represents a groundbreaking shift in the convergence of materials science and plant synthetic biology, offering promising avenues for the evolution of sustainable, adaptive, and responsive living material systems.

Governance effects of pollution reduction and carbon mitigation of carbon emission trading policy in China.

China's carbon emission trading policy plays a crucial role in achieving both its "3060" dual carbon objectives and the United Nations Sustainable Development Goal 13 (SDG 13) on climate action. The policy's effectiveness in reducing pollution and mitigating carbon emissions holds significant importance. This paper investigated whether China's carbon emission trading policy affects pollution reduction (PM2.5 and SO2) and carbon mitigation (CO2) in pilot regions, using panel data from 30 provinces and municipalities in China from 2005 to 2019 and employing a multi-period difference-in-differences (DID) model. Furthermore, it analyzed the heterogeneity of carbon market mechanisms and regional variations. Finally, it examined the governance pathways for pollution reduction and carbon mitigation from a holistic perspective. The results indicate that: (1) China's carbon emission trading policy has reduced CO2 emissions by 18% and SO2 emissions by 36% in pilot areas, with an immediate impact on the "carbon mitigation" effect, while the "pollution reduction" effect exhibits a time lag. (2) Higher carbon trading prices lead to stronger "carbon mitigation" effect, and larger carbon market scales are associated with greater "pollution reduction" effects on PM2.5. Governance effects on pollution reduction and carbon mitigation vary among pilot regions: Carbon markets of Beijing, Chongqing, Shanghai, and Tianjin show significant governance effects in both "pollution reduction" and "carbon mitigation", whereas Guangdong's carbon market exhibits only a "pollution reduction" effect, and Hubei's carbon market demonstrates only a "carbon mitigation" effect. (3) Currently, China's carbon emission trading policy achieves pollution reduction and carbon mitigation through "process management" and "end-of-pipe treatment". This study could provide empirical insights and policy implications for pollution reduction and carbon mitigation, as well as for the development of China's carbon emission trading market.

Hydrodynamics-Controlled Single-Particle Electrocatalysis.

Electrocatalysis is considered promising in renewable energy conversion and storage, yet numerous efforts rely on catalyst design to advance catalytic activity. Herein, a hydrodynamic single-particle electrocatalysis methodology is developed by integrating collision electrochemistry and microfluidics to improve the activity of an electrocatalysis system. As a proof-of-concept, hydrogen evolution reaction (HER) is electrocatalyzed by individual palladium nanoparticles (Pd NPs), with the development of microchannel-based ultramicroelectrodes. The controlled laminar flow enables the precise delivery of Pd NPs to the electrode-electrolyte interface one by one. Compared to the diffusion condition, hydrodynamic collision improves the number of active sites on a given electrode by 2 orders of magnitude. Furthermore, forced convection enables the enhancement of proton mass transport, thereby increasing the electrocatalytic activity of each single Pd NP. It turns out that the improvement in mass transport increases the reaction rate of HER at individual Pd NPs, thus a phase transition without requiring a high overpotential. This study provides new avenues for enhancing electrocatalytic activity by altering operating conditions, beyond material design limitations.

Room-temperature stabilizing strongly competing ferrielectric and antiferroelectric phases in PbZrO3 by strain-mediated phase separation.

PbZrO3 has been broadly considered as a prototypical antiferroelectric material for high-power energy storage. A recent theoretical study suggests that the ground state of PbZrO3 is threefold-modulated ferrielectric, which challenges the generally accepted antiferroelectric configuration. However, such a novel ferrielectric phase was predicted only to be accessible at low temperatures. Here, we successfully achieve the room-temperature construction of the strongly competing ferrielectric and antiferroelectric state by strain-mediated phase separation in PbZrO3/SrTiO3 thin film. We demonstrate that the phase separation occurs spontaneously in quasi-periodic stripe-like patterns under a compressive misfit strain and can be tailored by varying the film thickness. The ferrielectric phase strikingly exhibitsa threefold modulation period with a nearly up-up-down configuration, which could be stabilized and manipulated by the formation and evolution of interfacial defects under applied strain. The present results construct a fertile ground for further exploring the physical properties and applications based on the novel ferrielectric phase.

Activation of CGRP receptor-mediated signaling promotes tendon-bone healing.

Calcitonin gene-related peptide (CGRP), an osteopromotive neurotransmitter with a short half-life, shows increase while calcitonin receptor-like (CALCRL) level is decreased at the early stage in bone fractures. Therefore, the activation of CALCRL-mediated signaling may be more critical to promote the tendon-bone healing. We found CGRP enhanced osteogenic differentiation of BMSCs through PKA/CREB/JUNB pathway, contributing to improved sonic hedgehog (SHH) expression, which was verified at the tendon-bone interface (TBI) in the mice with Calcrl overexpression. The osteoblast-derived SHH and slit guidance ligand 3 were reported to favor nerve regeneration and type H (CD31hiEMCNhi) vessel formation, respectively. Encouragingly, the activation or inactivation of CALCRL-mediated signaling significantly increased or decreased intensity of type H vessel and nerve fiber at the TBI, respectively. Simultaneously, improved gait characteristics and biomechanical performance were observed in the Calcrl overexpression group. Together, the gene therapy targeting CGRP receptor may be a therapeutic strategy in sports medicine.

ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner.

BACKGROUND: Circular RNAs are highly stable regulatory RNAs that have been increasingly associated with tumorigenesis and progression. However, the role of many circRNAs in triple-negative breast cancer (TNBC) and the related mechanisms have not been elucidated. METHODS: In this study, we screened circRNAs with significant expression differences in the RNA sequencing datasets of TNBC and normal breast tissues and then detected the expression level of circRPPH1 by qRT‒PCR. The biological role of circRPPH1 in TNBC was then verified by in vivo and in vitro experiments. Mechanistically, we verified the regulatory effects between circRPPH1 and ZNF460 and between circRPPH1 and miR-326 by chromatin immunoprecipitation (ChIP), fluorescence in situ hybridization assay, dual luciferase reporter gene assay and RNA pull-down assay. In addition, to determine the expression of associated proteins, we performed immunohistochemistry, immunofluorescence, and western blotting. RESULTS: The upregulation of circRPPH1 in TNBC was positively linked with a poor prognosis. Additionally, both in vivo and in vitro, circRPPH1 promoted the biologically malignant behavior of TNBC cells. Additionally, circRPPH1 may function as a molecular sponge for miR-326 to control integrin subunit alpha 5 (ITGA5) expression and activate the focal adhesion kinase (FAK)/PI3K/AKT pathway. CONCLUSION: Our research showed that ZNF460 could promote circRPPH1 expression and that the circRPPH1/miR-326/ITGA5 axis could activate the FAK/PI3K/AKT pathway to promote the progression of TNBC. Therefore, circRPPH1 can be used as a therapeutic or diagnostic target for TNBC.

Locally delivered hydrogels with controlled release of nanoscale exosomes promote cardiac repair after myocardial infarction.

Compared with stem cells, exosomes as a kind of nanoscale carriers intrinsically loaded with diverse bioactive molecules, which had the advantages of high safety, small size, and ethical considerations in the treatment of myocardial infarction, but there are still problems such as impaired stability and rapid dissipation. Here, we introduce a bioengineered injectable hyaluronic acid hydrogel designed to optimize local delivery efficiency of trophoblast stem cells derived-exosomes. Its hyaluronan components adeptly emulates the composition and modulus of pericardial fluid, meanwhile preserving the bioactivity of nanoscale exosomes. Additionally, a meticulously designed hyperbranched polymeric cross-linker facilitates a gentle cross-linking process among hyaluronic acid molecules, with disulfide bonds in its molecular framework enhancing biodegradability and conferring a unique controlled release capability. This innovative hydrogel offers the added advantage of minimal invasiveness during administration into the pericardial space, greatly extending the retention of exosomes within the myocardial region. In vivo, this hydrogel has consistently demonstrated its efficacy in promoting cardiac recovery, inducing anti-fibrotic, anti-inflammatory, angiogenic, and anti-remodeling effects, ultimately leading to a substantial improvement in cardiac function. Furthermore, the implementation of single-cell RNA sequencing has elucidated that the pivotal mechanism underlying enhanced cardiac function primarily results from the promoted clearance of apoptotic cells by myocardial fibroblasts.

Hierarchical Label Distribution Learning for Disease Prediction.

The prediction of disease can facilitate early intervention, comprehensive diagnosis and treatment, thereby benefiting healthcare and reducing medical costs. While single class and multi-class learning methods have been applied for disease prediction, they are inadequate in distinguishing between primary and secondary diagnoses, which is crucial for treatments. In this paper, label distribution is suggested to describe the diagnosis, which assigns the description degree to quantify the diagnosis. Additionally, a novel hierarchical label distribution learning (HLDL) model is proposed to make fine-grained predictions based on the hierarchical classification of diseases, taking into account the relationship among diseases. The experimental results on real-world datasets demonstrate that the HLDL model outperforms the baselines with statistical significance.

Combination of hyperthermia and intravesical chemotherapy for the treatment of pT1 stage bladder cancer: A retrospectively clinical study.

PURPOSE: To evaluate the efficiency and safety of combined local bladder hyperthermia and intravesical chemotherapy (IVC) for the treatment of patients with pT1 stage bladder cancer. METHOD: A total of 189 patients with pT1 who underwent transurethral resection of bladder cancer (TURBT) were retrospectively reviewed. After TURBT, the patients with low-grade urothelial carcinoma (UC) were treated with either an IVC with pirarubicin (THP) protocol or chemo-thermotherapy (CHT) with THP protocol, whereas patients with high-grade UC were treated with either an intravesical immunotherapy (IVI) with bacillus Calmette-Guerin (BCG) protocol or CHT protocol, patients' characteristics, tumor biological features, and follow-up data were analyzed and compared between CHT and IVC group in low-grade UC, CHT, and IVI group in high-grade UC, respectively. RESULTS: The median follow-up time was 24 months. In patients with low-grade UC, the median recurrence free survival (RFS) interval and costs of treatment in CHT group were significantly higher than those in IVC group (p = .01, p < .001, respectively), CHT was associated with higher RFS compared with IVC by Kaplan-Meier analysis, and three patients in IVC group upgraded to high grade when tumor recurred, whereas no cases were found upgraded in CHT group, p = .38. In patients with high-grade UC, tumor recurrence rates at 12 (p = .004) and 24 months (p = .004) after TURBT, rate of complications (p = .04)-especially for hematuresis (p = .03) and irritation symptoms (p = .04)-the median costs of treatment (p < .001) in CHT group were significantly lower than those in IVI group, RFS interval, health-related quality of life) at 12 and 24 months after TURBT in CHT group was significantly higher than those in IVI group (p < .001, p = .002, and p < .001, respectively), and CHT was associated with higher RFS compared with IVI by Kaplan-Meier analysis. The rate of patients upstaged to pT2 in CHT group seemed lower than that in IVI group, but there was no significantly statistical difference (14.3% vs. 24%, p = .58). CONCLUSION: CHT has a beneficial prophylactic effect in patients with pT1 bladder cancer, especially in patients with high-grade UC, which is much more effective and safer than BCG, meanwhile it costs less compared with BCG.

Controlled Construction of Core-Shell Structured Prussian Blue Analogues towards Enhanced Oxygen Reduction.

Metal-organic frameworks-based electrocatalysts have been developed as highly desirable and promising candidates for catalyzing oxygen reduction reaction (ORR), which, however, usually need to be prepared at elevated temperatures and may suffer from the framework collapse in water environments, largely preventing its industrial application. Herein, this work demonstrates a facile low-temperature ion exchange method to synthesize Mn and Fe co-loaded Prussian blue analogues possessing core-shell structured frameworks and favorable water-tolerance. Among the catalysts prepared, the optimal HMPB-2.6Mn shows a high ORR electrocatalytic performance featuring a half-wave potential of 0.86 V and zinc-air battery power density of 119 mW cm-2 , as well as negligible degradation up to 60 h, which are comparable to commercial Pt/C. Such an excellent electrocatalytic performance is attributed to the special core-shell-like structure with Mn concentrated in outer shell, and the synergetic interactions between Mn and Fe, endowing HMPB-Mn with outstanding ORR activity and good stability.

Hyaluronic Acid-Based Reactive Oxygen Species-Responsive Multifunctional Injectable Hydrogel Platform Accelerating Diabetic Wound Healing.

Diabetic wounds are more likely to develop into complex and severe chronic wounds. The objective of this study is to develop and assess a reactive oxygen species (ROS)-responsive multifunctional injectable hydrogel for the purpose of diabetic wound healing. A multifunctional hydrogel (HA@Cur@Ag) is successfully synthesized with dual antioxidant, antibacterial, and anti-inflammatory properties by crosslinking thiol hyaluronic acid (SH-HA) and disulfide-bonded hyperbranched polyethylene glycol (HB-PBHE) through Michael addition; while, incorporating curcumin liposomes and silver nanoparticles (AgNPs). The HA@Cur@Ag hydrogel exhibits favorable biocompatibility, degradability, and injectivity. The outcomes of in vitro and in vivo experiments demonstrate that the hydrogel can effectively be loaded with and release curcumin liposomes, as well as silver ions, thereby facilitating diabetic wound healing through multiple mechanisms, including ROS scavenging, bactericidal activity, anti-inflammatory effects, and the promotion of angiogenesis. Transcriptome sequencing reveals that the HA@Cur@Ag hydrogel effectively suppresses the activation of the tumour necrosis factor (TNF)/nuclear factor κB (NF-κB) pathway to ameliorate oxidative stress and inflammation in diabetic wounds. These findings suggest that this ROS-responsive multifunctional injectable hydrogel, which possesses the ability to precisely coordinate and integrate intricate biological and molecular processes involved in wound healing, exhibits notable potential for expediting diabetic wound healing.