The treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) infection is severely hindered by the challenges of bacterial infection, excessive inflammation, and impaired osteogenesis. To address these challenges, we first develop an integrated nanoplatform (Se-CD@Cu-EGC) with concurrent anti-inflammatory, antibacterial, and osteogenic activities based on metal-phenolic networks (MPNs) and selenium-doped carbon dots (Se-CDs). Initially, a systematic investigation into the structure-activity relationship of MPNs is conducted using five polyphenol compounds with different numbers of phenolic hydroxyl groups. This reveals that Cu-EGC, assembled from Cu+ and (-)-epigallocatechin (EGC), possesses suitable pH-responsive degradation behaviors and exhibits strongest antibacterial activity owing to the synergistic membrane disruption and cuproptosis-like death. To further endow Cu-EGC with anti-inflammatory and osteogenic activities, Se-CDs with both immune regulation and osteogenic activity are loaded on Cu-EGC to form Se-CD@Cu-EGC nanoplatforms. The doping of Se element in CDs not only endows CDs with ROS scavenging performance and anti-inflammatory ability through reprogramming macrophages from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype, but also optimizes the surface charge state of CDs to activate BMP/Smad pathway for promoting osteogenic differentiation of BMSCs. Se-CD@Cu-EGC is then incorporated into GelMA hydrogel for the eradicating biofilms, mitigating inflammation, and promoting bone repair in a MRSA-induced osteomyelitis model. This work not only elucidates the precise influence of polyphenol structure on the antibacterial activity of MPNs but also presents a novel strategy for the rational design of multifunctional biomaterials against infectious osteomyelitis.

Osteoporotic rotator cuff tears represent a major clinical challenge owing to impaired tendon-bone interface (TBI) healing. To address this issue, we engineered an injectable Zein-based composite hydrogel (ZDC hydrogel) using electron-beam irradiation and, incorporated niacin-loaded mesoporous carbon nanospheres to achieve photothermal regulation and niacin release. The ZDC hydrogel exhibited favorable self-assembly, mechanical properties, photothermal performance, degradability, and biosafety. In vitro, ZDC hydrogel extracts enhanced the osteogenic differentiation of MC3T3-E1 cells and the tenogenic differentiation of tendon-derived stem cells (TDSCs). Mechanistically, ZDC hydrogel extracts increased intracellular nicotinamide adenine dinucleotide levels, suppressed p16 and p21 expression, and reduced cytosolic and mitochondrial reactive oxygen species (ROS) accumulation in MC3T3-E1 cells. In the osteoporotic rat rotator cuff repair model, ZDC hydrogels combined with near-infrared irradiation (NIR) enhanced new bone formation within the humeral head bone tunnel, improved fibrocartilaginous TBI reconstruction, and strengthened biomechanical properties of the repaired tendon-bone complex. Furthermore, in a rat skin wound model, ZDC hydrogels combined with NIR increased the expression of vascular endothelial growth factor (VEGF) and CD31 while reducing tumor necrosis factor-α levels, indicating enhanced angiogenesis and attenuated inflammatory responses. Collectively, these findings suggest that the injectable ZDC hydrogel is a promising strategy for osteoporotic rotator cuff tear repair.

In the development of clinically translatable triplet photosensitizers for hypoxia regulated photodynamic therapy (PDT), there is an unmet need for engineering sensitizers as near-infrared (NIR)-responsive, type I/type Ⅱ dual photosensitizers and mild photothermal agents. Herein, we develop a binary precursor-engineering strategy for precise regulation of the D-π-A configuration of carbon dots (CDs) as ultralong-lived triplet, type I/Ⅱ dual photosensitizers by utilizing phenolic hydroxyl as an electron-rich donor and pyridine N as an electron-withdrawing acceptor. The photodynamic performance of CDs is enhanced by intramolecular charge transfer and mild photothermal conversion. We further design M1-like macrophage-derived cell membrane‑camouflaged CDs to realize preferential tumor accumulation while guaranteeing rapid systemic clearance. D-π-A sensitized CD-mediated PDT induces anti-tumor activity against primary and distant tumors. Our work highlights the crucial roles of D-π-A sensitization of CDs in boosting PDT by triplet state tuning, surface charge transfer, and mild photothermal relief of hypoxia.

The design of biodegradable multimodal nanomedicines such as sonozymes is indispensable for clinical applications. It is thus required to develop NIR-fluorescence imaging technologies allowing for in-time monitoring of their metabolic dynamics in vivo for spatiotemporally precise treatments owing to their unpredictability in vivo degradation dynamics. To this end, a biodegradable Mn (III)-based sonozyme in the MnO2γ-phase was synthesized by atomic valence engineering (AVE) strategy based on hydrolysis and dismutation of Mn (III) ions. This synthetic strategy can tune the Mn (III) content from 70 % to 82 % and thus oxygen vacancy (VO) concentration at room temperature via charge compensation. As a result, VO-enhanced sonodynamic and nanozyme effects were observed. Moreover, NIR-fluorescent carbon dots (NIR-CDs) were in-situ assembled on the nanoflower surface by forming Mn (III)-N complexes, which quenched the fluorescence. In vitro and in vivo fluorescence imaging showed tumor-specific degradable dynamics owing to the biodegradation triggered by GSH overexpressed in the tumor microenvironment. Enhanced sonodynamic immunotherapy efficacy against both local and distant tumors was achieved by the synergism of VO-mediated sonodynamic enhancement, Mn (III)-mediated GSH depletion, hypoxia alleviation and STING activation. Our results revealed that the Mn (III)-regulated nanozyme system as a biodegradable "all in one" theranostic platform can facilitate spatiotemporally controlled NIR imaging guided multimodal treatments in combating metastatic cancers.

桡骨下1/3段骨折是临床常见的上肢骨折类型之一,该解剖区域涵盖桡骨远端关节面、干骺交界区与桡骨干远端等,是构成前臂旋转功能单元、维持腕关节生理功能的核心解剖结构.该区域骨折后不仅会导致局部疼痛肿胀,还易造成前臂旋转功能受限、腕关节功能障碍等,使患者生活质量严重下降[1].

Osteomyelitis remains a refractory orthopedic disease; it is urgent to develop osteomyelitis-microenvironment-responsive, dynamic-crosslinked hydrogels that could fight infection, regulate inflammation, and accelerate bone repair simultaneously for on-demand osteomyelitis therapy. Herein, we report an all-in-one hydrogel design based on a highly biocompatible, covalently interlinked, and multifunctional carbon dot (CD) platform for simultaneous regulation of antibacterial, anti-inflammatory, and osteogenic activities while enabling bacteria-specific and controllable release of CDs. To achieve this aim, CDs was significantly modified with two structural factors, i.e., catechol grafted at the edge and Se─Se bonds doped in the core, which play crucial roles in the precise regulation of their multiple functions for on-demand osteomyelitis therapy. Dynamically crosslinked composite hydrogels with dissociable borate ester bonds were constructed by utilizing catechol-functionalized Se-doped CDs as a triple bioactive ingredient. The CD-based composite hydrogels were demonstrated to enable near-complete healing of bone defects in a MRSA-induced osteomyelitis model. This work provides a paradigm for fabrication of dynamic-crosslinked hydrogels from multifunctional CDs for on-demand osteomyelitis therapy.

Osteoarthritis, featuring cartilage degeneration as a hallmark, is the leading cause of disability in structural joint disorders. Conventional imaging techniques fall short in precisely analyzing the molecular changes of the pathological processes, limiting their ability to guide timely interventions for retarding disease progression and alleviating socioeconomic burdens associated with long-term medical care. Anionic glycosaminoglycans (GAGs) are components that are critical to cartilage extracellular matrix integrity, exhibiting progressive depletion patterns during cartilage degeneration and are thereby potential biomarkers for precise degeneration diagnosis. However, achieving quantitative in situ detection of GAGs remains challenging. Here, a polysaccharide-polypyrrole (PS-PPy) nanoprobe is developed to enable quantitative photoacoustic imaging of GAGs for the monitoring of multi-stage osteoarthritis. Cationization of the polysaccharide component allows binding with GAGs by electrostatic interactions and enhancement of the colloidal stability, while the polypyrrole component imparts photoacoustic capabilities. A quantitative correlation is established between the photoacoustic intensity of PS-PPy and the GAG content, providing accurate degenerated information in mice and human cartilage samples. Furthermore, the method achieved in situ quantification of GAGs depletion arising from multi-stage osteoarthritis in mouse models. Collectively, this work establishes a nanoprobe-based quantitative photoacoustic platform for molecular-level spatiotemporal tracking of osteoarthritis staging. This non-invasive and precise OA staging platform enables timely interventions and therapeutic monitoring with great translational value for clinically personalized OA management.

To overcome ZnIn2S4's limitations (narrow-visible-light absorption, rapid charge-carrier recombination, and low efficiency), this study designed photosynthesis-inspired ZnIn2S4/AgVO3 heterojunctions guided by density functional theory (DFT) calculations. Combined DFT and experimental analysis confirmed a chloroplast-like Z-scheme charge-transfer mechanism within the heterojunction. Photocatalytic technology was then integrated with membrane separation via electrospinning to fabricate porous ZnIn2S4/AgVO3@PVDF membranes, solving recovery and secondary pollution issues. Experimental results showed that the ZnIn2S4/AgVO3@PVDF photocatalytic membrane containing 30 wt % AgVO3─referred to as P-ZA30─degraded 93.97% of sulfamethazine (SMT) within 80 min, demonstrating excellent photocatalytic performance. Meanwhile, DFT calculations elucidated the SMT degradation pathway. In addition, the membrane exhibited broad-spectrum antibacterial properties against both Gram-positive bacteria (e.g., Staphylococcus aureus) and Gram-negative bacteria (e.g., Escherichia coli). These findings provide valuable guidance for the design of heterojunction materials, offer considerable experimental and theoretical support for understanding the catalytic mechanism of Z-scheme heterojunctions, and help in the develop of strategies for the treatment of antibiotic-contaminated wastewater.

Diverse strategies to construct metal-organic framework (MOF)/polymer composites have been explored in recent decades due to the advanced properties benefited from their combination. However, regulating the critical parameters including size and spatial structure usually requires different strategies that interfere mutually thus complicating the systems. Herein, we reported a general approach to fabricate uniform polymer-in-MOF nanoparticles through functional ligands enabling both coordination modulation and in situ polymerization. Pyrrole ligand was first pre-coordinated with metal node Zn2+ and subsequently replaced by stronger 2-methylimidazole ligand to form the MOF structures. This two-step strategy allowed precise size control via regulation of MOF nucleation and growth while simultaneously facilitating the encapsulation and in situ polymerization of pyrrole within the MOF pores. As a showcase of this approach, the polypyrrole-containing MOF surface was further functionalized with cellulose to enhance biocompatibility, enabling biomedical applications for in vivo photoacoustic imaging and tumor photothermal therapy. This method provides a generalizable strategy for the synthesis of MOF/polymer composites with tunable size, architecture, and functionality for diverse biomedical applications.

For the effective activation of the adaptive immune response, it is crucial to promote the maturation of dendritic cells (DCs) and subsequently initiate cytotoxic T lymphocytes. Nevertheless, the immunosuppressive tumor microenvironments (TME) are believed to hinder DC maturation, leading to a significant decrease in the effectiveness of immunotherapy. In this work, we present the first instance of combining ROS-triggered immunogenic cell death (ICD), cholesterol depletion, and STING activation to achieve the cascade amplification of antitumor immune response. The Zr-based metal-organic frameworks (MOF) is utilized as the template for the synthesis of hollow MnO2 (H-MnO2). Carbon dots (CDs) with cholesterol depletion capability are then deposited on H-MnO2 to form heterojunctions. CD@H-MnO2 not only has improved ROS generation ability under ultrasound due to heterojunction construction, but also shows GSH-responsive degradation properties, enabling the targeted release of CDs and Mn ions in tumors. CD@H-MnO2-triggered cascade amplification of antitumor immune response is elucidated as follows: (1) Heterojunction construction, GSH depletion, and relief of hypoxia co-augmented ROS yield could significantly induce a robust ICD effect. (2) The released Mn ions stimulate DC maturation by activating the cGAS-STING pathway. (3) Direct enhancement of T cell toxicity can be realized by CDs through depleting cholesterol. Notable antitumor effects have been observed to eliminate primary tumors and stop the growth of distant tumors. This study presents a novel method to merge ROS-triggered ICD, cholesterol depletion, and STING activation into one nanomaterial to produce long-lasting and powerful immune responses.

Reactive oxygen species (ROS)‐mediated immunogenic cell death (ICD) is believed to stimulate DC maturation and initiate the infiltration of cytotoxic T lymphocytes. Nevertheless, the effectiveness of sonodynamic and nanocatalytic therapy (SDT/NCT) is hindered by the restricted ROS generation and immunosuppressive tumor microenvironments (TME). To address these issues, the first time the dual‐sensitization of Zr‐based metal–organic framework (Zr‐MOF) is reported through the loading of carbon dot (CD) sonosensitizers and the depositing of oxygen‐vacancy‐doped MnO 2−x nanozymes. The fabricated Z‐scheme CD/Zr‐MOF/MnO 2−x heterojunctions exhibit cascade amplification of ROS production owing to the enhanced SDT efficiency, hypoxia alleviation, POD‐like activity, and GSH consumption. The immunosuppressive TME is reversed by the cascade amplification of ROS generation, thereby inducing potent ICD and promoting DC maturation. The maturation of DCs is further amplified by the activation of the cGAS‐STING pathway through the tumor‐specific release of Mn ions. CD/Zr‐MOF/MnO 2−x ‐mediated combination therapy of SDT, NCT, and cGAS‐STING activation exhibits significant antitumor effects, resulting in the eradication of primary tumors and the inhibition of distant tumor growth. This study provides promising insights into the exploration of an Mn‐based nanoplatform that integrates sonosensitizer, nanozyme, and STING nanoagonist functions for cGAS‐STING activation enhanced sonocatalytic‐immunotherapy to produce long‐lasting and powerful immune responses.

Cuproptosis has been identified as a unique copper-dependent cell death mechanism that may provide new opportunities for improving tumor therapy outcomes. For currently developed cuproptosis inducers, nonspecific copper release and low levels of copper accumulation in tumors restrict their clinical applications. To precisely manage copper ion release in vivo, a stimuli-responsive ‘cuproptosis switch’ was designed as an intelligent platform with pH-sensitive ‘off’ and ‘on’ states, thereby inducing cancer-specific cuproptosis while guaranteeing biosecurity. A bilayer copper nanocapsule containing Cu2O and Cu2-xSe shells was demonstrated with a switch-like pH-dependent Cu+ release profile across a transition pH (6.8) based on their distinct degradable properties. To boost cuproptosis-targeted therapy efficacy, the STING activating agonist MSA-2 was encapsulated in the Cu2O/Cu2-xSe nanocapsule for establishing lasting and effective immune responses. Cuproptosis-sensitization effects induced by US irradiation and MSA-2 release were elucidated, including 1) up-regulating Cu influx transporter (SLC31A1) expression and down-regulating Cu efflux transporter (ATP7A) expression to increase intracellular copper overload; 2) facilitating rapid GSH depletion for cuproptosis sensitization in the cytoplasm; 3) increasing mitochondrion membrane permeability for intracellular released Cu+ ions entering the mitochondrion. The TME-specific Cu+ and MSA-2 release combined with US-irradiated, spatiotemporally located ROS amplification induced tumor-specific cuproptosis, initiated immunogenic cell death, and activated cGAS-STING pathway for boosting robust and durable antitumor efficacy. As a result, complete elimination of primary and distant tumors in mice was achieved at low doses without side effects. The US-sensitized cuproptosis switch may provide opportunities for elimination of local residual tumors and abscopal metastatic foci for final tumor eradication.

Inadequate bone differentiation and intractable biofilm formation due to stubborn bacterial infection complicate infected bone defect repair. Adding harmful antibiotics into scaffolds not only promotes multidrug-resistant bacteria but also decreases bone repair effect. Furthermore, dynamic monitor of scaffolds' degradation is crucial for achieving visualized bone defect repair, however, currently reported biomaterials do not have imaging tracing capabilities. On this basis, this work develops a scaffold material with triple functionality for visualized therapy of infected bone defects: antibacterial, osteogenesis, and near-infrared (NIR) imaging capabilities. Single-layer Ti3C2Tx with broad-spectrumantibacterial activity and negatively charged carbon dots (CDs) with osteogenic activity are synthesized for infected bone defect repair. To validate antibacterial and osteogenic activities in vivo, 3D injectable hydrogels encapsulated with Ti3C2Tx and CDs (CD/Ti3C2Tx/GelMA) are constructed. NIR imaging is used to monitor the degradation process of CD/Ti3C2Tx/GelMA hydrogels in infected bone defect models, which indicated that CDs are completely released from hydrogels in about 30 days. Owing to the continuous release of Ti3C2Tx and CDs, the obtained CD/Ti3C2Tx/GelMA hydrogels can efficiently promote the repair of infected bone defects within 60 days. These findings develop a new biomaterial with great performance for visualized antibacterial and osteogenic therapy of infected bone defects.

Introduction Proximal humeral fractures are increasingly common, particularly among older people, whereas the prognosis of surgical treatments for these fractures remains substantially uncertain. In China, where the ageing population is rapidly growing, high-quality prospective data on surgical outcomes, complications and cost-effectiveness are lacking. To address this gap, we propose to initiate a prospective, multicentre cohort study on surgical treatment for proximal humeral fractures in China—Cohort of Acute Shoulder Trauma (CAST) study.Methods and analysis The CAST is a multicentre, prospective cohort study enrolling patients with acute proximal humeral fractures undergoing surgical treatments at eight hospitals in China between May 2024 and December 2029. Patients can receive any of the surgical treatment methods which include percutaneous Kirschner wire fixation, external fixation, open reduction and internal fixation using locking plates or intramedullary nails, suture anchors and shoulder arthroplasty. We will collect patient-reported outcome measures (Quick Disabilities of the Arm, Shoulder and Hand), Constant-Murley, American Shoulder and Elbow Surgeons, EuroQol 5-Dimension and Visual Analogue Scale), physical examination results, imaging assessments (based on X-rays, ultrasound, CT and MRI scans), laboratory tests (including inflammatory cytokines) and data on medical costs. We will follow patients at 1 day, and at 1 month, 3 months, 6 months, 12 months and 24 months postoperatively. The planned sample size is 1500 patients.Ethics and dissemination The study protocol has been approved by the Ethics Committee of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University (Approval No. 2024-ky-104(K)). Written informed consent will be obtained from all participants. Findings from the CAST study will be disseminated through peer-reviewed journals and academic conferences.Study registration number ChiCTR2500109651.

Introduction The infrapatellar fat pad and synovium are the sites of immune cell infiltration and the origin of proinflammation. Studies have shown that Hoffa’s synovitis may be a sign of early-stage osteoarthritis (OA). However, there have been no effective interventions specifically for Hoffa’s synovitis.Methods and analysis We will conduct a multicentre, multi-blind (participant, physician, outcome assessor and data analyst blinded) randomised controlled trial to compare the effectiveness of an intra-infrapatellar fat glucocorticoid versus an intra-articular injection for Hoffa’s synovitis in patients with knee OA. We will recruit 236 knee OA patients with Hoffa’s synovitis at outpatient clinics in three centres. We will randomly allocate them to two groups in a 1:1 ratio. One group will receive ultrasound-guided injection of 40 mg (1 mL) triamcinolone acetonide into the infrapatellar fat pad; the other group will receive ultrasound-guided injection of 40 mg (1 mL) triamcinolone acetonide into the knee joint cavity. All patients will be followed up at 2, 4, 8, 12 and 24 weeks after the injection. Primary outcomes are (1) Hoffa’s synovitis improvement rate, measured with the MRI Osteoarthritis Knee Score system (superiority outcome) at 24 weeks and (2) pain intensity, measured with the Western Ontario and McMasters University Osteoarthritis Index (WOMAC) at 2 weeks post-injection. Secondary outcomes include Hoffa’s synovitis score at 2 weeks post-injection, pain intensity with the numerical rating scale, WOMAC questionnaire score improvements (function, joint stiffness and total score), improvement rates in effusion synovitis at 2 and 24 weeks, articular cartilage thickness changes at 2 and 24 weeks, Intermittent and Constant Osteoarthritis Pain score, quality of life measured with the EuroQol-5D, OARSI-OMERACT response indicators, co-interventions and side effects at 2, 4, 8, 12 and 24 weeks.Ethics and dissemination Ethical approval has been granted by the Medical Ethics Committee of the Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (2023–178). Written informed consent will be obtained from all patients prior to data collection. The findings of this research will be shared through presentations at academic conferences and publications in peer-reviewed journals.Trial registration number ChiCTR2400080474.

Cuproptosis-like-death-mediated antibacterial therapy has been regarded as a promising treatment strategy for eliminating multidrug-resistant (MDR) bacteria and stubborn biofilms. However, the release of Cu ions that are not specific to bacteria can trigger cuproptosis and lead to irreversible damage to healthy tissues. Herein, carbon dots (CDs) with triplet-mediated sonodynamic activity are deposited on cuproptosis inducer (Cu2O) to achieve the multiple amplification effects of antibacterial and antibiofilm activities. First, the sonodynamic and chemodynamic activities of single-component sonosensitizers/nanozymes are significantly augmented by the formation of heterojunction sonozymes. Second, Cu2O/CD with bacterial microenvironment (BME)-responsive degradation features realizes the bacterium-specific release of Cu+, CDs, and Cu2+, which can not only achieve cascade amplification of reactive oxygen species (ROS) production through depleting GSH but also realize the bacterium-specific cuproptosis-like death. Notably, transcriptome sequencing analysis indicates that Cu2O/CD-mediated combination therapy damaged bacterial ribosomes and ion transport, facilitating the influx of Cu ions and disrupting the bacterial TCA cycle. Collectively, the synergistic antibacterial treatments of SDT, CDT, and cuproptosis-like death via Cu2O/CD can realize the thorough sterilization and biofilm elimination. The work presents a novel perspective on how to optimize the function and safety of cuproptosis inducers, ultimately maximizing therapeutic advantages while minimizing harm to normal tissues.

The high-efficiency treatment of infected bone defects necessitates the concurrent antibacterial and osteogenic activities of biocompatible scaffold materials. However, traditional clinical treatment modalities frequently suffer from antibiotic resistance, stubborn biofilm formation, and insufficient bone differentiation activity. Herein, we present a self-assembly strategy based on the coordination between Cu ions and Alendronate (ALN) to boost both antibacterial and osteogenic activities for the repair of infected bone defects. The self-assembly of ALN into a carrier-free drug delivery system can be induced by Cu ions, not only endowing ALN with excellent sonodynamic and chemodynamic activities for high-efficiency antibacterial therapy but also resulting in improved bioavailability and avoiding the possible carrier dilemma of low loading efficiency and poor stability. Moreover, Cu/ALN nanoneedles can selectively release Cu+, Cu2+, and ALN in bacterial microenvironment (BME) by breaking the Cu-N/Cu-O coordination bond under acidic conditions. The presence of Cu2+ in Cu/ALN provides effective glutathione peroxidase (GSH-px)-mimic catalytic activity for depleting glutathione (GSH) in BME, thereby avoiding the consumption of chemodynamic therapy (CDT)-generated reactive oxygen species (ROS) and achieving cascade amplification of ROS generation. Finally, the injectable Cu/ALN/GelMA hydrogels are fabricated through a single-step photochemical crosslinking process to examine the in vivo antibacterial efficacy and bone-regenerative potential of Cu/ALN. As a result, Cu/ALN-incorporated Gelatin Methacryloyl (GelMA) hydrogels significantly promote the healing of infected bone defects after implanting for one month through the ALN-facilitated osteogenic differentiation and Cu-ion-mediated cascade amplification of antibacterial activity. Overall, this work presents a novel perspective on the self-assembly multifunctional nanoplatforms with concurrent antibacterial and osteogenic activities for the treatment of infected bone defects.

Cuproptosis has recently identified as a unique copper-dependent cell death mechanism that may provide new opportunities for improving the therapeutic effect of tumor therapy through triggering efficient adaptive immune responses. However, the poor delivery efficiency and non-tumor-specific release of Cu ions would restrict the potential clinical applications of cuproptosis inducers. Herein, we report for the first time the development of hollow Cu2-xSe nanocubes as the tumor microenvironment (TME)-responsive drug delivery systems and cuproptosis inducers for tumor-specific chemotherapy and cuproptosis. The presence of Cu vacancy endows Cu2-xSe with excellent sonodynamic and chemodynamic activity. The hollow Cu2-xSe nanocubes with TME-responsive degradation behaviors are further utilized to load graphene quantum dot (GQD) nanodrugs to form GQD/Cu2-xSe heterojunctions for achieving tumor-specific chemotherapy. The heterojunction-fabrication GQD/Cu2-xSe exhibits amplified ROS generation capabilities and improved TME regulation ability owing to the optimized electron-hole separation kinetics. More importantly, the significant increase in ROS levels and efficient cuproptosis could reverse the immunosuppressive TME and induce immunogenic cell death that stimulates strong systemic immune responses to eliminate tumors. Collectively, this work presents an innovative strategy for the utilization of TME-responsive cuproptosis inducers for tumor-specific chemotherapy and cuproptosis augmented sono-immunotherapy.

The occurrence of associated both-column acetabular fractures (ABC-AFs) is common in the elderly, yet their morphological characteristics compared to younger adults remain unclear. This retrospective study analyzed 123 cases of ABC-AFs: elderly patients (≥ 65 years, n = 47, group A) and younger adults (< 65 years, n = 76, group B). Using Mimics and 3-matic, fracture line (FL) distributions in the anterior column (AC), quadrilateral plate (QP), and posterior wall (PW) fragments were examined. Comparisons focused on the articular surface, ilium, QP area, and retro-acetabular surface (RAS). Harris hip scores (HHS) were recorded and compared one-year post-surgery. The distribution of FLs of the AC fragment on the anteroinferior wall, acetabulum, inner and outer sides of the ilium was similar between groups A and B except that group A had sparser FL distribution on the posterosuperior rim and fewer FLs extending into the sacroiliac joint. A comparable pattern of FLs of the QP fragments on the QP area and the RAS was also confirmed. On the RAS, group A exhibited fewer cranial transverse lines (8.5