Near-Infrared Carbon Dots With Antibacterial and Osteogenic Activities for Sonodynamic Therapy of Infected Bone Defects.

Repairing infected bone defects is hindered by the presence of stubborn bacterial infections and inadequate osteogenic activity. The incorporation of harmful antibiotics not only fosters the emergence of multidrug-resistant bacteria, but also diminishes the osteogenic properties of scaffold materials. In addition, it is essential to continuously monitor the degradation kinetics of scaffold materials at bone defect sites, yet the majority of bone repair materials lack imaging capability. To address these issues, this study reports for the first time the development of a single nanomaterial with triple functionality: efficient sonodynamic antibacterial activity, accelerated bone defect repair capability, and NIR imaging ability for visualized therapy of infected bone defects. Through rationally regulating the surface functional groups, the obtained multifunctional NIR carbon dots (NIR-CD) exhibit p-n junction-enhanced sonodynamic activity, narrow bandgap-facilitated NIR imaging capability, and negative charge-augmented osteogenic activity. The validation of NIR-CDs antibacterial and osteogenic activities in vivo is conducted by constructing 3D injectable hydrogels encapsulated by NIR-CDs (NIR-CD/GelMA). The implantation of multifunctional NIR-CD/GelMA hydrogel scaffolds in a model of MRSA-infected craniotomy defects results in almost complete restoration of the infected bone defects after 60 days. These findings will provide traceable, renewable, repairable and antibacterial candidate biomaterials for bone tissue engineering.

Graphene Quantum Dots Eradicate Resistant and Metastatic Cancer Cells by Enhanced Interfacial Inhibition.

Drug-resistant and metastatic cancer cells such as a small population of cancer stem cells (CSCs) play a crucial role in metastasis and relapse. Conventional small-molecule chemotherapeutics, however, are unable to eradicate drug-resistant CSCs owing to limited interface inhibitory effects. Herein, it is reported that enhanced interfacial inhibition leading to eradication of drug-resistant CSCs can be dramatically induced by self-insertion of bioactive graphene quantum dots (GQDs) into DNA major groove (MAG) sites in cancer cells. Since transcription factors regulate gene expression at the MAG site, MAG-targeted GQDs exert greatly enhanced interfacial inhibition, downregulating the expression of a collection of cancer stem genes such as ALDH1, Notch1, and Bmi1. Moreover, the nanoscale interface inhibition mechanism reverses cancer multidrug resistance (MDR) by inhibiting MDR1 gene expression when GQDs are used at a nontoxic concentration (1/4 × half-maximal inhibitory concentration (IC50)) as the MDR reverser. Given their high efficacy in interfacial inhibition, CSC-mediated migration, invasion, and metastasis of cancer cells can be substantially blocked by MAG-targeted GQDs, which can also be harnessed to sensitize clinical cytotoxic agents for improved efficacy in combination chemotherapy. These findings elucidate the inhibitory effects of the enhanced nano-bio interface at the MAG site on eradicating CSCs, thus preventing cancer metastasis and recurrence.

Single Atom Catalysts Remodel Tumor Microenvironment for Augmented Sonodynamic Immunotherapy.

The immunosuppressive tumor microenvironment (TME) is a huge hurdle in immunotherapy. Sono-immunotherapy is a new treatment modality that can reverse immunosuppressive TME, but the sonodynamic effects are compromised by overexpressed glutathione (GSH) and hypoxia in the TME. Herein, this work reports a new sono-immunotherapy strategy using Pdδ+ single atom catalysts to enhance positive sonodynamic responses to the immunosuppressive and sono-suppressive TME. To demonstrate this technique, this work employs rich and reductive Ti vacancies in Ti3-xC2Ty nanosheets to construct the atomically dispersed Pd-C3 single atom catalysts (SAC) with Pd content up to 2.5 wt% (PdSA/Ti3-xC2Ty). Compared with Pd nanoparticle loaded Ti3-xC2Ty, PdSA/Ti3-xC2Ty single-atom enzyme showed augmented sonodynamic effects that are ascribed to SAC facilitated electron-hole separation, rapid depletion of overexpressed GSH by ultrasound (US) excited holes, and catalytic decomposition of endogenous H2O2 for relieving hypoxia. Importantly, the sono-immunotherapy strategy can boost abscopal antitumor immune responses by driving maturation of dendritic cells and polarization of tumor-associated macrophages into the antitumoral M1 phenotype. Bilateral tumor models demonstrate the complete eradication of localized tumors and enhance metastatic regression. Th strategy highlights the potential of single-atom catalysts for robust sono-immunotherapy by remodeling the tumor microenvironment.

Aging-Related Rotator Cuff Tears: Molecular Mechanisms and Implications for Clinical Management.

Shoulder pain and disabilities are prevalent issues among the elderly population, with rotator cuff tear (RCT) being one of the leading causes. Although surgical treatment has shown some success, high postoperative retear rates remain a great challenge, particularly in elderly patients. Aging-related degeneration of muscle, tendon, tendon-to-bone enthesis, and bone plays a critical role in the development and prognosis of RCT. Studies have demonstrated that aging worsens muscle atrophy and fatty infiltration, alters tendon structure and biomechanical properties, exacerbates enthesis degeneration, and reduces bone density. Although recent researches have contributed to understanding the pathophysiological mechanisms of aging-related RCT, a comprehensive systematic review of this topic is still lacking. Therefore, this article aims to present a review of the pathophysiological changes and their clinical significance, as well as the molecular mechanisms underlying aging-related RCT, with the goal of shedding light on new therapeutic approaches to reduce the occurrence of aging-related RCT and improve postoperative prognosis in elderly patients.

Open reduction and internal fixation of crescent fracture-dislocation: anterior or posterior approach?

INTRODUCTION: To date, the approach that prevails in the open reduction and internal fixation of crescent fracture-dislocations (CFD) remains unknown. This study aimed to compare the outcomes of CFD treated via the anterior or posterior approach. MATERIALS AND METHODS: Data from 64 cases of CFDs openly reduced through an anterior (group A, n = 31) or a posterior (group B, n = 33) approach were retrospectively analyzed. Functional results, reduction quality, residual displacements in the axial and coronal planes, pelvic asymmetry deformity, and correlations between Day's classification were compared. Complications and fracture union were also recorded. All patients were followed up for at least 12 months. RESULTS: The functional scores were similar between the two groups, and all fractures achieved good or excellent reduction postoperatively. In the coronal plane, the excellent/good ratio in group B was higher than in group A. The mean residual displacement in the coronal plane was significantly higher in group A than in group B, with group A showing greater displacement in both planes for Day I fractures and in the coronal plane for Day II fractures. The residual displacement in both planes for Day III fractures was comparable between the groups. The pelvic asymmetry deformity was equal between the two groups and among the different Day's fracture types. CONCLUSIONS: Open reduction and internal fixation of CFDs obtained satisfactory outcomes through an anterior or posterior approach. The posterior approach achieved a better sacroiliac joint reduction. The optimal indication for the posterior approach was a Day I fracture, followed by a Day II fracture. No correlation was found between the surgical approach and reduction quality in Day III fractures.

N-Heterocycle Modified Graphene Quantum Dots as Topoisomerase Targeted Nanoantibiotics for Combating Microbial Infections.

Developing next-generation antibiotics to eliminate multidrug-resistant (MDR) bacteria/fungi and stubborn biofilms is challenging, because of the excessive use of currently available antibiotics. Herein, the fabrication of anti-infection graphene quantum dots (GQDs) is reported, as a new class of topoisomerase (Topo) targeting nanoantibiotics, by modification of rich N-heterocycles (pyridinic N) at edge sites. The membrane-penetrating, nucleus-localizing, DNA-binding GQDs not only damage the cell walls/membranes of bacteria or fungi, but also inhibit DNA-binding proteins, such as Topo I, thereby affecting DNA replication, transcription, and recombination. The obtained GQDs exhibit excellent broad-spectrum antimicrobial activity against non-MDR bacteria, MDR bacteria, endospores, and fungi. Beyond combating planktonic microorganisms, GQDs inhibit the formation of biofilms and can kill live bacteria inside biofilms. RNA-seq further demonstrates the upregulation of riboflavin biosynthesis genes, DNA repair related genes, and transport proteins related genes in methicillin-resistant S. aureus (MRSA) in response to the stress induced by GQDs. In vivo animal experiments indicate that the biocompatible GQDs promote wound healing in MRSA or C. albicans-infected skin wound models. Thus, GQDs may be a promising antibacterial and antifungal candidate for clinical applications in treating infected wounds and eliminating already-formed biofilms.

Comparison of augmentation effects of medial buttress plate versus trochanteric lag screw in the cannulated screw fixation of Pauwels type III femoral neck fractures: A retrospective clinical study.

OBJECTIVE: This study aimed to compare the effects of a medial buttress plate (MBP) or a trochanteric lag screw (TLS) to augment cannulated screws (CSs) in fixing Pauwels type III femoral neck fractures. METHODS: This retrospective study included 58 patients (21 female, 37 male; mean age=46 years; age=19-64 years) treated by CSs for Pauwels type III femoral neck fractures from 2014 to 2017. All the patients were divided into 2 groups based on the internal fixation patterns: the MBP-augmented group (group A, n=26) and the TLS group (group B, n=32). The mean age was 47 (range=24-57) years in group A and 45 (range=19-64) years in group B. The operation time, intraoperative blood loss, reduction quality, Harris score, and postoperative complications were recorded and compared between both groups. RESULTS: All patients were followed up for an average of 44.8 months in group A and 47.3 months in group B (P=.406). No significant difference was noted in reduction quality (P=1.000). However, group A had a longer operation time (100.2 vs. 64.3 minutes, P < .001) and greater intraoperative blood loss (153.1 vs. 30.0 mL, P < .001) than group B. At the final follow-up, the union rate was equal between group A (96.2%) and group B (90.6%) (P=.760). The mean bone union time was 21.6 weeks in group A and 23.6 weeks in group B (P=.431). The delayed union rate was lower in group A (0%) than in group B (15.6%) (P < .001). The incidence of postoperative complications in terms of implant failure (7.7% vs. 28.1%, P=.048) and femoral neck shortening (7.7% vs. 28.1%, P=.048) were lower in group A than in group B. No significant difference was noted in avascular femoral head necrosis (P=1.000) and the Harris score (P=.659) between the 2 groups. CONCLUSION: In the surgical treatment of Pauwels type III femoral neck fractures, medial buttress plating can offer fewer complications but equal avascular femoral head necrosis rate and functional outcome compared to trochanteric screw application. LEVEL OF EVIDENCE: Level III, Therapeutic study.

Giant cell tumors of the distal ulna: long-term recurrence rate and functional outcomes of en bloc resection versus curettage in a multicenter study.

OBJECTIVE: The wrist is the second most commonly involved location for GCTB, while distal ulna is a relatively rare location and limited evidence exists on which surgical approaches and reconstruction techniques are optimal. We carried out a multicenter retrospective study to evaluate the recurrence rate of distal ulna GCTB and the long-term functional outcomes of different surgery options. METHODS: All 28 patients received surgical treatment for distal ulna GCTB in one of three tertiary bone tumor centers between May 2007 and January 2021 with a minimum two-year follow-up. Surgical options included intralesional curettage or en bloc resection (one of 3 types). Functional outcomes were assessed by the MSTS score, the QuickDASH instrument, MWS, and MHQ according to the latest treatment. RESULTS: Overall recurrence rate was 14.2%. The curettage group (N = 7) had a significantly higher recurrence rate compared to en bloc resection (N = 21) (42.9% vs 4.8%) (mean follow-up: 88.8 mo). Seven patients received the Darrach procedure, 5 received the original Sauvé-Kapandji procedure, and 9 received the modified Sauvé-Kapandji procedure with extensor carpi ulnaris (ECU) tenodesis. Of the 4 patients having a recurrence, 1 received the Darrach EBR, 2 received the modified Sauvé-Kapandji procedure, and 1 received resection for soft tissue recurrence. Only MWS and esthetics in the MHQ scores were different (curettage, Darrach, Sauvé-Kapandji, and Sauvé-Kapandji with ECU tenodesis [MWS: 96.5 ± 1.3 vs 91.5 ± 4.7 vs 90.8 ± 2.8 vs 91.5 ± 3.6; esthetics in MHQ: 98.5 ± 3.1 vs 89.9 ± 4.7 vs 93.8 ± 4.4 vs 92.6 ± 3.8], respectively). CONCLUSIONS: En bloc resection for distal ulna GCTB had a significantly lower recurrence rate compared with curettage and achieved favorable functional outcome scores. Given the higher recurrence rate after curettage, patients should be well informed of the potential benefits and risks of selecting the distal radioulnar joint-preserving procedure. Moreover, reconstructions after tumor resection of the ulna head do not appear to be necessary.

Natural and biocompatible dressing unit based on tea carbon dots modified core-shell electrospun fiber for diabetic wound disinfection and healing.

Wound infection and healing in patients with diabetes is one of the complex problems in trauma treatment. Therefore, designing and preparing an advanced dressing membrane for treating the wounds of such patients is essential. In this study, a zein film with biological tea carbon dots (TCDs) and calcium peroxide (CaO2) as the main components for promoting diabetic wound healing was prepared by an electrospinning technique, which combines the advantages of natural degradability and biosafety. CaO2 is a biocompatible material with a microsphere structure that reacts with water to release hydrogen peroxide and calcium ions. TCDs with a small diameter were doped in the membrane to mitigate its properties while improving the antibacterial and healing effects of the membrane. TCDs/CaO2 was mixed with ethyl cellulose-modified zein (ZE) to prepare the dressing membrane. The antibacterial properties, biocompatibility and wound-healing properties of the composite membrane were investigated by antibacterial experiment, cell experiment and a full-thickness skin defect. TCDs/CaO2 @ZE exhibited significant anti-inflammatory and wound healing-promoting properties in diabetic rats, without any cytotoxicity. This study is meaningful in developing a natural and biocompatible dressing membrane for diabetic wound healing, which shows a promising application in wound disinfection and recovery in patients with chronic diseases.

Pyruvate dehydrogenase beta subunit (Pdhb) promotes peripheral axon regeneration by regulating energy supply and gene expression.

Key metabolic enzymes not only regulate Glucose, lipid, amino acid metabolism to serve the cellular energy needs, but also modulate noncanonical or nonmetabolic signaling pathway such as gene expression, cell-cycle progression, DNA repair, apoptosis and cell proliferation in regulating the pathologic progression of disease. However, the role of glycometabolism in peripheral nerve axon regeneration is little known. In this study, we investigated the expression of Pyruvate dehydrogenase E1(PDH), a key enzyme linking glycolysis and the tricarboxylic acid (TCA) cycle, with qRT-PCR and found that pyruvate dehydrogenase beta subunit (Pdhb) is up-regulated at the early stage during peripheral nerve injury. The knockdown of Pdhb inhibits neurite outgrowth of primary DRG neurons in vitro and restrains axon regeneration of sciatic nerve after crush injury. Pdhb overexpression promoting axonal regeneration is reversed by knockdown of Monocarboxylate transporter 2(Mct2), a transporter involved in the transport and metabolism of lactate, indicating Pdhb promoting axon regeneration depends on lactate for energy supply. Given the nucleus-localization of Pdhb, further analysis revealed that Pdhb enhances the acetylation of H3K9 and affecting the expression of genes involved in arachidonic acid metabolism and Ras signaling pathway, such as Rsa-14-44 and Pla2g4a, thereby promoting axon regeneration. Collectively, our data indicates that Pdhb is a positive dual modulator of energy generation and gene expression in regulating peripheral axon regeneration.

Morphological analysis of the posterior elements of associated both-column acetabular fractures.

BACKGROUND: It is still in dispute as to whether a posterior approach is applied to reduce the posterior fractures of associated both-column acetabular fractures (ABC-AFs). PURPOSE: To analyze the morphological changes in the posterior elements including the posterior column (PC) and/or associated posterior wall (PW) fragments to provide a reference for surgical planning. MATERIAL AND METHODS: The 3D computed tomography (CT) data of 100 cases of ABC-AFs were retrospectively analyzed using Mimics and 3-Matic software. The line distribution of the retroacetabular surface (RAS), the acetabular fossa, and the size of the PW fragments were analyzed. RESULTS: Fracture lines (n = 89) on RAS appeared in three patterns: transverse lines (n = 41) on the cephalic (65.8%) and caudal (29.3%) thirds; oblique lines (n = 34) on the mid-caudal thirds; and multifragmentary lines (n = 14). The lines of the displaced PW fragment (n = 61) were widely distributed in intra- and extra-articular regions. The mean radian of the PW fragments was >90° in 67.2% of cases and involved anteriorly to the vertex in 90.2% of cases. The average fracture span on the RAS was 0.60-1.00 in 63.9% of cases. The mean length of the spike of PW fragments was >20 mm in 80.3% of cases. DISCUSSION: For PC fractures, transverse lines on the cephalic third of RAS indicated a possibility of the anterior approach, while transverse lines on the distal third or oblique and multifragmentary lines suggest the posterior approach. A displaced PW fragment was involved more extensively both intra-and extra-articularly and may be optimally treated via a posterior approach.

Antibacterial Z-scheme ZnIn2S4/Ag2MoO4 composite photocatalytic nanofibers with enhanced photocatalytic performance under visible light.

Considering the biocompatibility of natural proteins and the strong photo-redox capability of Z-scheme heterojunctions, we fabricated Z-scheme ZnIn2S4/Ag2MoO4@Zein (Z ZA) photocatalytic membranes via electrospinning and in-situ precipitation for enrofloxacin (ENR) degradation. Z ZA exhibit a fiber structure wrapped with ZnIn2S4/Ag2MoO4 heterojunctions. Photocatalytic studies and various characterization results certified that the Z-scheme structure between ZnIn2S4 and Ag2MoO4 significantly increases the lifetime and separation efficiency of photogenerated carriers, which in turn enhances the photodegradation of ENR. The degradation rate of Z ZA-10 (ZnIn2S4/10 wt% Ag2MoO4@Zein) with the highest catalytic activity could reach 100% within 120 min compared with other samples. For ENR degradation, •O2- radicals were certified to be the primary active species by trapping experiments, and several possible conversion pathways of ENR in photocatalytic reactions were proposed. Furthermore, the antibacterial rates of Z ZA-20 (ZnIn2S4/20 wt% Ag2MoO4@Zein) against B. subtilis, P. aeruginosa, S. aureus, and E. coli could reach 90.09%, 89.78%, 84.34%, and 95.31%, respectively. Antibacterial evaluations and cytotoxicity assays demonstrated that Z ZA photocatalytic films had desirable antibacterial properties and low cytotoxicity, rendering them safe and effective for use in the treatment of antibiotic wastewater.

Near-infrared phosphorescent carbon dots for sonodynamic precision tumor therapy.

Theranostic sonosensitizers with combined sonodynamic and near infrared (NIR) imaging modes are required for imaging guided sonodynamic therapy (SDT). It is challenging, however, to realize a single material that is simultaneously endowed with both NIR emitting and sonodynamic activities. Herein, we report the design of a class of NIR-emitting sonosensitizers from a NIR phosphorescent carbon dot (CD) material with a narrow bandgap (1.62 eV) and long-lived excited triplet states (11.4 µs), two of which can enhance SDT as thermodynamically and dynamically favorable factors under low-intensity ultrasound irradiation, respectively. The NIR-phosphorescent CDs are identified as bipolar quantum dots containing both p- and n-type surface functionalization regions that can drive spatial separation of e--h+ pairs and fast transfer to reaction sites. Importantly, the cancer-specific targeting and high-level intratumor enrichment of the theranostic CDs are achieved by cancer cell membrane encapsulation for precision SDT with complete eradication of solid tumors by single injection and single irradiation. These results will open up a promising approach to engineer phosphorescent materials with long-lived triplet excited states for sonodynamic precision tumor therapy.

Enhanced echo intensity of skeletal muscle is associated with poor physical function in hemodialysis patients: a cross-sectional study.

BACKGROUND: Patients on hemodialysis often suffer from reduced muscle strength and exercise capacity due to the decreased quantity and quality of muscle. Cumulative studies showed ultrasound echo intensity (EI) had great potential in evaluating muscle quality. The objective of this study was to evaluate the relationship between EI of skeletal muscle and physical function of patients on maintenance hemodialysis. METHODS: Cross-sectional area (CSA) and mean EI of the right rectus femoris were measured by ultrasound to evaluate the quantity and quality of the muscle, respectively. Physical function was measured by handgrip strength (HGS), gait speed, sit-to-stand 60 s (STS-60) test, and instrumental activities of daily living (IADL) scale. RESULTS: A total of 107 patients on hemodialysis were included, with women accounting for 37.3% (n = 40), and a mean age of 53.53 ± 12.52 years. Among the patients on hemodialysis, EI was moderately and negatively correlated with HGS (r = - 0.467, P < 0.001), gait speed (r = - 0.285, P = 0.003), and STS-60 (r = - 0.313, P = 0.001). Multiple regression analyses adjusted for CSA showed that the enhanced EI of patients on hemodialysis remained associated with worse HGS (ß = - 0.207, P = 0.047), lower gait speed (ß = - 0.002, P = 0.001), less STS-60 (ß = - 0.136, P = 0.049), and a higher likelihood of dependency in IADL (Odds Ratio: 1.070, 95% CI: [1.033-1.111], P = 0.001). CONCLUSIONS: In patients on hemodialysis, enhanced EI in the skeletal muscle measured via ultrasound was correlated with poor physical performance. The combined muscle quality and muscle quantity evaluation provide more information for assessing the level of physical function of the patients.

Three-dimensional morphological analysis of quadrilateral plate fragments in associated both-column acetabular fractures.

OBJECTIVE: To investigate whether the fracture morphology of quadrilateral plate (QP) fragments is associated with the anterior and posterior columns in associated both-column (ABC) fractures. MATERIALS AND METHODS: Three-dimensional computed tomography data of 100 ABC fractures treated at our hospital from August 2016 to August 2019 were retrospectively analyzed using Mimics and 3-matic software. The distribution of fracture lines was described using the fracture mapping technique. RESULTS: One fragment presented on the QP was confirmed in 88% of the patients. The QP fragments' fracture lines were divided into the anterior oblique (AO), superior posterior oblique (SPO), and mid-posterior oblique (MPO) lines, occurring in 100, 86, and 8 cases, respectively. AO lines were distributed along the arcuate line. SPO lines were continuations of the AO lines, which were distributed to the posterior column from the greater sciatic notch to the lesser sciatic notch. MPO lines were involved in the QP's central area. A simple fracture was found at the proximal AO and SPO lines in 80% and 86% of all displaced fractures, respectively. AO lines distal to the superior rim of the acetabula were confirmed to be comminuted fractures in 32% of all cases. CONCLUSIONS: In ABC fractures, there was only one QP fragment in nearly 90% of all cases. The QP fractures were mainly present in the QP's peripheral area. More than 80% of the fracture patterns on the cephalic side of the QP were simple. The reduction and internal fixation of QP fractures in ABC fractures should be in the cephalic region.

Graphitic-N-doped graphene quantum dots for photothermal eradication of multidrug-resistant bacteria in the second near-infrared window.

Developing efficient therapeutic strategies for combating bacterial infection remains a challenge owing to the indiscriminate utilization of antibiotics and the prevalence of multidrug-resistant (MDR) bacteria. Herein, highly graphitic-N-doped graphene quantum dots (N-GQDs) with efficient NIR-II photothermal conversion properties were synthesized for the first time for photothermal antibacterial therapy. The obtained N-GQDs exhibited strong NIR absorption ranging from 700 to 1200 nm, achieving high photothermal conversion efficiency of 77.8% and 50.4% at 808 and 1064 nm, respectively. Outstanding antibacterial and antibiofilm activities against MDR bacteria (methicillin-resistant Staphylococcus aureus, MRSA) were achieved by the N-GQDs in the presence of an 808 or 1064 nm laser. In vivo investigations verified that the generation of hyperthermia by N-GQDs plus a NIR-II laser can combat MDR bacterial infections and thus significantly accelerate wound healing. Our work provides a novel carbon-based nanomaterial as a photothermal antibacterial agent for efficiently avoiding bacterial resistance and fighting MDR bacterial infections.

Platinum Crosslinked Carbon Dot@TiO2-x p-n Junctions for Relapse-Free Sonodynamic Tumor Eradication via High-Yield ROS and GSH Depletion.

Sonodynamic therapy as a promising noninvasive modality is being developed for tumor therapy, but there is a lack of next-generation sonosensitizers that can generate full ROS at high yields and simultaneously deplete elevated levels of glutathione (GSH) in tumor cells. Semiconductor p-n junctions are engineered as high-efficacy sonosensitizers for sonodynamic tumor eradication using pyridine N-doped carbon dots (N-CDs) as a p-type semiconductor and oxygen-deficient TiO2-x nanosheets as a n-type semiconductor. The rate constants of 1 O2 and •OH generation by ultrasound-excited N-CD@TiO2-x p-n junctions are 4.3 and 4.5 times higher than those of TiO2 , respectively. A Z-scheme carrier migration mechanism in the p-n junction achieving the rapid spatial separation of the ultrasound-generated electron-hole pairs for enhanced full ROS production is proposed. GSH-cleavable, Pt-crosslinked, N-doped CD fluorescent probes to detect the presence of intracellular GSH are also constructed. A GSH-responsive, p-n junction platform (Pt/N-CD@TiO2-x ) with integrated GSH detection, GSH depletion, and enhanced sonodynamic performance is then assembled. Malignant tumors are completely eradicated without relapse via intravenous administration of low-dose Pt/N-CD@TiO2-x under ultrasound irradiation. This work substantiates the great potential of biocompatible, GSH-responsive p-n junctions as next-generation sonosensitizers via p-n junction-enhanced ROS generation and metal ion oxidation of intracellular GSH.

W-Doped TiO2 Nanorods for Multimode Tumor Eradication in Osteosarcoma Models under Single Ultrasound Irradiation.

Sonosensitizers play crucial roles in the controlled production of reactive oxygen species (ROS) under ultrasound (US) irradiation with high tissue-penetration depth for noninvasive solid tumor therapy. It is desirable to fabricate structurally simple yet multifunctional sonosensitizers from ultrafine nanoparticles for ROS-based multimode therapy to overcome monomode limitations such as low ROS production yields and endogenous reductive glutathione (GSH) to ROS-based treatment resistance. We report the facile high-temperature solution synthesis of ultrafine W-doped TiO2 (W-TiO2) nanorods for exploration of their sonodynamic, chemodynamic, and GSH-depleting activities in sonodynamic-chemodynamic combination tumor therapy. We found that W5+ and W6+ ions doped in W-TiO2 nanorods play multiple roles in enhancing their ROS production. First, W doping narrows the band gap from 3.2 to 2.3 eV and introduces oxygen and Ti vacancies for enhancing their sonodynamic performance. Second, W5+ doping endows W-TiO2 nanorods with Fenton-like reaction activity to produce •OH from endogenous H2O2 in the tumor. Third, W6+ ions reduce endogenous GSH to glutathione disulfide (GSSG) and, in turn, form W5+ ions that further enhance their chemodynamic activity, which greatly modifies thae oxidation-reduction tumor microenvironment in the tumor. In vivo experiments display the excellent ability of W-TiO2 nanorods for enhanced tumor eradication in human osteosarcoma models under single US irradiation. Importantly, the ultrafine nanorod morphology facilitates rapid excretion from the body, displaying no significant systemic toxicity. Our work suggests that multivalent metal doping in ultrafine nanomaterials is an effective and simple strategy for the introduction of new functions for ROS-based multimode therapy.

Carbon Dot-Passivated Black Phosphorus Nanosheet Hybrids for Synergistic Cancer Therapy in the NIR-II Window.

Metal-free layered black phosphorus (BP) nanosheets with an excellent photothermal effect and large surface areas have been widely applied in biomedicine but are easily oxidized in ambient conditions yielding insulating phosphorus oxides adsorbed on its surface. Several chemical-functionalized strategies have been explored to protect thin layers of BP; however, the performance of passivated BP often decreases significantly, falling behind the single BP due to the strong structure perturbation. Herein, we designed and constructed 0D/2D hybrid photothermal agents by assembling NIR-II-responsive carbon dots (NIR-II-CDs) on BP nanosheets. NIR-II-CDs improve the ambient stability of BP by isolating them from water and oxygen and enhance the photothermal properties of BP nanosheets. Such NIR-II-CD/BP hybrids strengthen the light-harvesting ability, achieving high photothermal conversion efficiencies in the NIR-I (77.3%) and NIR-II (61.4%) windows, which is significantly higher than that of pristine BP (49.5 and 28.4% at 808 and 1064 nm). Owing to the intrinsic advantage of 1064 nm laser and the excellent PTT effect of our NIR-II-CD/BP hybrids, complete tumor eradication was realized in a deep-tissue tumor model.

Circ-Spidr enhances axon regeneration after peripheral nerve injury.

Accumulating evidence suggests that circular RNAs (circRNAs) are abundant and play critical roles in the nervous system. However, their functions in axon regeneration after neuronal injury are unclear. Due to its robust regeneration capacity, peripheral nervous system is ideal for seeking the regulatory circRNAs in axon regeneration. In the present work, we obtained an expression profile of circRNAs in dorsal root ganglions (DRGs) after rat sciatic nerve crush injury by RNA sequencing (RNA-Seq) and found the expression level of circ-Spidr was obviously increased using quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, circ-Spidr was proved to be a circular RNA enriched in the cytoplasm of DRG neurons. Through in vitro and in vivo experiments, we determined that down-regulation of circ-Spidr could suppress axon regeneration of DRG neurons after sciatic nerve injury partially through modulating PI3K-Akt signaling pathway. Together, our results reveal a crucial role for circRNAs in regulating axon regeneration after neuronal injury which may further serve as a potential therapeutic avenue for neuronal injury repair.