Fe3O4@polydopamine nanoparticle-loaded human umbilical cord mesenchymal stem cells improve the cognitive function in Alzheimer's disease mice by promoting hippocampal neurogenesis.

One of the most promising treatments for neurodegenerative diseases is the stem cell therapy; however, there are still some limitations in the treatment of Alzheimer's disease. In this study, superparamagnetic nanoparticles composed of magnetic Fe3O4 and polydopamine shells were used to label human umbilical cord mesenchymal stem cells (hUC-MSCs) in order to increase the targeting of hUC-MSCs. Our data suggested that Fe3O4@PDA labeling increase the efficiency of hUC-MSCs entering the brain. Moreover, the water maze test showed that compared with hUC-MSCs only, Fe3O4@PDA-labeled hUC-MSCs improved the cognitive ability of APP/PS1 transgenic mice more significantly. Other experimental data showed that the expression of essential proteins in the hippocampus, such as Aß, synaptophysin, brain-derived neurotrophic factor, are affected by Fe3O4@PDA coated-hUC-MSCs. The regulation of Fe3O4@PDA coated-hUC-MSCs could improve the memory and cognitive ability of AD mice by excessive generation of neuroprotective factors, which might be considered a viable therapy to treat AD.

Influencing Factors of Horizontal Movement Distance of Bodies in High Falling Deaths.

OBJECTIVES: To explore the influencing factors of the horizontal distance of bodies in the high falling scene and the feasibility of inferring the falling mode based on it. METHODS: A total of 614 high falling deaths and 15 cases of corpse dumping from high altitudes were collected. The relationship between the horizontal distance and the falling height, as well as the sex, age and manner of death (suicide, accident and corpse dumping) were observed. RESULTS: The horizontal distance increased with the increase of falling height, and the difference among the height groups was statistically significant. The horizontal distance decreased with the increase of the age of the deceased, in each height group, the difference between the group over 60 years old and other age groups was statistically significant (P<0.05). The horizontal distance of male deceased was (1.99±0.27) m, which was greater than that of female deceased (1.88±0.19) m, and the difference was statistically significant in partial height groups (P<0.05). Roof falls had a greater horizontal movement distance than window falls. Except for the >20-30 m group, there was no significant difference in horizontal distance between suicide high falls and accidental high falls in other height groups. CONCLUSIONS: The horizontal distance is affected by the falling height, the sex and age of the victim, and the spatial characteristics of the falling starting point.

LncRNA HCP5 as a potential therapeutic target and prognostic biomarker for various cancers: a meta­analysis and bioinformatics analysis.

BACKGROUND: Accumulating studies indicated that dysregulated long non-coding RNA human histocompatibility leukocyte antigen (HLA) Complex P5 (HCP5) may functions as an potential prognostic predictor in multiple cancers. This meta-analysis was performed to systematically collect studies and conduct an evidence-based evaluation of the prognostic role of HCP5 in malignancies. METHODS: Four databases (PubMed, Web of Science, Embase and Cochrane library) were comprehensively retrieved from their initiation date to November 9, 2021. Hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) were used to assess the associations between the expression level of HCP5 and prognosis or clinical characteristics. Moreover, results were validated by Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and the National Genomics Data Center (NGDC). Subsequently, the molecular mechanism of HCP5 was predicted based on MEM and StarBase databases. The study protocol was registered at PROSPERO (ID: CRD42021274208). RESULTS: 9 studies, containing 641 patients, were included in this meta-analysis. Our results revealed that HCP5 overexpression was associated with poor overall survival (OS), tumor type, histological differentiation, and lymph node metastasis in most cancers, but was not associated with age, gender and tumor size; down-regulation of HCP5 was associated with worse OS, advanced tumor stage, positive distal metastasis and lymph node metastasis in skin cutaneous melanoma (SKCM). HCP5 was significantly up-regulated in four cancers and down-regulated in SKCM, which was validated by the GEPIA2 cohort. HCP5 expression in various types of cancer was also verified in NGDC. Further functional prediction revealed that HCP5 may participate in some cancer-related pathways. CONCLUSION: There is a significantly association between dysregulation of HCP5 and both prognosis and clinicopathological features in various cancers. HCP5 may be functions as a novel potential prognostic biomarker and therapeutic target in multiple human cancers.

IL1ß inhibits differentiation of cementoblasts via microRNA-325-3p.

Cementum regeneration is considered the gold standard for the treatment of periodontitis. As one of the most important primary proinflammatory cytokines, interleukin 1ß (IL1ß) plays an essential role during the early stage of periodontitis and its amounts simultaneously increase dramatically during this stage. Though promising, the differentiation of cementoblasts upon IL1ß-induced inflammation of the microenvironment and the relative interaction mechanism are still unknown. Here, we found that IL1ß inhibited cementoblast differentiation and microRNA-325-3p (miR-325-3p) was increased during IL1ß-stimulated cementoblasts. Bioinformatics analysis and luciferase reporter assay demonstrated miR-325-3p targeted runt-related transcription factor 2 directly. Transfection of miR-325-3p suppressed cementoblast differentiation in vitro and the formation of cementum-like tissues in vivo. The inhibitor of miR-325-3p could mitigate the above effects induced by IL1ß. Accordingly, our finding suggests a critical role of miR-325-3p in linking inflammation to impaired cementum regeneration and provides a potential possibility for applying miR-325-3p inhibitors in the treatment of periodontitis-related bone loss.

The interference of DEHP in precocious puberty of females mediated by the hypothalamic IGF-1/PI3K/Akt/mTOR signaling pathway.

DEHP is reported to cause precocious puberty of females in both humans and rodents, but the underlying mechanisms were largely unknown. This study was designed to clarify the effects and the mechanisms of DEHP on the pathogenesis of sexual precocity. Prepubertal female rats were treated with DEHP for 4 weeks. Key organs were analyzed in control conditions and after exposure to 0.2, 1, and 5 mg/kg/day DEHP in pubertal female rats. To determine the role of the IGF-1/PI3K/Akt/mTOR signaling pathway in DEHP-induced female precocious puberty, 36 rats were treated with 5 mg/kg/day DEHP to establish a model of female precocious puberty. And we investigated the expression of genes and proteins related to IGF-1 pathway in rat hypothalamus after treatment with inhibitors. In the present study, we observed that DEHP treatment resulted in earlier vaginal opening time, higher number of Nissl bodies in the hypothalamus neurons, lower apoptosis of hypothalamic cells, higher IGF-1 and GnRH levels in the serum and hypothalamus. DEHP could also upregulated the expression of IGF-1/PI3K/Akt/mTOR pathway and GnRH in the hypothalamus of adolescent female rats, and inhibition of IGF-1R and mTOR in hypothalamus could block the activation of Kiss-1, GPR54, and GnRH by DEHP. In summary, our study suggested that DEHP might activate the hypothalamic GnRH neurons prematurely through the IGF-1 signaling pathway and promote GnRH release, leading to the initiation of female sexual development. Our results provide a new molecular mechanism underlying reproductive and developmental toxicity in pubertal female rats induced by DEHP.

Impact of acetabular reaming depth on reconstruction of rotation center in primary total hip arthroplasty.

PURPOSE: To study the impact of acetabular reaming depth on reconstruction of rotation center (RC) in unilateral primary total hip arthroplasty (UPTHA) and guide individualized preoperative design. METHODS: 200 postoperative standard bilateral hip anteroposterior radiographs after UPTHA were included, which were collected from January, 2013 to June, 2017 in our hospital. Osteonecrosis of femoral head was the only diagnosis in this cohort. The parameters were measured on the anteropoterior radiographs by using RadiAnt DICOM viewer. RESULTS: The average of the thickness of the teardrop is about 6.13 ± 1.42 mm. The parameter a (the difference value of the distance of bilateral RC and midline) was positively correlated with the parameter e (the acetabular reaming depth), and the Pearson correlation coefficient was 0.49 when P = 0.05. Furthermore, the value of parameter (e) was 8.25 mm when a2 (the distance from the center of the prosthesis femoral head to the vertical line across the midpoint of pubic symphysis) equaled a1 (the distance from RC of the healthy femoral head to the vertical line across the midpoint of pubic symphysis). CONCLUSIONS: The reaming depth of the acetabulum could influence the reconstruction of RC during UPTHA. When the medial margin of the cup was placed about 2 mm to the lateral border of the ipsilateral teardrop (the bottom of the ovum), the rotation center would be accurately restored.

Glenoid morphology and the safe zone for protecting the suprascapular nerve during baseplate fixation in reverse shoulder arthroplasty.

PURPOSE: The purpose of this study was to investigate glenoid morphology and define the safe zone for protecting the suprascapular nerve baseplate screw during baseplate fixation in reverse shoulder arthroplasty (RSA) in a Chinese population. METHODS: Shoulder computed tomography (CT) scans from 56 subjects were retrospectively reviewed. Three-dimensional (3D) reconstruction was performed using Mimics software, and corresponding bony references were used to evaluate glenoid morphology. To standardize evaluation, the coronal scapular plane was defined. Safe fixation distances and screw placements were investigated by constructing a simulated cutting plane of the baseplate during RSA. RESULTS: Mean glenoid height was 35.83 ± 2.95 mm, and width was 27.32 ± 2.78 mm, with significant sexual dimorphism (p < 0.01). According to the cutting plane morphology, the average baseplate radius was 13.84 ± 1.34 mm. The distances from the suprascapular notch and from two bony reference points at the base of the scapular spine to the cutting plane were 30.27 ± 2.77 mm, 18.39 ± 1.67 mm and 16.52 ± 1.52 mm, respectively, with a gender-related difference. Based on the clock face indication system, the danger zone caused by the suprascapular nerve projection was oriented between the two o'clock and eight o'clock positions in reference to the right shoulder. CONCLUSIONS: Glenoid size and the safe zone for screw fixation during RSA were characterized in a Chinese population. Careful consideration of baseplate fixation and avoidance of suprascapular nerve injury are important for improved clinical outcome.

Dynamical analysis of strongly nonlinear fractional-order Mathieu-Duffing equation.

In this paper, the computation schemes for periodic solutions of the forced fractional-order Mathieu-Duffing equation are derived based on incremental harmonic balance (IHB) method. The general forms of periodic solutions are founded by the IHB method, which could be useful to obtain the periodic solutions with higher precision. The comparisons of the approximate analytical solutions by the IHB method and numerical integration are fulfilled, and the results certify the correctness and higher precision of the solutions by the IHB method. The dynamical analysis of strongly nonlinear fractional-order Mathieu-Duffing equation is investigated by the IHB method. Then, the effects of the excitation frequency, fractional order, fractional coefficient, and nonlinear stiffness coefficient on the complex dynamical behaviors are analyzed. At last, the detailed results are summarized and the conclusions are made, which present some useful information to analyze and/or control the dynamical response of this kind of system.

Interaction of proteins with aluminum(III)-chlorophosphonazo III by resonance Rayleigh scattering method.

In weak acid medium, aluminum(III) can react with chlorophosphonazo III [CPA(III), H(8)L] to form a 1:1 coordination anion [Al(OH)(H(4)L)](2-). At the same time, proteins such as bovine serum albumin (BSA), lysozyme (Lyso) and human serum albumin (HSA) existed as large cations with positive charges, which further combined with [Al(OH)(H(4)L)](2-) to form a 1:4 chelate. This resulted in significant enhancement of resonance Rayleigh scattering (RRS), second-order scattering (SOS) and frequency doubling scattering (FDS). In this study, we investigated the interaction between [Al(OH)(H(4)L)](2-) and proteins, optimization of the reaction conditions and the spectral characteristics of RRS, SOS and FDS. The maximum RRS wavelengths of different protein systems were located at 357-370 nm. The maximum SOS and FDS wavelengths were located at 546 and 389 nm, respectively. The scattering intensities (ΔI) of the three methods were proportional to the concentration of the proteins, within certain ranges, and the detection limits of the most sensitive RRS method were 2.6-9.3 ng/mL. Moreover, the chelate reaction mechanism or the reasons for the enhancement of RRS were discussed through absorption spectra, fluorescence spectra and circular dichroism (CD) spectra.

Thermodynamics-Guided High-Throughput Discovery of Eutectic High-Entropy Alloys for Rapid Solidification.

Excellent castability, significantly refined microstructure, and good mechanical properties make eutectic high-entropy alloys (EHEAs) a natural fit for rapid solidification processes, e.g., additive manufacturing. Previous investigations have focused on developing EHEAs through trial and error and mixing known binary eutectic materials. However, eutectic compositions obtained from near-equilibrium conditions do not guarantee a fully eutectic microstructure under rapid solidifications. In this work, a thermodynamically guided high-throughput framework is proposed to design EHEAs for rapid solidification. Empirical formulas derived from past experimental observations and thermodynamic computations are applied and considered phase growth kinetics under rapid solidification (skewed phase diagram). The designed alloy candidate, Co25.6Fe17.9Ni22.4Cr19.1Ta8.9Al6.1 (wt.%), contains nanostructured eutectic lamellar and shows a high Vickers hardness of 675 Hv. In addition to this specific composition, the alloy design toolbox enables the development of new EHEAs for rapid solidification without the limitation of previous knowledge.

Fluorescence quenching method for the determination of carbazochrome sodium sulfonate with aromatic amino acids.

In Britton-Robinson (BR) buffer medium (pH 3.3), carbazochrome sodium sulfonate (CSS) can react with some aromatic amino acids such as tryptophan (Trp), tyrosine (Tyr) and phenylalanine (Phe) to form a 1:1 complex by electrostatic attraction, aromatic stacking interaction and Van der Waals' force, resulting in fluorescence quenching of these amino acids. Maximum quenching wavelengths were located at 352 nm (CSS-Trp system), 303 nm (CSS-Tyr system) and 284 nm (CSS-Phe system), respectively. The fluorescence quenching value (ΔF) was proportional to the concentration of CSS in a certain range. The fluorescence quenching method for the determination of CSS showed high sensitivity, with detection limits of 31.3 ng/mL (CSS-Trp system), 44.6 ng/mL (CSS-Tyr system) and 315.0 ng/mL (CSS-Phe system), respectively. The optimum conditions of the reaction conditions and the effect of coexisting substances were investigated and results showed that the method had good selectivity. The method was successfully applied for the rapid determination of CSS in blood and urine samples. Based on the bimolecular quenching constant Kq , the effect of temperature and Stern-Volmer plots, this study showed that quenching of fluorescence of amino acids by CSS was a static quenching process.

Linear measurements of healthy adults' coronal section of hippocampus on brain magnetic resonance imaging.

To figure out hippocampal anatomy features, which can be used as reference in determination of hippocampus-related disease, we rebuilt 3-dimensional brain models with magnetic resonance imaging; then, we chose 1 coronal section of the hippocampus and took 22 linear measurements of each section in 74 healthy adults. In each section, we took paired sample T test for the left and right measurements comparison, independent sample T test for sex difference comparison, and correlation analysis for relationships between age and other measurements. For the left and right comparison, 9 measurements have no significant difference (P > 0.05). For sex difference, 8 measurements have significant differences (P < 0.05). In age linear regression analysis, 5 measurements have significance in statistical analysis. All results above demonstrate that measurements of this section have little significance in L/R difference, but for different sexes, these measurements show significant results, which means male and female were different. As for age linear regression analysis, brain shape and distances were age related. This study provides reference for diagnosis of hippocampal atrophy, and it is an easy approach instead of areal and volumetric measurements in clinical practice.

Combined surface functionalization of MSC membrane and PDA inhibits neurotoxicity induced by Fe3O4 in mice based on apoptosis and autophagy through the ASK1/JNK signaling pathway.

The extensive utilization of iron oxide nanoparticles in medical and life science domains has led to a substantial rise in both occupational and public exposure to these particles. The potential toxicity of nanoparticles to living organisms, their impact on the environment, and the associated risks to human health have garnered significant attention and come to be a prominent area in contemporary research. The comprehension of the potential toxicity of nanoparticles has emerged as a crucial concern to safeguard human health and facilitate the secure advancement of nanotechnology. As nanocarriers and targeting agents, the biocompatibility of them determines the use scope and application prospects, meanwhile surface modification becomes an important measure to improve the biocompatibility. Three different types of iron oxide nanoparticles (Fe3O4, Fe3O4@PDA and MSCM-Fe3O4@PDA) were injected into mice through the tail veins. The acute neurotoxicity of them in mice was evaluated by measuring the levels of autophagy and apoptosis in the brain tissues. Our data revealed that iron oxide nanoparticles could cause nervous system damage by regulating the ASK1/JNK signaling pathway. Apoptosis and autophagy may play potential roles in this process. Exposure to combined surface functionalization of mesenchymal stem cell membrane and polydopamine showed the neuroprotective effect and may alleviate brain nervous system disorders.

Development of a new, fully automated system for electron backscatter diffraction (EBSD)-based large volume three-dimensional microstructure mapping using serial sectioning by mechanical polishing, and its application to the analysis of special boundaries in 316L stainless steel.

We report the development of a fully automatic large-volume 3D electron backscatter diffraction (EBSD) system (ELAVO 3D), consisting of a scanning electron microscope (ZEISS crossbeam XB 1540) with a dedicated sample holder, an adapted polishing automaton (Saphir X-change, QATM), a collaborative robotic arm (Universal Robots UR5), and several in-house built devices. The whole system is orchestrated by an in-house designed software, which is also able to track the process and report errors. Except for the case of error, the system runs without any user interference. For the measurement of removal thickness, the samples are featured with markers put on the perpendicular lateral surface, cut by plasma focused ion beam (PFIB) milling. The individual effects of both 1 µm diamond suspension and oxide polishing suspension polishing were studied in detail. Coherent twin grain boundaries (GBs) were used as an internal standard to check the removal rates measured by the side markers. The two methods for Z-spacing measurements disagreed by about 10%, and the inaccurate calibration of the PFIB system was found to be the most probable reason for this discrepancy. The angular accuracy of the system was determined to be ∼2.5°, which can be significantly improved with more accurate Z-spacing measurements. When reconstructed grain boundary meshes are sufficiently smoothed, an angular resolution of ±4° is achieved. In a 3D EBSD dataset of a size of 587 × 476 × 72 µm3, we focused on the investigation of coincidence site lattice ∑9 GBs. While bearing predominantly a pure tilt character, ∑9 GBs can be categorized into three groups based on correlative 3D morphologies and crystallography.

Advantages of interstitial radioactive seed implantation for the treatment of Stage III pancreatic cancer.

OBJECTIVE: The objective of the study was to identify the advantages of interstitial radioactive seed implantation for the treatment of Stage III pancreatic cancer. MATERIALS AND METHODS: Clinical data of 160 patients with pancreatic cancer implanted with radioactive seeds were retrospectively analyzed. Patients were grouped according to tumor size, lymph node metastasis, and tumor invasion to important blood vessels, and survival time statistics were obtained. RESULTS: The mean postoperative survival time (months) was 24.80 for Stage I, 12.89 for Stage II, 13.51 for Stage III, and 7.49 for Stage IV patients, and the difference between Stage II and Stage III patients was not statistically significant. The efficacy of radioactive seed implantation therapy for pancreatic cancer was strongly associated with tumor size and number of lymph node metastases but not significantly associated with tumor invasion to blood vessels. CONCLUSIONS: Radioactive seed implantation obviously advantageous for the treatment of Stage III pancreatic cancer.

Co-modification with MSC membrane and PDA prevents Fe3O4-induced pulmonary toxicity in mice via AMPK-ULK1 axis.

Fe3O4 nanoparticles are widely used in the diagnosis and treatment of diseases due to their superparamagnetism, but their toxicity in vivo, which can result in apoptosis or autophagy, cannot be ignored. It has been reported that polydopamine (PDA) modification can reduce the toxicity of Fe3O4 and increase its biocompatibility. However, more research is warranted to further improve the modification method. We therefore developed a new method to coat Fe3O4@PDA nanoparticles with the mesenchymal stem cell membrane (MSCM) and evaluated the toxicity of the modified particles in the lungs of mice. We found that the MSCM modification significantly reduced lung injury induced by Fe3O4 particles in mice. Compared with Fe3O4@PDA nanoparticles, co-modification with MSCM and PDA significantly reduced autophagy and apoptosis in mouse lung tissue, and reduced activation of autophagy mediated by the AMPK-ULK1 pathway axis. Thus, co-modification with MSCM and PDA prevents Fe3O4-induced pulmonary toxicity in mice by inhibiting autophagy, apoptosis, and oxidative stress.

Glycolysis Rate-Limiting Enzymes: Novel Potential Regulators of Rheumatoid Arthritis Pathogenesis.

Rheumatoid arthritis (RA) is a classic autoimmune disease characterized by uncontrolled synovial proliferation, pannus formation, cartilage injury, and bone destruction. The specific pathogenesis of RA, a chronic inflammatory disease, remains unclear. However, both key glycolysis rate-limiting enzymes, hexokinase-II (HK-II), phosphofructokinase-1 (PFK-1), and pyruvate kinase M2 (PKM2), as well as indirect rate-limiting enzymes, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), are thought to participate in the pathogenesis of RA. In here, we review the latest literature on the pathogenesis of RA, introduce the pathophysiological characteristics of HK-II, PFK-1/PFKFB3, and PKM2 and their expression characteristics in this autoimmune disease, and systematically assess the association between the glycolytic rate-limiting enzymes and RA from a molecular level. Moreover, we highlight HK-II, PFK-1/PFKFB3, and PKM2 as potential targets for the clinical treatment of RA. There is great potential to develop new anti-rheumatic therapies through safe inhibition or overexpression of glycolysis rate-limiting enzymes.

Osteomyelitis variolosa, an issue inherited from the past: case report and systematic review.

BACKGROUND: Osteomyelitis variolosa is a self-limiting disease triggered by variola virus that cannot be prevented or repaired. Smallpox has been eradicated for 40 years, and complications that remain after smallpox has been cured have become a remarkable diagnostic challenge for contemporary physicians. In this systematic review, we searched PubMed (MEDLINE), Web of Science, and Google Scholar for cases on complications, diagnosis, and treatment for osteomyelitis variolosa between January 1980 and February 2021. RESULTS: Ten papers and eleven finished cases, all patients from India, were included for comparison with the present case. In total, 100% of patients presented with bilateral elbow deformities, the ankle was the second most common site of lesion in 50%, and knee lesions accounted for 25% in this study. Flexion contracture, joint instability, secondary arthritis, and fracture are common complications of osteomyelitis variolosa, and most patients receive conservative treatment, while internal fixation has good results for combined fractures. CONCLUSIONS: Although osteomyelitis variolosa is not a direct threat to the safety of patients, severe skeletal deformities can have a significant impact on quality of life. With advances in surgical techniques, clinicians are offering an increasing number of treatment options for patients with osteomyelitis variolosa. However, most importantly, smallpox has basically been removed from the historical arena, and for areas where smallpox was once endemic, physicians need to deepen the understanding of this disease again.

Polydopamine Nanoparticles Camouflaged by Stem Cell Membranes for Synergistic Chemo-Photothermal Therapy of Malignant Bone Tumors.

PURPOSE: Nanoparticle (NP)-based chemo-photothermal therapy (CPT) has been shown to be a promising non-invasive approach for antitumor treatment. However, NPs must overcome the limitations of opsonization, clearance of the reticuloendothelial system, and ineffective targeting of tumor tissue sites. To solve these problems, stem cell membrane (SCM)-camouflaged polydopamine nanoparticles (PDA@SCM NPs) carrying the hydrophobic anticancer drug 7-ethyl-10-hydroxycamptothecin (SN38) were constructed for CPT of malignant bone tumors. METHODS: We developed umbilical-cord mesenchymal stem cell membrane-coated polydopamine nanoparticles encapsulating SN38 (PDA-SN38@SCM NPs) as an efficient tumor-targeting drug-delivery platform for CPT of malignant bone tumors. We characterized PDA@SCM NPs and evaluated the biocompatibility and anti-phagocytosis properties of PDA@SCM NPs. The antitumor activity of PDA-SN38@SCM NPs was evaluated in MG63 lines and an MG63 xenograft model in mice. RESULTS: Synthesized PDA-SN38@SCM NPs retained an excellent photothermal effect after SN38 loading. The drug release of PDA-SN38@SCM NPs could be triggered by near-infrared irradiation and an acidic stimulus. PDA@SCM NPs exhibited lower nonspecific macrophage uptake, longer retention in blood, and more effective accumulation at tumor sites than that shown by PDA NPs. Confocal laser scanning microscopy (CLSM) and flow cytometry showed that MG63 cells took up more PDA-SN38@SCM NPs than PDA-SN38 NPs. In vitro and in vivo antitumor studies demonstrated the outstanding performance of PDA-SN38@SCM NPs in synergistic CPT for bone tumors. CONCLUSION: PDA-SN38@SCM NPs demonstrated an extraordinary synergistic CPT effect and could be a promising strategy for the treatment of malignant bone tumors.