METTL16 promotes osteosarcoma progression by downregulating VPS33B in an m6 A-dependent manner.

N6-methyladenosine (m6 A) is one of the main epitranscriptomic modifications that accelerates the progression of malignant tumors by modifying RNA. Methyltransferase-like 16 (METTL16) is a newly identified methyltransferase that has been found to play an important oncogenic role in a few malignancies; however, its function in osteosarcoma (OS) remains unclear. In this study, METTL16 was found to be upregulated in OS tissues, and associated with poor prognosis in OS patients. Functionally, METTL16 substantially promoted OS cell proliferation, migration, and invasion in vitro and OS growth in vivo. Mechanistically, vacuolar protein sorting protein 33b (VPS33B) was identified as the downstream target of METTL16, which induced m6 A modification of VPS33B and impaired the stability of the VPS33B transcript, thereby degrading VPS33B. In addition, VPS33B was found to be downregulated in OS tissues, VPS33B knockdown markedly attenuated shMETTL16-mediated inhibition on OS progression. Finally, METTL16/VPS33B might facilitate OS progression through PI3K/AKT pathway. In summary, this study revealed an important role for the METTL16-mediated m6 A modification in OS progression, implying it as a promising target for OS treatment.

High-Density Au Anchored to Ti3C2-Based Colorimetric-Fluorescence Dual-Mode Lateral Flow Immunoassay for All-Domain-Enhanced Performance and Signal Intercalibration.

In this work, a novel MXene-Au nanoparticle (Ti3C2@Au) was synthesized with a high molar extinction coefficient, strong fluorescence quenching ability, ultrahigh antibody affinity, high stability, and good dispersibility, and it was used to develop a colorimetric-fluorescence dual-mode lateral flow immunoassay (LFIA). The detection limits of this method for the detection of dexamethasone in milk, beef, and pork were 0.0018, 0.12, and 0.084 µg/kg in the "turn-off" mode (colorimetric signal), and 0.0013, 0.080, and 0.070 µg/kg in the "turn-on" mode (fluorescent signal), respectively, which was up to 231-fold more sensitive compared with that of the reported LFIAs. The recovery rates ranged from 81.1-113.7%, and 89.2-115.4%, with the coefficients of variation ranging from 1.4-15.0%, and 1.9-14.8%, respectively. The results of the LC-MS/MS confirmation test on 30 real samples had a good correlation with that of our established method (R2 > 0.97). This work not only developed novel nanocarriers for antibody-based LFIA but also ensured high-performance detection.

Bruceantinol targeting STAT3 exerts promising antitumor effects in in vitro and in vivo osteosarcoma models.

Bruceantinol (BOL) is a quassinoid compound found in the fruits of Brucea javanica. Previous research has highlighted the manifold physiological and pharmacological activities of BOL. Notably, BOL has demonstrated antitumor cytotoxic and antibacterial effects, lending support to its potential as a promising therapeutic agent for various diseases. Despite being recognized as a potent antitumor inhibitor in multiple cancer types, its efficacy against osteosarcoma (OS) has not been elucidated. In this work, we investigated the antitumor properties of BOL against OS. Our findings showed that BOL significantly decreased the proliferation and migration of OS cells, induced apoptosis, and caused cell death without affecting the cell cycle. We further confirmed that BOL potently suppressed tumor growth in vivo. Mechanismly, we discovered that BOL directly bound to STAT3, and prevent the activation of STAT3 signaling at low nanomolar concentrations. Overall, our study demonstrated that BOL potently inhibited the growth and metastasis of OS, and efficiently suppressed STAT3 signaling pathway. These results suggest that BOL could be a promising therapeutic candidate for OS.

Clinical characteristics analysis of pediatric spinal cord injury without radiological abnormality in China: a retrospective study.

PURPOSE: This study aims to analyze the clinical characteristics of Chinese children with spinal cord injury (SCI) without radiographic abnormality (SCIWORA) and explore their contributing factors and mechanisms of occurrence. METHODS: A retrospective analysis was conducted on the clinical data of pediatric patients diagnosed with SCIWORA from January 2005 to May 2020. Epidemiological, etiological, mechanistic, therapeutic, and outcome aspects were analyzed. RESULTS: A total of 47 patients with SCIWORA were included in this study, comprising 16 males and 31 females. The age range was 4 to 12 years, with an average age of 7.49 ± 2.04 years, and 70% of the patients were below eight. Sports-related injuries constituted 66%, with 70% attributed to dance backbend practice. Thoracic segment injuries accounted for 77%. In the American Spinal Injury Association (ASIA) classification, the combined proportion of A and B grades accounted for 88%. Conservative treatment was chosen by 98% of the patients, with muscle atrophy, spinal scoliosis, hip joint abnormalities, and urinary system infections being the most common complications. CONCLUSION: SCIWORA in Chinese children is more prevalent in those under eight years old, with a higher incidence in females than males. Thoracic spinal cord injuries are predominant, dance backbend as a primary contributing factor, and the social environment of "neijuan" is a critical potential inducing factor. Furthermore, the initial severity of the injury plays a decisive role in determining the prognosis of SCIWORA.

Magnetic Field Boosts the Transmembrane Transport Efficiency of Magnesium Ions from PLLA Bone Scaffold.

In the system of magnesium-loaded scaffolds, the effect of magnesium ions (Mg2+ ) on the osteogenesis induction is restricted due to the low transmembrane transport efficiency of Mg2+ into the cell, which limits the application for bone defect repair. Inspired by the fact that magnetic field can regulate ion channel proteins on the cell membrane, magnetite nanoparticle is introduced into the poly (l-lactic acid) /magnesium oxide composite in this study, and a magnetic magnesium-loaded bone scaffold is prepared via selective laser sintering . Notably, the activities of the Mg2+ channel protein (MAGT1) on the membrane of bone marrow mesenchymal stem cells (rBMSCs) are enhanced via magnetic torque effect (via integrin αV ß3/actin), under the action of static magnetic field (SMF), which promoted rBMSCs to capture Mg2+ in the microenvironment and induced osteogenesis. In vitro experiments showed that the magnetic magnesium-loaded scaffold, under the action of SMF, can accelerate the inflow of Mg2+ from surrounding microenvironment, which improved cellular activities, osteogenesis-related gene expression (ALP, Runx2, OCN, and OPN), and mineralization. Besides, in vivo skull defect repair experiments showed that the scaffolds possessed good ability to promote bone differentiation and new bone regeneration.

RNA adenosine modifications related to prognosis and immune infiltration in osteosarcoma.

BACKGROUND: RNA adenosine modifications, which are primarily mediated by "writer" enzymes (RMWs), play a key role in epigenetic regulation in various biological processes, including tumorigenesis. However, the expression and prognostic role of these genes in osteosarcoma (OS) remain unclear. METHODS: Univariate and multivariate Cox analyses were used to construct the RMW signature for OS using Target datasets. RMW expression in OS tissue was detected by qPCR analysis. Xcell and GSVA were used to determine the relationship between RMWs and immune infiltration. The DGIdb and CMap databases were used for drug prediction. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS. RESULTS: A 3-RMW (CSTF2, ADAR and WTAP) prognostic signature in OS was constructed using the Target dataset and verified using GEO datasets and 63 independent OS tissues via qPCR analysis. High-risk OS patients had poor overall survival, and the prognostic signature was an independent prognostic factor for OS. Functional studies showed that tumour-, metabolism-, cell cycle- and immune-related pathways were related to high risk. Next, we found that RMW-derived high-risk patients exhibited increased infiltration of M2 macrophages and cDCs. Furthermore, we predicted the potential drugs for OS using the DGIdb and CMap databases. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS by repressing cell growth and inducing cell cycle arrest at the G1 phase. CONCLUSION: The 3-RWM-based prognostic signature established in this study is a novel gene signature associated with immune infiltration, and strophanthidin was identified as a candidate therapy for OS by repressing OS cell growth and the cell cycle.

MBD2 mediates renal cell apoptosis via activation of Tox4 during rhabdomyolysis-induced acute kidney injury.

Our study investigated the role of Methyl-CpG-binding domain protein 2 (MBD2) in RM-induced acute kidney injury (AKI) both in vitro and in vivo. MBD2 was induced by myoglobin in BUMPT cells and by glycerol in mice. MBD2 inhibition via MBD2 small interfering RNA and MBD2-knockout (KO) attenuated RM-induced AKI and renal cell apoptosis. The expression of TOX high mobility group box family member 4 (Tox4) induced by myoglobin was markedly reduced in MBD2-KO mice. Chromatin immunoprecipitation analysis indicated that MBD2 directly bound to CpG islands in the Tox4 promoter region, thus preventing promoter methylation. Furthermore, siRNA inhibition of Tox4 attenuated myoglobin-induced apoptosis in BUMPT cells. Finally, MBD2-KO mice exhibited glycerol-induced renal cell apoptosis by inactivation of Tox4. Altogether, our results suggested that MBD2 plays a role in RM-induced AKI via the activation of Tox4 and represents a potential target for treatment of RM-associated AKI.

Mg2+ in ß-TCP/Mg-Zn composite enhances the differentiation of human bone marrow stromal cells into osteoblasts through MAPK-regulated Runx2/Osx.

Inducing the osteogenic differentiation from bone marrow stromal cells (BMSCs) might be a potent strategy for treating bone loss and nonunion during fracture and improving fracture healing. Among several signaling pathways involved, mitogen-activated protein kinases (MAPKs) have been reported to play a critical role. Magnesium (Mg)-based alloys, including Mg-Zn alloy, have been used clinically as implants in the musculoskeletal field and could promote BMSC osteogenic differentiation. However, the underlying mechanisms remain unclear. In this study, we produced Mg-Zn alloy consists of Mg and low concentrations of Zn, calcium carbonate, and ß-tricalcium phosphate (ß-TCP; manifesting process not shown), prepared Mg, Zn, and Mg-Zn extracts, and investigated the specific effects of these extracts on human BMSC (hBMSC) osteogenic differentiation and MAPK signaling. Mg extracts and Mg-Zn extracts could significantly promote the osteogenic differentiation of hBMSCs as manifested as increased alkaline phosphatase levels, enhanced calcium nodules formation, and increased messenger RNA expression and protein levels of osteogenesis markers, including BMPs, Col-I, Runx2, and Osx; in the meantime, Mg culture medium (CM) and Mg-Zn CM both significantly enhanced the activation of MAPK signaling in hBMSCs. By adding ERK1/2 signaling, p38 signaling, or JNK signaling inhibitor to Mg-Zn CM, or conducting p38 MAPK silence in hBMSCs, we revealed that these extracts might promote hBMSC osteogenic differentiation via p38 MAPK signaling and MAPK-regulated Runx2/Osx. In conclusion, Mg2+ in ß-TCP/Mg-Zn extract promotes the osteogenic differentiation of hBMSCs via MAPK-regulated Runx2/Osx interaction.

[Study on biocompatibility of carbon-based composites].

Silicon carbide (SiC) film and silicon dioxide (SiO 2) film were deposited on the surface of carbon/carbon composite (C/C) by low pressure chemical vapor deposition (LPCVD). The biocompatibility of the three carbon-based composites, e. g. C/C, C/C-SiC, C/C-SiO 2 were investigated by cytotoxicity test, cell direct contact and cell adhesion experiments. Cytotoxicity, cell direct contact and cell adhesion showed that the three materials had no toxic effect on mouse fibroblasts (L929 cells). However, the particles dropped off from the three materials had a great impact on evaluation accuracy of the thiazolyl blue (MTT) test. More the particles were lost, more growth inhibition to L929 cells. The evaluation accuracy of MTT method can be kept with the filtered extract of materials. Furthermore, the results of surface particles shedding experiment showed that the amount of surface particles shed from C/C-SiO 2 was the most, followed by C/C and C/C-SiC in 72 hours. Particles shedding curves showed there was a peak reached at eighth hour and then declined to the thirty-sixth hour. The filtrate analysis showed that there was no ion exchange between the three materials and simulated body fluid (SBF) solution. The results of this study on biocompatibility of carbon-based composites have certain guiding significance for their future application in clinical filed.

NEAT1/miR-181c Regulates Osteopontin (OPN)-Mediated Synoviocyte Proliferation in Osteoarthritis.

Osteoarthritis (OA) is characterized by progressive destruction of articular cartilage, resulting in significant disability. Inflammatory cytokines commonly initiate the extreme changes in the synovium and cartilage microenvironment of the OA patients, subsequently resulting in cell dysfunctions, especially synoviocyte dysfunction. We revealed that the expression of osteopontin (OPN), which has been reported to regulate expression of various inflammatory factors associating with the pathogenesis of OA including matrix metalloprotease 13 (MMP13), interlukine-6 and 8 (IL-6 and IL-8), is significantly upregulated in OA tissues. In the present study, online tools were used to screen out the candidate miRNAs of OPN. Among the candidate miRNAs, miR-181c inhibited OPN mRNA expression the most strongly. Ectopic expression of miR-181c significantly repressed synoviocyte proliferation, as well as the levels of OPN, MMP13, IL-6, and IL-8. Further, the candidate lncRNAs of miR-181c were screened out by using DianaTools; among which NEAT1 showed to inversely regulate miR-181c. By performing Luciferase assays, we revealed that NEAT1 competed with OPN for miR-181c binding. After NEAT1 knockdown, MMP13, IL-6, and IL-8 expression was reduced; the synoviocyte proliferation was repressed, as well as OPN protein levels; the suppressive effect of NETA1 knockdown on synoviocyte proliferation and the indicated factors were partially reversed by miR-181c inhibition. In OA tissues, OPN mRNA, and NEAT1 expression was upregulated, whereas miR-181c expression was downregulated, indicating that targeting NEAT1 to rescue miR-181c expression so as to inhibit OPN expression and synoviocyte proliferation might be an efficient strategy for OA treatment. J. Cell. Biochem. 118: 3775-3784, 2017. © 2017 Wiley Periodicals, Inc.

Reduced expression of miRNA-1237-3p associated with poor survival of spinal chordoma patients.

PURPOSE: Aberrant expression of miRNAs has been demonstrated to contribute to human carcinogenesis. This study was aimed at profiling differentially expressed miRNAs in formalin-fixed and paraffin-embedded tissues of spinal chordoma and testing the potential for using altered expression of miRNAs as prognostic markers for spinal chordoma patients. METHODS: A miRNA array was used to profile differentially expressed miRNAs in spinal chordoma and nucleus pulposus tissues. Four of these differentially expressed miRNAs was then validated in spinal chordoma and control patients using quantitative RT-PCR. Bioinformatical analysis identified potential GO terms and signaling pathways affected by these microRNAs. Altered miR-1237-3p expression was then found to be associated with clinicopathological characteristics and prognosis of spinal chordoma patients. RESULTS: The miRNA arrays identified 29 differentially expressed miRNAs in spinal chordoma tissues, four of which were verified by qRT-PCR in 42 spinal chordomas and 14 control tissues. Bioinformatical analysis revealed that the potential target genes of these miRNAs were mainly involved in gene transcription, cell junction proteins, and gene pathways in cancer and endocytosis. Reduced miR-1237-3p expression was associated with tumor invasion and worse recurrence-free survival of spinal chordoma patients (χ (2) = 16.217, p = 0.000, log-rank test). Multivariate analyses showed that miR-1237-3p expression was an independent prognostic factor for patients with spinal chordoma (HR = 0.001, 95 % CI 0.000-0.136, p = 0.005). CONCLUSION: The data from the current study identified a total of 29 differentially expressed miRNAs in chordoma tissues and reduced miR-1237-3p expression was associated with chordoma invasion and worse recurrence-free survival of the patients.

Clinical therapeutic effect of surgery on upper cervical spinal cord tumors.

OBJECTIVE: To evaluate the long-term clinical therapeutic effect of polyaxial screw-rod system for posterior cervical arthrodesis on patients with upper cervical spinal cord tumors.
 METHODS: From March 2007 to May 2013, 22 patients with upper cervical spinal cord tumors underwent tumor resection and posterior cervical arthrodesis in our institution. The medical records of these patients were reviewed respectively. There were 10 males and 12 females with ages ranging from 16 to 60 years old. Posterior cervical arthrodesis by polyaxial screw-rod was performed at the upper cervical spine (C1-3). All patients were followed-up clinically and radiographically.
 RESULTS: The average follow-up was 65.5 months. Twenty-two patients were enrolled and a total of 114 screws were placed in this study. Histopathology revealed neurinoma, meningioma, ganglioneuroma and ganglioglioma in 16, 3, 1 and 1 case (s), respectively. The mixed tumor with component of ganglioneuroma and neurinoma was observed in 1 case. All patients received tumor resection and posterior athrodesis by polyaxial screw-rod system. Cervical kyphosis was encountered in one patient and this patient suffered the recurrence of tumor. Solid fusion was achieved in all patients. The average postoperative Japanese Orthopaedic Association (JOA) score was 13.9 and the average recovery rate was 51.4%. Neurologic deterioration was found in 2 patients. No complications, such as spinal cord or vertebral artery injury, postoperative radiculopathy or instrumentation failure, were observed.
 CONCLUSION: The long-term clinical therapeutic effects of posterior cervical arthrodesis using polyaxial screw-rod system on upper cervical spinal cord tumors are satisfactory, with no severe complication.

Liquid phase sintered ceramic bone scaffolds by combined laser and furnace.

Fabrication of mechanically competent bioactive scaffolds is a great challenge in bone tissue engineering. In this paper, ß-tricalcium phosphate (ß-TCP) scaffolds were successfully fabricated by selective laser sintering combined with furnace sintering. Bioglass 45S5 was introduced in the process as liquid phase in order to improve the mechanical and biological properties. The results showed that sintering of ß-TCP with the bioglass revealed some features of liquid phase sintering. The optimum amount of 45S5 was 5 wt %. At this point, the scaffolds were densified without defects. The fracture toughness, compressive strength and stiffness were 1.67 MPam1/2, 21.32 MPa and 264.32 MPa, respectively. Bone like apatite layer was formed and the stimulation for apatite formation was increased with increase in 45S5 content after soaking in simulated body fluid, which indicated that 45S5 could improve the bioactivity. Furthermore, MG-63 cells adhered and spread well, and proliferated with increase in the culture time.

Current progress in bioactive ceramic scaffolds for bone repair and regeneration.

Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review of the application of bioactive ceramics for bone repair and regeneration. The review systematically summarizes the types and characters of bioactive ceramics, the fabrication methods for nanostructure and hierarchically porous structure, typical toughness methods for ceramic scaffold and corresponding mechanisms such as fiber toughness, whisker toughness and particle toughness. Moreover, greater insights into the mechanisms of interaction between ceramics and cells are provided, as well as the development of ceramic-based composite materials. The development and challenges of bioactive ceramics are also discussed from the perspective of bone repair and regeneration.

Biomechanical response of decompression alone in lower grade lumbar degenerative spondylolisthesis--A finite element analysis.

BACKGROUND: Previous studies have demonstrated the clinical efficacy of decompression alone in lower-grade spondylolisthesis. A higher rate of surgical revision and a lower rate of back pain relief was also observed. However, there is a lack of relevant biomechanical evidence after decompression alone for lower-grade spondylolisthesis. PURPOSE: Evaluating the biomechanical characteristics of total laminectomy, hemilaminectomy, and facetectomy for lower-grade spondylolisthesis by analyzing the range of motion (ROM), intradiscal pressure (IDP), annulus fibrosus stress (AFS), facet joints contact force (FJCF), and isthmus stress (IS). METHODS: Firstly, we utilized finite element tools to develop a normal lumbar model and subsequently constructed a spondylolisthesis model based on the normal model. We then performed total laminectomy, hemilaminectomy, and one-third facetectomy in the normal model and spondylolisthesis model, respectively. Finally, we analyzed parameters, such as ROM, IDP, AFS, FJCF, and IS, for all the models under the same concentrate force and moment. RESULTS: The intact spondylolisthesis model showed a significant increase in the relative parameters, including ROM, AFS, FJCF, and IS, compared to the intact normal lumbar model. Hemilaminectomy and one-third facetectomy in both spondylolisthesis and normal lumbar models did not result in an obvious change in ROM, IDP, AFS, FJCF, and IS compared to the pre-operative state. Moreover, there was no significant difference in the degree of parameter changes between the spondylolisthesis and normal lumbar models after undergoing the same surgical procedures. However, total laminectomy significantly increased ROM, AFS, and IS and decreased the FJCF in both normal lumbar models and spondylolisthesis models. CONCLUSION: Hemilaminectomy and one-third facetectomy did not have a significant impact on the segment stability of lower-grade spondylolisthesis; however, patients with LDS undergoing hemilaminectomy and one-third facetectomy may experience higher isthmus stress on the surgical side during rotation. In addition, total laminectomy changes the biomechanics in both normal lumbar models and spondylolisthesis models.

Synergistic effects of laser powder bed fusion and annealing on the texture-selective recrystallization of magnetostrictive Fe-Ga-NbC alloys for biomedical applications.

INTRODUCTION: Magnetostrictive Fe-Ga alloys have garnered extensive attention owing to their excellent magnetic properties and acceptable biocompatibility. Nevertheless, the polycrystalline Fe-Ga alloys currently available tend to display random texture orientations, which constrain their magnetostrictive performance. OBJECTIVES: To regulate the texture orientation of Fe-Ga-NbC alloys and thereby enhancing magnetostriction. METHODS: In this study, a processing route comprising laser powder bed fusion (LPBF) followed by secondary recrystallization annealing (800, 1000, and 1200 °C, respectively) was developed to prepare Fe-Ga-NbC alloys. RESULTS: The results showed that the LPBF-ed (Fe81Ga19)99(NbC)1 alloys exhibited a high content of high energy grain boundaries (HEGBs) due to the repeated melting and solidification. In subsequent annealing process, the migration of HEGBs induced the rearrangement and recrystallization of grains, during which NbC was found to locate at the grain boundaries and influence the migration path of HEGBs via selective pinning, thereby resulting in a strong Goss texture. With the rise in annealing temperature, the content of Goss texture gradually increased from the initial 3.9 % to 71.3 % at 1200 °C, leading to enhanced magnetostriction, lower saturation magnetization and coercivity. Furthermore, in alternating magnetic fields, the alloys annealed at 1200 °C also exhibited higher magnetostriction than the LPBF-ed alloys. And a noteworthy grain coarsening was also observed after annealing, accompanied by a discernible inclination of magnetic domains towards strip domains. Additional, cell tests demonstrated that the prepared alloys had satisfactory biocompatibility and the ability to promote osteogenic differentiation. CONCLUSION: These findings indicated that the LPBF-ed and annealed Fe-Ga-NbC alloys might be a promising alternative as magnetostrictive-driven materials for biomedical applications.

Ultrasensitive Ti3C2Tx@Pt-Based Immunochromatography with Catalytic Amplification and a Dual Signal for the Detection of Chloramphenicol in Animal-Derived Foods.

Herein, a catalytic amplification enhanced dual-signal immunochromatographic assay (ICA) based on Pt nanoparticles (Pt NPs) modified with Ti3C2Tx MXene (Ti3C2Tx@Pt) was first developed for chloramphenicol (CAP) in animal-derived foods. Due to the large specific surface area and abundant active sites of Ti3C2Tx@Pt, they can be loaded with hundreds of Pt NPs to enhance their catalytic activity, resulting in a significant increase in the detection sensitivity; the sensitivity was up to 50-fold more sensitive than the reported ICA for CAP. The LODs of the developed method for milk/chicken/fish were 0.01 µg/kg, the LOQs were 0.03 µg/kg and the recovery rates were 80.5-117.0%, 87.2-118.1% and 92.7-117.9%, with corresponding variations ranging from 3.1 to 9.6%, 6.0 to 12.7% and 6.0 to 13.6%, respectively. The linear range was 0.0125-1.0 µg/kg. The results of the LC-MS/MS confirmation test on 30 real samples had a good correlation with that of our established method (R2 > 0.98), indicating the practical reliability of the established method. The above results indicated that an ICA based on the Ti3C2Tx@Pt nanozyme has excellent potential as a food safety detection tool.

Single-cell RNA-seq reveals T cell exhaustion and immune response landscape in osteosarcoma.

Background: T cell exhaustion in the tumor microenvironment has been demonstrated as a substantial contributor to tumor immunosuppression and progression. However, the correlation between T cell exhaustion and osteosarcoma (OS) remains unclear. Methods: In our present study, single-cell RNA-seq data for OS from the GEO database was analysed to identify CD8+ T cells and discern CD8+ T cell subsets objectively. Subgroup differentiation trajectory was then used to pinpoint genes altered in response to T cell exhaustion. Subsequently, six machine learning algorithms were applied to develop a prognostic model linked with T cell exhaustion. This model was subsequently validated in the TARGETs and Meta cohorts. Finally, we examined disparities in immune cell infiltration, immune checkpoints, immune-related pathways, and the efficacy of immunotherapy between high and low TEX score groups. Results: The findings unveiled differential exhaustion in CD8+ T cells within the OS microenvironment. Three genes related to T cell exhaustion (RAD23A, SAC3D1, PSIP1) were identified and employed to formulate a T cell exhaustion model. This model exhibited robust predictive capabilities for OS prognosis, with patients in the low TEX score group demonstrating a more favorable prognosis, increased immune cell infiltration, and heightened responsiveness to treatment compared to those in the high TEX score group. Conclusion: In summary, our research elucidates the role of T cell exhaustion in the immunotherapy and progression of OS, the prognostic model constructed based on T cell exhaustion-related genes holds promise as a potential method for prognostication in the management and treatment of OS patients.

Single-Atom Cu Nanozyme-Loaded Bone Scaffolds for Ferroptosis-Synergized Mild Photothermal Therapy in Osteosarcoma Treatment.

The rapid multiplication of residual tumor cells and poor reconstruction quality of new bone are considered the major challenges in the postoperative treatment of osteosarcoma. It is a promising candidate for composite bone scaffold which combines photothermal therapy (PTT) and bone regeneration induction for the local treatment of osteosarcoma. However, it is inevitable to damage the normal tissues around the tumor due to the hyperthermia of PTT, while mild heat therapy shows a limited effect on antitumor treatment as the damage can be easily repaired by stress-induced heat shock proteins (HSP). This study reports a new type of single-atom Cu nanozyme-loaded bone scaffolds, which exhibit exceptional photothermal conversion properties as well as peroxidase and glutathione oxidase mimicking activities in vitro experiments. This leads to lipid peroxidation (LPO) and reactive oxygen species (ROS) upregulation, ultimately causing ferroptosis. The accumulation of LPO and ROS also contributes to HSP70 inactivation, maximizing PTT efficiency against tumors at an appropriate therapeutic temperature and minimizing the damage to surrounding normal tissues. Further, the bone scaffold promotes bone regeneration via a continuous release of bioactive ions (Ca2+, P5+, Si4+, and Cu2+). The results of in vivo experiments reveal that scaffolds inhibit tumor growth and promote bone repair.

Clinical efficacy of different surgical approaches in the treatment of thoracolumbar tuberculosis: a multicenter retrospective case-control study with a minimum 10-year follow-up.

OBJECTIVE: To evaluate the long-term clinical efficacy of three different surgical approaches in treating thoracolumbar tuberculosis. METHODS: A total of 176 patients with thoracolumbar tuberculosis, treated with open surgery at two hospitals, were retrospectively analyzed. Patients were stratified into three groups based on the surgical approach: anterior-only (AO), posterior-only (PO), and anterior-posterior combined (AP) approaches. Collected data encompassed operative duration, intraoperative blood loss, hospital stay length, complications, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI), American Spinal Injury Association (ASIA) classification, and radiographic measurements of segmental lordotic Cobb angles, correction angles, and correction rates. RESULTS: The minimum duration of follow-up among all patients was 10 years. Postoperatively, all patients experienced a reduction in ESR and CRP, with normalization occurring within 3 months and sustained normal at the last follow-up. The AP group had a longer operative duration and higher intraoperative blood loss than the other two groups. The Cobb correction rates for AO, PO, and AP were (56.33±6.62)%, (72.82±5.66)%, and (74.45±5.78)%, respectively. The correction loss of Cobb angles for AO, PO, and AP were (2.85±1.01)°, (1.42±0.97)°, and (1.19±0.89)°, respectively. Patients in all groups showed significant improvement in VAS scores and ODI postoperatively, with no notable intergroup differences. The neurological recovery rates for the AO, PO, and AP groups were 84.62, 87.10, and 83.72%, respectively, while the complication rates were 12.73, 16.98, and 22.06%, respectively. CONCLUSION: An anterior-only approach is recommended for cases with localized lesions and smaller angular deformities. For patients with multisegmental lesions and larger angular deformities, a posterior-only or anterior-posterior combined approach is advised, with a preference for the posterior-only approach.