Nucleotide polymorphism-based study utilizes human plasma liposomes to discover potential therapeutic targets for intervertebral disc disease.

Background: While intervertebral disc degeneration (IVDD) is crucial in numerous spinally related illnesses and is common among the elderly, the complete understanding of its pathogenic mechanisms is still an area of ongoing study. In recent years, it has revealed that liposomes are crucial in the initiation and progression of IVDD. However, their intrinsic mediators and related mechanisms remain unclear. With the development of genomics, an increasing amount of data points to the contribution of genetics in the etiology of disease. Accordingly, this study explored the causality between liposomes and IVDD by Mendelian randomization (MR) analysis and deeply investigated the intermediary roles of undetected metabolites. Methods: According to MR analysis, 179 liposomes and 1400 metabolites were evaluated for their causal association with IVDD. Single nucleotide polymorphisms (SNPs) are strongly associated with the concentrations of liposomes and metabolites. Consequently, they were employed as instrumental variables (IVs) to deduce if they constituted risk elements or protective elements for IVDD. Furthermore, mediation analysis was conducted to pinpoint possible metabolic mediators that link liposomes to IVDD. The inverse variance weighting (IVW) was the main analytical technique. Various confidence tests in the causality estimates were performed, including consistency, heterogeneity, pleiotropy, and sensitivity analyses. Inverse MR analysis was also utilized to estimate potential reverse causality. Results: MR analysis identified 13 liposomes and 79 metabolites markedly relevant to IVDD. Moreover, the mediation analysis was carried out by choosing the liposome, specifically the triacylglycerol (48:2) levels, which were found to be most notably associated with an increased risk of IVDD. In all, three metabolite-associated mediators were identified (3-methylcytidine levels, inosine 5'-monophosphate (IMP) to phosphate ratio, and adenosine 5'-diphosphate (ADP) to glycine ratio). Conclusion: The analysis's findings suggested possible causal connections between liposomes, metabolites, and IVDD, which could act as both forecast and prognosis clinical indicators, thereby aiding in the exploration of the pathogenesis behind IVDD.

Penfluridol regulates p62 / Keap1 / Nrf2 signaling pathway to induce ferroptosis in osteosarcoma cells.

The cure rate for patients with osteosarcoma (OS) has stagnated over the past few decades. Penfluridol, a first-generation antipsychotic, has demonstrated to prevent lung and esophageal malignancies from proliferation and metastasis. However, the effect of penfluridol on OS and its underlying molecular mechanism remains unclear. This study revealed that penfluridol effectively inhibited cell proliferation and migration, and induced G2/M phase arrest in OS cells. In addition, penfluridol treatment was found to increased reactive oxygen species (ROS) levels in OS cells. Combined with the RNA-Seq results, the anti-OS effect of penfluridol was hypothesized to be attributed to the induction of ferroptosis. Western blot results showed that penfluridol promoted intracellular Fe2+ concentration, membrane lipid peroxidation, and decreased intracellular GSH level to induce ferroptosis. Further studies showed that p62/Keap1/Nrf2 signaling pathway was implicated in penfluridol-induced ferroptosis in OS cells. Overexpression of p62 effectively reversed penfluridol-induced ferroptosis. In vivo, penfluridol effectively inhibited proliferation and prolonged survival in xenograft tumor model. Therefore, penfluridol is a promising drug targeting OS in the future.

The association between osteoporosis and frailty: a cross-sectional observational study and mendelian randomization analysis.

BACKGROUND: Osteoporosis and frailty are two common features in the elderly population. Despite many review articles mentioning the association between osteoporosis and frailty, there is a lack of original research directly investigating their relationship. Therefore, this study was conducted to examine the correlation between osteoporosis and frailty. METHODS: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES), using logistic regression analysis to assess the association of osteoporosis with the frailty index. In addition, we further explored the causal relationship between them using Mendelian randomization (MR) study. RESULTS: In the cross-sectional study, 19,091 non-frailty participants and 5878 frailty participants were included in this study. We observed a significant positive association between osteoporosis and frailty after adjusting for demographic characteristics, body mass index (BMI), smoking, and alcohol use (OR = 1.454, 95% CI [1.142,1.851], P = 0.003). Moreover, the MR study showed a bidirectional causal relationship between osteoporosis and frailty. When osteoporosis was used as an exposure factor, the frailty pooled OR value calculated utilizing the inverse variance weighted (IVW) method was 2.81 (95% CI [1.69, 4.68], P = 6.82 × 10- 5). When frailty was used as an exposure factor, the OR value calculated using the IVW method was 1.01 (95% CI [1.00,1.01], P = 3.65 × 10- 7). CONCLUSIONS: Osteoporosis was positively correlated with frailty, and the results remained robust after adjusting for covariates. Further, MR studies have shown a bidirectional causal relationship between osteoporosis and frailty.

Discovering Potential Mechanisms of Intervertebral Disc Disease Using Systematic Mendelian Randomization of Human Circulating Immunocytomics.

BACKGROUND: Although intervertebral disc degeneration (IVDD) is a critical factor in many spine-related diseases and has an extremely high prevalence in the aging population, the potential pathogenesis remains to be clarified entirely. Immune cells have been found to perform an essential function during the onset and progression of IVDD in recent years. Therefore, we explored the association between immune cell characteristics and IVDD through Mendelian randomization (MR) analysis and further delved into the mediating role of potential metabolites. METHODS: Based on the MR analysis, the association of 731 immune cell phenotypes and 1400 metabolites on IVDD were assessed. Single nucleotide polymorphisms were closely associated the expression levels of immune cell characteristics and the concentrations of metabolites and have been used as instrumental variables for deducing them as risk factors or protective factors for IVDD. In addition, mediation analyses have been performed to identify potential metabolite mediators between immune cell characteristics and IVDD. RESULTS: MR analysis identified 27 immune cell phenotypes and 79 metabolites significantly associated with IVDD. In addition, mediation analysis was performed by selecting the immune cell phenotype that most significantly increased the risk of IVDD - CD86 on monocytes. A total of 4 metabolite-mediated mediation relationships were revealed (3 b-hydroxy-5-cholenoic acid, X-22509, N-acetyl-L-glutamine, and N2-acetyl, N6, N6-dimethyllysine). CONCLUSIONS: The findings of this analysis identified underlying association between immune cell phenotypes, metabolite, and IVDD that may serve as predictive and prognostic clinical biomarkers and benefit IVDD pathogenesis research.

PCSK9 inhibitors and osteoporosis: mendelian randomization and meta-analysis.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent an effective strategy for reducing cardiovascular disease risk. Yet, PCSK9's impact on osteoporosis remains unclear. Hence, we employed Mendelian randomization (MR) analysis for examining PCSK9 inhibitor effects on osteoporosis. METHODS: Single nucleotide polymorphisms (SNPs) for 3-hydroxy-3-methylglutaryl cofactor A reductase (HMGCR) and PCSK9 were gathered from available online databases for European pedigrees. Four osteoporosis-related genome-wide association studies (GWAS) data served as the main outcomes, and coronary artery disease (CAD) as a positive control for drug-targeted MR analyses. The results of MR analyses examined by sensitivity analyses were incorporated into a meta-analysis for examining causality between PCSK9 and HMGCR inhibitors and osteoporosis. RESULTS: The meta-analysis involving a total of 1,263,102 subjects, showed that PCSK9 inhibitors can increase osteoporosis risk (P < 0.05, I2, 39%). However, HMGCR inhibitors are not associated with osteoporosis risk. Additionally, a replication of the analysis was conducted with another exposure-related GWAS dataset, which led to similar conclusions. CONCLUSION: PCSK9 inhibitors increase osteoporosis risk. However, HMGCR inhibitors are unremarkably linked to osteoporosis.

Therapeutic potential of single-nucleotide polymorphism-mediated IL6R inhibitors in ankylosing spondylitis treatment.

Objective: Interleukin-6 (IL-6) is a multiple-effect cell factor implicated in the etiopathogenesis of several rheumatologic disorders. The blockade of the IL-6 pathway via IL6R inhibitors effectively treats these disorders. However, the clinical significance of the IL6R blockade for ankylosing spondylitis (AS) therapy remains controversial. With advances in genomics, increasing evidence has revealed the role of heritability in the etiology of disease, and Mendelian randomization (MR) analyses are being used more broadly to infer causation. Therefore, this MR study aims to evaluate the potential therapeutic utility of IL6R-targeted approaches in AS. Methods: The C-reactive protein (CRP) level was used as an exposure factor, and rheumatoid arthritis (RA) was used as a positive control. As-related genome-wide association study (GWAS) data were used as the primary outcome of drug-targeted MR analyses to test the relation between IL6R blockers and AS. Inverse variance weighting (IVW) is the primary analytical approach. Various sensitivity tests were performed to check the robustness and trustworthiness of the causality estimation, including consistency, heterogeneity, and pleiotropy analyses. In addition, repeated analysis was conducted using different GWAS data related to exposures and outcomes to examine the results for stability. Results: According to the IVW results, IL6R inhibitors significantly reduced the risk of AS in ukb-b-18194 (OR: 0.995, 95% CI 0.993-0.996, P = 5.12 × 10-08) and ukb-a-88 (OR: 0.994, 95% CI 0.993-0.996, P = 6.25 × 10-15). Moreover, repeated analyses were performed using different exposure-related GWAS data, yielding similar results, ukb-b-18194 (OR: 0.995, 95% CI 0.993-0.997, P = 1.25 × 10-06) and ukb-a-88 (OR: 0.995, 95% CI 0.994-0.997, P = 7.81 × 10-09). Heterogeneity analyses and pleiotropy analyses indicated no significant heterogeneity or pleiotropy. Conclusion: This MR analysis result further validates that the IL-6 pathway may contribute to the pathogenesis of AS and that the inhibition of IL6R reduces the risk of AS. These findings may guide future studies and provide more favorable drug treatment options for people at high risk of AS.

Development and validation of a deep-learning model for the detection of non-displaced femoral neck fractures with anteroposterior and lateral hip radiographs.

Background: Hip fractures, including femoral neck fractures, are a significant cause of morbidity and mortality in the elderly population and are typically diagnosed using plain radiography. However, diagnosing non-displaced femoral neck fractures can be challenging due to their subtle appearance on hip radiographs. Previous deep-learning models have shown low accuracy in identifying these fractures on anteroposterior (AP) radiographs; however, no studies have used lateral radiographs. This study aimed to evaluate the potential of using deep-learning with both AP and lateral hip radiographs to automatically identify non-displaced femoral neck fractures. Methods: We conducted a retrospective analysis of patients with femoral neck fractures at The First Affiliated Hospital of Xiamen University. All the hip radiographs were reviewed, and cases of non-displaced femoral neck fractures were included in the study. Additionally, 439 participants with normal hip radiographs were also included in the study. A vision transformer (Vit) model was developed using 1,536 AP and lateral hip radiograph. The model's performance was compared to the performance of two groups of human observers: an expert group comprising orthopedic surgeons and radiologists, and a non-expert group, including emergency physicians and general practice doctors. We also carried out the external validation using two additional data sets to assess the generalizability of the model. Results: The Vit model showed exceptional performance in detecting non-displaced femoral neck fractures on paired AP and lateral hip radiographs, achieving a binary accuracy of 95.8% [95% confidence interval (CI): 94.9%, 96.8%] and an area under the curve (AUC) of 0.988. Compared to the human observers, the model had a higher accuracy of 96.7% (95% CI: 93.9%, 99.5%) on the paired AP and lateral hip radiographs, while the accuracy of the expert group was 90.5% (95% CI: 85.7%, 95.2%). Further, the model maintained good performance during the external validation, with an AUC of 0.959 on the paired AP and lateral views. Conclusions: Our Vit model showed expert-level performance in identifying non-displaced femoral neck fractures on paired AP and lateral hip radiographs. This model has the potential to enhance diagnosis accuracy and improve patient outcomes by reducing the need for additional examinations and preoperative time.

Genetically predicted triglycerides mediate the relationship between type 2 diabetes Mellitus and intervertebral disc degeneration.

BACKGROUND: To validate the causal relationship between type 2 diabetes mellitus (T2DM) and intervertebral disc degeneration (IVDD) and to identify and quantify the role of triglycerides (TGs) as potential mediators. METHODS: A two-sample Mendelian randomization (MR) analyses of T2DM (61,714 cases and 1178 controls) and IVDD (20,001 cases and 164,682 controls) was performed using genome-wide association studies (GWAS). Moreover, two-step MR was employed to quantify the proportionate impact of TG-mediated T2DM on IVDD. RESULTS: MR analysis showed that T2DM increased IVDD risk (OR: 1.0466, 95% CI 1.0049-1.0899, P = 0.0278). Reverse MR analyses demonstrated that IVDD does not affect T2DM risk (P = 0.1393). The proportion of T2DM mediated through TG was 11.4% (95% CI 5.5%-17.4%). CONCLUSION: This work further validates the causality between T2DM and IVDD, with a part of the effect mediated by TG, but the greatest impacts of T2DM on IVDD remain unknown. Further studies are needed to identify other potential mediators.

An unusual presentation of ossified spinal meningioma: case report and literature review.

Background: Spinal meningioma is a common intraspinal tumor, which mainly occurs in the thoracic spine. Ossified meningioma (OSM) is an extremely rare histological variant. Our article reports a rare patient with dorsal complete OSM and reviews this subject. Case presentation: A 68-year-old woman presented with a one-year history of progressive weakness in both lower limbs with gait disturbance. Physical examination revealed hypoesthesia with a sensory level below T10. Babinski and pathological signs on both sides were weakly positive. Magnetic resonance imaging (MRI) showed a mass at the T10 to T11 level causing severe compression of the spinal cord. Computed tomography (CT) showed complete ossification of the mass. 18F-Fluoro-deoxy-glucose positron emission tomography CT (18F-FDG PET/CT) scan combined with MRI revealed that the mass was an intradural extramedullary high-density ossified nodule. The patient underwent a gross total resection of the mass and pathologic examination indicated that the mass was a meningioma with diffused psammomatous bodies. Conclusion: We identified a rare case of dorsal complete OSM occurring in a 68-year-old woman. After complete surgical resection, although there were complications such as cerebral fluid leakage and fever, the patient finally recovered with a satisfactory result.

Leukoreduced PRP enhanced proliferation and ECM production yet inhibited senescence, inflammation, and multi-differentiation potential of AFSCs by downregulating HMGB1.

BACKGROUND: This study assessed the role and potential mechanism of platelet-rich plasma (PRP) in the progression of intervertebral disk degeneration (IVDD). METHODS: Annulus fibrosus (AF)-derived stem cells (AFSCs) from New Zealand white rabbits received the transfection with high mobility group box 1 (HMGB1) plasmids and the subsequent treatment with bleomycin, 10% leukoreduced PRP or leukoconcentrated PRP. Dying cells were indicated by immunocytochemistry analysis for senescence-associated ß-galactosidase (SA-ß-gal) staining. The proliferation of these cells was evaluated based on the population doubling time (PDT). The expressions of HMGB1, pro-aging and anti-aging molecules, extracellular matrix (ECM)-related catabolic/anabolic factors, and inflammatory genes at the molecular or transcriptional levels were quantified via Western blot or reverse transcription-quantitative PCR (RT-qPCR). Besides, the adipocytes, osteocytes, and chondrocytes were separately dyed by Oil Red O, Alizarin Red S, and Safranin O staining. RESULTS: Bleomycin enhanced the senescent morphological changes and increased the PDT and the expressions of SA-ß-gal, pro-aging molecules, ECM-related catabolic factors, inflammatory genes, and HMGB1 while suppressing the expressions of anti-aging and anabolic molecules. Leukoreduced PRP reversed the effects of bleomycin and inhibited the differentiation of AFSCs into adipocytes, osteocytes, and chondrocytes. Besides, HMGB1 overexpression offset the roles of leukoreduced PRP in AFSCs. CONCLUSION: Leukoreduced PRP promotes cell proliferation and ECM production of AFSCs, while inhibiting their senescence, inflammation, and multi-differentiation potentials via downregulating HMGB1 expression.

Pan-cancer analysis of the intervertebral-disc-degeneration-related innate immunity gene NAIP.

BACKGROUND: Intervertebral disc degeneration (IDD) is a progressive chronic condition that commonly causes low back pain. Cancer is among the primary reasons for deaths worldwide. Our purpose was to identify the characteristic genes of IDD and explore the potential association between IDD and cancer. METHODS: Immune cell infiltration and differentially expressed analysis were conducted utilizing data from the GSE124272 database. Enrichment analysis of differentially expressed genes (DEGs) was performed to explore the possible mechanisms underlying IDD development. Moreover, weighted gene correlation network analysis (WGCNA) was applied to select IDD-related hub genes. The immune-related key genes were determined by intersecting DEGs, IDD-related hub genes, and immune genes. Subsequently, machine learning models based on these genes were built to identify and verify the characteristic genes. RNA sequencing and clinical data of 33 carcinoma categories were obtained from the Cancer Genome Atlas (TCGA). The association between NAIP expression and prognosis was calculated using the Kaplan-Meier analysis. To gain a deeper understanding of the impact of NAIP in tumor immunotherapy, the association between NAIP and immune infiltration and two immunotherapeutic biomarkers were explored. Ultimately, the association between NAIP and immunotherapeutic response was investigated utilizing two independent cohorts. RESULTS: NAIP was identified as an immune-related characteristic gene between IDD and normal intervertebral disc tissue. In certain carcinoma categories, NAIP expression levels were elevated (4/33) and significantly correlated to the respective tumor stage (4/21). Survival analysis revealed that the expression levels of NAIP have prognostic significance in different cancer types. Generally, NAIP presented a strong association with immune cell infiltration and modulators. NAIP may influence immunotherapy effects through tumor mutational burden and microsatellite instability. No remarkable association between NAIP and immunotherapy response was found in either cohort. CONCLUSION: Our study is the first to identify NAIP as an immune-related characteristic gene. Pan-cancer analysis revealed that NAIP could serve as a novel clinical prognostic marker and therapeutic target for a variety of carcinoma categories, reducing the risk of IDD in tumor patients.

Overexpression Pattern of miR-301b in Osteosarcoma and Its Relevance with Osteosarcoma Cellular Behaviors via Modulating SNX10.

Prior studies have noted the importance of microRNAs (miRNAs) in development and progression of osteosarcoma (OS), but the influence of miR-301b is less investigated. This investigation aimed to explore the biological role of miR-301b/SNX10 in OS. GSE28423 and GSE28424 arrays delivered the corresponding miR-301b and sorting nexin 10 (SNX10) expression levels in OS samples. miR-301b and SNX10 expressions were also measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting in cells. Cell counting kit (CCK)-8 and transwell analysis were applied to measure cell characteristics. Luciferase reporter assay and Pearson correlation analysis were used to detect the relevance between miR-301b and SNX10. miR-301b was extremely increased in OS tissues compared with normal tissues, while SNX10 was decreased. The proliferation, invasion, and migration capabilities were limited following a low expression level of miR-301b whereas miR-301b overexpression promoted cellular malignant behaviors. miR-301b negatively targeted SNX10. The elevated SNX10 expression highlighted the inhibitory function on cell proliferation, migration, and invasion in OS cells treated by miR-301b inhibitor. Reduction of miR-301b induced the decrease of epithelial-mesenchymal transition (EMT)-related markers including N-cadherin, Vimentin, and matrix metallo-proteinase 9 (MMP)9. These results are added to the complete expanding field of the potential effects of miR-301b in OS cell malignant behaviors and demonstrate its promising role for further use to treat human OS.

MECHANISM OF MIR-25-3P CARRIED BY EXTRACELLULAR VESICLES DERIVED FROM PLATELET-RICH PLASMA IN IL-1ß-INDUCED NUCLEUS PULPOSUS CELL DEGENERATION VIA THE SOX4/CXCR7 AXIS.

ABSTRACT: Objectives: Nucleus pulposus (NP) cell degeneration promotes the progression of intervertebral disc (IVD) degeneration. MicroRNAs (miRs) are associated with IVD degeneration. This study expounded the mechanism of microRNA (miR)-25-3p carried by extracellular vesicles (EVs) derived from platelet-rich plasma (PRP) in interleukin (IL)-1ß-induced NP cell degeneration. Methods: Platelet-rich plasma from mouse blood was obtained, and EVs were isolated from PRP (EVs derived from PRP [PRP-EVs]) and identified. Nucleus pulposus cells were isolated from the mouse lumbar IVD and treated with IL-1ß to induce NP cell degeneration. Extracellular vesicles derived from PRP were added into NP cell culture medium. Afterward, intracellular miR-25-3p, sex determining region Y-related high-mobility-group box 4 (SOX4), and CXC chemokine receptor 7 (CXCR7) levels were examined. Nucleus pulposus cell viability, apoptosis, and inflammation were detected. Extracellular vesicles derived from PRP were labeled by PKH67 to obverse the uptake of EVs by NP cells. The binding relations between SOX4 and miR-25-3p and CXCR7 were predicted and examined. Functional rescue experiments were performed to investigate the roles of miR-25-3p, SOX4, and CXCR7 in NP cell degeneration. Results: miR-25-3p was downregulated, whereas SOX4 and CXCR7 were upregulated in IL-1ß-induced NP cells. Extracellular vesicles derived from PRP increased the cell viability, and decreased apoptosis and inflammation. miR-25-3p carried by PRP-EVs into NP cells alleviated NP cell degeneration. miR-25-3p inhibited SOX4 expression and limited CXCR7 transcription. Silencing miR-25-3p or overexpressing SOX4 or CXCR7 reversed the alleviating role of PRP-EVs in NP cell degeneration. Conclusion: miR-25-3p carried by PRP-EVs into NP cells elevated intracellular miR-25-3p expression, which suppressed SOX4 expression and further limited CXCR7 transcription, thus alleviating IL-1ß-induced NP cell degeneration. Extracellular vesicles derived from PRP containing miR-25-3p may be a new method for IVD treatment.

Photoluminescence-based sensing of ethanol gas with ultrafine WO3 nanorods.

Ultrafine one-dimensional WO3 nanorods (NRs) with diameters of 10-200 nm have been fabricated using a hydrothermal synthesis method. The optical performance of the WO3 NRs strongly depends on their various defects as well as their crystal quality. Upon exposure to trace quantities of ethanol gas, the photoluminescence (PL) spectra of these nanorod samples under ultraviolet illumination showed a large variation in intensity. WO3-NR-based ethanol gas sensing via PL spectra variation demonstrated a 100 ppm sensitivity detection limit and a wide linear detection range of 200-2000 ppm at 100°C. This outstanding optical ethanol sensing performance can be ascribed to the very large surface area to volume ratio of this material, which increases the density of active sites for ethanol adsorption and reaction with adsorbed oxygen species.

circSKIL promotes the ossification of cervical posterior longitudinal ligament by activating the JNK/STAT3 pathway.

Ossification of the posterior longitudinal ligament (OPLL) is a hyperostotic spinal condition that involves genetic factors as well as non-genetic factors, and its underlying molecular mechanism is largely unknown. Recently, circular RNAs (circRNAs) have been attracting the attention of researchers since they have important regulatory roles in many diseases, including bone metabolism disorders. The present study aimed to investigate the role of circRNA SKI-like proto-oncogene (circSKIL) in OPLL disease progression. First, primary posterior longitudinal ligament cells from patients with cervical spondylotic myelopathy (CSM) without OPLL (control group) and CSM patients with OPLL (OPLL group) were isolated, and the expression levels of circSKIL in ligament cells was found to be significantly increased in the OPLL group compared with control. This result was also confirmed in OPLL tissues. Next, circSKIL was overexpressed in control ligament cells, and the proliferation, mineralization, and osteogenic differentiation of ligament cells were found to be significantly enhanced; the phosphorylation levels of both JNK and STAT3 were upregulated. By contrast, the knockdown of circSKIL in OPLL ligament cells inhibited proliferation, mineralization, and osteogenic differentiation and inactivated the JNK/STAT3 pathway. Therefore, circSKIL may have a significant role in osteogenic differentiation and could serve as a potential target to prevent OPLL progression.

Upregulated Plant Homeodomain Finger Protein 6 Promotes Extracellular Matrix Degradation in Intervertebral Disc Degeneration Based on Microarray Analysis.

STUDY DESIGN: mRNA analysis. OBJECTIVE: The aim of this study was to identify differentially expressed genes (DEGs) in disc degeneration, analyze the potential biological functions of DEGs, and screen for a new target to prevent the degeneration. SUMMARY OF BACKGROUND DATA: Intervertebral disc degeneration (IDD) is an irreversible process and causes long-term heavy socioeconomic burdens. Existing and therapies under development are unable to prevent disc degeneration in a safe and effective manner. Therefore, elucidating the potential mechanism underlying degeneration and the development of new targets for IDD therapy are urgently required. METHODS: Nucleus pulposus (NP) cells from mild and severe IDD (Ctrl and IDD groups) were separated, and DEGs of the two groups were identified with mRNA microarray analysis, followed by bioinformatics analysis.Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to verify the microarray results. Gene over-expression and silencing technologies were used to study the role of plant homeodomain finger protein 6 (PHF6). qRT-PCR and western blot analyses were used to detect the expressions of collagen II (COL2), matrix metalloproteinases 13 (MMP13), and ADAM metallopeptidase with thrombospondin type 1 motif 4 (ADAMTS4). RESULTS: The study identified 377 up- and 116 downregulated DEGs in NP cells from two groups. These DEGs were mainly involved in cellular and metabolic processes and enriched in immune system and nucleotide metabolism pathways. Upregulated PHF6, with the highest verified fold change, was significantly increased in the IDD group. Over-expressing PHF6 in Ctrl NP cells significantly inhibited the expression of COL2 and enhanced the expressions of MMP13 and ADAMTS4, whereas silencing PHF6 in IDD NP cells reversed such expression alterations. CONCLUSION: Upregulated PHF6 caused IDD by promoting extracellular matrix degradation; therefore, PHF6 could be developed as a potential novel target to prevent the degeneration. Our DEG profiling of NP cells from IDD patients provided a database to identify the key genes involved in IDD. LEVEL OF EVIDENCE: N/A.

Enhanced osteogenic proliferation and differentiation of human adipose-derived stem cells on a porous n-HA/PGS-M composite scaffold.

This study explored the applicability, cellular efficacy, and osteogenic activities of porous nano-hydroxyapatite/Poly (glycerol sebacate)-grafted maleic anhydride (n-HA/PGS-g-M) composite scaffolds. Nuclear magnetic resonance (NMR) analyses indicated that approximately 43% of the hydroxide radicals in PGS were displaced by maleic anhydride. Resonance bands at 1036 cm-1 occurred in scaffolds containing nHA powders, and peak areas increased when n-HA weight increased in PGS-M-n-HA-0.4, PGS-M-n-HA-0.5, and PGS-M-n-HA-0.6 scaffolds. The n-HA/PGS-g-M composite scaffolds exhibited porous microstructure with average pore size of 150-300 µm in scanning electron microscopy (SEM) analysis. Differential scanning calorimetry (DSC) identified the glass transition temperature (Tg) as -25-30 °C, indicative of quality resilience. The modulus of compressibility increased when n-HA content increased. Interestingly, viability of human adipose-derived stem cells (hADSCs) in vitro and expression of the osteogenic related genes RUNX2, OCN, and COL1A1 was enhanced in the n-HA/PGS-g-M composite scaffolds compared to those factors observed in PGS-g-M scaffolds. Finally, simulated body fluid (SBF) tests indicated more apatite deposits on the surface of n-HA/PGS-g-M scaffolds compared to PGS-g-M scaffolds. Overall, porous n-HA/PGS-g-M composite scaffolds possessed acceptable biocompatibility and mechanical properties, and they stimulated hADSC cell proliferation and differentiation. Given these qualities, the composite scaffolds have potential applications in bone tissue engineering.

Study of the Microstructure, Mechanical, and Magnetic Properties of LaFe11.6Si1.4Hy/Bi Magnetocaloric Composites.

We have successfully synthesized LaFe11.6Si1.4Hy/Bi composites by cold pressing together with vacuum annealing technology, and systematically investigated the microstructure, magnetism, mechanical performance, and magnetocaloric properties. LaFe11.6Si1.4Hy particles are well surrounded by metallic Bi, without the formation of new phase. The maximum values of the volumetric magnetic entropy change -ΔSM are as high as 51, 49, and 35 mJ/cm³K around 263 K, for the composites with 5, 10 and 15 wt % Bi contents, respectively. The maximum value of the compressive strength for LaFe11.6Si1.4Hy/Bi composites increased continuously from 155 to 358 MPa with increasing Bi content, from 0 to 15 wt %.

Feasibility of interlaminar lumbar discectomy through percutaneous transforaminal endoscopy and blunt perforation of the ligamentum flavum.

AIM: To determine the efficacy, safety, and clinical value of a novel surgical procedure involving the blunt perforation of the ligamentum flavum (LF) during endoscopic interlaminar lumbar discectomy. MATERIAL AND METHODS: This was a prospective study of 50 patients (27 males, 17-51 years of age) undergoing lumbar discectomy for single segment L4/L5 or L5/S1 disk herniation were grouped into the control (cutting of the LF; n=28) and test (blunt perforation; n=22) groups. Intraoperative injury to the LF was evaluated by electrophysiological monitoring. The time required for perforation, total surgical time, and proportion of epidural sac and nerve root injury were assessed. RESULTS: Among the enrolled patients, 90% showed herniation of the L4/5 segment and 10% of the L5/S1 segment. The success rate for the perforation of the LF was 93%. The intraoperative observation showed mild self-closing injury to the LF tissue. The test group showed shorter overall surgical time (43 vs. 56 min) and shorter duration to go through the LF (1 vs. 13 min, p 0.001). No dural sac or nerve root injury resulting from blunt perforation of the LF was observed. CONCLUSION: Compared to cutting, blunt perforation of the LF could reduce surgical time and injury to LF and surrounding tissues. Thus, it could be a safe and efficient surgical technique for patients undergoing intralaminar lumbar discectomy.

[XPS and UPS characterization for Cr and Mn in high-temperature oxide films of bulk nanocrystalline 304 stainless steel].

The authors studied the binding energies of valence electrons of two oxide scales, the atomic percentages of Cr and Mn elements in two oxide films, the work function of two oxide films on bulk nanocrystalline 304 stainless steel (BN-SS304) and conventional polycrystalline 304 stainless steel (CP-SS304). BN-SS304 was prepared by severe rolling technique, and the two oxide films were formed in atmosphere at 900 degrees C for 24 hours oxidation on BN-SS304 and CP-SS304 surfaces. In the two oxide films, Cr and Mn elements exist in the forms of Cr3+, Cr0, Mn4+ and Mn0. The atomic percentage ratios of Cr+ / (Cr3+ + Cr0) and Mn4+ / (Mn4+ + Mn0) in the oxide film on BN-SS304 are lower than those in the oxide film on CP-SS304. The interactions of the two oxides and the valence electrons of elements are Mn-O, Cr-O,3d and 4s of Mn0 and Cr0. The binding energies of the valence electrons in the oxide film on BN-SS304 are larger than those in the oxide film on CP-SS304, the work function of the oxide film on BN-SS304 is 0.07 eV larger than that on CP-SS304.