Geometry optimization of cantilever-based optical microphones.

The introduction of cantilever-based fiber-optic microphones (FOMs) has proven to be effective in acoustic sensing. Further improvements in cantilevers face two key constraints: the challenge of achieving minimal sizes with sufficient reflective area and the trade-off between sensitivity and response bandwidth. Herein, we present a geometry optimization framework for a cantilever-based FOM that addresses this issue. Employing drumstick-shaped cantilevers housed within a Fabry-Perot (F-P) interferometric structure, we showcase a heightened sensitivity of 302.8 mV/Pa at 1 kHz and a minimum detectable acoustic pressure (MDP) of 2.35 µPa/H z. Notably, these metrics outperform those of the original rectangular cantilever with identical dimensions. Furthermore, our proposed cantilever effectively mitigates the reduction in resonance frequencies, thereby improving the response bandwidth. This geometry optimization framework offers considerable design flexibility and scalability, making it especially suitable for high-performance acoustic sensing applications.

Effectiveness of Physiotherapeutic Scoliosis-Specific Exercises on 3-Dimensional Spinal Deformities in Patients With Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-analysis.

OBJECTIVE: To investigate the effects of physiotherapeutic scoliosis-specific exercises (PSSE) on coronal, horizontal, and sagittal deformities of the spine in adolescent idiopathic scoliosis (AIS) as well as how curve severity, intervention duration, and intervention type could modify these effects. DATA SOURCES: Data sources included PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases, which were searched from their inception to September 5, 2023. STUDY SELECTION: Clinical controlled trials reporting the effects of PSSE on the Cobb angle, angle of trunk rotation (ATR), thoracic kyphosis (TK), or lumbar lordosis in patients with AIS aged 10-18 years. The experimental groups received PSSE; the control groups received standard care (observation or bracing) or conventional exercise such as core stabilization exercise, Pilates, proprioceptive neuromuscular facilitation, and other nonspecific exercises. DATA EXTRACTION: Two researchers independently extracted key information from eligible studies. The quality of the studies was assessed using the Cochrane Handbook version 5.1.0 risk of bias assessment and the JBI Center for Evidence-Based Health Care (2016) of quasi-experimental research authenticity assessment tool. The level and certainty of evidence were rated according to the Grading of Recommendations, Assessment, Development, and Evaluation framework. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The protocol for this study was registered in PROSPERO (CRD42023404996). DATA SYNTHESIS: Twelve randomized controlled trials (RCTs) and 5 non-RCTs were meta-analyzed separately. The results indicated that compared with other nonsurgical management, PSSE significantly improved the Cobb angle, ATR, and TK, whereas the lumbar lordosis improvement was not statistically significant. Additionally, the efficacy of PSSE on Cobb angle was not significant in patients with curve severity ≥30° compared with controls. Nevertheless, the pooled effect of PSSE on Cobb angle was not significantly modified by intervention duration and intervention type and that on ATR was not significantly modified by intervention duration. The overall quality of evidence according to Grading of Recommendations, Assessment, Development, and Evaluation was moderate to low for RCT and very low for non-RCT. CONCLUSIONS: PSSE exhibited positive benefits on the Cobb angle, ATR, and TK in patients with AIS compared with other nonsurgical therapies. In addition, the effectiveness of PSSE may be independent of intervention duration and intervention type but may be influenced by the initial Cobb angle. However, more RCTs are needed in the future to validate the efficacy of PSSE in moderate AIS with a mean Cobb angle ≥30°. Current evidence is limited by inconsistent control group interventions and small sample size of the studies.

Safety and Efficacy of Polyetheretherketone (PEEK) Cages and Cadaveric Allografts in Transforaminal Lumbar Interbody Fusion (TLIF) for Treating Lumbar Pyogenic Spondylodiscitis.

Purpose: There have been many studies in the operative management of pyogenic spondylodiscitis with foreign materials. However, it still remains an issue of debate on whether the allografts may be used in pyogenic spondylodiscitis. This study sought to evaluate the safety and effectiveness of PEEK cages and the cadaveric allograft in transforaminal lumbar interbody fusion (TLIF) for treating lumbar pyogenic spondylodiscitis. Methods: From January 2012 to December 2019, 56 patients underwent surgery for lumbar pyogenic spondylodiscitis. The posterior debridement of all patients and their fusion with allografts, local bone grafts, and bone chip cages were performed before posterior pedicle screw fusion. An assessment of the residual pain, the grade of neurological injury, and the resolution of infection was conducted on 39 patients. The clinical outcome was evaluated using a visual analog scale (VAS) and the Oswestry Disability Index (ODI), and neurological outcomes were appraised based on Frankel grades. The radiological outcomes were evaluated via focal lordosis, lumbar lordosis, and the state of the fusion. Results: Staphylococcus aureus and Staphylococcus epidermidis were the most common causative organisms. The mean preoperative focal lordosis was -1.2° (-11.4° to 5.7°), and the mean postoperative focal lordosis increased to 10.3° (4.3°-17.2°). At the final follow-up, there were five cases with subsidence of the cage, no case of recurrence, and no case with cage and screw loosening or migration. The mean preoperative VAS and ODI scores were 8.9 and 74.6%, respectively, and improvements in VAS and ODI were 6.6 ± 2.2 and 50.4 ± 21.3%, respectively. The Frankel grade D was found in 10 patients and grade C in 7. Following the final follow-up, only one patient improved from Frankel grade C to grade D while the others recovered completely. Conclusion: The PEEK cage and cadaveric allograft combined with local bone grafts is a safe and effective choice for intervertebral fusion and restoring sagittal alignment without increased incidence of relapse for treating lumbar pyogenic spondylodiscitis.

Acceptable Fusion Rate of Single-Level OLIF Using Pure Allograft Combined with Posterior Instrumentation through the Wiltse Approach: A 2-Year Follow-Up Study.

OBJECTIVE: Autogenic bone grafts have shown successful fusion rates in the treatment of degenerative lumbar disorders, but taking too many autogenic bones may result in donor site ischemia or infection. This study aimed to evaluate the outcomes of single-level oblique lumbar interbody fusion (OLIF) using pure allograft combined with posterior pedicle screw instrumentation through the Wiltse approach. METHODS: A retrospective case analysis was performed on a series of consecutive patients who received a single-level OLIF procedure combined with posterior pedicle screw instrumentation through the Wiltse approach between July 1, 2017, and December 31, 2019, in which pure allogenic bone graft was used and filled in the large window of the cage. The patients were followed up as scheduled at 1 day and 3, 6, 12, 24 months after operation. Clinical outcome was assessed by multiple questionnaires, including Oswestry disability index (ODI), Japanese Orthopaedic Association (JOA) score rating system, short form-36 health survey (SF-36), and visual analog scale (VAS) for low back pain. Radiographic outcome was evaluated by measuring the parameters such as disc height, lumbar lordosis, and segmental angle on the standard standing lateral radiographs, and the space angle of the fusion level on the dynamic views of the lateral radiographs. Subsidence of the cage and intervertebral fusion status were evaluated on both the radiographic and CT scan images. RESULTS: A total of 34 patients were finally included in this study. At 2-year follow-up, the VAS for low back pain, ODI, JOA, and SF-36 scores all had significant improvement (p < 0.001). Substantial increase of anterior and posterior disc heights was observed (p < 0.001). Both lumbar lordosis and segmental angle became larger (p < 0.05). No visible change of the space angle of the fusion level was found on the dynamic views. The 1-year fusion rate of 73.5% on CT scans proceeded to 82.4% at 2-year follow-up. The fusion rate was as high as 91.2% according to Bridwell interbody fusion grading system on radiographic images. The clinical outcomes in patients with incomplete fusion were just as good as those with complete fusion. The six patients with cage subsidence had higher ODI (p < 0.001) and lower JOA (p < 0.001) and SF-36 PCS (p = 0.011) scores than those without cage subsidence. CONCLUSION: The use of pure allograft in single-level OLIF resulted in an acceptable fusion rate and satisfactory clinical effect at 2-year follow-up. Supplementation of posterior pedicle screw through the minimally invasive Wiltse approach ensured the favorable outcomes both clinically and radiographically.

Constitutive and conditional gene knockout mice for the study of intervertebral disc degeneration: Current status, decision considerations, and future possibilities.

There have been an increasing number of patients with degenerative disc diseases due to the aging population. In light of this, studies on the pathogenesis of intervertebral disc degeneration have become a hot topic, and gene knockout mice have become a valuable tool in this field of research. With the development of science and technology, constitutive gene knockout mice can be constructed using homologous recombination, zinc finger nuclease, transcription activator-like effector nuclease technology and clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) system, and conditional gene knockout mice can be constructed using the Cre/LoxP system. The gene-edited mice using these techniques have been widely used in the studies on disc degeneration. This paper reviews the development process and principles of these technologies, functions of the edited genes in disc degeneration, advantages, and disadvantages of different methods and possible targets of the specific Cre recombinase in intervertebral discs. Recommendations for the choice of suitable gene-edited model mice are presented. At the same time, possible technological improvements in the future are also discussed.

Increased Expression of Prolyl Endopeptidase Induced by Oxidative Stress in Nucleus Pulposus Cells Aggravates Intervertebral Disc Degeneration.

A healthy microenvironment of the intervertebral disc tissue is characterized by hypoxia owing to its sparse vascular distribution. Oxidative stress plays a pivotal role in the pathological development of intervertebral disc degeneration (IVDD). We found that the expression of prolyl endopeptidase (PREP) increased in degenerative nucleus pulposus (NP) tissues. The purpose of this study was to determine whether PREP is involved in oxidative-stress-induced IVDD. Tertbutyl hydroperoxide can inhibit the expression of PREP by activating the PI3K/AKT signaling pathway at low concentrations in NP cells. Knockdown of PREP protected NP cells from apoptosis induced by oxidative stress, whereas overexpression of PREP exacerbated the apoptosis of NP cells. We also investigated the connection between the PI3K/AKT signaling pathway and PREP and found that the activation of the PI3K/AKT signaling pathway downregulated the expression of PREP by inhibiting p53. As a crucial transcription factor, p53 binds to the PREP promoter region and promotes its transcription. Overexpression of PREP also impairs protein secretion in the extracellular matrix of NP cells. Furthermore, the in vivo knockout of PREP could attenuate puncture-induced IVDD. These findings suggested that the downregulation of PREP might maintain the viability of NP cells and attenuate IVDD under oxidative stress.

Oxidative Stress Aggravates Apoptosis of Nucleus Pulposus Cells through m6A Modification of MAT2A Pre-mRNA by METTL16.

The process of intervertebral disc degeneration (IVDD) is complex, and its mechanism is considered multifactorial. Apoptosis of oxidative stressed nucleus pulposus cells (NPCs) should be a fundamental element in the pathogenesis of IVDD. In our pilot study, we found that the expression of MAT2A decreased, and METTL16 increased in the degenerative nucleus pulposus tissues. Previous studies have shown that the balance of splicing, maturation, and degradation of MAT2A pre-mRNA is regulated by METTL16 m6A modification. In the current study, we aimed to figure out whether this mechanism was involved in the aberrant apoptosis of NPCs and IVDD. Human NPCs were isolated and cultured under oxidative stress. An IVDD animal model was established. It showed that significantly higher METTL16 expression and lower MAT2A expression were seen in either the NPCs under oxidative stress or the degenerative discs of the animal model. MAT2A was inhibited with siRNA in vitro or cycloleucine in vivo. METTL16 was overexpressed with lentivirus in vitro or in vivo. Downregulation of MAT2A or upregulation of METTL16 aggravated nucleus pulposus cell apoptosis and disc disorganization. The balance of splicing, maturation, and degradation of MAT2A pre-mRNA was significantly inclined to degradation in the NPCs with the overexpression of METTL16. Increased apoptosis of NPCs under oxidative stress could be rescued by reducing the expression of METTL16 using siRNA with more maturation of MAT2A pre-mRNA. Collectively, oxidative stress aggravates apoptosis of NPCs through disrupting the balance of splicing, maturation, and degradation of MAT2A pre-mRNA, which is m6A modified by METTL16.

Anterior cervical discectomy and fusion to treat cervical instability with vertigo and dizziness: A single center, retrospective, observational study.

Purpose: The current study attempts to investigate the role of anterior cervical discectomy and fusion (ACDF) in alleviating symptoms in patients with cervical vertigo associated with cervical instability. Methods: The patients of cervical instability with vertigo and dizziness who underwent ACDF between January 2011 and December 2019 were followed-up for more than two years. Demographic data (age, sex, follow up period and levels of instable cervical segments) were assessed; Symptoms of vertigo and dizziness before and after surgery were assessed by the 15-item version of the Vertigo Symptom Scale (VSS) and the 25-item Dizziness Handicap Inventory (DHI). The severity and frequency of other symptoms like neck and occipital pain, gastrointestinal discomfort, nausea, vomiting, tinnitus, palpitations, headache, diplopia and blurring of vision before and after surgery were also assessed. Results: A total of 92 patients underwent ACDF for cervical instability with vertigo and dizziness between January 2011 and December 2019, of which 79 patients were included in the final analysis. The number of instable levels had no correlation with VSS and DHI scores before surgery (p > 0.05), while patients with C3/4 instability suffering a severer vertigo than other levels. Both DHI and VSS scores were significantly reduced after ACDF and this was sustained within two years after surgery (p < 0.001). Although there was no statistical difference in the ratio of patients with vertigo relief, patients with one-level cervical instability demonstrated a more rapid recovery than patients with multi-level cervical instability (p = 0.048). Also, there was improvement in other symptoms such as neck and occipital pain, gastrointestinal discomfort, nausea, vomiting, tinnitus, palpitations, headache and blurring of vision after surgery. Conclusions: Vertigo caused by C3/4 instability was severer than other levels such as C4/5 and C5/6. During 2 years' follow-up the significant relief of vertigo and dizziness was observed after anterior cervical surgery. Other accompanying symptoms except hypomnesia were also extenuated in follow-up period.

The m6A "reader" YTHDF1 promotes osteogenesis of bone marrow mesenchymal stem cells through translational control of ZNF839.

N6-methyladenosine (m6A) is required for differentiation of human bone marrow mesenchymal stem cells (hBMSCs). However, its intrinsic mechanisms are largely unknown. To identify the possible role of m6A binding protein YTHDF1 in hBMSCs osteogenesis in vivo, we constructed Ythdf1 KO mice and showed that depletion of Ythdf1 would result in decreased bone mass in vivo. Both deletion of Ythdf1 in mouse BMSCs and shRNA-mediated knockdown of YTHDF1 in hBMSCs prevented osteogenic differentiation of cells in vitro. Using methylated RNA immunoprecipitation (Me-RIP) sequencing and RIP-sequencing, we found that ZNF839 (a zinc finger protein) served as a target of YTHDF1. We also verified its mouse homolog, Zfp839, was translationally regulated by Ythdf1 in an m6A-dependent manner. Zfp839 potentiated BMSC osteogenesis by interacting with and further enhancing the transcription activity of Runx2. These findings should improve our understanding of the mechanism of BMSC osteogenesis regulation and provide new ideas for the prevention and treatment of osteoporosis.

Beraprost ameliorates postmenopausal osteoporosis by regulating Nedd4-induced Runx2 ubiquitination.

Bone health requires adequate bone mass, which is maintained by a critical balance between bone resorption and formation. In our study, we identified beraprost as a pivotal regulator of bone formation and resorption. The administration of beraprost promoted differentiation of mouse bone mesenchymal stem cells (M-BMSCs) through the PI3K-AKT pathway. In co-culture, osteoblasts stimulated with beraprost inhibited osteoclastogenesis in a rankl-dependent manner. Bone mass of p53 knockout mice remained stable, regardless of the administration of beraprost, indicating that p53 plays a vital role in the bone mass regulation by beraprost. Mechanistic in vitro studies showed that p53 binds to the promoter region of neuronal precursor cell-expressed developmentally downregulated 4 (Nedd4) to promote its transcription. As a ubiquitinating enzyme, Nedd4 binds to runt-related transcription factor 2 (Runx2), which results in its ubiquitination and subsequent degradation. These data indicate that the p53-Nedd4-Runx2 axis is an effective regulator of bone formation and highlight the potential of beraprost as a therapeutic drug for postmenopausal osteoporosis.

MicroRNA-744 promotes proliferation of osteosarcoma cells by targeting PTEN.

MicroRNAs (miRNAs/miRs) are non-coding RNAs that regulate protein synthesis by targeting mRNAs for translational repression or degradation. Previous studies have reported that aberrant expression of miR­744 may be involved in human osteosarcoma; however, the underlying mechanisms remain elusive. In the present study, the expression levels of miR­744 and its downstream signals were determined by reverse transcription­quantitative PCR and western blotting. Cell proliferation was assessed using the bromodeoxyuridine assay, and the target of miR­744 was investigated using a dual­luciferase activity assay. The present study identified a significant upregulation of miR­744 in osteosarcoma tissues compared with adjacent non­tumor tissues. Furthermore, it was demonstrated that ectopic overexpression of miR­744 induced by a miR­744 precursor significantly enhanced proliferation of the osteosarcoma cell line MG63, whereas opposite results were observed following suppression of miR­744 with its inhibitor. Moreover, as a unique anti­oncogene, PTEN was identified as a direct target of miR­744. It was confirmed that miR­744 downregulated PTEN expression in MG63 cells by targeting the PTEN 3'untranslated region, and that the downstream AKT signal was also regulated by miR­744. Collectively, the present results suggested that miR­744 promoted proliferation of human osteosarcoma cells by directly regulating the PTEN/AKT signaling pathway.

Inhibition of Y1 Receptor Promotes Osteogenesis in Bone Marrow Stromal Cells via cAMP/PKA/CREB Pathway.

Inhibition of neuropeptide Y1 receptor stimulates osteogenesis in vitro and in vivo. However, the underlying mechanisms involved in these effects remain poorly understood. Here we identify the effects of Y1 receptor deficiency on osteogenic differentiation in human bone marrow stromal cells (BMSCs) by using genetic and pharmacological regulation, and to explore the pathways mediating these effects. In BMSCs, inhibition of Y1 receptor stimulates osteogenesis and upregulates the expression levels of the master transcriptional factor RUNX2. Mechanistically, Y1 receptor deficiency increases the levels of intracellular cAMP, which via protein kinase A (PKA) mediated pathways results in activation of phospho-CREB (p-CREB). We find RUNX2 activation induced by Y1 receptor deficiency is reversed by H-89, a PKA inhibitor. These results indicate Y1 receptor deficiency activates PKA-mediated phosphorylation of CREB, leading to activation of RUNX2 and enhances osteogenic differentiation in BMSCs. In conclusion, these data indicate that Y1 receptor deficiency promotes osteogenic differentiation by RUNX2 stimulation through cAMP/PKA/CREB pathway.

Characterization of LncRNA SNHG22 as a protector of NKIRAS2 through miR-4492 binding in osteosarcoma.

Many studies have revealed the function of long noncoding RNA (LncRNA) in regulating tumorigenesis of osteosarcoma (OS). As a subgroup of LncRNA, small nucleolar RNA host genes (SNHGs) have emerged as potentially important in OS. According to our recent findings, small nucleolar RNA host gene 22 (SNHG22) plays an important role in inhibiting the growth and metastasis of OS. However, the underlying mechanism of SNHG22 in regulating OS progression remains unknown. In this study, we confirmed that SNHG22 was downregulated in OS, and the overexpression of SNHG22 significantly inhibited OS progression in vivo and in vitro. Meanwhile, overexpression of SNHG22 also inhibited the migration and proliferation of human umbilical vein endothelial cells (HUVECs) and prevented the epithelial-to-mesenchymal transition (EMT) in OS. Furthermore, the interaction between miR-4492 and SNHG22 we previously predicted was validated by RNA pull-down assays and RNA immunoprecipitation assays. Dual-luciferase reporter assays showed that SNHG22 could directly interact with miR-4492 and upregulate the expression of NK-κB inhibitor-interacting Ras-like 2 (NKIRAS2) by its competing endogenous RNA (ceRNA) activity on miR-4492. In conclusion, our study has clarified the function of SNHG22 in OS progression and suggests a novel therapeutic target for OS.

Newly designed anterolateral and posterolateral locking anatomic plates for lateral tibial plateau fractures: a finite element study.

BACKGROUND: Lateral column tibial plateau fracture fixation with a locking screw plate has higher mechanical stability than other fixation methods. The objectives of the present study were to introduce two newly designed locking anatomic plates for lateral tibial plateau fracture and to demonstrate their characteristics of the fixation complexes under the axial loads. METHODS: Three different 3D finite element models of the lateral tibial plateau fracture with the bone plates were created. Various axial forces (100, 500, 1000, and 1500 N) were applied to simulate the axial compressive load on an adult knee during daily life. The equivalent maps of displacement and stress were output, and relative displacement was calculated along the fracture lines. RESULTS: The displacement and stresses in the fixation complexes increased with the axial force. The equivalent displacement or stress map of each fixation under different axial forces showed similar distributing characteristics. The motion characteristics of the three models differed, and the max-shear stress of trabecula increased with the axial load. CONCLUSIONS: These two novel plates could fix lateral tibial plateau fractures involving anterolateral and posterolateral fragments. Motions after open reduction and stable internal fixation should be advised to decrease the risk of trabecular microfracture. The relative displacement of the posterolateral fragments is different when using anterolateral plate and posterolateral plate, which should be considered in choosing the implants for different posterolateral plateau fractures.

The morphological features of different Schatzker types of tibial plateau fractures: a three-dimensional computed tomography study.

BACKGROUND: Tibial plateau fractures are of great challenge to treat with open reduction and internal fixation, because fractures vary from simple to complex, with little or extensive articular involvement. Hence, recognition and comprehension of the fracture features will help orthopedic surgeons understand the injury mechanism better and manage these fractures by planning optimal surgical procedures. This study aimed to evaluate the morphological characteristics of tibial plateau fractures based on the Schatzker classification. METHODS: A total of 186 patients with 188 tibial plateau fractures from 2010 to 2014 in our hospital were reviewed using a computed tomography scan and three-dimensional (3D) reconstruction. The main fracture line angles (FLA) of Schatzker types I, II, and IV were measured. For each fracture, depression depth was measured, and the depression zone was also located. Depression zones were overlapped to obtain a frequency diagram. RESULTS: Schatzker type I and II fractures had three subtypes: single anterolateral fracture, single posterolateral fracture, and complex fracture (the anterolateral and posterolateral parts). Schatzker type IV fractures were also divided into three subtypes: single posteromedial fracture, single anteromedial fracture, and the whole medial fracture. For various Schatzker types and subtypes of fracture, fracture depression clustered and occurred at different locations of the tibial plateau. A significant difference was observed in the depression depth among the different Schatzker types (P < 0.01, Kruskal-Wallis test), especially between Schatzker type III and other types (Nemenyi test). There was no difference in the depression depth among the subtypes of Schatzker type II, whereas the difference was significant between the two subtypes of Schatzker type IV. CONCLUSIONS: Schatzker type I, II, and IV fractures could be divided into three corresponding subtypes by FLA. Various Schatzker types of fractures differed in location and depth of depression. A proper operative approach should be made based on the morphological characteristics of individual types of tibial plateau fractures.