Novel Risk Factors for Cervical Facet Joint Degeneration in the Subaxial Cervical Spine: Correlation with Cervical Sagittal Alignment and Bone Mineral Density.

OBJECTIVE: The impact of cervical sagittal alignment on cervical facet joint degeneration (CFD) and the risk factors for CFD in patients with degenerative cervical myelopathy (DCM) were investigated in the current study. METHODS: A total of 250 surgical patients with DCM were recruited. The clinical data and radiographical characteristics, including CFD, cervical sagittal balance parameters, Hounsfield unit (HU) values, disc degeneration (DD), and modic change, were collected. The detailed correlation between these characteristics and CFD was analyzed. Characteristics, including CFD, were compared among the various cervical alignment types and different CFD groups. Finally, the risk factors for CFD were revealed via logistic regression. RESULTS: CFD was prevalent in DCM patients. Age, cervical sagittal vertical axis (cSVA), range of motion, T1 slope, thoracic inlet angle, DD, HU value, and modic change correlated with CFD segmentally and globally (P < 0.05). The lordosis and sigmoid types had a significantly higher CFD prevalence (P < 0.05). Furthermore, the average CFD threshold for the severe CFD group was 1.625 (area under the curve, 0.958). Additionally, 167 patients with average CFD <1.625 and 83 patients with CFD of ≥1.625 were classified into the mild CFD group and severe CFD group, respectively. Finally, multivariate analysis was performed, and age, cSVA, HU value, modic change, and DD were determined to be independent risk factors for CFD. CONCLUSIONS: The load distribution tends to shift to a more shear-like pattern in the sigmoid and kyphosis types and in those with a higher cSVA, thereby promoting CFD. Aging, cervical malalignment, low bone mineral density, DD, and modic change were revealed to result in high risks of CFD.

Glutamine Mitigates Oxidative Stress-Induced Matrix Degradation, Ferroptosis, and Pyroptosis in Nucleus Pulposus Cells via Deubiquitinating and Stabilizing Nrf2.

Aims: Intervertebral disc degeneration (IDD) is closely related to low back pain, which is a prevalent age-related problem worldwide; however, the mechanism underlying IDD is unknown. Glutamine, a free amino acid prevalent in plasma, is recognized for its anti-inflammatory and antioxidant properties in various diseases, and the current study aims to clarify the effect and mechanism of glutamine in IDD. Results: A synergistic interplay was observed between pyroptosis and ferroptosis within degenerated human disc specimens. Glutamine significantly mitigated IDD in both ex vivo and in vivo experimental models. Moreover, glutamine protected nucleus pulposus (NP) cells after tert-butyl hydroperoxide (TBHP)-induced pyroptosis, ferroptosis, and extracellular matrix (ECM) degradation in vitro. Glutamine protected NP cells from TBHP-induced ferroptosis by promoting the nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation by inhibiting its ubiquitin-proteasome degradation and inhibiting lipid oxidation. Innovation and Conclusions: A direct correlation is evident in the progression of IDD between the processes of pyroptosis and ferroptosis. Glutamine suppressed oxidative stress-induced cellular processes, including pyroptosis, ferroptosis, and ECM degradation through deubiquitinating Nrf2 and inhibiting lipid oxidation in NP cells. Glutamine is a promising novel therapeutic target for the management of IDD.

Glutamine suppresses senescence and promotes autophagy through glycolysis inhibition-mediated AMPKα lactylation in intervertebral disc degeneration.

Regulating metabolic disorders has become a promising focus in treating intervertebral disc degeneration (IDD). A few drugs regulating metabolism, such as atorvastatin, metformin, and melatonin, show positive effects in treating IDD. Glutamine participates in multiple metabolic processes, including glutaminolysis and glycolysis; however, its impact on IDD is unclear. The current study reveals that glutamine levels are decreased in severely degenerated human nucleus pulposus (NP) tissues and aging Sprague-Dawley (SD) rat nucleus pulposus tissues, while lactate accumulation and lactylation are increased. Supplementary glutamine suppresses glycolysis and reduces lactate production, which downregulates adenosine-5'-monophosphate-activated protein kinase α (AMPKα) lactylation and upregulates AMPKα phosphorylation. Moreover, glutamine treatment reduces NP cell senescence and enhances autophagy and matrix synthesis via inhibition of glycolysis and AMPK lactylation, and glycolysis inhibition suppresses lactylation. Our results indicate that glutamine could prevent IDD by glycolysis inhibition-decreased AMPKα lactylation, which promotes autophagy and suppresses NP cell senescence.

Application of a Magnetic Resonance Imaging-Based Lumbar Vertebral Bone Quality Scoring System in Patients with Degenerative Lumbar Scoliosis.

BACKGROUND: Although dual-energy X-ray absorptiometry is still the gold standard for diagnosing osteoporosis, it can lead to inaccurate bone mineral density measurements due to lumbar degeneration and scoliosis. Many researchers have investigated diagnostic methods for osteoporosis in patients with degenerative lumbar scoliosis (DLS). This study aimed to investigate the differences between conventional vertebral bone quality (VBQ) scores and modified VBQ scores in patients with DLS and the influence of lumbar scoliosis on VBQ scores. METHODS: We retrospectively collected the clinical and radiological data of 68 patients with DLS admitted to Sun Yat-sen Memorial Hospital from July 2018 to April 2023. The patients were classified into one of 2 groups based on the T score of the left femoral neck. VBQ scores relative to cerebrospinal fluid at different levels, VBQ scores on different planes and single-level VBQ scores were compared. Receiver operating characteristic analysis was also performed. Different modified VBQ scores were compared between the moderate scoliosis group (10°

Constructing a novel type-â ¡ ZnO/BiOCOOH heterojunction microspheres for the degradation of tetracycline and bacterial inactivation.

A novel ZnO/BiOCOOH microsphere photocatalyst with a type-Ⅱ mechanism was developed for the first time. This strategy was accomplished by immobilizing ZnO onto 3D BiOCOOH microspheres via a single-step hydrothermal synthesis method. The ability to degrade tetracycline (TC) in water under visible light and inactivate bacteria of as-catalyst were analyzed. Among the prepared samples, the ZnO/BiOCOOH composite, with a mass ratio of 40%(Zn/Bi), exhibited the highest photocatalytic activity, which was able to degrade 98.22% of TC in just 90 min and completely eradicated Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in 48 h, and had potential application in solving water resource environmental pollution. The photoelectric characteristics of the photocatalysts were examined by means of electrochemical impedance spectroscopy (EIS) and photoluminescence (PL) spectroscopy. The findings indicated that the superior photocatalytic performance could be credited to the dissociation of electrons (e-) and holes (h+) in heterojunction composites. Finally, electron paramagnetic resonance (EPR) and capture experiments were conducted to confirm the photocatalytic mechanism of the type-Ⅱ heterojunction. This work provides a new Bi-base photocatalyst for aqueous environmental control.

The impact of dyslipidemia on lumbar intervertebral disc degeneration and vertebral endplate modic changes: a cross-sectional study of 1035 citizens in China.

BACKGROUND: Intervertebral disc degeneration (IDD) and vertebral endplate Modic changes (MCs) are common lumbar degenerative phenotypes related to low back pain (LBP). Dyslipidemia has been linked to LBP but its associations with IDD and MCs have not been fully elucidated. The present study aimed to address the possible link between dyslipidemia, IDD and MCs in the Chinese population. METHODS: 1035 citizens were enrolled in the study. The levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were collected. IDD was evaluated based on the Pfirrmann grading system and subjects with an average grade ≥ 3 were defined as having degeneration. MCs were classified into typical types 1, 2 and 3. Covariables, including age, sex, BMI and fasting plasma glucose, were included for the adjustment of the logistic analyses. RESULTS: The degeneration group included 446 subjects while the nondegeneration group included 589 subjects. The degeneration group had significant higher levels of TC and LDL-C (p < 0.001) whereas TG and HDL-C were not significantly different between the two groups. TC and LDL-C concentrations were significantly positively correlated with average IDD grades (p < 0.001). Multivariate logistic regression revealed that high TC (≥ 6.2 mmol/L, adjusted OR = 1.775, 95% CI = 1.209-2.606) and high LDL-C (≥ 4.1 mmol/L, adjusted OR = 1.818, 95% CI = 1.123-2.943) were independent risk factors for IDD. Type 1 MC presented in 84 (8.12%) subjects, type 2 MC presented in 244 (23.57%) subjects, type 3 MC presented in 27 (2.61%) subjects and no MC was observed in the remaining 680 (65.70%) subjects. The type 2 MC group demonstrated a higher level of TC, but the association between serum lipids and MCs could not be confirmed in further multivariate logistic regression. CONCLUSIONS: High TC (≥ 6.2 mmol/L) and LDL-C (≥ 4.1 mmol/L) concentrations were independent risk factors for IDD for citizens in China. However, the association between dyslipidemia and MCs could not be determined. The effect of excess serum cholesterol may be critical for IDD and cholesterol lowering treatment may provide new opportunities in the management of lumbar disc degeneration.

Tail nerve electrical stimulation promoted the efficiency of transplanted spinal cord-like tissue as a neuronal relay to repair the motor function of rats with transected spinal cord injury.

Following transected spinal cord injury (SCI), there is a critical need to restore nerve conduction at the injury site and activate the silent neural circuits caudal to the injury to promote the recovery of voluntary movement. In this study, we generated a rat model of SCI, constructed neural stem cell (NSC)-derived spinal cord-like tissue (SCLT), and evaluated its ability to replace injured spinal cord and repair nerve conduction in the spinal cord as a neuronal relay. The lumbosacral spinal cord was further activated with tail nerve electrical stimulation (TNES) as a synergistic electrical stimulation to better receive the neural information transmitted by the SCLT. Next, we investigated the neuromodulatory mechanism underlying the action of TNES and its synergism with SCLT in SCI repair. TNES promoted the regeneration and remyelination of axons and increased the proportion of glutamatergic neurons in SCLT to transmit brain-derived neural information more efficiently to the caudal spinal cord. TNES also increased the innervation of motor neurons to hindlimb muscle and improved the microenvironment of muscle tissue, resulting in effective prevention of hindlimb muscle atrophy and enhanced muscle mitochondrial energy metabolism. Tracing of the neural circuits of the sciatic nerve and tail nerve identified the mechanisms responsible for the synergistic effects of SCLT transplantation and TNES in activating central pattern generator (CPG) neural circuits and promoting voluntary motor function recovery in rats. The combination of SCLT and TNES is expected to provide a new breakthrough for patients with SCI to restore voluntary movement and control their muscles.

Group percolation in interdependent networks with reinforcement network layer.

In many real-world interdependent network systems, nodes often work together to form groups, which can enhance robustness to resist risks. However, previous group percolation models are always of a first-order phase transition, regardless of the group size distribution. This motivates us to investigate a generalized model for group percolation in interdependent networks with a reinforcement network layer to eliminate collapse. Some backup devices that are equipped for a density ρ of reinforced nodes constitute the reinforcement network layer. For each group, we assume that at least one node of the group can function in one network and a node in another network depends on the group to function. We find that increasing the density ρ of reinforcement nodes and the size S of the dependency group can significantly enhance the robustness of interdependent networks. Importantly, we find the existence of a hybrid phase transition behavior and propose a method for calculating the shift point of percolation types. The most interesting finding is the exact universal solution to the minimal density ρ of reinforced nodes (or the minimum group size S) to prevent abrupt collapse for Erdos-Rényi, scale-free, and regular random interdependent networks. Furthermore, we present the validity of the analytic solutions for a triple point ρ (or S ), the corresponding phase transition point p , and second-order phase transition points p in interdependent networks. These findings might yield a broad perspective for designing more resilient interdependent infrastructure networks.

Construction of a niche-specific spinal white matter-like tissue to promote directional axon regeneration and myelination for rat spinal cord injury repair.

Directional axon regeneration and remyelination are crucial for repair of spinal cord injury (SCI), but existing treatments do not effectively promote those processes. Here, we propose a strategy for construction of niche-specific spinal white matter-like tissue (WMLT) using decellularized optic nerve (DON) loaded with neurotrophin-3 (NT-3)-overexpressing oligodendrocyte precursor cells. A rat model with a white matter defect in the dorsal spinal cord of the T10 segment was used. The WMLT transplantation group showed significant improvement in coordinated motor functions compared with the control groups. WMLT transplants integrated well with host spinal cord white matter, effectively addressing several barriers to directional axonal regeneration and myelination during SCI repair. In WMLT, laminin was found to promote development of oligodendroglial lineage (OL) cells by binding to laminin receptors. Interestingly, laminin could also guide linear axon regeneration via interactions with specific integrins on the axon surface. The WMLT developed here utilizes the unique microstructure and bioactive matrix of DON to create a niche rich in laminin, NT-3 and OL cells to achieve significant structural repair of SCI. Our protocol can help to promote research on repair of nerve injury and construction of neural tissues and organoids that form specific cell niches.

Stem cell-derived neuronal relay strategies and functional electrical stimulation for treatment of spinal cord injury.

The inability of adult mammals to recover function lost after severe spinal cord injury (SCI) has been known for millennia and is mainly attributed to a failure of brain-derived nerve fiber regeneration across the lesion. Potential approaches to re-establishing locomotor function rely on neuronal relays to reconnect the segregated neural networks of the spinal cord. Intense research over the past 30 years has focused on endogenous and exogenous neuronal relays, but progress has been slow and the results often controversial. Treatments with stem cell-derived neuronal relays alone or together with functional electrical stimulation offer the possibility of improved repair of neuronal networks. In this review, we focus on approaches to recovery of motor function in paralyzed patients after severe SCI based on novel therapies such as implantation of stem cell-derived neuronal relays and functional electrical stimulation. Recent research progress offers hope that SCI patients will one day be able to recover motor function and sensory perception.

Efficacy and Safety of Rivaroxaban Therapy for Patients With Peripheral Artery Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: We performed a systematic review and meta-analysis to evaluate the efficacy and safety of rivaroxaban in patients with PAD for the first time. METHODS: We searched MEDLINE, EMBASE and the Cochrane Library database for randomized controlled trials (RCTs) conducted for PAD. RESULTS: Three trials which contained 14873 patients were included for final meta-analysis. The results showed patients with rivaroxaban was associated with reduction in primary efficacy outcome (RR 0.83; 95% CI 0.76 to 0.90; p < 0.001). The RR was 0.85 (0.71 to 1.01) for patients with rivaroxaban alone and 0.81 (0.74 to 0.89) for those with rivaroxaban plus aspirin (p for heterogeneity between groups = 0.65). Patients with rivaroxaban showed a lower rate of acute limb ischemia (0.56; 0.47 to 0.66; p < 0.001). There was a trend toward a reduction in the rate of major amputation for vascular causes in the rivaroxaban arm (0.81; 0.63 to 1.03; p = 0.08). Compared with control, rivaroxaban therapy did not reduce the risks of myocardial infarction (0.87, 0.73 to 1.04, p = 0.12), ischemic stroke (0.85, CI 0.68 to 1.06, p = 0.15), death from cardiovascular causes (0.99, 0.85 to 1.15, p = 0.91) or death from any cause (1.00, 0.90 to 1.12, p = 0.98). Rivaroxaban therapy was associated with a 1.57-fold higher major bleeding rate as compared with those with aspirin or warfarin alone. CONCLUSIONS: Overall, the risks of the primary efficacy outcomes or adverse limb events were significantly lower with rivaroxaban than with aspirin or warfarin alone in patients with PAD. It also points out the significant major bleeding that occur because of such therapies.

Decellularized optic nerve functional scaffold transplant facilitates directional axon regeneration and remyelination in the injured white matter of the rat spinal cord.

Axon regeneration and remyelination of the damaged region is the most common repair strategy for spinal cord injury. However, achieving good outcome remains difficult. Our previous study showed that porcine decellularized optic nerve better mimics the extracellular matrix of the embryonic porcine optic nerve and promotes the directional growth of dorsal root ganglion neurites. However, it has not been reported whether this material promotes axonal regeneration in vivo. In the present study, a porcine decellularized optic nerve was seeded with neurotrophin-3-overexpressing Schwann cells. This functional scaffold promoted the directional growth and remyelination of regenerating axons. In vitro, the porcine decellularized optic nerve contained many straight, longitudinal channels with a uniform distribution, and microscopic pores were present in the channel wall. The spatial micro topological structure and extracellular matrix were conducive to the adhesion, survival and migration of neural stem cells. The scaffold promoted the directional growth of dorsal root ganglion neurites, and showed strong potential for myelin regeneration. Furthermore, we transplanted the porcine decellularized optic nerve containing neurotrophin-3-overexpressing Schwann cells in a rat model of T10 spinal cord defect in vivo. Four weeks later, the regenerating axons grew straight, the myelin sheath in the injured/transplanted area recovered its structure, and simultaneously, the number of inflammatory cells and the expression of chondroitin sulfate proteoglycans were reduced. Together, these findings suggest that porcine decellularized optic nerve loaded with Schwann cells overexpressing neurotrophin-3 promotes the directional growth of regenerating spinal cord axons as well as myelin regeneration. All procedures involving animals were conducted in accordance with the ethical standards of the Institutional Animal Care and Use Committee of Sun Yat-sen University (approval No. SYSU-IACUC-2019-B034) on February 28, 2019.

Resistive switching and synaptic learning performance of a TiO2 thin film based device prepared by sol-gel and spin coating techniques.

A resistance random access memory device based on TiO2 thin films was fabricated using a sol-gel spin and coating techniques. The composition, surface morphology, and microstructure of the TiO2 films were characterized using x-ray diffraction, Raman spectroscopy, scanning electronic microscopy, and transmission electron microscopy, respectively. The fabricated Al/TiO2 film/fluorine-doped tin oxide device exhibited electroforming-free bipolar resistive switching characteristics with a stable ON/OFF ratio higher than 300. The performance of the endurance cycling was still good after 100 direct sweeping cycles. A retention time of no less than 104 s was confirmed. A switching mechanism is systematically discussed based on the test results, and space-charge-limited current was found to be responsible for the switching behavior. Multilevel memory performance was realized in the as-fabricated devices. The synaptic performance was investigated by applying consecutive positive (0-2 V) and negative (0 to -1.6 V) voltage sweeps. The fabricated devices were found to exhibit 'learning-experience' behavior.

[A new purification methods of small DNAs--the purification methods with silica wool].

The principal purpose of this study is to set up efficient purification techniques of small DNAs which are suitable for isolation of from tens to three hundred bases of genes. On the bases of the technique, purification methods for big DNA fragments are established. In the experiment, the DNA bands were cut after agarose gel electrophoresis and put into 0.5 mL of tubes with silica wool, glass wood, absorbent cotton and cotton at the bottom. And then 10 000 r/min for 2 min, the liquid was collected. The results indicated that silica wool was the best of the materials. The recovery rate for DNAs below 200bp was over 90%, 85% to approximately 90% for 300bp. And the technique can be applied to purify bigger DNA fragments. The kits for DNA purification hardly recovered DNA below 150bp. The recovery rate for 150bp of DNA was 5%, 60% even for 300bp. The efficiencies of enzymic digestion and enzymic connection for the DNAs purified by the technique were the same as those for the DNAs isolated by the kits. So, the technique is obviously superior to kit purification methods.