Ca-Doping Cobalt-Free Double Perovskite Oxide as a Cathode Material for Intermediate-Temperature Solid Oxide Fuel Cell.

Mixed oxygen ion and electron-conducting materials are viable cathodes for solid oxide fuel cells due to their excellent oxygen transport kinetics and mixed electrical conductivity, which ensure highly efficient operation at low and medium temperatures. However, iron-based double perovskite oxides usually exhibit poor electrocatalytic activity due to low electron and oxygen ion conductivity. In this paper, Ca is doped in PrBaFe2O5+δ A-site to improve the electrochemical performance of PrBaFe2O5+δ. Results show that replacing Pr with Ca does not change the crystal structure, and the Ca doping effectively increases the adsorbed oxygen content and accelerates the migration and diffusion rate of O2- to the electrolyte|cathode interface. The polarization resistance of the symmetric cell PC0.15BF|CGO|PC0.15BF is 0.033 Ω·cm2 at 800 °C, which is about 56% lower than that of PBF, confirming the enhancement of the mixed conduction of oxygen ions and electrons. In addition, the anode-supported single cell has a peak power density of 512 mW·cm-2 at 800 °C.

Novel Anion-Doped Cathode Material SrFe1-x Si x O3-δF y for Intermediate-Temperature Solid Oxide Fuel Cells.

SrFe1-x Si x O3-δF y cathode materials (x = 0.05, 0.1, 0.15; y = 0, 0.1, 0.5) were prepared via a solid-state method. X-ray diffraction results show that the synthesized F doping samples were perovskite structure. X-ray photoelectron spectroscopy findings show that F- anions were doped into SrFe1-x Si x O3-δ. Transmission electron microscopy and energy-dispersive spectroscopy were performed to analyze the microstructure and element distribution in the materials, respectively. Double-layer composite cathode symmetric cells were prepared through a screen printing method. Scanning electron microscopy images revealed that the double-layer composite cathode adhered well to the electrolyte. The doping with F- can increase the coefficient of thermal expansion of SrFe1-x Si x O3-δ. The electrochemical impedance spectroscopy results indicate that the oxygen transport capacity of the SrFe0.95Si0.05O3-δ material can be improved by doping with F-, but such a method can decrease the oxygen transport capacity of SrFe0.9Si0.1O3-δ. At 800 °C, the peak power density of the single cell supported by an anode and SrFe0.9Si0.1O3-δF0.1 as the cathode reached 388.91 mW/cm2. Thus, the incorporation of F- into SrFe1-x Si x O3-δ cathode materials can improve their electrochemical performance and enable their application as cathode materials for solid-oxide fuel cells.

Construction and Validation of a Gastric Cancer Diagnostic Model based on Blood Groups and Tumor Markers.

Objective: The aim of this study is to explore the value of combined detection of ABO blood group and tumor markers in the diagnosis of gastric cancer. Methods: A total of 3650 gastric cancer patients treated in our center from January 2015 to December 2019, and 5822 controls were recruited, and divided into training set and validation set according to 7:3. The diagnostic and predictive model of gastric cancer was constructed by binary logistic regression method in the training set. The diagnostic value of the prediction model for gastric cancer was evaluated by calculating the prediction probability P value and drawing the Receiver operating characteristic (ROC) curve, and was verified in the validation set. Results: The Area under the curve (AUC) of the diagnosis and prediction model in the training set was 0.936 (95%CI: 0.926-0.941), the sensitivity was 81.66%, and the specificity was 98.61%. In the validation set, the AUC was 0.941 (95%CI: 0.932-0.950), the sensitivity was 82.33%, and the specificity was 99.02%. Furthermore, the diagnostic model obtained in this study had a high diagnostic value for early gastric cancer patients in the healthy population (AUC of training set, validation set and total population were 0.906, 0.920 and 0.908, respectively). Conclusions: We constructed a diagnostic model for gastric cancer including blood group and tumor markers, which has high reference value for the diagnosis of gastric cancer patients, and the model can better distinguish early gastric cancer from healthy people.

Fe-based double perovskite with Zn doping for enhanced electrochemical performance as intermediate-temperature solid oxide fuel cell cathode material.

This study aims to investigate the implications of transition-metal Zn doping at the B-site on the crystal structure, average thermal expansion coefficient (TEC), electrocatalytic activity, and electrochemical performance of LaBaFe2O5+δ by preparing LaBaFe2-xZnxO5+δ (x = 0, 0.05, 0.1, 0.15, 0.2, LBFZx). The X-ray diffraction (XRD) results show that Zn2+ doping does not change the crystal structure, the unit cell volume increases, and the lattice expands. The X-ray photoelectron spectroscopy (XPS) and mineral titration results show that the oxygen vacancy concentration and Fe4+ content gradually increase with the increase in doping amount. TEC decreases with the increase in Zn2+ doping amount, and the TEC of LBFZ0.2 is 11.4 × 10-6 K-1 at 30-750 °C. The conductivity has the best value of 103 S cm-1 at the doping amount of x = 0.1. The scanning electron microscopy (SEM) images demonstrate that the electrolyte CGO(Gd0.1Ce0.9O1.95) becomes denser after high-temperature calcination, and the cathode material is well attached to the electrolyte. The electrochemical impedance analysis shows that Zn2+ doping at the B-site can reduce the (Rp) polarization resistance, and the Rp value of the symmetric cell with LaBaFe1.8Zn0.2O5+δ as cathode at 800 °C is 0.014 Ω cm2. The peak power density (PPD) value of the anode-supported single cell is 453 mW cm-2, which shows excellent electrochemical performance.

Effects of Lactobacillus acidophilus and L. reuteri on bone mass and gut microbiota in ovariectomized mice.

Lactobacillus acidophilus is widely used as a food additive or medication in our daily lives. The objective of this study was to investigate the effects of L. acidophilus and L. reuteri on bone mass in OVX mice and their associated mechanisms. Fifty 6-week-old female C57BL/6J mice were subjected to five different treatments: sham surgery, OVX surgery, OVXandL. reuteri fed, OVXandL. acidophilus fed, OVXandboth L. reuteri and L. acidophilus co-fed, respectively. Serum samples were collected, and IL-1ß,IL-6,TNF-α, and OCN levels were determined. The bone volume fraction and trabecular number, trabecular thickness, trabecular separation, and cortical thickness of the mice were analyzed by micro-CT in both femurs. Mice feces were taken for Illumina high-throughput sequencing to analyze the microbial composition and characteristics. After probiotic feeding, the bone volume fraction, the trabecular number, and the trabecular thickness increased, and the trabecular separation decreased in OVX mice. IL-1ß, IL-6, and TNF-α in the blood significantly decreased. The observed Chao1 and ACE indexes increased significantly. Changes in intestinal microorganisms occurred in all groups of mice. The change of index in the gut microbes, may indicate that the bone mass of OVX mice is changing. L. acidophilus shares the same role as L. reuteri in preventing bone loss in OVX mice. The mechanism of action may be through inhibition of the activation of inflammatory factors in the osteoclast activation pathway in bone metabolism, modulation of gut microbial diversity, and alteration of the richness of specific microorganisms that lead to attenuation of bone loss.

Cu-doped Nd0.6Sr0.4Co1-xCuxO3-δ (x = 0, 0.05, 0.1, 0.15, 0.2) as the cathode for intermediate-temperature solid oxide fuel cells.

Nd0.6Sr0.4Co1-xCuxO3-δ (x = 0, 0.05, 0.1, 0.15, 0.2) (NSCCx) was prepared by replacing Co with Cu. Its chemical compatibility, electrical conductivity, and electrochemical properties were studied by X-ray powder diffractometry, scanning electron microscopy, and X-ray photoelectron spectroscopy. The conductivity, AC impedance spectra, and output power of the single cell were tested in an electrochemical workstation. Results showed that the thermal expansion coefficient (TEC) and electrical conductivity of the sample decreased with the increase in Cu content. The TEC of NSCC0.1 decreased by 16.28% in the temperature range of 35 °C-800 °C, and its conductivity was 541 S cm-1 at 800 °C. Furthermore, a single cell was constructed with NSCCx as the cathode, NiO-GDC as the anode, and GDC as the electrolyte. The peak power of the cell at 800 °C was 444.87 mW·cm-2, which was similar to that of the undoped sample. Compared with the undoped NSCC, NSCC0.1 showed lower TEC while maintaining its output power. Therefore, this material can be used as a cathode for solid oxide fuel cells.

Collaborative Passivation for Dual Charge Transporting Layers Based on 4-(chloromethyl)benzonitrile Additive toward Efficient and Stable Inverted Perovskite Solar Cells.

Poor carrier transport capacity and numerous surface defects of charge transporting layers (CTLs), coupled with misalignment of energy levels between perovskites and CTLs, impact photoelectric conversion efficiency (PCE) of inverted perovskite solar cells (PSCs) profoundly. Herein, a collaborative passivation strategy is proposed based on 4-(chloromethyl) benzonitrile (CBN) as a solution additive for fabrication of both [6,6]-phenyl-C61-butyric acid methylester (PCBM) and poly(triarylamine) (PTAA) CTLs. This additive can improve wettability of PTAA and reduce the agglomeration of PCBM particles, which enhance the PCE and device stability of the PSCs. As a result, a PCE exceeding 20% with a remarkable short circuit current of 23.9 mA cm-2 , and an improved fill factor of 81% is obtained for the CBN- modified inverted PSCs. Devices maintain 80% and 70% of the initial PCE after storage under 30% and 85% humidity ambient conditions for 1000 h without encapsulation, as well as negligible light state PCE loss. This strategy demonstrates feasibility of the additive engineering to improve interfacial contact between the CTLs and perovskites for fabrication of efficient and stable inverted PSCs.

Preparation and Electrochemical Properties of Cathode Materials Ln2-x Y x CuO4+δ for Solid Oxide Fuel Cell.

Ln2-x Y x CuO4+δ (Ln = Pr, Nd, Sm; x = 0, 0.025, 0.05, 0.1) cathode materials were synthesized using a sol-gel method and calcination at 1000 °C for 24 h. The phase structure, coefficient of thermal expansion (CTE), electrical conductivity, and electrochemical impedance of cathode materials were characterized. X-ray diffraction (XRD) patterns show that the cell volume of each cathode material decreases with the increase in the Y3+ doping amount and has good chemical compatibility with the Sm0.2Ce0.8O1.9 electrolyte. The thermal expansion test shows that the increase in Y3+ doping reduces the average CTE of Ln2CuO4+δ. The conductivity test shows that Y3+ doping increases the conductivity of Ln2CuO4+δ, and Pr1.975Y0.025CuO4+δ has the highest conductivity of 256 S·cm-1 at 800 °C. The AC impedance test shows that Y3+ doping reduces the polarization impedance of Ln2CuO4+δ, and Pr1.9Y0.1CuO4+δ has a minimum area-specific resistance (ASR) of 0.204 Ω·cm2 at 800 °C. In conclusion, Pr1.975Y0.025CuO4+δ has the best performance and is more suitable as a cathode material for a solid oxide fuel cell (SOFC).

Comprehensive Evaluation and Analysis of Human Settlements' Suitability in the Yangtze River Delta Based on Multi-Source Data.

The suitability of human settlements is critical for quality of life and regional development. As comprehensive evaluations and research on the suitability of human settlements are lacking, a comprehensive evaluation of human settlements in the Yangtze River Delta (YRD) was carried out in 2020 by combining natural and human environmental elements based on multi-source data such as digital elevation models, Landsat remote sensing images, meteorological station data, and points of interest, other multi-source data, and constructions of the human settlements' suitability indexes. The results showed the following: (1) The spatial suitability of the natural environment in the YRD is significantly affected by the topographic conditions and distance from the sea, showing an increasing spatial differentiation from southwest to northeast, with Shanghai and Yancheng having the best natural environment suitability. (2) The suitability of the human environment in urban areas is better than that in non-urban areas and shows a decreasing trend from the south to the north circle. Shanghai, Zhoushan, and Huaibei have the best human environment suitability. (3) The comprehensive suitability of human settlements includes both the spatial differentiation characteristics of the suitability of natural and human environments. Shanghai and Zhoushan have the mosy comprehensive suitability for human settlements, while Huaibei and Xuzhou have the worst. (4) Land with a comprehensive suitability for human settlements of greater than 0.580 accounts for 23.60% of the total and contains 30.08% of the population and 32.31% of the economy, indicating that areas with a high suitability index have been fully utilized, and the populations and economies with human settlements suitability have a high degree of matching.

m6A-Related Angiogenic Genes to Construct Prognostic Signature, Reveal Immune and Oxidative Stress Landscape, and Screen Drugs in Hepatocellular Carcinoma.

Background: m6A modification plays a key role in the development of hepatocellular carcinoma (HCC). Angiogenesis-related genes (ARGs) are increasingly being used to define signatures predicting patient prognosis. The correlations between m6A-related ARGs (mARGs), clinical outcomes, and the immune and oxidative stress landscape are unclear. Methods: Univariate Cox regression analysis of 24 mARGs yielded 13 prognostic genes, which were then analyzed for their enriched functions and pathways. After LASSO regression analysis, a prognostic signature was constructed and its reliability validated. Patients were grouped by risk using the signature score, and then the clinical prognosis, the immune landscape, and the oxidative stress landscape between the two groups were analyzed. Drug sensitivity analysis was performed to identify potentially efficient therapeutic agents. Results: Thirteen prognosis-related mARGs consistently clustered patients with HCC into four groups with significantly different prognosis. Four mARGs (EGF, ITGA5, ITGAV, and PLG) were used to construct a prognostic signature and define risk groups. Among them, EGF, ITGA5, and ITGAV, were defined as prognostic risk factors, while PLG was defined as a prognostic protective factor. Compared to low-risk patients, HCC patients in the high-risk group had a poorer prognosis and showed significant differences in clinical characteristics, enriched pathways, tumor stemness, and tumor microenvironment. The drug sensitivity of oxaliplatin and LDK-378 negatively correlated with ITGAV expression. Ten drugs had lower IC50s in the high-risk group, indicating better antitumor efficacy than in the low-risk group, with epothilone B having the lowest IC50 value. Conclusions: A prognostic model consisting of mARGs can be used to predict the prognosis of HCC patients. The risk grouping of our model can be used to reveal differences in the tumor immune microenvironment of patients with HCC. Further in-depth study may provide new targets for future treatment.

M2-like tumor-associated macrophage-related biomarkers to construct a novel prognostic signature, reveal the immune landscape, and screen drugs in hepatocellular carcinoma.

Background: M2-like tumor-associated macrophages (M2-like TAMs) have important roles in the progression and therapeutics of cancers. We aimed to detect novel M2-like TAM-related biomarkers in hepatocellular carcinoma (HCC) via integrative analysis of single-cell RNA-seq (scRNA-seq) and bulk RNA-seq data to construct a novel prognostic signature, reveal the "immune landscape", and screen drugs in HCC. Methods: M2-like TAM-related genes were obtained by overlapping the marker genes of TAM identified from scRNA-seq data and M2 macrophage modular genes identified by weighted gene co-expression network analysis (WGCNA) using bulk RNA-seq data. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were carried out to screen prognostic genes from M2-like TAM-related genes, followed by a construction of a prognostic signature, delineation of risk groups, and external validation of the prognostic signature. Analyses of immune cells, immune function, immune evasion scores, and immune-checkpoint genes between high- and low-risk groups were done to further reveal the immune landscape of HCC patients. To screen potential HCC therapeutic agents, analyses of gene-drug correlation and sensitivity to anti-cancer drugs were conducted. Results: A total of 127 M2-like TAM-related genes were identified by integrative analysis of scRNA-seq and bulk-seq data. PDLIM3, PAM, PDLIM7, FSCN1, DPYSL2, ARID5B, LGALS3, and KLF2 were screened as prognostic genes in HCC by univariate Cox regression and LASSO regression analyses. Then, a prognostic signature was constructed and validated based on those genes for predicting the survival of HCC patients. In terms of drug screening, expression of PAM and LGALS3 was correlated positively with sensitivity to simvastatin and ARRY-162, respectively. Based on risk grouping, we predicted 10 anticancer drugs with high sensitivity in the high-risk group, with epothilone B having the lowest half-maximal inhibitory concentration among all drugs tested. Conclusions: Our findings enhance understanding of the M2-like TAM-related molecular mechanisms involved in HCC, reveal the immune landscape of HCC, and provide potential targets for HCC treatment.

Preliminary Study of an Adjustable, Wearable, Noninvasive Vest Providing Chest Compression to Assist with Breathing.

Respiratory muscle paralysis caused by acute cervical spinal cord injury usually leads to pulmonary ventilation dysfunction and even death from respiratory failure. In addition to invasive treatments such as mechanical ventilation, the utilization of noninvasive respiratory support equipment plays an important role in long-term assisted breathing. In this study, we describes a wearable, noninvasive vest with adjustable pressure that enables assisted breathing and with an automatic alarm, and we aims to explore its safety and effectiveness on healthy adult participants. The vest monitors the human heart rate and the blood oxygen index data in real time, the alarm is automatically activated when the data is abnormal. Eight healthy participants had no obvious discomfort during the test while wearing the vest. Lung volumes, antero-posterior diameters, and left-right diameters at the second, fourth, and sixth ribs levels were acquired before and after inflation of the vest airbag, the data acquired by the imaging analysis using chest computed tomography showed significant differences before and after the inflation (p < 0.05). Thus, The vest designed for this study can achieve uniform and effective compression of the thorax, significantly changed the size of the thorax and lungs. It is expected to be applied as noninvasive support for patients with respiratory dysfunction.

Serum Total Bile Acids in Relation to Gastrointestinal Cancer Risk: A Retrospective Study.

Background: Bile acids (BAs) have been proposed to promote gastrointestinal cells carcinogenesis. However, studies on serum total bile acid (TBA) levels and gastrointestinal cancers (GICs) risk are rare. Methods: We conducted a retrospective case-control study from 2015 to 2019 at the First Affiliated Hospital of Air Force Military Medical University, in which 4,256 GICs cases and 1,333 controls were recruited. Patients' demographic, clinical and laboratory data were collected. The odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using binary logistic regression models. Results: Positive associations were observed between serum TBA levels and risks of esophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC). Overall, ORs of EC, GC and CRC risk rose with the TBA levels increasing. After adjustment for potential confounders, the OR of TBA-positive for EC risk was 4.89 (95% CI: 3.20-7.49), followed by GC (OR: 3.92, 95% CI: 2.53-6.08), and CRC (OR: 3.32, 95% CI: 2.04-5.11). Patients aged 60 years or older have a higher risk of GICs, especially for EC patients. Males are associated with a higher risk of GC, while females are associated with a higher risk of CRC. Preoperative serum TBA positive and negative was significantly different in the presence or absence of hematogenous metastasis among EC patients (P=0.014), and lymph node metastasis among GC patients (P=0.018). Conclusions: This retrospective study showed positive associations between serum TBA level and GICs risk, and a higher serum TBA level constitutes a risk factor for GICs.

Evaluation of Nd0.8-x Sr0.2Ca x CoO3-δ (x = 0, 0.05, 0.1, 0.15, 0.2) as a cathode material for intermediate-temperature solid oxide fuel cells.

A series of Nd0.8-x Sr0.2Ca x CoO3-δ (x = 0, 0.05, 0.1, 0.15, 0.2) cathode materials was synthesized by sol-gel method. The effect of Ca doping amount on the structure was examined by scanning electron microscopy (SEM), X-ray diffraction (XRD), thermal expansion, and X-ray photoelectron spectroscopy (XPS). Electrochemical properties were evaluated for possible application in solid oxide fuel cell (SOFC) cathodes. Results showed that second phase NdCaCoO4+δ is generated when the Ca doping amount is higher than 0.1. The increase in Ca limits the electronic compensation capacity of the material, resulting in a decrease in thermal expansion coefficient (TEC). With the increase of Ca content, the conductivity increases at first and then decreases, and the highest value of 443 S cm-1 is at x = 0.1 and T = 800 °C. Nd0.7Sr0.2Ca0.1CoO3-δ exhibits the lowest area specific resistance of 0.0976 Ω cm2 at 800 °C. The maximum power density of Nd0.7Sr0.2Ca0.1CoO3-δ at 800 °C is 409.31 mW cm-2. The Ca-doped material maintains good electrochemical properties under the coefficient of thermal expansion (CTE) reduction and thus can be used as an intermediate-temperature SOFC (IT-SOFC) cathode.

3D-Printed Bionic Titanium Alloy Artificial Lamina Prevents Epidural Adhesion and Restores the Stability After Laminectomy in Pigs.

Laminectomy can cause the dura mater to adhere to the surrounding scar tissue, leading to soft spinal stenosis after surgery. Although artificial laminae are considered ideal substitutes, they present challenges such as insecure fixation and insufficient bionics. In this study, we fabricated a bionic titanium alloy artificial lamina using three-dimensional (3D)-printing technology and evaluated its adhesion prevention and stability after laminectomy in pigs. An in vitro biomechanical pull-out resistance test indicated that the pull-out strength of the artificial lamina was close to that of a single pedicle screw and was significantly higher than that of a cortical screw. In vivo animal implantation results indicated precise laminectomy and artificial lamina implantation, as well as a safe operation process with the assistance of guide plates. X-ray and computed tomography results indicated the well fixation of bionic titanium alloy artificial lamina and screws 10 weeks after laminectomy. The artificial lamina was not loosened after being removed from pigs (postoperative week 12), exhibiting good stability. Additionally, no adhesion was observed in the artificial lamina group, whereas a large amount of scar tissue in the spinal canal covered the dural surface in the control group. Thus, 3D-printed bionic titanium alloy artificial lamina can prevent epidural adhesion after laminectomy, while restoring the structural stability of the posterior complex, suggesting the potential of lamina substitutes for adhesion prevention after laminectomy.

Effect of Urban fringes green space fragmentation on ecosystem service value.

In this study, an urban fringe green space classification system was established to explore the spatiotemporal variation of green space landscape and ecosystem service value (ESV) based on multi-source land-use data of Ganjingzi district from 2000 to 2018. (1) Results show that the total green space area declined from 359.57 to 213.46 km2 over the study period. Green space large plaque index (LPI) and class area both gradually declined, whereas the number of plaques (NP) and plaque density (PD) gradually increased, indicating green space landscape fragmentation. (2) Additionally, the value of green space ecosystem services reduced from 397.42 to 124.93 million yuan. The dynamic degree of ESV change in green space increased or decreased moderately, always being < 0 and showing a decreasing trend of ESV. From a spatial variation perspective, dynamic degrees of ESV variation in the western and northern regions with relatively intensive green space were higher than those in the east. Regarding ESV of various green space types, forest land had the highest functional values of ecological regulation and support, whereas arable land provided the highest functional values of production supply. (3) The ecological service function value of green space system is negatively correlated with PD, NP, edge density, landscape shape index, and Shannon's diversity index, and positively correlated with aggregation index, contagion metrics, and LPI. The correlation coefficient between the climate regulation function of forest and the change of number of plaques is -0.874. The correlation coefficient of the recreation and culture of the wetland to the plaque density change is no less than -0.214.

Spatiotemporal trends in burden of uterine cancer and its attribution to body mass index in 204 countries and territories from 1990 to 2019.

BACKGROUND: Uterine cancer is one of the most common female cancers worldwide, with huge heterogeneity in morbidity and mortality. Although a high body-mass index (BMI) has been linked to uterine cancer, systematic reports about the influence of high BMI and its temporal trends are scarce. METHODS: The annual morbidity, mortality, and disability-adjusted life years (DALYs) of uterine cancer in 204 countries or territories were retrieved from the GBD 2019 study. To reflect trends in disease burden, we also calculated the estimated annual percentage change (EAPC) based on the age-standardized rates of uterine cancer from 1990 to 2019. RESULTS: The global incident cases of uterine cancer increased 2.3 times from 187,190 in 1990 to 435,040 in 2019. Although the age-standardized incidence rate (ASIR) of uterine cancer increased worldwide from 8.67/100,000 in 1990 to 9.99/100,000 in 2019, the age-standardized death rate (ASDR) and DALY rate decreased during the same period. High socio-demographic index (SDI) countries tended to have a higher ASIR than developing regions, and their increasing trend in ASIR was also more pronounced. The disease was rare before 40 years old, but its risk rose sharply among women aged 50-70. A high BMI was linked to more than one-third of deaths from uterine cancer in 2019. CONCLUSIONS: The incidence in developed areas was significantly higher than in developing areas and also increased much more rapidly. Elderly females, especially those with a high BMI, have a higher risk of uterine cancer. Therefore, more health resources may be needed to curb the rising burden in specific populations.

Single Impact Injury of Vertebral Endplates Without Structural Disruption, Initiates Disc Degeneration Through Piezo1 Mediated Inflammation and Metabolism Dysfunction.

STUDY DESIGN: In vitro experimental study. OBJECTIVE: To establish an axial impact injury model of intervertebral disc (IVD) and to investigate if a single impact injury without endplate structural disruption could initiate intervertebral disc degeneration (IDD), and what is the roles of Piezo1 in this process. SUMMARY OF BACKGROUND DATA: Although IDD process has been confirmed to be associated with structural failures such as endplate fractures, whether a single impact injury of the endplates without structural disruption could initiate IDD remains controversial. Previous studies reported that Piezo1 mediated inflammation participated in the progression of IDD induced by mechanical stretch; however, the roles of Piezo1 in IVD impact injury remain unknown. METHODS: Rats spinal segments were randomly assigned into Control, Low, and High Impact groups, which were subjected to pure axial impact loading using a custom-made apparatus, and cultured for 14 days. The degenerative process was investigated by using histomorphology, real-time Polymerase Chain Reaction(PCR), western-blot, immunofluorescence, and energy metabolism of IVD cell. The effects of Piezo1 were investigated by using siRNA transfection, real-time PCR, western-blot, and immunofluorescence. RESULTS: The discs in both of the impact groups presented degenerative changes after 14 days, which showed significant up-regulation of Piezo1, NLRP3 inflammasome, the catabolic (MMP-9, MMP-13), and pro-inflammatory gene (IL-1ß) expression than that of the control group (P < 0.05), accompanied by significantly increased release of ATP, lactate, nitric oxide (NO), and glucose consumption of IVD cells at first 7 days. Silencing Piezo1 reduced the activation of NLRP3 inflammasome and IL-1ß expression in the nucleus pulposus induced by impact injury. CONCLUSION: It demonstrated that not only fracture of the endplate but also a single impact injury without structural impairment could also initiate IDD, which might be mediated by activation of Piezo1 induced inflammation and abnormal energy metabolism of IVD cells.Level of Evidence: N/A.