Search

TC4 alloy is widely used in dental implantation due to its excellent biocompatibility and low density. However, it is necessary to further improve the corrosion resistance and surface hardness of the titanium alloy to prevent surface damage that could result in the release of metal ions into the oral cavity, potentially affecting oral health. In this study, Ti-N-O layers were fabricated on the surface of TC4 alloy using a two-step hollow cathode plasma source oxynitriding technique. This resulted in the formation of TiN, Ti2N, TiO2, and nitrogen-stabilized α(N)-Ti phases on the TC4 alloy, forming a Ti-N-O modified layer. The microhardness of the samples treated with plasma oxynitriding (PNO) was found to be 300–400% higher than that of untreated (UN) samples. The experimental conditions were set at 520 °C, and the corrosion current density of the PNO sample was measured to be 7.65 × 10−8 A/cm2, which is two orders of magnitude lower than that of the UN sample. This indicates that the PNO-treated TC4 alloy exhibited significantly improved corrosion resistance in the artificial saliva solutions.

Given the nonlinear and complex industrial fermentation system, the process analytical technology offers significant advantages for direct and real-time monitoring, control and evaluation of synthetic processes. Here, we introduced a Raman spectroscopy in-line monitoring method for ethanol production by Saccharomyces cerevisiae. First, the feature selection methods in machine learning were used to reduce the dimension of Raman spectral data. The results showed that the model training time is reduced by more than 90% after feature selection, while the prediction performance of glycerol and cell concentration is improved by 14.20% and 17.10% at the RMSE level. Then, 15 machine learning algorithms were called to retrain the model, and hyperparameters were adjusted by grid search. The results demonstrated that the model after adjusting the hyperparameters improved the RMSE of ethanol, glycerol, glucose, and biomass by 9.73%, 4.33%, 22.22%, and 13.79%, respectively. Finally, BaggingRegressor, Support vector regression, BayesianRidge, and VotingRegressor are suitable machine learning algorithms corresponding to the models for predicting glucose, ethanol, glycerol, and cell concentrations, respectively. In addition, the R-squared values were 0.89–0.97, and the RMSE values were 0.06–2.59 g/L on the testing datasets, respectively. The results suggested that machine learning methods can be effectively applied in the modeling and analysis of Raman spectroscopy. Moreover, it is conducive to promoting the optimization of Raman spectroscopy in biological process monitoring, thereby improving industrial production efficiency, and providing novel modeling ideas.

Repairing and regenerating injured neural tissue remains a worldwide challenge. Tissue engineering (TE) has been highlighted as a potential solution to provide functional substitutes for damaged organs or tissue. Among the biocompatible and biodegradable materials, poly-L-lactic-acid (PLLA) has been widely investigated in the TE field because of its tunable mechanical properties and tailorable surface functionalization. PLLA-based biomaterials can be engineered as scaffolds that mimic neural tissue extracellular matrix and modulate inflammatory responses. With technological advances, PLLA-based scaffolds can also have well-controlled three-dimensional sizes and structures to facilitate neurite extension. Furthermore, PLLA-based scaffolds have the potential to be used as drug-delivery carriers with controlled release. Moreover, owing to the good piezoelectric properties and capacity to carry conductive polymers, PLLA-based scaffolds can be combined with electrical stimulation to maintain stemness and promote axonal guidance. This mini-review summarizes and discusses the fabrication and modification techniques utilized in the PLLA-based biomaterial scaffolds for neural TE. Recent applications in peripheral nerve and spinal cord regeneration are also presented, and it is hoped that this will guide the future development of more effective and multifunctional PLLA-based nerve scaffolds.

In this letter, we demonstrate a reconfigurable logic-memory hybrid device (R-LMHD), which can be dynamically and reversibly switched between the logic- and memory- mode. The logic-mode device exhibits a $2.5\times 10^{6}$ ON/ OFF current ratio and nearly zero hysteresis, which indicates the weak influence of defects trapping and de-trapping. The memory-mode device shows a large memory window up to 2.19 V and the window maintains up to 1.44 V after 106 program/erase cycles. The excellent performance can be attributed to the high crystalline quality of ferroelectric Hf0.5Zr0.5O2 (HZO) and the insertion of internal metal gate (IMG) between HZO and dielectric layer. Such R-LMHD features run-time tuning of threshold voltage and hysteresis, electrically reconfigurable. Furthermore, the subthreshold swing ( SS ) is electrically tunable with a minimum SS ( $SS_{min}$ ) of 35 mV/decade and a maintainability of sub-60 mV/decade about 3 orders. The R-LMHD provides a promising way to realize future in-memory computing and low power consumption applications.

Background: Exosome (Exo) secretion by hypoxic pretreatment adipose-derived mesenchymal stem cells (ADSCs) promotes spinal cord repair after spinal cord injury (SCI). But the mechanism remains unclear. Methods: High-throughput sequencing was used to investigate abnormal expression of circRNA in hypoxic pretreatment ADSCs exosome (HExo) and ADSCs exosome (Exo). The abnormal expression of mRNA in spinal cord tissues after Exo or HExo treatment were also analysis using high-throughput sequencing. Bioinformatics analysis and luciferase reporting analysis were used to clarify the interacted relationship among circRNA, miRNA and mRNA. BV2 cells were employ to analysis the apoptosis, inflammatory cytokines expression under OGD condition by using immunofluorescence, ELISA detection. SCI mice model were constructed and the therapeutic effect of Exo were detected using immunohistochemistry, immunofluorescence. Results: The result show that HExo have more therapeutic effect on spinal cord repair after SCI by activation of autophagy. High-throughput sequencing detection show that circ-Astn1 play a role in HExo mediated spinal cord repair after SCI. Downregulation circ-Astn1 decreased the therapeutic effect of HExo to spinal cord repair after SCI. The study also found that Atg7 play a role in HExo mediated spinal cord repair after SCI. Luciferase reporting analysis confirmed that both miR-138-5p and Atg7 were downstream targets of circ-Astn1. Downregulation of Atg7 or overexpression of miR-138-5p reversed the protective effect of circ-Astn1 to BV2 after exposure to OGD condition. Upregulation circ-Astn1 increased the therapeutic effect of Exo to spinal cord repair after SCI by activation autophagy. Conclusions: In conclusion, ADSC-Exos containing circ-Astn1 promotes spinal cord repair after SCI by targeting miR-138-5p/Atg7 pathway mediated autophagy.

The CrFeCoNi coating was fabricated by the laser remelting method. The microstructure of the coating was detected. The corrosion behavior of coating at different temperatures was investigated by electrochemical measurements. Potentiodynamic polarization test results indicated that the corrosion current density increased with the increase in corrosion solution temperature in 3.5 wt% NaCl and 0.5 mol/L H2SO4 solutions, suggesting that the CrFeCoNi coating exhibited higher resistance to corrosion attack at lower solution temperature. The breakdown potential of the CrFeCoNi coating exhibited a decreasing trend with increasing solution temperature in 3.5 wt% NaCl solution. This indicated that the passive film formed at low temperatures had higher stability. The electrochemical impedance spectroscopy test indicated that the CrFeCoNi coating possessed higher charge transfer resistance at lower solution temperatures. The corrosion mechanisms of the coating at different temperatures were also revealed.

Toll-like receptor 4 (TLR4) participates in the initiation of neuroinflammation in various neurological diseases, including central nervous system injuries. NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated microglial pyroptosis is crucial for the inflammatory response during secondary spinal cord injury (SCI). However, the underlying mechanism by which TLR4 regulates NLRP3 inflammasome activation and microglial pyroptosis after SCI remains uncertain.We established an in vivo mouse model of SCI using TLR4-knockout (TLR4-KO) and wild-type (WT) mice. The levels of pyroptosis, tissue damage and neurological function recovery were evaluated in the three groups (Sham, SCI, SCI-TLR4-KO). To identify differentially expressed proteins, tandem mass tag (TMT)-based proteomics was conducted using spinal cord tissue between TLR4-KO and WT mice after SCI. For our in vitro model, mouse microglial BV2 cells were exposed to lipopolysaccharides (1 µg/ml, 8 h) and adenosine triphosphate (ATP) (5 mM, 2 h) to induce pyroptosis. A series of molecular biological experiments, including Western blot (WB), real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), immunofluorescence (IF), immunohistochemical (IHC), chromatin immunoprecipitation (ChIP), Dual-Luciferase Reporter assay (DLA) and co-immunoprecipitation (Co-IP), were performed to explore the specific mechanism of microglial pyroptosis in vivo and in vitro.Our results indicated that TLR4 promoted the expression of dead-box helicase 3 X-linked (DDX3X), which mediated NLRP3 inflammasome activation and microglial pyroptosis after SCI. Further analysis revealed that TLR4 upregulated the DDX3X/NLRP3 axis by activating the JAK2/STAT1 signalling pathway, and importantly, STAT1 was identified as a transcription factor promoting DDX3X expression. In addition, we found that biglycan was increased after SCI and interacted with TLR4 to jointly regulate microglial pyroptosis through the JAK2/STAT1/DDX3X/NLRP3 axis after SCI.Our study preliminarily identified a novel mechanism by which TLR4 regulates NLRP3 inflammasome-mediated microglial pyroptosis in response to SCI-providing a novel and promising therapeutic target for SCI.

Compact, transparent, and flexible 5G multiple-input multiple-output (MIMO) and millimeter wave (mmW) array antennas with Ni-based embedded metallic mesh (EMM) nanotechnology are presented for the next-generation wireless communication in emerging applications, such as smart wearable devices, vehicle radars, and smart 5G remote devices. The EMM has the advantages of high conductivity, superior transparency, and mechanical stability. To simultaneously enhance the transparency and radiation efficiency, the selected structures of EMM are proposed and analyzed. The designed 5G MIMO antenna based on the EMM exhibits superior transparency of 93%, optimal radiation efficiency up to 85%, isolation above 20 dB, envelope correlation coefficient (ECC) under 0.005, and operation in 5G n79 band (4.4–5 GHz). The measured results are in good agreement with the simulated results. In addition, transparent and flexible 5G mmW arrays with a maximum gain of 9.6 dBi and a scanning angle of approximately ±75° are demonstrated in the 26 and 28 GHz bands.

Ti6Al4V titanium alloys, with high specific strength and good biological compatibility with the human body, are ideal materials for medical surgical implants. However, Ti6Al4V titanium alloys are prone to corrosion in the human environment, which affects the service life of implants and harms human health. In this work, hollow cathode plasm source nitriding (HCPSN) was used to generate nitrided layers on the surfaces of Ti6Al4V titanium alloys to improve their corrosion resistance. Ti6Al4V titanium alloys were nitrided in NH3 at 510 °C for 0, 1, 2, and 4 h. The microstructure and phase composition of the Ti-N nitriding layer was characterized by high-resolution transmission electron microscopy, atomic force microscopy, scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. This modified layer was identified to be composed of TiN, Ti2N, and α-Ti (N) phase. To study the corrosion properties of different phases, the nitriding 4 h samples were mechanically ground and polished to obtain the various surfaces of Ti2N and α-Ti (N) phases. The potentiodynamic polarization and electrochemical impedance measurements were conducted in Hank’s solution to characterize the corrosion resistance of Ti-N nitriding layers in the human environment. The relationship between corrosion resistance and the microstructure of the Ti-N nitriding layer was discussed. The new Ti-N nitriding layer that can improve corrosion resistance provides a broader prospect for applying Ti6Al4V titanium alloy in the medical field.

The discovery of ferroelectricity in hafnium zirconium oxide (HZO) thin films has attracted wide attention from academia to industry due to the application in ferroelectric non-volatile random access memories (FeRAM) with prominent performance in scalability and CMOS process compatibility. Dielectric behavior of ferroelectric HZO thin films is a key factor affecting the dynamic effect, piezoelectric and electrostrictive effect. Interface between HZO and capping electrodes plays an important role in regulating the dielectric properties. In this paper, the impedance frequency response and dielectric spectrum of ferroelectric HZO thin films were analyzed. Parameters of the interface were extracted to analyze the regulating effect on the dielectric properties based on an impedance model with constant phase element (CPE). Besides, dielectric spectrums at elevated temperatures were identified to verify this analysis.

Most hilly areas are dotted with gullies, some of which contain plenty of water, especially in rainy seasons. Once surface water penetrates the underground working face, it will lead to an increased water inflow of the working face. Even worse, it may induce water and sand burst accidents. To prevent geological disasters such as water and sand burst and ensure the safe production in coal mines, it is necessary to reveal the development law of “two zones” in the overburden caused by shallow-seam fully mechanized top coal caving high-intensity mining in hilly areas with exposed bedrock and timely grasp the communication between the water-flowing fractured zone (WFFZ) and the water in surface gullies. In this study, the working face P2 of the exposed bedrock surface in the Coal Mine DN is taken as the research object. First, the characteristics of overburden movement and the law of exposed bedrock surface movement in areas with exposed bedrock were investigated through similar simulation. Meanwhile, the temporal–spatial evolution of overburden movement caused by shallow-seam fully mechanized top coal caving high-intensity mining was clarified, and the mode of overburden movement was revealed. Moreover, the reason why the water inflow of the underground working face increases suddenly was theoretically explained. The following conclusions were drawn: Under shallow-seam fully mechanized top coal caving high-intensity mining, the WFFZ of the working face P2 is directly connected to the exposed bedrock surface, and the movement of the overburden is subject to the typical “two-zone” mode. The development height of the WFFZ is greater than the value in the traditional “three-zone” mode calculated according to the empirical formulas. The ratio of the WFFZ height to the mining thickness is 43.75. Under the “two-zone” mode, a water-flowing channel exists in the overburden near the open-off cut and the stopping line. When the surface water source is in the right position, the water inflow of the underground working face will increase suddenly.

Spinal cord injury (SCI) may lead to severe motor and sensory dysfunction, causing high mortality and disability rates. Adipose tissue-derived mesenchymal stem/stromal cells (ADSCs), especially hypoxia-pretreated ADSCs, represent an effective therapy for SCI by promoting the secretion of exosomes (Exos). Here, we investigated the therapeutic efficacy of exosomes secreted by ADSCs under hypoxia (HExos) and explored potential target molecules. We utilized nanoparticle tracking analysis, electron microscopy, qRT-PCR, and western blotting to analyze differences between HExos and Exos groups. The expression of long noncoding RNAs (lncRNAs) was examined by high-throughput sequencing. The therapeutic effects of different Exos treatments were compared in vitro and in an SCI model in vivo. The interaction between lncRNAs, microRNAs, and mRNA was examined by luciferase reporter experiments. We employed enzyme-linked immunosorbent assay and immunofluorescence to measure inflammatory factor expression and microglial polarization. The results showed that HExos was more effective than Exos for repairing SCI by suppressing inflammatory factor expression, promoting functional recovery, and shifting microglia from M1 to M2 polarization. High-throughput sequencing showed that LncGm37494 expression was significantly higher in HExos than Exos, and its upregulation promoted microglial M1/M2 polarization by inhibiting miR-130b-3p and promoting PPARγ expression, as shown by luciferase reporter experiments. Exos from lncGm37494 overexpressing ADSCs showed a similar therapeutic effect than HExos. The results indicated that HExos repair SCI by delivering lncGm37494, advising that lncGm3749 functions importantly in microenvironmental regulation and shows possibility for SCI treatments.

The formation and diffusion of plasma are complex and critical processes in plasma nitriding. A stable and high-concentration plasma atmosphere can effectively increase the diffusion rate and the thickness of the diffusion layer. In this study, a two-dimensional multi-physics model integrating physical kinetics, energy transfer, mass transfer, and electromagnetic induction was developed. The effect of a hollow-cathode structure on plasma distribution was investigated, and the edge effect observed on nitrided metals was eliminated. The impacts of the essential plasma diffusion parameters were simulated using the developed model. A simple but effective experiment was designed to validate the model. A diffusion furnace with DC and RF dual discharge was designed by adding a high-frequency coil to existing equipment. Subsequently, the effects of the two plasma excitation sources on the overall distribution of plasma were analyzed. Notably, the proposed model is a high-fidelity one based on actual device dimensions; therefore, it can be used to simulate, predict, and control the plasma formation process in the diffusion furnace. In addition, the model can provide reference data and guidance for optimizing the diffusion process and structural design of diffusion furnaces.

To investigate and compare split-hand phenomenon quantified by motor unit number index (MUNIX) between patients with cervical spondylotic amyotrophy (CSA) and those with amyotrophic lateral sclerosis (ALS).MUNIX was performed on abductor pollicis brevis (APB), abductor digiti minimi (ADM) and first dorsal interosseous (FDI) in 46 CSA patients, 39 ALS patients and 41 healthy subjects. Split-hand measurements including split-hand index (SHI=ABP×FDI/ADM), ratio of APB to ADM (AA), ratio of FDI to ADM (FA) were measured by compound muscle action potential (CMAP) and MUNIX.There was a significant difference in both AA and SHI measured by two different methods between ALS and CSA patients (P0.05). Receiver operating characteristic (ROC) curve and logistic regression analysis demonstrated good differential diagnostic accuracy for AA, SHI and their combination between ALS and CSA. A larger area under the curve (AUC) was observed in these measurements calculated by MUNIX than those measured by CMAP (AA: 0.885 vs. 0.700, SHI: 0.865 vs. 0.703, Combination: 0.925 vs. 0.750; P0.05). Sub-group analysis of ROC curves revealed an AUC of 0.893 for AABoth AA and SHI measured by two different methods are useful in distinguishing ALS from CSA, and those quantified by MUNIX may be a better differential diagnostic marker to provide an accurate and noninvasive additional test for distinguishing CSA from ALS, even in their early stages.

Spinal cord injury (SCI) is a serious affliction that can lead to insufficient blood supply to the spinal cord, resulting in nutrient and energy deficiency in nerve cells such as neurons. In the present study, a spinal cord injury mouse model was constructed using wild-type (WT) and ecto-5'-nucleotidase (CD73)-/- mice. The results of TUNEL and immunofluorescence assays indicated that the apoptosis of neurons in CD73-/- mice was increased after spinal cord injury. Dorsal root ganglion (DRG) neurons from WT and CD73-/- mice were cultured in low glucose and hypoxic conditions to simulate the effects of spinal cord injury on neurons. Subsequently, a western blot assay was used to detect the expression of CD73, caspase-3 and Bcl-2. Flow cytometry was used to detect cell apoptosis and the corresponding kits were used to detect changes in lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), reactive oxygen species (ROS), adenosine triphosphate (ATP) and cell activity. The results revealed that the apoptosis level of CD73-overexpressing DRG neurons was decreased under anoxia and glucose deficiency. The release of LDH, MDA and the production of ROS in CD73 DRG neurons was decreased, while the synthesis of ATP, the activity of SOD and cell activity increased after hypoxia-hypoglycemia treatment. Additional cellular studies demonstrated that blocking the expression and hydrolase activity of CD73 with α,β-methylene ADP (APCP) could counteract the protective effect of CD73 on neuronal apoptosis, while adenosine (Ado) could rescue the increased apoptosis caused by CD73 deletion. In addition, the cAMP/ protein kinase A (PKA)/cAMP response element-binding protein (CREB) signaling pathway was also positively regulated by CD73 and Ado. In conclusion, CD73 could inhibit DRG neuronal apoptosis by promoting the Ado/cAMP/PKA/CREB pathway.

CrFeCoNi and CrMnFeCoNi coatings were prepared by laser remelting method. The grain boundary characteristics distribution of both coatings was investigated by electron backscattered diffraction technique. The results showed that the CrFeCoNi coating exhibited higher fraction of low angle grain boundaries and Σ3 boundaries compared to the CrMnFeCoNi coating. The corrosion properties of the CrFeCoNi and CrMnFeCoNi coatings in 3.5 wt% NaCl solution were identified by electrochemical method and localized electrochemical impedance spectroscopy technique. The results indicated that the CrFeCoNi coating had a higher corrosion resistance than the CrMnFeCoNi coating. The better corrosion resistance of the CrFeCoNi coating could be attributed to the high fraction of Σ3 boundaries and low fraction of the high angle boundaries.

BackgroundMicroglia pyroptosis-induced neuroinflammation has been one of the potential treatment targets for spinal cord injury (SCI). And melatonin is reported to have anti-neuroinflammation effect on SCI, but the underlying mechanism is largely unexplored. In addition, the potential regulatory role of stimulator of interferon genes (STING) mediated innate immune response in the SCI-induced neuroinflammation also remains unknown. The aim of this study is to identify the potential molecular mechanism of the anti-neuroinflammation effect of melatonin in SCI mice and to explore whether STING-mediated signal pathway is involved in this pharmacological process. MethodsIn vivo, the C57BL/6 female mice underwent SCI injury or Sham surgery (laminectomy alone). Melatonin and selective STING antagonist C-176 were administered intraperitoneally after injury in the SCI group once a day for 3 or 28 consecutive days for different experiments. The BMS score system was adopted to assess the motor function of mice. In vitro, the Lipopolysaccharide (LPS)/ATP was combinedly used to induce cell pyroptosis in BV2 microglia and the adenovirus was used to overexpress STING. A series of molecular experiments including Western blot (WB), quantitative real-time polymerase chain reaction (RT-qPCR), enzyme linked immunosorbent assay (ELISA) and immunofluorescence (IF) were performed in vivo and in vitro. ResultsOur results showed that melatonin effectively suppressed NLRP3 inflammasome-induced pyroptosis and STING-mediated pathway after SCI. In addition, C-176 also alleviated the NLRP3 inflammasome-mediated pyroptosis and promoted functional recovery in vivo. In vitro, we also found that melatonin abrogated NLRP3 inflammasome activation in LPS/ATP-induced BV2 cells, while overexpression of STING reversed the anti-pyroptotic role of melatonin. Subsequent results together indicated that the role of melatonin on STING-dependent NLRP3 inflammasome activation may be mediated by decreasing ROS production and cytosolic mtDNA release. ConclusionThis study preliminarily demonstrated that melatonin exerts its anti-neuroinflammation role on SCI by alleviating the NLRP3 inflammasome-mediated pyroptosis, which was mediated by blocking the ROS/mtDNA/STING pathway. It provides us a better understanding of the pathological mechanism after SCI and offer experiment evidence to promote the use of melatonin for SCI.

Study design Finite element analysis. Objective To determine and compare the biomechanical stability of the bicortical short C2 pars screw fixation for high-riding vertebral artery (HRVA) with the C2 pedicle screw and C2 translaminar screw fixation in finite element models. Summary of background data Fixation of C2 is technically demanding in the case of HRVA. However, there is no consensus on the alternative technique for the C2 screw fixation for HRVA in the literature. Methods A finite element (FE) model of the upper cervical spine (C0-C2) with HRVA had been developed. C1 pedicle screw was applied at C1 by using notching technique. Bicortical short C2 pars screws, C2 pedicle screws, and C2 translaminar screws were used in each model. Then a vertical load of 50 N and a 1.5 Nm torque were applied to the C0 to simulate flexion, extension, lateral bending, and axial rotation respectively. Results Compared with C2 pedicle screw fixation, the bicortical short C2 pars screw fixation increased the range of motion (ROM) by -1.45%, 2.13%, 62.0%, and 22.0% under flexion, extension, lateral bending, and axial rotation, respectively; However, the C2 translaminar screw fixation increased the ROM by 43.6%, 17.8%, 423.4%, and 19.9%, respectively. In terms of the peak von Mises stress, compared with C2 pedicle screw fixation, bicortical short C2 pars screw decreased 46.1%, 41.6%, 71.3%, and -12.5% under flexion, extension, lateral bending, and axial rotation, respectively; C2 translaminar screw decreased -2.66%, -4.87%, 73.0% and -10.1%, respectively. Conclusion For a patient with HRVA, bicortical short C2 pars screw fixation provides sufficient stability and exhibited a smaller von Mises distribution on the screw-rod construct, indicating it could be an effective C2 internal fixation method for HRVA to promote C1-C2 stability and avoid the vertebral artery injury.Level of Evidence: N/A.

Saccharopolyspora erythraea is considered to be an effective host for erythromycin. However, little is known about the regulation in terms of its metabolism. To develop an accurate model-driven strategy for the efficient production of erythromycin, a genome-scale metabolic model (iJL1426) was reconstructed for the industrial strain. The final model included 1426 genes, 1858 reactions, and 1687 metabolites. The accurate rates of the growth predictions for the 27 carbon and 31 nitrogen sources available were 92.6% and 100%, respectively. Moreover, the simulation results were consistent with the physiological observation and 13C metabolic flux analysis obtained from the experimental data. Furthermore, by comparing the single knockout targets with earlier published results, four genes coincided within the range of successful knockouts. Finally, iJL1426 was used to guide the optimal addition strategy of n-propanol during industrial erythromycin fermentation to demonstrate its ability. The experimental results showed that the highest erythromycin titer was 1442.8 μg/mL at an n-propanol supplementation rate of 0.05 g/L/h, which was 45.0% higher than that without n-propanol supplementation, and the erythromycin-specific synthesis rate was also increased by 30.3%. Therefore, iJL1426 will lead to a better understanding of the metabolic capabilities and, thus, is helpful in a systematic metabolic engineering approach.

Purpose. Bioabsorbable Mg-based implants were previously assessed due to their intrinsic advantages, but Mg-based cage related research is limited. The specific blood supply and stress of the intervertebral environment can affect the function of Mg-based implants. The objective of this study was to investigate the performance of a bioabsorbable Mg-Zn alloy cage in anterior cervical discectomy and fusion (ACDF) and evaluate the control of degradation of the Mg-Zn cage surface modified by microarc oxidation (MAO) technology containing Si under an intervertebral microenvironment. Methods. Twenty-four goats were divided into four groups according to the experimental period and all underwent ACDF at C2-3 and C4-5 with porous Mg-Zn cage covered with a MAO/Si-containing coating in one intervertebral space and with autologous iliac bone in another space. After 3, 6, 12, or 24 weeks after operation, the cervical spine specimens were harvested to evaluate the biocompatibility, fusion status, and degradation conditions using blood analysis, radiology, biomechanical testing, histology, and micro-CT. Results. The Mg-Zn cages showed ideal biocompatibility and biomechanical characterization; however, the fusion state, as evaluated with radiology and histology, was not acceptable. Modified by the MAO/Si-containing coating, the degradation rate of the Mg-Zn cages was controllable but slower than expected. Conclusion. MAO/Si-containing coating Mg-Zn alloy cages demonstrated excessive control of degradation and fusion failure after 24 weeks postoperatively. We conclude that further studies should be designed to improve the using of Mg-based materials at the intervertebral space.

Background: The aim of this study was to evaluate the biomechanical stability of a lumbar internal fixation system with 3 different fixation techniques by the establishment of a three-dimensional finite element (FE) model of lumbar single level fixation.Methods: A three-dimensional osseoligamentous nonlinear FE model of osteoporosis lumbar 4-5 (male, aged 57 years, height 170 cm, weight 70 kg, bone mineral density T value -2.8SD) was built to detect the biomechanical stability of an internal fixation system with the following 3 screw trajectories: traditional pedicle screw trajectory fixation (TT), cortical bone trajectory (CBT) screw and hybrid pedicle screw fixation (CBT + TT). The location and area of maximal equivalent stress and the angular displacement of this lumbar model with different screw trajectories were measured in anterior bending, posterior extension, lateral bending and during rotation.Results: The angular displacement of this lumbar model with the 3 different screw trajectories was similar, all of which could restrict the angular displacement of lumbar vertebrae. The maximal equivalent stress was located at the border of the CBT screw and rod, with the hybrid screw fixation technique in axial rotation. Conclusion: The use of CBT and TT screws in lumbar internal fixation had similar stability. The CBT screw could be an alternative solution to lumbar short-segmented fixation, but temporary immobilization would be required to avoid the failure of CBT screw fixation due to the increasing stress in position of extensive lateral bending and rotation.

Background Neuroinflammation‐induced secondary injury is an important cause of sustained progression of spinal cord injury. Inflammatory programmed cell death pyroptosis executed by the pore‐forming protein gasdermin D (GSDMD) is an essential step of neuroinflammation. However, it is unclear whether CD73, a widely accepted immunosuppressive molecule, can inhibit pyroptosis via mediating GSDMD. Methods C57BL/6J CD73 deficient mice and wild‐type mice, Lipopolysaccharide (LPS)‐induced primary microglia and BV2 cells were respectively used to illustrate the effect of CD73 on microglia pyroptosis in vivo and in vitro. A combination of molecular and histological methods was performed to assess pyroptosis and explore the mechanism both in vivo and in vitro. Results We have shown molecular evidence for CD73 suppresses the activation of NLRP3 inflammasome complexes to reduce the maturation of GSDMD, leading to decreased pyroptosis in microglia. Further analysis reveals that adenosine‐A2B adenosine receptor‐PI3K‐AKT‐Foxo1 cascade is a possible mechanism of CD73 regulation. Importantly, we determine that CD73 inhibits the expression of GSDMD at the transcriptional level through Foxo1. What's more, we confirm the accumulation of HIF‐1α promotes the overexpression of CD73 after spinal cord injury (SCI), and the increased CD73 in turn upregulates the expression of HIF‐1α, eventually forming a positive feedback regulatory loop. Conclusion Our data reveal a novel function of CD73 on microglia pyroptosis, suggesting a unique therapeutic opportunity for mitigating the disease process in SCI., Inflammatory programmed cell death pyroptosis executed by the pore‐forming protein gasdermin D (GSDMD) is an essential step of neuroinflammation after spinal cord injury. We demonstrated that CD73, a widely accepted immunosuppressive molecule, can inhibit pyroptosis via mediating GSDMD through PI3K/AKT/Foxo1 signaling.

Neuroinflammation plays a crucial role in the secondary phase of spinal cord injury (SCI), and is initiated following the activation of toll-like receptor 4 (TLR4). However, the downstream mechanism remains unknown. Pyroptosis is a form of inflammatory programmed cell death, which is closely involved in neuroinflammation, and it can be regulated by TLR4 according to a recent research. In addition, several studies have shown that long non-coding RNAs (lncRNAs) based mechanisms were related to signal transduction downstream of TLR4 in the regulation of inflammation. Thus, in this study, we want to determine whether TLR4 can regulate pyroptosis after SCI via lncRNAs. Our results showed that TLR4 was activated following SCI and promoted the expression of lncRNA-F630028O10Rik. This lncRNA functioned as a ceRNA for miR-1231-5p/Col1a1 axis and enhanced microglial pyroptosis after SCI by activating the PI3K/AKT pathway. Furthermore, we determined STAT1 was the upstream transcriptional factor of IncRNA-F630028O10Rik and was induced by the damage-responsive TLR4/MyD88 signal. Our findings provide new insights and a novel therapeutic strategy for treating SCI.

The growth factor receptor-bound protein 2 (Grb2)-Sos1 interaction, mediated by modular domains, plays an essential role in the oncogenic MAPK signaling pathway in osteosarcoma (OS). Recently, a dual-targeting peptide that targets the epidermal growth factor receptor and Grb2-Src homology 3 domain in OS cells was designed and synthesized.We investigated the synergistic effects of the peptide and salinomycin (Sal), a chemotherapeutic drug with effective anti-OS properties in clinical therapy.Flow cytometry was used to measure the targeting efficacy of the peptide. Migration and CCK-8 assays were used to explore whether Sal and the peptide could synergistically inhibit OS cell behavior. Western blotting was used to detect apoptosis.Data were analyzed using the GraphPad Prism 5.01. Statistical analysis was performed using the Student's t-test for the direct comparisons and one-way analysis of variance for the comparisons among the multiple groups. Statistical significance was set at P0.05.The peptide was shown to target OS cells. When applied together, Sal and the peptide synergistically inhibited OS cell migration, invasion, and proliferation through the inhibition of Grb2-Sos1. This synergistic treatment also promoted the apoptosis of OS cells and inhibited tumor volume in vivo.These data provide valuable insights into the molecular mechanisms of OS and may be beneficial in clinical therapy.

Neuroinflammation-induced secondary injury is an important cause of sustained progression of spinal cord injury. Inflammatory programmed cell death pyroptosis executed by the pore-forming protein gasdermin D (GSDMD) is recently regarded as an essential step of neuroinflammation. However, it is unclear whether CD73, a widely accepted immunosuppressive molecule, can inhibit pyroptosis via mediating GSDMD. Here, we reported molecular evidence for CD73 suppresses the activation of NLRP3 inflammasome complexes to reduce the maturation of GSDMD, leading to decreased pyroptosis in macrophages/microglia. Further analysis revealed that adenosine-A2B adenosine receptor-NF-κB cascade is a possible mechanism of CD73 regulation. Importantly, we determined that CD73 inhibited the expression of GSDMD at the transcriptional level through NF-κB, thereby alleviating macrophages/microglia pyroptosis. What’s more, we confirmed the accumulation of HIF-1α promotes the overexpression of CD73 after SCI, and the increased CD73 in turn upregulates the expression of HIF-1α, eventually forming a positive feedback regulatory loop. In summary, our results demonstrate that CD73 alleviates GSDMD-mediated pyroptosis of macrophages/microglia in spinal cord injury by blocking NF-κB signal. Our data reveal a novel function of CD73 on microphages/microglia pyroptosis, suggesting a unique therapeutic opportunity for mitigating the disease process in SCI. Funding Statement: This work was supported by the National Natural Science Foundation of China [grant number 81772385, 81871522]. Declaration of Interests: The authors declare that they do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted. Ethics Approval Statement: All study surgical procedures and experiment protocols were performed in accordance with standard guidelines approved by the Ethics Committee of Experimental Research, Shanghai Medical College, Fudan University (Shanghai, China). The animal experiments were approved by the Institutional Animal Care and Use Committee of Fudan University.

The kinematic characteristics of Modic changes (MCs) in the lumbar spine have rarely been reported; furthermore, the effect of disc degeneration (DD) on segmental motion has not been considered in analyzing the motion characteristics of MCs. Therefore, this study was designed to evaluate the kinematic characteristics of MCs based on different DD grades.894 patients with 4470 lumbar segments were reviewed, and those with MCs were selected for segmental motion evaluation. MC type was defined as 0, I, II, and III, and DD grade was classified into 5 groups from grade A to grade E. Segmental angular and translational motion were calculated from X-ray images in positions of flexion and extension, and the absolute values of the differences were recorded.MCs were observed in 308 segments from 260 patients. No MC was found in DD grade A, and MC III was not observed in DD grade B. MC I was found to significantly increase angular motion in the DD grade E group, and MC II could enlarge translational motion in the DD grade D group (all P0.05); MC III had the lowest segmental motion in both angular and translational motion; There was no statistical difference in angular and translational motion between MC I and II in all DD grade groups (all P0.05).MC III indicates the final stable phase of segmental motion. MC I might increase angular motion, and MC II would increase certain translational motions in the segments that were believed to be stable.

STUDY DESIGN Experimental in vivo and in vitro study of intervertebral disc (IVD) degeneration and the mechanism exploration. OBJECTIVE This report aims to verify the expression of Sirt1 in IVD degeneration of different grades and explore its potential mechanism in human nucleus pulposus cells. SUMMARY OF BACKGROUND DATA Silent mating type information regulator 2 homolog 1 (Sirt1) has draw immense attention because of its influence on a variety of aging-related diseases. The present study is a continuation and complement of our former in vivo study of Sirt1 and its role in puncture-induced rodent disc degeneration model. METHODS Sirt1 protein expression level and histological morphology were evaluated in the discs of different degeneration levels, which is graded according to the Pfirrmann grading scale. Then the mRNA and protein expression levels of type II collagen, MMP-13, ADAMTS-5, p21, p16, cell proliferation, and apoptosis ratio were tested in vitro nucleus pulposus cells that expressed different levels of Sirt1 by reverse transcription polymerase chain reaction, western blot analysis, CCK-8 assay, and flow cytometry analysis. RESULTS Sirt1 protein expression level decreased in the discs of high Pfirrmann grade and the score of histological morphology of human intervertebral disc is consistent with the Pfirrmann grade. Besides, when resveratrol activated Sirt1, nucleus pulposus cells proliferation increased while the cell apoptosis ratio decreased; the expression of type II collagen increased while MMP-13, ADAMTS-5 decreased. It showed the opposite results when the cells were transfected by Sirt1 siRNA. In addition, the expression of both p21 and p16 decreased when Sirt1 was activated. CONCLUSION Sirt1 is a protective mediator in IVD degeneration and the expression of Sirt1 decreases in degenerative disc. Activation of Sirt1 works on suppressing cellular senescence, promoting cell proliferation, and restraining the apoptosis of nucleus pulposus cells. LEVEL OF EVIDENCE N/A.

Slicing is one of the core parts of the additive manufacturing software system, which completes the function of transforming the 3D model into a 2D profile. The adaptive slicing algorithm uses different layer thicknesses for layering in different areas according to the changes in the geometry of the mesh model. Where the model is more complex and the curvature changes a lot, a smaller layer thickness is used to approximate the model. In areas of large curvature of the model, maximum layer thickness is used to improve printing efficiency. With the development of additive manufacturing technology, grid model files such as STL have become larger and larger, and the amount of data needed to be processed by slicing software has increased dramatically. Existing slicing software is limited by computer hardware and cannot process massive data model. It greatly limits the development of additive manufacturing technology, so it is urgent to propose a new method to solve the rapid stratification of mass data model. In this paper, we proposed an adaptive slicing approach for processing STL massive data model in batches based on layer merging. At the same time, it is compared with the fixed-layer thickness slicing method, which shows that the algorithm can improve printing efficiency under the premise of ensuring accuracy.

Ferroelectric memories with ultralow‐power‐consumption are attracting a great deal of interest with the ever‐increasing demand for information storage in wearable electronics. However, sufficient scalability, semiconducting compatibility, and robust flexibility of the ferroelectric memories remain great challenges, e.g., owing to Pb‐containing materials, oxide electrode, and limited thermal stability. Here, high‐performance flexible nonvolatile memories based on ferroelectric Hf0.5Zr0.5O2 (HZO) via quasi‐van der Waals heteroepitaxy are reported. The flexible ferroelectric HZO exhibits not only high remanent polarization up to 32.6 µC cm−2 without a wake‐up effect during cycling, but also remarkably robust mechanical properties, degradation‐free retention, and endurance performance under a series of bent deformations and cycling tests. Intriguingly, using HZO as a gate, flexible ferroelectric thin‐film transistors with a low operating voltage of ±3 V, high on/off ratio of 6.5 × 105, and a small subthreshold slope of about 100 mV dec−1, which outperform reported flexible ferroelectric transistors, are demonstrated. The results make ferroelectric HZO a promising candidate for the next‐generation of wearable, low‐power, and nonvolatile memories with manufacturability and scalability., Flexible quasi‐van der Waals hafnium‐based oxides are fabricated and investigated systematically. Due to high remanent polarization, robust mechanical properties, and degradation‐free retention and endurance, the nonvolatile memories based on ferroelectric capacitors and thin‐film transistors show excellent performance and mechanical durability, which outperform reported flexible ferroelectric devices. The findings provide a pathway for wearable nonvolatile memories with manufacturability and scalability.

Purpose. Because Hirayama disease is stereotyped as a self-limited disease in the absence of a definite pathology, we investigated the potential relationship between snake-eyes appearance (SEA) and Hirayama disease to bring a new perspective in the pathological process of Hirayama disease based on relevant radiological and clinical evidence. Methods. A total of 30 cases observed SEA were selected from 293 patients with Hirayama disease to constitute the SEA group, and an equal number of cases were randomly selected from the remaining patients to form the non-SEA group. Cervical magnetic resonance imaging (MRI) was performed and subsequently used to measure the anteroposterior diameter and anterior shifting of the spinal cord. Additionally, clinical data, such as age, sex, duration of symptoms, symptoms, and signs, were collected and analyzed. Results. Of 293 patients, 10.6% appeared with the SEA, which was mainly multisegmental (86.7%), particularly at the C5-6 segment (73.3%), and intense with a well-defined border (70.0%). The SEA group was an older population (p < 0.0001) with a longer duration (p < 0.0001) and a higher incidence of Hoffmann signs and knee hyperreflexia (p < 0.0001, p = 0.0038, respectively). The degree of spinal cord atrophy demonstrated a close association with the SEA, as it was significantly worse in the SEA group and SEA segment (p = 0.0008, p < 0.0001, respectively). The degree of spinal cord atrophy was positively related to both age and duration (p = 0.0095, p = 0.0176, respectively). Conclusions. Confirmed as an irreversible lesion and an indication of poor prognosis, SEA appears during the late stage of Hirayama disease and is closely related to pyramidal signs and spinal cord atrophy.

Background Immune activation, specifically activation of macrophages and resident microglia, leading to inflammation is a key component in the progression of spinal cord injury (SCI). Macrophages/microglia exist in two states—the classically activated M1 phenotype that confers pro-inflammatory effects or the alternatively activated M2 phenotype that confers anti-inflammatory effects. Ecto-5′-nucleotidase (CD73) is an immunosuppressive molecule intricately involved in adaptive and innate immune responses and is able to dephosphorylate AMP to adenosine. However, it is not known if CD73 is able to modulate the macrophages/microglia transformation between the M1 and M2 phenotypes. Methods We used gene-deficient mice to determine the role of CD73 in macrophages/microglia polarization post-SCI in vivo. We used small interference RNA (siRNA) or pcDNA3.1 to inhibit or overexpress CD73 in BV2 cells to verify anterior discovery in vitro. A combination of molecular and histological methods was used to detect the macrophages/microglia polarization and explore the mechanism both in vivo and in vitro. Results We found that SCI induced the upregulation of CD73 expression. CD73 deficient mice were noted to demonstrate overwhelming immune responses, few anti-inflammatory phenotype macrophages/microglia, and had a poorer locomotor recovery in comparison to wild-type mice that were also inflicted with SCI. In vitro studies found that CD73 suppression inhibited the expression of characteristic microglial anti-inflammatory polarization markers in BV2 cells, while the converse was noted in CD73 overexpression. Subsequent experiments confirmed that CD73 promoted microglia alternative activation by stimulating p38 MAPK. Conclusion We were able to conclude that CD73 imparts neuroprotective effects by mediating macrophages/microglia polarization. These findings allow for better understanding of the modulatory factors involved in triggering the change in macrophages/microglia phenotypes, therefore uncovering additional molecules and pathways that may be targeted in the innovation of novel SCI therapies. Electronic supplementary material The online version of this article (10.1186/s12974-018-1183-8) contains supplementary material, which is available to authorized users.

CD73 deficiency increased marrow edema and enhancement. Representative micro-MRI images of spinal cord at 3Â days post-injury. (PDF 459Â kb)

Transposons are widely used for genetic engineering in various model organisms. Recently, piggyBac (PB) has been developed as a transposable and efficient gene transfer tool in mammalian cells. In the present study, we developed three types of PB transposon systems containing a dual plasmid system (DPS), a single plasmid system (SPS), and a DNA-mRNA combined system (DRPS) and characterized their basic properties in HEK293 cells. The basic elements of the donor plasmid included a selectable-reporter gene expression cassette, two loxP sites in the same orientation, a multiple cloning site, and two chicken β-globin insulator core elements. We further identified the function of the selectable-reporter and examined PB integration sites in the human genome. Moreover, we compared the transposition efficacy and found that SPS transposed more efficiently, as compared to DPS; integration into the host genome was determined by measuring PBase activity. Results discovered the loss of PBase activity in the DRPS, indicating that this system is much more biologically safe, as compared to DPS and SPS. Finally, we employed the DRPS to successfully perform a gene delivery into bovine mammary epithelial cells (BMECs). Taken together, the information from this study will improve the flexibility of PB transposon systems and reduce the genotoxicity of PBase in genetic engineering.

In Chinese Lake Taihu, the algal quantity was significantly larger in summer than late spring (p 0.01). In summer, compared with the dredged area including neither zoobenthos nor submerged macrophytes, the algal biomass and density were significantly lower in the area filled with the submerged macrophytes. Interestingly, the minimum algal bloom was observed in the combined area containing submerged macrophytes and zoobenthos, which was due to the synergistic interaction between the zoobenthos and the macrophytes. The metabolite extracts from the numerically dominant zoobenthos Limnodrilus hoffmeisteri had significant algal inhibitory effects of Microcystis aeruginosa, and displayed stimulatory effects on seed germination, seedling growth, and peroxidase activity of the prevalent submerged macrophyte Potamogeton malaianus. 27 active compounds in the worm metabolites were identified by gas chromatography-mass spectrometry (GC-MS). Among these compounds three chemicals arachidonic acid, eicosapentaenoic acid, and linoleic acid with concentrations of 13.92 ± 1.11, 10.57 ± 2.52, 2.75 ± 0.73 mg/kg dry weight, respectively, were confirmed as the typical allelochemicals with algal inhibition potential. In short, the metabolites allelopathy of L. hoffmeisteri can form and assist the synergistic effect between L. hoffmeisteri and P. malaianus on algal suppression. Thus, it is feasible to simultaneously restore submerged macrophytes and zoobenthos community in the disturbed eutrophic lakes for removing harmful algae.

To determine if the retroperitoneal oblique corridor will be affected by right lateral decubitus position.Forty volunteers were randomly enrolled and MRI scan was performed from L1 to L5 in supine and right lateral decubitus positions, respectively. In images across the center of each disc, O was defined as the center of a disc and A (supine) or A' (right lateral decubitus) was located in left lateral border of the aorta or the iliac artery; B (supine) or B' (right lateral decubitus) was on the anterior medial border of the psoas. The distance of AB and A'B' (Recorded as A-Ps and A-Pr, respectively) at each level was recorded and compared to each other. The relationships between A-Pr, sex, BMI and relative psoas cross-sectional area (PCSA) at each level were also evaluated.A-Pr was significantly smaller than A-Ps at L1/2, L2/3 and L3/4 (All p 0.05); there was no significantly difference of A-Pr between all levels (p = 0.105), but L1/2 seemed to be larger than L3/4, followed by L2/3 and L4/5; A-Pr at each level was not affected by sex (All p 0.05); linear relationships were found between A-Pr, BMI and PCSA at L1/2 and L3/4.ROC at L1/2, L2/3 and L3/4 will significantly decrease from supine to right lateral decubitus position and the reason may be due to the relaxed psoas deformation. Using MRI images in supine position for pre-operatively ROC evaluation is not accurate. Spine surgeon should also be more cautious when OLIF is performed at L4/5 where ROC is the smallest. Patients from Asia and those with strong psoas major at L1/2 and L3/4 are also associated with relatively narrow ROC.

Needle-like aragonite was synthesized with a reversible solution reaction from limestone without calcinations. Scan Electron Microscope (SEM) and X-ray Diffraction (XRD) were used to characterize the morphology and the crystal structure of aragonite. The synthesis of aragonite whisker involves two steps. At first GCC (Ground Calcium Carbonate) was dissolved in an aqueous solution of magnesium chloride with reflux and air flush. Then CO 2 was bubbled into the suspension at a low temperature to produce aragonite whisker. An in-house designed reactor and acid–base titration analysis were used to measure the remaining GCC content in the reaction mixture. A kinetics equation of GCC dissolution was developed, which showed a first-order kinetic feature to magnesium chloride concentration. A reaction rate constant of 0.04234 h −1 was obtained. The dissolution rate of GCC in magnesium chloride is much higher than that in the magnesium sulfate solution. Some aragonite whiskers with a length of ca. 20 μm and an aspect ratio of 8–12 can be synthesized.

Much attention has been paid to the processing of inorganic whisker, especially calcium carbonate whisker, which can be used as reinforcement materials of polymer composite due to its low price. Unfortunately, the present synthesis technique of calcium carbonate whisker starts from calcinations of limestone, which involves high energy consumption and furthermore is a highly environment polluting reaction. In this report, needle-like aragonite was synthesized with a reversible solution reaction from limestone without calcination. Optical microscopy, scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques were used to characterize the morphology and crystal structure of intermediates as well as that of the product, aragonite. GCC (grinding calcium carbonate) powder was dissolved in an aqueous solution of magnesium sulfate with reflux and air flush. EDTA titration was used to evaluate reaction rate of the dissolution. A kinetics equation of the dissolution reaction was constructed, which di...