Programmable Ferroelectricity in Hf0.5Zr0.5O2 Enabled by Oxygen Defect Engineering.

Ferroelectricity, especially the Si-compatible type recently observed in hafnia-based materials, is technologically useful for modern memory and logic applications, but it is challenging to differentiate intrinsic ferroelectric polarization from the polar phase and oxygen vacancy. Here, we report electrically controllable ferroelectricity in a Hf0.5Zr0.5O2-based heterostructure with Sr-doped LaMnO3, a mixed ionic-electronic conductor, as an electrode. Electrically reversible extraction and insertion of an oxygen vacancy into Hf0.5Zr0.5O2 are macroscopically characterized and atomically imaged in situ. Utilizing this reversible process, we achieved multilevel polarization states modulated by the electric field. Our study demonstrates the usefulness of the mixed conductor to repair, create, manipulate, and utilize advanced ferroelectric functionality. Furthermore, the programmed ferroelectric heterostructures with Si-compatible doped hafnia are desirable for the development of future ferroelectric electronics.

Allelopathy appraisal of worm metabolites in the synergistic effect between Limnodrilus hoffmeisteri and Potamogeton malaianus on algal suppression.

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 ±â€¯1.11, 10.57 ±â€¯2.52, 2.75 ±â€¯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.

Ecto-5'-nucleotidase (CD73) attenuates inflammation after spinal cord injury by promoting macrophages/microglia M2 polarization in mice.

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.

Quantitative analysis of near-implant magnesium accumulation for a Si-containing coated AZ31 cage from a goat cervical spine fusion model.

BACKGROUND: Magnesium (Mg) released from Mg-based implants degradation is believed to be effective in improving osteogenesis, however, studies focusing on Mg-based interbody cages are limited and fusion success was never reported. As excessive Mg accumulation can inhibit new bone formation, this study is designed to explain the possible reasons for the fusion failure of Mg-based cages by analyzing the relationships between the intervertebral Mg accumulation and the resulting interbody fusion. METHODS: The experimental cage was consisted of magnesium alloy (AZ31) substrate and Silicon (Si) -containing coating. C3/C4 and C5/C6 of 24 goats were implanted with cage or autologous iliac crest bone graft (Control group), which were analyzed at 3, 6, 12, and 24 weeks post-operatively. Intervertebral Mg concentrations, Mg-related Calcium (Ca)/ Phosphorus (P) ratios, radiological evaluations and histological findings were recorded for analyzing the relationships between the three of cage corrosion, Mg accumulation, and interbody fusion. RESULTS: Intervertebral Mg levels were significantly increased after cage implantation, especially in the areas that were closer to the cages at 3 weeks post-operatively, and these increased concentrations could persist up to 12 weeks post-operatively, indicating a relatively rapid corrosion process. Significantly lower Mg levels were only found at 24 weeks post-operatively, but these levels were still higher than those of the control group. In addition, Mg was found to be widely distributed at the intervertebral space since high Mg concentrations could even be detected at the posterior boundary of the vertebral body. Under this Mg accumulation profile, interbody fusion was not achieved, as indicated by the decreased Ca/P ratios, low CT fusion scores and negative histological results. CONCLUSIONS: Intervertebral excessive Mg accumulation might be the primary reason for interbody fusion failure. Quantitative Mg analysis can offer insight into the association between cage degeneration and biological response.

Does right lateral decubitus position change retroperitoneal oblique corridor? A radiographic evaluation from L1 to L5.

PURPOSE: To determine if the retroperitoneal oblique corridor will be affected by right lateral decubitus position. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Production of transgenic cattle highly expressing human serum albumin in milk by phiC31 integrase-mediated gene delivery.

Transgenic cattle expressing high levels of recombinant human serum albumin (HSA) in their milk may as an alternative source for commercial production. Our objective was to produce transgenic cattle highly expressing HSA in milk by using phiC31 integrase system and somatic cell nuclear transfer (SCNT). The mammary-specific expression plasmid pIACH(-), containing the attB recognition site for phiC31 integrase, were co-transfected with integrase expression plasmid pCMVInt into bovine fetal fibroblast cells (BFFs). PhiC31 integrase-mediated integrations in genome of BFFs were screened by nested inverse PCR. After analysis of sequence of the PCR products, 46.0% (23/50) of the both attB-genome junction sites (attL and attR) were confirmed, and four pseudo attP sites were identified. The integration rates in BF3, BF11, BF19 and BF4 sites were 4.0% (2/50), 6.0% (3/50), 16.0% (8/50) and 20.0% (10/50), respectively. BF3 is located in the bovine chromosome 3 collagen alpha-3 (VI) chain isomer 2 gene, while the other three sites are located in the non-coding region. The transgenic cell lines from BF11, BF19 and BF4 sites were used as donors for SCNT. Two calves from transgenic cells BF19 were born, one died within a few hours after birth, and another calf survived healthy. PCR and Southern blot analysis revealed integration of the transgene in the genome of cloned calves. The nested reverse PCR confirmed that the integration site in cloned calves was identical to the donor cells. The western blotting assessment indicated that recombinant HSA was expressed in the milk of transgenic cattle and the expression level was about 4-8 mg/mL. The present study demonstrated that phiC31 integrase system was an efficient and safety gene delivery tool for producing HSA transgenic cattle. The production of recombinant HSA in the milk of cattle may provide a large-scale and cost-effective resource.

Enhancing erythromycin production in Saccharopolyspora erythraea through rational engineering and fermentation refinement: A Design-Build-Test-Learn approach.

Industrial production of bioactive compounds from actinobacteria, such as erythromycin and its derivatives, faces challenges in achieving optimal yields. To this end, the Design-Build-Test-Learn (DBTL) framework, a systematic metabolic engineering approach, was employed to enhance erythromycin production in Saccharopolyspora erythraea (S. erythraea) E3 strain. A genetically modified strain, S. erythraea E3-CymRP21-dcas9-sucC (S. erythraea CS), was developed by suppressing the sucC gene using an inducible promoter and dcas9 protein. The strain exhibited improved erythromycin synthesis, attributed to enhanced precursor synthesis and increased NADPH availability. Transcriptomic and metabolomic analyses revealed altered central carbon metabolism, amino acid metabolism, energy metabolism, and co-factor/vitamin metabolism in CS. Augmented amino acid metabolism led to nitrogen depletion, potentially causing cellular autolysis during later fermentation stages. By refining the fermentation process through ammonium sulfate supplementation, erythromycin yield reached 1125.66 mg L-1, a 43.5% increase. The results demonstrate the power of the DBTL methodology in optimizing erythromycin production, shedding light on its potential for revolutionizing antibiotic manufacturing in response to the global challenge of antibiotic resistance.

Exosomes from hypoxic ADSCs ameliorate neuronal damage post spinal cord injury through circ-Wdfy3 delivery and inhibition of ferroptosis.

BACKGROUND: Exosomes generated from adipose-derived mesenchymal stem cells (Exos), and in particular hypoxia-pretreated ADSCs (HExos), possess therapeutic properties that promote spinal cord repair following spinal cord injury (SCI). Nevertheless, the regulatory mechanisms through which HExos exert their effects remain unclear. METHODS: Here, next-generation sequencing (NGS) was utilized to examine abnormal circRNA expression comparing HExos to Exos. Bioinformatics analysis and RNA pulldown assays together with luciferase reporter assays were applied to determine interactions among miRNAs, mRNAs and circRNAs. ELISA and immunofluorescence staining were used to examine inflammatory cytokine levels, apoptosis and ROS deposition in LPS-treated HT-22 cells, respectively. The therapeutic effects of Exos and HExos on a mouse model of SCI were analyzed by immunohistochemistry and immunofluorescence staining. RESULTS: Our findings confirmed that HExos have more significant therapeutic influences on decreasing ROS and inflammatory cytokine levels post-SCI than Exos. NGS revealed that circ-Wdfy3 expression levels were significantly higher in HExos than Exos. Downregulation of circ-Wdfy3 led to a decrease in HExo-induced therapeutic effects on spinal cord repair post-SCI, indicating that circ-Wdfy3 has a critical role in the regulation of HExo-mediated protection against SCI. Our bioinformatics, RNA pulldown and luciferase reporter data demonstrated that GPX4 and miR-423-3p were downstream targets of circ-Wdfy3. GPX4 downregulation or miR-423-3p overexpression reversed the protective effects of circ-Wdfy3 on LPS-treated HT-22 cells. Furthermore, overexpression of circ-Wdfy3 led to an in increase in the Exo-induced therapeutic effects on spinal cord repair post-SCI through the inhibition of ferroptosis. CONCLUSIONS: circ-WDfy3-overexpressing Exos promote spinal cord repair post-SCI through mediation of ferroptosis via the miR-138-5p/GPX4 pathway.

Hydroxyapatite Nanoparticles Promote the Development of Bone Microtissues for Accelerated Bone Regeneration by Activating the FAK/Akt Pathway.

Scaffold-free bone microtissues differentiated from mesenchymal stem cell (MSC) spheroids offer great potential for bottom-up bone tissue engineering as a direct supply of cells and osteogenic signals. Many biomaterials or biomolecules have been incorporated into bone microtissues to enhance their osteogenic abilities, but these materials are far from clinical approval. Here, we aimed to incorporate hydroxyapatite (HAP) nanoparticles, an essential component of bone matrix, into MSC spheroids to instruct their osteogenic differentiation into bone microtissues and further self-organization into bone organoids with a trabecular structure. Furthermore, the biological interaction between HAP nanoparticles and MSCs and the potential molecular mechanisms in the bone development of MSC spheroids were investigated by both in vitro and in vivo studies. As a result, improved cell viability and osteogenic abilities were observed for the MSC spheroids incorporated with HAP nanoparticles at a concentration of 30 µg/mL. HAP nanoparticles could promote the sequential expression of osteogenic markers (Runx2, Osterix, Sclerostin), promote the expression of bone matrix proteins (OPN, OCN, and Collagen I), promote the mineralization of the bone matrix, and thus promote the bone development of MSC spheroids. The differentiated bone microtissues could further self-organize into linear, lamellar, and spatial bone organoids with trabecular structures. More importantly, adding FAK or Akt inhibitors could decrease the level of HAP-induced osteogenic differentiation of bone microtissues. Finally, excellent new bone regeneration was achieved after injecting bone microtissues into cranial bone defect models, which could also be eliminated by the Akt inhibitor. In conclusion, HAP nanoparticles could promote the development of bone microtissues by promoting the osteogenic differentiation of MSCs and the formation and mineralization of the bone matrix via the FAK/Akt pathway. The bone microtissues could act as individual ossification centers and self-organize into macroscale bone organoids, and in this meaning, the bone microtissues could be called microscale bone organoids. Furthermore, the bone microtissues revealed excellent clinical perspectives for injectable cellular therapies for bone defects.

Electrospun Composite PLLA-PPSB Nanofiber Nerve Conduits for Peripheral Nerve Defects Repair and Regeneration.

Peripheral nerve injury (PNI) is a common clinical problem and regenerating peripheral nerve defects remain a significant challenge. Poly(polyol sebacate) (PPS) polymers are developed as promising materials for biomedical applications due to their biodegradability, biocompatibility, elastomeric properties, and ease of production. However, the application of PPS-based biomaterials in nerve tissue engineering, especially in PNI repair, is limited. In this study, PPS-based composite nanofibers poly(l-lactic acid)-poly(polycaprolactone triol-co-sebacic acid-co-N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid sodium salt) (PLLA-PPSB) are aimed to construct through electrospinning and assess their in vitro biocompatibility with Schwann cells (SCs) and in vivo repair capabilities for peripheral nerve defects. For the first time, the biocompatibility and bioactivity of PPS-based nanomaterial are examined at the molecular, cellular, and animal levels for PNI repair. Electrospun PLLA-PPSB nanofibers display favorable physicochemical properties and biocompatibility, providing an effective interface for the proliferation, glial expression, and adhesion of SCs in vitro. In vivo experiments using a 10-mm rat sciatic nerve defect model show that PLLA-PPSB nanofiber nerve conduits enhance myelin formation, axonal regeneration, angiogenesis, and functional recovery. Transcriptome analysis and biological validation indicate that PLLA-PPSB nanofibers may promote SC proliferation by activating the PI3K/Akt signaling pathway. This suggests the promising potential of PLLA-PPSB nanomaterial for PNI repair.

Anatomical Brushite-Coated Mg-Nd-Zn-Zr Alloy Cage Promotes Cervical Fusion: One-Year Results in Goats.

In this study, an anatomical brushite-coated Mg-Nd-Zn-Zr alloy cage was fabricated for cervical fusion in goats. The purpose of this study was to investigate the cervical fusion effect and degradation characteristics of this cage in goats. The Mg-Nd-Zn-Zr alloy cage was fabricated based on anatomical studies, and brushite coating was prepared. Forty-five goats were divided into three groups, 15 in each group, and subjected to C2/3 anterior cervical decompression and fusion with tricortical bone graft, Mg-Nd-Zn-Zr alloy cage, or brushite-coated Mg-Nd-Zn-Zr alloy cage, respectively. Cervical radiographs and computed tomography (CT) were performed 3, 6, and 12 months postoperatively. Blood was collected for biocompatibility analysis and Mg2+ concentration tests. The cervical spine specimens were obtained at 3, 6, and 12 months postoperatively for biomechanical, micro-CT, scanning electron microscopy coupled with energy dispersive spectroscopy, laser ablation-inductively coupled plasma-time-of-flight mass spectrometry, and histological analysis. The liver and kidney tissues were obtained for hematoxylin and eosin staining 12 months after surgery for biosafety analysis. Imaging and histological analysis showed a gradual improvement in interbody fusion over time; the fusion effect of the brushite-coated Mg-Nd-Zn-Zr alloy cage was comparable to that of the tricortical bone graft, and both were superior to that of the Mg-Nd-Zn-Zr alloy cage. Biomechanical testing showed that the brushite-coated Mg-Nd-Zn-Zr alloy cage achieved better stability than the tricortical bone graft at 12 months postoperatively. Micro-CT showed that the brushite coating significantly decreases the corrosion rate of the Mg-Nd-Zn-Zr alloy cage. In vivo degradation analysis showed higher Ca and P deposition in the degradation products of the brushite-coated Mg-Nd-Zn-Zr alloy cage, and no hyperconcentration of Mg was detected. Biocompatibility analysis showed that both cages were safe for cervical fusion surgery in goats. To conclude, the anatomical brushite-coated Mg-Nd-Zn-Zr alloy cage can promote cervical fusion in goats, and the brushite-coated Mg-Nd-Zn-Zr alloy is a potential material for developing absorbable fusion cages.

EGFR-targeting peptide conjugated polymer-lipid hybrid nanoparticles for delivery of salinomycin to osteosarcoma.

CONTEXT: Salinomycin (SAL) is a chemotherapeutic drug with anti-osteosarcoma efficacy, but its hydrophobic properties have hindered its application. Nanoparticles have been widely used as drug carriers to improve the solubility of hydrophobic drugs. The dodecapeptide GE11 has been shown to have great binding affinity to the epidermal growth factor receptor (EGFR), which is highly overexpressed in osteosarcoma. MATERIALS AND METHODS: We designed novel SAL-loaded GE11-conjugated polymer-lipid hybrid nanoparticles (GE11-NPs-SAL) to target osteosarcoma. The characterization and antitumor activity of GE11-NPs-SAL were evaluated both in vitro and in vivo. RESULTS: The results showed that GE11-NPs-SAL had a size of ~100 nm with a high encapsulation efficacy of ~80%. Compared with the non-targeted nanoparticles, GE11-NPs-SAL showed increased internalization in osteosarcoma cells and improved therapeutic efficacy in osteosarcoma both in vitro and in vivo. CONCLUSIONS: GE11-NPs-SAL is a promising treatment for osteosarcoma.

Corrosion Behavior of Nitrided Layer of Ti6Al4V Titanium Alloy by Hollow Cathodic Plasma Source Nitriding.

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.

Brushite-coated Mg-Nd-Zn-Zr alloy promotes the osteogenesis of vertebral laminae through IGF2/PI3K/AKT signaling pathway.

Biodegradable magnesium (Mg) alloys have been extensively investigated in orthopedic implants due to their suitable mechanical strength and high biocompatibility. However, no studies have reported whether Mg alloys can be used to repair lamina defects, and the biological mechanisms regulating osteogenesis are not fully understood. The present study developed a lamina reconstruction device using our patented biodegradable Mg-Nd-Zn-Zr alloy (JDBM), and brushite (CaHPO4·2H2O, Dicalcium phosphate dihydrate, DCPD) coating was developed on the implant. Through in vitro and in vivo experiments, we evaluated the degradation behavior and biocompatibility of DCPD-JDBM. In addition, we explored the potential molecular mechanisms by which it regulates osteogenesis. In vitro, ion release and cytotoxicity tests revealed that DCPD-JDBM had better corrosion resistance and biocompatibility. We found that DCPD-JDBM extracts could promote MC3T3-E1 osteogenic differentiation via the IGF2/PI3K/AKT pathway. The lamina reconstruction device was implanted on a rat lumbar lamina defect model. Radiographic and histological analysis showed that DCPD-JDBM accelerated the repair of rat lamina defects and exhibited lower degradation rate compared to uncoated JDBM. Immunohistochemical and qRT-PCR results showed that DCPD-JDBM promoted osteogenesis in rat laminae via IGF2/PI3K/AKT pathway. This study shows that DCPD-JDBM is a promising biodegradable Mg-based material with great potential for clinical applications.

Landauer-QFLPS Model for Mixed Schottky-Ohmic Contact Two-Dimensional Transistors.

Two-dimensional material-based field-effect transistors (2DM-FETs) are playing a revolutionary role in electronic devices. However, before electronic design automation (EDA) for 2DM-FETs can be achieved, it remains necessary to determine how to incorporate contact transports into model. Reported methods compromise between physical intelligibility and model compactness due to the heterojunction nature. To address this, quasi-Fermi-level phase space theory (QFLPS) is generalized to incorporate contact transports using the Landauer formula. It turns out that the Landauer-QFLPS model effectively overcomes the issue of concern. The proposed new formula can describe 2DM-FETs with Schottky or Ohmic contacts with superior accuracy and efficiency over previous methods, especially when describing non-monotonic drain conductance characteristics. A three-bit threshold inverter quantizer (TIQ) circuit is fabricated using ambipolar black phosphorus and it is demonstrated that the model accurately predicts circuit performance. The model could be very effective and valuable in the development of 2DM-FET-based integrated circuits.

Recent advances in PLLA-based biomaterial scaffolds for neural tissue engineering: Fabrication, modification, and applications.

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.

Identifying the natural reserve area of Cistanche salsa under the effects of multiple host plants and climate change conditions using a maximum entropy model in Xinjiang, China.

Cistanche salsa (C. A. Mey.) G. Beck, a holoparasitic desert medicine plant with multiple hosts, is regarded as a potential future desert economic plant. However, as a result of excessive exploitation and poaching, its wild resources have become scarce. Thus, before developing its desert economic value, this plant has to be protected, and the identification of its natural reserve is currently the top priority. However, in previous nature reserve prediction studies, the influence of host plants has been overlooked, particularly in holoparasitic plants with multiple hosts. In this study, we sought to identify the conservation areas of wild C. salsa by considering multiple host-plant interactions and climate change conditions using the MaxEnt model. Additionally, a Principal Component Analysis (PCA) was used to reduce the autocorrelation between environmental variables. The effects of the natural distribution of the host plants in terms of natural distribution from the perspective of niche similarities and extrapolation detection were considered by filtering the most influential hosts: Krascheninnikovia ceratoides (Linnaeus), Gueldenstaedt, and Nitraria sibirica Pall. Additionally, the change trends in these hosts based on climate change conditions combined with the change trends in C. salsa were used to identify a core protection area of 126483.5 km2. In this article, we corrected and tried to avoid some of the common mistakes found in species distribution models based on the findings of previous research and fully considered the effects of host plants for multiple-host holoparasitic plants to provide a new perspective on the prediction of holoparasitic plants and to provide scientific zoning for biodiversity conservation in desert ecosystems. This research will hopefully serve as a significant reference for decision-makers.

Bicortical Short C2 Pars Screw Fixation for High-Riding Vertebral Artery Provided Sufficient Biomechanical Stability: A Finite Element Study.

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 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 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 range of motion 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.

Synergistic effect of growth factor receptor-bound protein 2/epidermal growth factor receptor dual-targeting peptide inhibitor and salinomycin on osteosarcoma.

Context: 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. Aims: We investigated the synergistic effects of the peptide and salinomycin (Sal), a chemotherapeutic drug with effective anti-OS properties in clinical therapy. Subjects and Methods: 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. Statistical Analysis Used: 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 P < 0.05. Results: 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. Conclusions: These data provide valuable insights into the molecular mechanisms of OS and may be beneficial in clinical therapy.

TLR4 aggravates microglial pyroptosis by promoting DDX3X-mediated NLRP3 inflammasome activation via JAK2/STAT1 pathway after spinal cord injury.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.