Substrate-directed regioselective alkene functionalizations of (E)-ß,γ-unsaturated carboxylic acids.

A carboxylate-directed regioselective Heck-type alkenylation and alkenylative lactonization of (E)-ß,γ-unsaturated carboxylic acids by simply substrate control is reported. (E)- and (Z)-alkenyl bromides reacted to give energetically more favorable palladacyles, allowing access to fully stereocontrolled conjugated 1,3-dienes and alkenyled γ-lactones. Mechanistic studies suggest that excellent regioselectivity may be strongly influenced by the steric factors of reactants involved in the palladacycle intermediates.

Research status and prospects of biodegradable magnesium-based metal guided bone regeneration membranes.

Biodegradable magnesium-based metal guided bone regeneration (GBR) membranes possess excellent mechanical properties, biodegradability, and osteopromotive capabilities, making them ideal implants for the treatment of maxillofacial bone defects. This review summarizes the current status and future research trends related to magnesium-based GBR membranes. First, the research history and application fields of magnesium-based metals are introduced, and the advantages of the use of magnesium-based materials for GBR membranes, including their mechanical properties, biocompatibility, osteopromotive performance, and underlying mechanisms are discussed. Finally, this review addresses the current limitations of magnesium-based GBR membranes and their applications and prospects in the field of dentistry. In conclusion, considerable advancements have been in fundamental and translational research on magnesium-based GBR membranes, which lays a crucial foundation for the treatment of maxillofacial bone defects.

Photocatalytically self-cleaning graphene oxide nanofiltration membranes reinforced with bismuth oxybromide for high-performance water purification.

Graphene oxide (GO) membranes have emerged as promising candidates for water purification applications, owing to their unique physicochemical attributes. Nevertheless, the trade-off between permeability and selectivity, coupled with their vulnerability to membrane fouling, poses significant challenges to their widespread industrial deployment. In this study, we introduce an innovative in-situ growth and layer-by-layer assembly technique for fabricating multilayer GO membranes reinforced with bismuth oxybromide (BiOBr) on commonly employed Nylon substrates. This method allows for the creation of two-dimensional lamellar membranes capable of photocatalytic self-cleaning and tunable nanochannel dimensions. The synthesized GO/BiOBr composite membranes exhibit remarkable water permeance rates (approximately 493.9 LMH/bar) and high molecular rejection efficiency (>99 % for Victoria Blue B and Congo Red dyes). Notably, these membranes showcase an enhanced photocatalytic self-cleaning performance upon exposure to visible light. Our work provides a viable route for the fabrication of functionalized GO-based nanofiltration membranes with BiOBr inclusions, offering a synergistic combination of high water permeability, modifiable nanochannels, and effective self-cleaning capabilities through photocatalysis.

Duplex Fluorinated and Atomic Layer Deposition-Derived ZrO2 Coatings Improve the Corrosion Resistance and Mechanical Properties of Mg-2Zn-0.46Y-0.5Nd (wt.%) Alloy Plates and Screws.

This study investigated the corrosion resistance and mechanical properties of Mg-2Zn-0.46Y-0.5Nd (wt.%) alloy plates and screws with fluorinated coatings and atomic layer deposition (ALD)-derived zirconia (ZrO2) coatings in vitro under physiological stress conditions. Synthetic polyurethane hemimandible replicas were split and fixed as the following three groups of magnesium alloy plates and screws: no additional surface coating treatment (Group A), with fluorinated coatings (Group B), and with duplex fluorinated and ALD-derived 100 nm ZrO2 coatings (Group C). A circulating stress of 1-10 N was applied to the distal bone segment, and a 4-week simulated body fluid immersion test was employed to study the remaining material volume and the mechanical properties of the different groups. Compared with Group A and Group B, the degradation rate of magnesium alloy plates and screws' head regions was significantly slowed down under the protection of duplex MgF2/ZrO2 coatings (p < 0.01). There was no significant difference in the degradation rate of the screw shaft region between groups (p = 0.077). In contrast to fluoride coatings, duplex MgF2/ZrO2 coatings maintained the mechanical strength of magnesium alloy plates and screws after a 14 day in vitro SBF immersion test. We conclude that duplex MgF2/ZrO2 coatings exhibited a certain protective effect on the Mg alloy plates and screws under physiological stress conditions.

Optimal tooth sectioning using a surgical handpiece and elevator: a finite element study of horizontally deeply impacted mandibular third molars.

OBJECTIVES: To conduct a finite element analysis of the impact of different variables on tooth sectioning efficiency and trauma to surrounding tissues when utilizing high-speed surgical handpieces and elevators. METHODS: CBCT data from the horizontally impacted third mandibular molar (M3M) of a patient were utilized to establish digital models of the M3M, adjacent M2M, and surrounding bone. To simulate tooth sectioning, a 3D finite element model was established with the following variables: remaining tooth tissue thickness (1-5 mm), tooth section fissure width (1-3 mm), elevator depth in fissure (2-6 mm), elevator position (buccal, lingual, central), elevator width (2-5 mm), and application of force (rotating, levering). Using this model, the distribution of stress on the M3M and the surrounding tissue was assessed while measuring tooth sectioning efficiency and trauma to the surrounding tissue. RESULTS: Factors associated with uniform stress at the site of sectioning included thin (≤ 3 mm) remaining tooth tissue, appropriate fissure width (~ 2 mm), a wide (≥ 4 mm) elevator, and central elevator positioning. Levering the elevator yielded greater stress on the M3M than rotating force. Greater sectioning efficiency was associated with increased stress placed on the distobuccal side of M2M. CONCLUSIONS: Tooth sectioning efficiency can be improved by adjusting the high-speed surgical handpiece and elevator. However, it is important to remain attentive to the trauma to which adjacent teeth are exposed during this process. CLINICAL SIGNIFICANCE: These results offer guidance for approaches to improving operator efficiency and reducing trauma to surrounding tissues during tooth sectioning.

Deep-computer-generated holography with temporal-focusing and a digital propagation matrix for rapid 3D multiphoton stimulation.

Deep learning-based computer-generated holography (DeepCGH) has the ability to generate three-dimensional multiphoton stimulation nearly 1,000 times faster than conventional CGH approaches such as the Gerchberg-Saxton (GS) iterative algorithm. However, existing DeepCGH methods cannot achieve axial confinement at the several-micron scale. Moreover, they suffer from an extended inference time as the number of stimulation locations at different depths (i.e., the number of input layers in the neural network) increases. Accordingly, this study proposes an unsupervised U-Net DeepCGH model enhanced with temporal focusing (TF), which currently achieves an axial resolution of around 5 µm. The proposed model employs a digital propagation matrix (DPM) in the data preprocessing stage, which enables stimulation at arbitrary depth locations and reduces the computation time by more than 35%. Through physical constraint learning using an improved loss function related to the TF excitation efficiency, the axial resolution and excitation intensity of the proposed TF-DeepCGH with DPM rival that of the optimal GS with TF method but with a greatly increased computational efficiency.

Introducing gradient Er ions and oxygen defects into SrCoO3 for regulating structural, electrical and magnetic transport properties.

The SrCoO3-δ system has broad application potential due to its diverse crystal structures, oxidation stoichiometric ratio, and significant electrical and magnetic properties. However, it faces the challenges of a complex crystal structure and oxygen defect control in this material system. Herein, we introduce oxygen defects into SrCoO3-δvia Er doping to regulate the structural, electrical and magnetic transport properties. Sr1-xErxCoO3-δ (x = 0-0.25) undergoes an evolution of structure and oxygen content (measured using the iodometric method) from hexagonal SrCoO2.626 (H + Co3O4) to cubic perovskite Sr0.9Er0.1CoO2.689 (CP) and finally to ordered tetragonal Sr0.8Er0.2CoO2.635 (OT). Among the three phases, Sr0.9Er0.1CoO2.689 (CP) exhibits the lowest resistivity, only 4.06 mΩ cm at room temperature, which is attributed to its high three-dimensional symmetry, overlap of O 2p and Co 3d orbitals at high oxygen ion concentration. Further introduction of Er ions and oxygen defects promotes the transformation from low spin Co4+ (LS, t52ge0g, S = 1/2) to high spin Co3+ (HS, t42ge2g, S = 2), and from the CoO6 octahedron (low magnetic moment transformation) to the CoO4.25 tetrahedron (high magnetic moment). The oxygen-deficient CoO4.25 layer appears, which can enhance the ordering of A sites and oxygen vacancies, and the CP phase transforms into room-temperature ferromagnetic Sr0.8Er0.2CoO2.635 (OT, TC∼330 K). Er ions provide unpaired electrons in the 2f orbital, which results in a strong magnetization of Sr0.8Er0.2CoO2.635 (OT, 4.66 µB/Co) at low temperatures.

C-C Motif Chemokine 2 Regulates Macrophage Polarization and Contributes to Myocardial Infarction Healing.

Macrophages are crucial immune cells that play essential roles in the healing of myocardial infarction (MI), undergoing continuous polarization throughout this process. C-C motif chemokine 2 (CCL2) is a chemokine that regulates inflammatory responses during MI. However, the extent to which CCL2 influences macrophage polarization and MI healing remains incompletely understood. In this study, we investigate the role of CCL2 in macrophage polarization and MI healing. Our findings reveal that CCL2 is differentially expressed in lipopolysaccharide (LPS)-induced M1 and interleukin (IL)-4-induced M2 RAW264.7 macrophages. Knockdown of CCL2 attenuates TNF-α secretion stimulated by LPS, while overexpression of CCL2 mitigates IL-10 production triggered by IL-4 in these macrophages. Moreover, CCL2 deficiency disrupts LPS-induced M1 polarization, whereas CCL2 overexpression reduces M2 polarization of RAW264.7 macrophages induced by IL-4. Further exploration indicates that the promotion of M1 polarization by CCL2 is significantly impaired by inhibition of the p38-mediated MAPK pathway and NF-κB pathway. In a MI mouse model, CCL2 knockdown remarkably reduces infarct size, collagen synthesis, and the expression of cardiac fibrosis and hypertrophy markers. The activity of the p38-mediated MAPK pathway and NF-κB pathway is downregulated by CCL2 knockdown as well. Additionally, the number of total macrophages and M1 macrophages in the infarct decreases, while the number of M2 macrophages increases upon CCL2 deficiency. In conclusion, these results suggest that CCL2 is a key regulator of macrophage polarization, controlling MI healing in vivo.

Long-Term Temporospatial Complementary Relationship between Degradation and Bone Regeneration of Mg-Al Alloy.

The utilization of guided tissue regeneration membranes is a significant approach for enhancing bone tissue growth in areas with bone defects. Biodegradable magnesium alloys are increasingly being used as guided tissue regeneration membranes due to their outstanding osteogenic properties. However, the degradation rates of magnesium alloy bone implants documented in the literature tend to be rapid. Moreover, many studies focus only on the initial 3-month period post-implantation, limiting their applicability and impeding clinical adoption. Furthermore, scant attention has been given to the interplay between the degradation of magnesium alloy implants and the adjacent tissues. To address these gaps, this study employs a well-studied magnesium-aluminum (Mg-Al) alloy membrane with a slow degradation rate. This membrane is implanted into rat skull bone defects and monitored over an extended period of up to 48 weeks. Observations are conducted at various intervals (2, 4, 8, 12, 24, and 48 weeks) following the implantation. Assessment of degradation behavior and tissue regeneration response is carried out using histological sections, micro-CT scans, and scanning electron microscopy (SEM). The findings reveal that the magnesium alloy membranes demonstrate remarkable biocompatibility and osteogenic capability over the entire observation duration. Specifically, the Mg-Al alloy membranes sustain their structural integrity for 8 weeks. Notably, their osteogenic ability is further enhanced as a corrosion product layer forms during the later stages of implantation. Additionally, our in vitro experiments employing extracts from the magnesium alloy display a significant osteogenic effect, accompanied by a notable increase in the expression of osteogenic-related genes. Collectively, these results strongly indicate the substantial potential of Mg-Al alloy membranes in the context of guided tissue regeneration.

Multiple-phase evolution and electrical transport of Sr4-xYxCo4O12-δ (x = 0-1.0): an ordered phase transition process.

The transition metal oxide (TMO) SrCoO3-δ family with rich structural diversity has been widely studied in the phase transition and energy application fields. We report the multiple-phase structure evolution, phase transitions during sintering, and electrical transport of A-site doped Sr4-xYxCo4O12-δ (x = 0-1.0) ceramics. Sr6Co5O15 (x = 0) adopts a hexagonal structure (H), Sr4-xYxCo4O12-δ (x = 0.2-0.4) ceramics adopts a cubic perovskite (CP) structure, and Sr4-xYxCo4O10.5+δ' (x = 0.8-1.0) ceramics adopts an ordered-tetragonal (OT) structure; moreover, their phase transitions during the sintering processing of samples are systematically investigated. Combining the thermal analysis and X-ray diffraction results, the exothermic peak and weight gain of Sr3YCo4O10.5 (x = 1.0, T) at 1042 °C are considered to correspond to an ordered phase transition (T → OT) occurring. Finally, a systematic phase schema of the Sr4-xYxCo4O12-δ (x = 0-1.0) state dependence on the Y content and sintering temperature is obtained. The high-energy Y-O bond stabilizes the high-temperature CP structure (x = 0.2-0.4) and induces a structural evolution from the CP to OT structure (x = 0.8-1.0). In addition, all Sr4-xYxCo4O12-δ (x = 0-1.0) ceramics show semiconductive electrical transport behavior. Sr6Co5O15 (H) with a one-dimensional chain structure has the highest resistivity, while Sr3.8Y0.2Co4O12-δ (CP) with a three-dimensional corner-sharing structure exhibits the lowest resistivity, and Sr4-xYxCo4O12-δ (x = 0.2-1.0) ceramics show an increasing tendency in resistivity due to the hole carrier Co4+ converting to Co3+. We studied multiple-phase evolution and ordered phase transition in Sr4-xYxCo4O12-δ (x = 0-1.0) ceramics through Y-O bonding.

Damage Monitoring of Composite Adhesive Joint Integrity Using Conductivity and Fiber Bragg Grating.

Adhesive joints possess a number of advantages over traditional joining methods and are widely used in composite structures. Conventional non-destructive examination techniques do not readily reveal joint degradation before the formation of explicit defects. Embedded fiber Bragg grating (FBG) sensors and the resistance of carbon nanotube (CNT)-doped conductive joints have been proposed to monitor the structural integrity of adhesive joints. Both techniques will be employed and compared in the current work to monitor damage development in adhesive joints under tensile and cyclic fatigue loading. Most of the previous works took measurements under an applied load, which by itself will affect the monitoring signals without the presence of any damage. Moreover, most FBG works primarily relied on the peak shifting phenomenon for sensing. Degradation of adhesive and inter-facial defects will lead to non-uniform strain that may chirp the FBG spectrum, causing complications in the peak shifting measurement. In view of the above shortfalls, measurements are made at some low and fixed loads to preclude any unwanted effect due to the applied load. The whole FBG spectrum, instead of a single peak, will be used, and a quantitative parameter to describe spectrum changes is proposed for monitoring purposes. The extent of damage is revealed by a fluorescent penetrant and correlated with the monitoring signals. With these refined techniques, we hope to shed some light on the relative merits and limitations of the two techniques.

Surface modification of zirconia ceramics through cold plasma treatment and the graft polymerization of biomolecules.

Background/purpose: Although zirconia ceramics were highly versatile as dental implants, their long-term presence in the human body may slow down healing and impede cell growth in the past. To enhance the cytocompatibility of zirconia ceramics, surface activation modification was used to immobilize biopolymers such that a biomimetic environment was created. Materials and methods: Hexamethyldisilazane thin films were deposited onto the surface of inorganic zirconia through cold plasma treatment under various power and deposition time settings to form an organosilane interface layer. Next, oxygen plasma treatment was performed to activate the free radicals on the surface. Subsequently, ultraviolet light was employed to graft and polymerize acrylic acid for generating carboxyl groups on the surface. This was followed by a condensation reaction with biopolymers (chitosan, chitosan/poly-γ-glutamic acid, and gelatin). Results: Under a 20-min deposition time at 40 W and 150 mTorr, the thin films had a maximum graft density of 2.1 mg/cm2. MG-63 cells (human osteosarcoma cells) were employed to evaluate cell compatibility. Chitosan and chitosan/poly-γ-glutamic acid promoted the compatibility of MG-63 cells (a human osteosarcoma cell line) with zirconia ceramics, whereas gelatin reduced this compatibility. Conclusion: The findings confirm that cold plasma treatment and graft polymerization can promote the immobilization of biomolecules and improve the biocompatibility of zirconia ceramics. This approach can be applied to the modification of zirconia ceramic implants.

A Weighted Heterogeneous Graph-Based Dialog System.

Knowledge-based dialog systems have attracted increasing research interest in diverse applications. However, for disease diagnosis, the widely used knowledge graph (KG) is hard to represent the symptom-symptom and symptom-disease relations since the edges of traditional KG are unweighted. Most research on disease diagnosis dialog systems highly relies on data-driven methods and statistical features, lacking profound comprehension of symptom-symptom and symptom-disease relations. To tackle this issue, this work presents a weighted heterogeneous graph-based dialog system for disease diagnosis. Specifically, we build a weighted heterogeneous graph based on symptom co-occurrence and the proposed symptom frequency-inverse disease frequency. Then, this work proposes a graph-based deep Q -network (graph-DQN) for dialog management. By combining graph convolutional network (GCN) with DQN to learn the embeddings of diseases and symptoms from both the structural and attribute information in the weighted heterogeneous graph, graph-DQN could capture the symptom-disease relations and symptom-symptom relations better. Experimental results show that the proposed dialog system rivals the state-of-the-art models. More importantly, the proposed dialog system can complete the task with fewer dialog turns and possess a better distinguishing capability on diseases with similar symptoms.

Low expression of ESR1 correlates with ascending aortic dilation and acute type A aortic dissection.

BACKGROUND: The common genetic signatures of ascending aortic dilation and acute type A aortic dissection (AAAD) remained unclear. This study aims to investigate the role of ESR1 in ascending aortic dilation and AAAD via a multi-omics approach combining transcriptome-wide association study (TWAS) and mRNA expression profiles. METHODS: The TWAS analysis was performed by integrating expression quantitative trait loci (eQTL) data of aorta and the GWAS dataset of ascending aortic diameter using the FUSION software. Joint/Conditional Analysis was used to screen conditionally independent genes from TWAS significant regions. mRNA expression profiles were used to confirm the differential expression of ESR1 in ascending aortic dilation and AAAD. An independent mRNA expression profile dataset was used to validate the diagnostic efficiency of ESR1 expression on thoracic aortic aneurysm (TAA). Gene set enrichment analysis (GSEA) was utilized to explore the potential molecular function of ESR1 in mouse aorta. Immune infiltration analysis was performed to evaluate the association between ESR1 and immune infiltration in AAAD. RESULTS: ESR1 was among the top 10 most significant genes identified by TWAS of ascending aortic diameter (Z score = -7.3, PTWAS = 3.30 × 10-13). mRNA expression profiles confirmed the low expression of ESR1 both in ascending aortic dilation (PmRNA = 0.0361) and AAAD (PmRNA = 0.0142). The diagnostic efficiency of peripheral blood ESR1 expression on TAA was further validated by an independent mRNA expression profile dataset. GSEA showed that GO terms and KEGG pathways mainly involved in metabolism and oxidoreductase activity were enriched in aortic tissue of ERα knockout mice. The immune infiltration ration of naive CD8 + T cells was significantly lower in AAAD compared with normal aorta, and was positively correlated with ESR1 expression. CONCLUSION: Low expression of ESR1 is associated with ascending aortic dilation and AAAD. Peripheral blood ESR1 expression may be a novel diagnostic biomarker of TAA. ESR1 expression is positively correlated with immune infiltration ration of naive CD8 + T cells in AAAD.

Programmed Death-1 Deficiency Aggravates Motor Dysfunction in MPTP Model of Parkinson's Disease by Inducing Microglial Activation and Neuroinflammation in Mice.

Abundant reactive gliosis and neuroinflammation are typical pathogenetic hallmarks of brains in Parkinson's disease (PD) patients, but regulation mechanisms are poorly understood. We are interested in role of programmed death-1 (PD-1) in glial reaction, neuroinflammation and neuronal injury in PD pathogenesis. Using PD mouse model and PD-1 knockout (KO) mice, we designed wild-type-control (WT-CON), WT-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (WT-MPTP), PD-1-KO-control (KO-CON) and PD-1-KO-MPTP (KO-MPTP), and observed motor dysfunction of animal, morphological distribution of PD-1-positive cells, dopaminergic neuronal injury, glial activation and generation of inflammatory cytokines in midbrains by motor behavior detection, immunohistochemistry and western blot. WT-MPTP mouse model exhibited decrease of PD-1/Iba1-positive microglial cells in the substantia nigra compared with WT-CON mice. By comparison of four groups, PD-1 deficiency showed exacerbation in motor dysfunction of animals, decreased expression of TH protein and TH-positive neuronal protrusions. PD-1 deficiency enhanced microglial activation, production of proinflammatory cytokines like inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1ß and interleukin-6, and expression and phosphorylation of AKT and ERK1/2 in the substantia nigra of MPTP model. We concluded that PD-1 deficiency could aggravate motor dysfunction of MPTP mouse model by inducing microglial activation and neuroinflammation in midbrains, suggesting that PD-1 signaling abnormality might be possibly involved in PD pathogenesis.

Case Report: Using Medtronic AP360 mechanical prosthesis in mitral valve replacement for patients with mitral insufficiency after primum atrial septal defect repair to reduce left ventricular outflow tract obstruction risk.

Background: Atrial septal defect is one of the most common congenital heart diseases in adults. Primum atrial septal defect (PASD) accounts for 4%-5% of congenital heart defects. Patients with PASD frequently suffer mitral insufficiency (MI), and thus, mitral valvuloplasty (MVP) or mitral valve replacement (MVR) is often required at the time of PASD repair. Unfortunately, recurrent unrepairable severe mitral regurgitation can develop in many patients undergoing PASD repair plus MVP in either short- or long-term after the repair surgery, requiring a re-do MVR. In those patients, the risk of left ventricular outflow tract obstruction (LVOTO) has increased. Case presentation: We present five such cases, ranging in age from 24 to 47 years, who had a PASD repair plus MVP or MVR for 14-40 years while suffering moderate to severe mitral regurgitation. Using Medtronic AP360 mechanical mitral prostheses, only one patient experienced mild LVOTO. Conclusions: The use of Medtronic AP360 mechanical mitral prostheses to perform MVR in patients with MI who had a history of PASD repair can potentially reduce the risk of LVOTO. Long-term follow-up is required to further confirm this clinical benefit associated with AP360 implantation in patients with PASD.

Palladium-Catalyzed Regiospecific Decarboxylative Allylation of (Cyclohexadienylidene)malononitriles: Access to α-Allyl-α-aryl Malononitriles.

A palladium-catalyzed regiospecific decarboxylative ε-allylation of (cyclohexadienylidene)malononitriles is presented for the synthesis of functionalized α-allyl-α-aryl malononitriles. This reaction proceeds via a resonance-stabilized α-aryl malononitrile anion, resulting in a wide range of α-allyl-α-aryl malononitriles in high yields with excellent linear product selectivity. We have also shown that the resulting products can be transformed into valuable synthetic intermediates by decyanation and Mizoroki-Heck arylation. In addition, an enantioselective decarboxylative allylation reaction is also presented.

Bilateral Cavernous Sinus Dural Arteriovenous Fistulae : The Strategies for Endovascular Treatment.

PURPOSE: Most cavernous sinus dural arteriovenous fistulas (CSDAVF) are unilateral; however, simultaneous bilateral CSDAVFs occasionally may be found. This article reports on 141 patients and compares the angioarchitecture and outcomes of embolization of bilateral CSDAVFs with those of unilateral CSDAVFs, with reference to limited demographics (sex and age) of the patients. METHOD: From January 2010 to February 2018 a total of 141 consecutive patients with CSDAVFs were referred for transvenous embolization. Bilateral CSDAVFs were found in 20 patients (14.2%, with a mean age of 62.2 years). The angioarchitecture of the 141 patients with CSDAVFs were evaluated by conventional cerebral angiography. We compared the angioarchitecture and treatment outcomes of 20 bilateral and 121 unilateral CSDAVFs, and in relation to the patients' sex and age. RESULTS: Female patients significantly dominated the bilateral CSDAVFs (90%, p = 0.043). Bilateral eye symptoms were significantly more common in bilateral CSDAVFs (p = 0.011), with dominant orbital and cavernous symptoms, and showed statistical significance (p = 0.049 and 0.011, respectively). Occlusion of one CSDAVF may significantly decrease the fistula flow of the other untreated side (n = 13, 65%), leading to less coil utilization for embolization in bilateral CSDAVFs (p < 0.001). There was no statistical significance in the occurrence of occlusion of the inferior petrous sinus(s), in pial vein reflux, and treatment outcomes in the unilateral and bilateral CSDAVFs. CONCLUSION: Bilateral CSDAVFs were more dominant in female patients and frequently presented with orbital and cavernous symptoms. Fewer coils were used per lesion in the bilateral CSDAVFs. There was no statistical significance in bilateral and unilateral CSDAVFs in terms of impact of venous drainage, pial vein reflux and treatment outcomes.

Reactive Astrocytes Display Pro-inflammatory Adaptability with Modulation of Notch-PI3K-AKT Signaling Pathway Under Inflammatory Stimulation.

Astrocytes are major glial cells critical in assisting the function of the central nervous system (CNS), but the functional changes and regulation mechanism of reactive astrocytes are still poorly understood in CNS diseases. In this study, mouse primary astrocytes were cultured, and inflammatory insult was performed to observe functional changes in astrocytes and the involvement of Notch-PI3K-AKT signaling activation through immunofluorescence, PCR, Western blot, CCK-8, and inhibition experiments. Notch downstream signal Hes-1 was clearly observed in the astrocytes, and Notch signal inhibitor GSI dose-dependently decreased the cleaved Notch-l level without an influence on cell viability. Inflammatory insult of lipopolysaccharide plus interferon-γ (LPS+IFNγ) induced an increase in pro-inflammatory cytokines, that is, iNOS, IL-1ß, IL-6, and TNF, at the protein and mRNA levels in activated astrocytes, which was reduced or blocked by GSI treatment. The cell viability of the astrocytes did not show significant differences among different groups. While an increase in MyD88, NF-кB, and phosphor-NF-кB was confirmed, upregulation of PI3K, AKT, and phosphor-AKT was observed in the activated astrocytes with LPS+IFNγ insult and was reduced by GSI treatment. Inhibitor experiments showed that inhibition of Notch-PI3K-AKT signaling activation reduced the pro-inflammatory cytokine production triggered by LPS+IFNγ inflammatory insult. This study showed that the reactive astrocytes displayed pro-inflammatory adaptability through Notch-PI3K-AKT signaling activation in response to inflammatory stimulation, suggesting that the Notch-PI3K-AKT pathway in reactive astrocytes may serve as a promising target against CNS inflammatory disorders.

Reactive astrocytes increase expression of proNGF in the mouse model of contused spinal cord injury.

Astrocytes are major glial cells critically in maintaining stability of the central nervous system and functional activation of astrocytes occurs rapidly in various diseased or traumatic events. We are interested in functional changes of astrocytes during the spinal cord injury, and studied expression of nerve growth factor (NGF) in activated astrocytes by mouse model of contused spinal cord injury and cell culture experiment. It revealed that the spinal cord injury resulted in apparent activation of astrocytes and microglial cells and decreased BMS scores. A larger number of astrocytes showed immunoreactivity to proNGF in the injured spinal cord areas, and proNGF expression increased and remained high level at 7 to 14dpi, which was coincided with upregulation of glial fibrillary acidic protein. The proNGF was clearly localized in both exosome-like vesicles and cytoplasm of astrocytes in culture. Electron microscopy confirmed exosome-like vesicles with proNGF-immunoreactivity in diameter sizes of 50-100 nm. Finally, cell culture with lipopolysaccharide (LPS) experiment indicated increasing expression and release of proNGF in the astrocytes with LPS exposure. This study demonstrated that reactive astrocytes increased proNGF expression after spinal cord injury, also suggesting involvement of exosome-like proNGF transport or release in triggering neuronal apoptosis and aggravating progression of spinal cord injury.