Phosphatidylinositol (3,5)-bisphosphate machinery regulates neurite thickness through neuron-specific endosomal protein NSG1/NEEP21.

Phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P2] is a critical signaling phospholipid involved in endolysosome homeostasis. It is synthesized by a protein complex composed of PIKfyve, Vac14, and Fig4. Defects in PtdIns(3,5)P2 synthesis underlie a number of human neurological disorders, including Charcot-Marie-Tooth disease, child onset progressive dystonia, and others. However, neuron-specific functions of PtdIns(3,5)P2 remain less understood. Here, we show that PtdIns(3,5)P2 pathway is required to maintain neurite thickness. Suppression of PIKfyve activities using either pharmacological inhibitors or RNA silencing resulted in decreased neurite thickness. We further find that the regulation of neurite thickness by PtdIns(3,5)P2 is mediated by NSG1/NEEP21, a neuron-specific endosomal protein. Knockdown of NSG1 expression also led to thinner neurites. mCherry-tagged NSG1 colocalized and interacted with proteins in the PtdIns(3,5)P2 machinery. Perturbation of PtdIns(3,5)P2 dynamics by overexpressing Fig4 or a PtdIns(3,5)P2-binding domain resulted in mislocalization of NSG1 to nonendosomal locations, and suppressing PtdIns(3,5)P2 synthesis resulted in an accumulation of NSG1 in EEA1-positive early endosomes. Importantly, overexpression of NSG1 rescued neurite thinning in PtdIns(3,5)P2-deficient CAD neurons and primary cortical neurons. Our study uncovered the role of PtdIns(3,5)P2 in the morphogenesis of neurons, which revealed a novel aspect of the pathogenesis of PtdIns(3,5)P2-related neuropathies. We also identified NSG1 as an important downstream protein of PtdIns(3,5)P2, which may provide a novel therapeutic target in neurological diseases.

Research progress on natural preservatives of meat and meat products: classifications, mechanisms and applications.

Meat and meat products are highly susceptible to contamination by microorganisms and foodborne pathogens, which cause serious economic losses and health hazards. The large consumption and waste of meat and meat products means that there is a need for safe and effective preservation methods. Furthermore, toxicological aspects of chemical preservation techniques related to major health problems have sparked controversies and have prompted consumers and producers to turn to natural preservatives. Consequently, natural preservatives are being increasingly used to ensure the safety and quality of meat products as a result of customer preferences and biological efficacy. However, information on the current status of these preservatives is scattered and a comprehensive review is lacking. Here, we review current knowledge on the classification, mechanisms of natural preservatives and their applications in the preservation of meat and meat products, and also discuss the potential of natural preservatives to improve the safety of meat and meat products. The current status and the current research gaps in the extraction, application and controlled-release of natural antibacterial agents for meat preservation are also discussed in detail. This review may be useful to the development of efficient food preservation techniques in the meat industry. © 2024 Society of Chemical Industry.

Glucometer-based biosensor for the determination of ractopamine in animal-derived foods using rolling circle amplification.

Screening for persistent organic pollutants (POPs) in food is a complex and challenging process, as POPs can be present in very low levels and can be difficult to detect. Herein, we developed an ultrasensitive biosensor based on a rolling circle amplification (RCA) platform using a glucometer to determine POP. The biosensor was constructed using gold nanoparticle probes modified with antibodies and dozens of primers, magnetic microparticle probes conjugated with haptens, and targets. After competition, RCA reactions are triggered, numerous RCA products hybridize with the ssDNA-invertase, and the target is successfully transformed into glucose. Using ractopamine as a model analyte, this strategy obtained a linear detection range of 0.038-5.00 ng mL-1 and a detection limit of 0.0158 ng mL-1, which was preliminarily verified by screening in real samples. Compared with conventional immunoassays, this biosensor utilizes the high efficiency of RCA and the portable properties of a glucometer, which effectively improves the sensitivity and simplifies the procedures using magnetic separation technology. Moreover, it has been successfully applied to ractopamine determination in animal-derived foods, revealing its potential as a promising tool for POP screening.

NB-3 signaling mediates the cross-talk between post-traumatic spinal axons and scar-forming cells.

Little is known about the molecules mediating the cross-talk between post-traumatic axons and scar-forming cells after spinal cord injury. We found that a sustained NB-3 induction was simultaneously present in the terminations of post-traumatic corticospinal axons and scar-forming cells at the spinal lesion site, where they were in direct contact when axons tried to penetrate the glial scar. The regrowth of corticospinal axons was enhanced in vivo with NB-3 deficiency or interruption of NB-3 trans-homophilic interactions. Biochemical, in vitro and in vivo evidence demonstrated that NB-3 homophilically interacted in trans to initiate a growth inhibitory signal transduction from scar-forming cells to neurons by modulating mTOR activity via CHL1 and PTPσ. NB-3 deficiency promoted BMS scores, electrophysiological transmission, and synapse reformation between regenerative axons and neurons. Our findings demonstrate that NB-3 trans-homophilic interactions mediate the cross-talk between post-traumatic axons and scar-forming cells and impair the intrinsic growth ability of injured axons.

Highly Sensitive Microstructure-Based Flexible Pressure Sensor for Quantitative Evaluation of Motor Function Recovery after Spinal Cord Injury.

Behavioral assessment, such as systematic scoring or biomechanical measurement, is often used to evaluate the extent of the damage and the degree of recovery after spinal cord injury. However, the use of these methods in standardized evaluation is limited because they are subjective and require complex test systems to implement. Here, we report a novel, flexible, microstructure-based pressure sensor and demonstrate its superior sensitivity (235.12 kPa-1 for 5.5~135 Pa and 2.24 kPa-1 for 0.6~25 kPa), good waterproofness, fast response and recovery times (response time: 8 ms, recovery time: 12 ms), stable response over 8000 loading/unloading cycles, and wide sensing range. These features readily allow the sensor to be comfortably attached to the hindlimbs of mice for full-range, real-time detection of their behavior, such as crawling and swimming, helping to realize quantitative evaluation of animal motor function recovery after spinal cord injury.

Mst-1 deficiency promotes post-traumatic spinal motor neuron survival via enhancement of autophagy flux.

The mammalian Ste20-like kinase 1 (Mst-1) is a serine-threonine kinase and a component of the Hippo tumor suppressor pathway, which reacts to pathologically relevant stress and regulates cell death. However, little is known about its role in spinal cord injury. Here, we found that p-Mst-1, the activated form of Mst-1, was induced in the post-traumatic spinal motor neurons. In vivo evidence demonstrated that Mst-1 deficiency promoted post-traumatic spinal motor neuron survival, Basso mouse scale scores, and synapse survival. Moreover, we found that autophagosome formation and autolysosome degradation enhanced by Mst-1 deficiency were crucial to attenuate the death of injured spinal motor neurons. Taken together, our findings demonstrate that Mst-1 deficiency promotes post-traumatic spinal motor neuron survival via enhancement of autophagy flux.

Kartogenin-loaded polyvinyl alcohol/nano-hydroxyapatite composite hydrogel promotes tendon-bone healing in rabbits after anterior cruciate ligament reconstruction.

Accumulating evidence supports the role of cartilage tissue engineering in cartilage defect repair, but the biological function has yet to be fully explained. In this work, kartogenin (KGN), an emerging chondroinductive nonprotein small molecule, was incorporated into a composite hydrogel of polyvinyl alcohol/nano-hydroxyapatite (PVA/n-HA) to fabricate an appropriate microenvironment for tendon-bone healing after anterior cruciate ligament (ACL) reconstruction. KGN/PVA/n-HA composite hydrogel scaffolds were prepared by in situ synthesis and physical adsorption, followed by characterization under a scanning electron microscope. The scaffolds were transplanted into healthy New Zealand White (NZW) rabbits. It was confirmed that KGN/PVA/n-HA scaffolds were successfully prepared and exhibited good supporting properties and excellent biocompatibility. Unilateral ACL reconstruction was constructed with tendon autograft in NZW rabbits, and the morphology and diameter of collagen fiber were analyzed. The scaffolds were shown to promote ACL growth and collagen fiber formation. Furthermore, microcomputerized tomography analysis and bone formation histology were performed to detect new bone formation. KGN/PVA/n-HA scaffolds effectively alleviated cartilage damage and prevented the occurrence of osteoarthritis. Meanwhile, ligament-bone healing and bone formation were observed in the presence of KGN/PVA/n-HA scaffolds. In conclusion, these results suggest that the KGN/PVA/n-HA scaffolds can facilitate tendon-bone healing after ACL reconstruction and might be considered novel hydrogel biomaterials in cartilage tissue engineering.

Chitosan-Enhanced pH-Sensitive Anthocyanin Indicator Film for the Accurate Monitoring of Mutton Freshness.

Natural anthocyanin indicator films with an excellent pH response enable the visual assessment of meat freshness. In this investigation, chitosan was initially employed as a colorimetric enhancer, leading to the development of a pH-sensitive indicator film that was enhanced in colorimetry. The characteristics of this indicator film were thoroughly analyzed, and the mechanism responsible for the increased sensitivity of anthocyanin within the chitosan matrix, as indicated by the color response, was elucidated. The recrystallization of chitosan impeded the hydration of AH+ as the pH increased from 6.0 to 8.0, leading to distinct color changes. Moreover, the application of this indicator film was extended to the monitoring of mutton meat freshness. It facilitated the differentiation of mutton meat into three distinct stages, namely, fresh, sub-fresh, and spoiled, based on alterations in color. Additionally, a robust positive correlation was established between the color difference value of the indicator film and the total volatile basic nitrogen and bacterial count of the mutton meat, enabling quantitative analysis. The present study, therefore, demonstrated a novel function of chitosan, i.e., the enhancement of the color of anthocyanin, which could be useful in designing and fabricating indicator films with a high color response.

Aptamer and sodium alginate decorated graphene oxide composite material with ion responsiveness for Low-density lipoprotein trapping.

The accumulation of excess Low-density lipoprotein (LDL) is strongly associated with the occurrence of heart failure, coronary artery disease and hypercholesterolaemia, and is a major factor in cardiovascular and cerebrovascular disease. Concerns about the ways to decrease LDL level have continuously arisen. In this study, an ionic stimulation-responsive composite (i.e., GO@Apt@SA) is prepared with modification of graphene oxide (GO) utilising LDL-aptamer (Apt) and sodium alginate (SA). The ion-responsive behaviour of GO@Apt@SA synergistically interacts with the specific recognition property of the aptamer, enabling adsorption of LDL with higher capacity and specificity. Under the optimal experimental conditions, the maximum adsorption capacity of GO@Apt@SA for LDL is 730.6 µg mg-1. Interestingly, the aptamer complementary chain could trigger the release of LDL with favourable elution efficiency, which competitively binds with LDL-specific aptamer to trigger LDL release. More importantly, GO@Apt@SA exhibits satisfactory adsorption performances for LDL in goat serum, meaning that the composite material and technology are available for the extraction of LDL from complex sample matrices.

Enhanced pH-sensitive anthocyanin film based on chitosan quaternary ammonium salt: A promising colorimetric indicator for visual pork freshness monitoring.

An intelligent pH response indicator film is an easy-to-use device for the real-time monitoring of meat freshness during transport and storage. Therefore, a novel pH-sensitive anthocyanin indicator film composed of polyvinyl alcohol-blueberry anthocyanin (BA)-2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC) called PAH-2.0 with 1.2 mg/mL HACC to monitor meat freshness using HACC as the colorimetric enhancer has been developed. BA and HACC were mixed and immobilized in the polyvinyl alcohol matrix by hydrogen bonds, as confirmed via Fourier-transform infrared spectroscopy and X-ray diffraction. The inclusion of HACC improved the color stability and antioxidant and antibacterial properties of the PAH-2.0 film. When applied to pork for freshness monitoring at 4 °C, three freshness stages, including fresh, sub-fresh, and spoiled, could be clearly distinguished based on the color variations of the PAH-2.0 film. The distinct hierarchical color change from purple to blue-violet and finally to grayish-blue was highly correlated with the indicators of pork freshness: pH values, total volatile basic nitrogen, and total viable count. This study provides a simple and promising approach for fabricating meat freshness indicator films with high color recognition accuracy, thereby offering new possibilities for visual meat freshness monitoring.

Facile fabricate sandwich-structured molecularly imprinted dopamine polymer for simultaneously specific capture of Low-density lipoprotein and eliminate "bad cholesterol".

A simplified approach for preparation of sandwich type molecularly imprinted polymers (PPDA-MIPs) is proposed for simultaneously identify Low-density lipoprotein (LDL) and dispose "bad cholesterol". Porous polydopamine nanosphere (PPDA) is applied as a matrix for immobilization of LDL, and the imprinted layer is formed by dopamine acting as a functional monomer. Since imprinted cavities exhibit shape memory effects in terms of recognizing selectivity, the PPDA-MIPs exhibit excellent selectivity toward LDL and a substantial binding capacity of 550.3 µg mg-1. Meanwhile, six adsorption/desorption cycles later, the adsorption efficiency of 83.09 % is still achieved, indicating the adequate stability and reusability of PPDA-MIPs. Additionally, over 80 % of cholesterol is recovered, indicating the completeness of "bad cholesterol" removal in LDL. Lastly, as demonstrated by gel electrophoresis, PPDA-MIPs performed satisfactory behavior for the removal of LDL from the goat serum sample.

An Innovative and Efficient Fluorescent Detection Technique for Salmonella in Animal-Derived Foods Using the CRISPR/Cas12a-HCR System Combined with PCR/RAA.

Here, we present a method for Salmonella detection using clustered regularly interspaced short palindromic repeats associated with the CRISPR-associated protein 12a-hybridization chain reaction (CRISPR/Cas12a-HCR) system combined with polymerase chain reaction/recombinase-assisted amplification (PCR/RAA) technology. The approach relies on the Salmonella invA gene as a biorecognition element and its amplification through PCR and RAA. In the presence of the target gene, Cas12a, guided by crRNA, recognizes and cleaves the amplification product, initiating the HCR. Fluorescently labeled single-stranded DNA (ssDNA) H1 and H2 were introduced, and the Salmonella concentration was determined based on the fluorescence intensity from the triggered HCR. Both assays demonstrate high specificity, sensitivity, simplicity, and rapidity. The detection range was 2 × 101-2 × 109 CFU/mL, with an LOD of 20 CFU/mL, and the entire process enabled specific and rapid Salmonella detection within 85-105 min. Field-incurred spiked recovery tests were conducted in mutton and beef samples using both assays, demonstrating satisfactory recovery and accuracy in animal-derived foods. By combining CRISPR/Cas12a with hybridization chain reaction technology, this study presents a rapid and sensitive Salmonella detection method that is crucial for identifying pathogenic bacteria and monitoring food safety.

Celastrol Ameliorates Neuronal Mitochondrial Dysfunction Induced by Intracerebral Hemorrhage via Targeting cAMP-Activated Exchange Protein-1.

Mitochondrial dysfunction contributes to the development of secondary brain injury (SBI) following intracerebral hemorrhage (ICH) and represents a promising therapeutic target. Celastrol, the primary active component of Tripterygium wilfordii, is a natural product that exhibits mitochondrial and neuronal protection in various cell types. This study aims to investigate the neuroprotective effects of celastrol against ICH-induced SBI and explore its underlying mechanisms. Celastrol improves neurobehavioral and cognitive abilities in mice with autologous blood-induced ICH, reduces neuronal death in vivo and in vitro, and promotes mitochondrial function recovery in neurons. Single-cell nuclear sequencing reveals that the cyclic adenosine monophosphate (cAMP)/cAMP-activated exchange protein-1 (EPAC-1) signaling pathways are impacted by celastrol. Celastrol binds to cNMP (a domain of EPAC-1) to inhibit its interaction with voltage-dependent anion-selective channel protein 1 (VDAC1) and blocks the opening of mitochondrial permeability transition pores. After neuron-specific knockout of EPAC1, the neuroprotective effects of celastrol are diminished. In summary, this study demonstrates that celastrol, through its interaction with EPAC-1, ameliorates mitochondrial dysfunction in neurons, thus potentially improving SBI induced by ICH. These findings suggest that targeting EPAC-1 with celastrol can be a promising therapeutic approach for treating ICH-induced SBI.

Dual electrical stimulation at spinal-muscular interface reconstructs spinal sensorimotor circuits after spinal cord injury.

The neural signals produced by varying electrical stimulation parameters lead to characteristic neural circuit responses. However, the characteristics of neural circuits reconstructed by electrical signals remain poorly understood, which greatly limits the application of such electrical neuromodulation techniques for the treatment of spinal cord injury. Here, we develop a dual electrical stimulation system that combines epidural electrical and muscle stimulation to mimic feedforward and feedback electrical signals in spinal sensorimotor circuits. We demonstrate that a stimulus frequency of 10-20 Hz under dual stimulation conditions is required for structural and functional reconstruction of spinal sensorimotor circuits, which not only activates genes associated with axonal regeneration of motoneurons, but also improves the excitability of spinal neurons. Overall, the results provide insights into neural signal decoding during spinal sensorimotor circuit reconstruction, suggesting that the combination of epidural electrical and muscle stimulation is a promising method for the treatment of spinal cord injury.

Promoting axon regeneration by inhibiting RNA N6-methyladenosine demethylase ALKBH5.

A key limiting factor of successful axon regeneration is the intrinsic regenerative ability in both the peripheral nervous system (PNS) and central nervous system (CNS). Previous studies have identified intrinsic regenerative ability regulators that act on gene expression in injured neurons. However, it is less known whether RNA modifications play a role in this process. Here, we systematically screened the functions of all common m6A modification-related enzymes in axon regeneration and report ALKBH5, an evolutionarily conserved RNA m6A demethylase, as a regulator of axonal regeneration in rodents. In PNS, knockdown of ALKBH5 enhanced sensory axonal regeneration, whereas overexpressing ALKBH5 impaired axonal regeneration in an m6A-dependent manner. Mechanistically, ALKBH5 increased the stability of Lpin2 mRNA and thus limited regenerative growth associated lipid metabolism in dorsal root ganglion neurons. Moreover, in CNS, knockdown of ALKBH5 enhanced the survival and axonal regeneration of retinal ganglion cells after optic nerve injury. Together, our results suggest a novel mechanism regulating axon regeneration and point ALKBH5 as a potential target for promoting axon regeneration in both PNS and CNS.

Nerve cells, or neurons, are the key communication components of the body. Each neuron takes signals from many inputs and transmits them through a single output called the axon. In the central nervous system, which consists of the brain and spinal cord, damaged neurons do not generally repair themselves. But in the peripheral nervous system, where neurons branch out to other parts of the body, they can regenerate. For this to happen, genes which promote axon regrowth must be expressed. Messenger RNA carries DNA information from the nucleus of a cell to the cytoplasm where it serves as instructions for generating proteins. Certain enzymes can modify messenger RNA, changing how long it lasts, where it goes in the cell and what proteins it makes. It has been suggested that a particular RNA modification, known as m⁶A, plays an important role in axon regrowth as increased m⁶A levels have been reported in some neurons after a peripheral nerve injury. Wang et al. studied the impact of m⁶A modifications on axon regrowth by examining the effects of several genes associated with these modifications in rats. The experiments showed that expression of a gene called Alkbh5 ­ which codes for an enzyme that removes m⁶A modifications ­ regulates the amount of axon regrowth following an injury to peripheral nerves. Reducing the amount of Alkbh5 expression rates increased axon regrowth, whereas in rats where Alkbh5 was overexpressed, regrowth was reduced. Further experiments showed that the ALKBH5 enzyme helps to make mRNA from the gene Lpin2 more stable, which affects how it processes fats and lipids during the regeneration process. Moreover, in the central nervous system, reducing Alkbh5 expression enhanced survival and axon regrowth of neurons in the eye after they were injured in mice. The findings suggest that Alkbh5 influences axon regrowth and are an important step towards understanding how biological systems repair nerve damage. Future work should investigate if stopping Alkbh5 expression allows injured neurons to recover their function and how different m⁶A-associated enzymes work together in this process.

Personal glucose meters coupled with signal amplification technologies for quantitative detection of non-glucose targets: Recent progress and challenges in food safety hazards analysis.

Ensuring food safety is paramount worldwide. Developing effective detection methods to ensure food safety can be challenging owing to trace hazards, long detection time, and resource-poor sites, in addition to the matrix effects of food. Personal glucose meter (PGM), a classic point-of-care testing device, possesses unique application advantages, demonstrating promise in food safety. Currently, many studies have used PGM-based biosensors and signal amplification technologies to achieve sensitive and specific detection of food hazards. Signal amplification technologies have the potential to greatly improve the analytical performance and integration of PGMs with biosensors, which is crucial for solving the challenges associated with the use of PGMs for food safety analysis. This review introduces the basic detection principle of a PGM-based sensing strategy, which consists of three key factors: target recognition, signal transduction, and signal output. Representative studies of existing PGM-based sensing strategies combined with various signal amplification technologies (nanomaterial-loaded multienzyme labeling, nucleic acid reaction, DNAzyme catalysis, responsive nanomaterial encapsulation, and others) in the field of food safety detection are reviewed. Future perspectives and potential opportunities and challenges associated with PGMs in the field of food safety are discussed. Despite the need for complex sample preparation and the lack of standardization in the field, using PGMs in combination with signal amplification technology shows promise as a rapid and cost-effective method for food safety hazard analysis.

Unveiling heterocyclic aromatic amines (HAAs) in thermally processed meat products: Formation, toxicity, and strategies for reduction - A comprehensive review.

This comprehensive review focuses on heterocyclic aromatic amines (HAAs), a class of chemicals that commonly form during the cooking or processing of protein-rich foods. The International Agency for Research on Cancer (IARC) has categorized certain HAAs as probable human carcinogens, highlighting the significance of studying their formation and control in food safety research. The main objective of this review is to address the knowledge gaps regarding HAAs formation and propose approaches to reduce their potential toxicity during thermal processing. By summarizing the mechanisms involved in HAAs formation and inhibition, the review encompasses both conventional and recent detection methods. Furthermore, it explores the distribution of HAAs in thermally processed meats prepared through various cooking techniques and examines their relative toxicity. Additionally, considering that the Maillard reaction, responsible for HAAs formation, also contributes to the unique flavors and aromas of cooked meat products, this review investigates the potential effects of inhibiting HAAs formation on flavor substances. A thorough understanding of these complex interactions provides a foundation for developing targeted interventions to minimize the formation of HAAs and other harmful compounds during food processing.

Positive diversifying selection on Plasmodium vivax RON2 protein.

Plasmodium rhoptry neck protein 2 (RON2), which is released from the neck portion of the merozoite rhoptries and interacts with the microneme protein Apical Membrane Antigen 1 (AMA1), plays a crucial role in erythrocyte invasion. In this study, we sequenced the Plasmodium vivax RON2 gene from 19 P. vivax isolates collected in central China in order to establish whether this protein is under positive diversifying selection, which may occur as a result of protective host immune pressure†. In comparison with the P. vivax Sal-1 reference line, we found 10 amino acid substitutions dispersed throughout the open reading frame as well as indels caused by polymorphism in a repeat unit (21-23 repeats of (Q/E/K/N/H)(G/D)G(H/L/Y/P)G) in the second tandem repeat region located at amino acid positions 541-650. A McDonald-Kreitman test with RON2 sequences from the primate malaria parasite Plasmodium knowlesi, detected significant departure from neutrality in the PvRON2 3' region (nucleotide positions 2668-6609). These results suggest that the PvRON2 gene has evolved under positive diversifying selection.

Grafted human ESC-derived astroglia repair spinal cord injury via activation of host anti-inflammatory microglia in the lesion area.

Grafted astroglia/astrocytes exhibit neuroprotective effects and improve functional recovery after injury to the central nervous system. This study sought to elucidate their ability to repair spinal cord lesions and the underlying mechanisms. Methods: Complete spinal transection, transplantation of astroglia generated from human ESC-derived neural progenitor cells (NPC-Astros) or Olig2-GFP knock-in progenitors (Olig2PC-Astros), and immunostaining were used to determine the survival of astroglia. CUBIC tissue-clearing, immunostaining, electromyography, and functional tests such as the Basso Mouse Scale score and gait analysis were applied to analyze the recovery of the lesion area, axon regeneration, synapse formation, and motor function. Sholl analysis, immunostaining, depletion of anti-inflammatory microglia, and western blotting were employed to explore the cellular and molecular mechanisms underlying spinal cord repair. Results: Grafted NPC- or Olig2PC-Astros survived in the lesion area and assisted wound healing by reducing scar formation and promoting regrowth of descending serotonergic axons and synapse reformation beyond the lesion area. These positive effects resulted in increased Basso Mouse Scale scores and improved hindlimb function as determined by electromyography and gait analysis. Activated microglia in the lesion area were shifted towards an anti-inflammatory phenotype after transplantation of NPC- or Olig2PC-Astros, and depletion of anti-inflammatory microglia reversed the observed improvements in the lesion area and axon regeneration. Transplantation of NPC- or Olig2PC-Astros elevated the expression of interleukin-4 and promoted the phenotypic shift of microglial via interleukin-4 downstream signaling. Conclusion: Our findings indicate that grafted human ESC-derived NPC- or Olig2PC-Astros promote recovery of the injured spinal cord by shifting microglia towards an anti-inflammatory state in the lesion area and activating interleukin-4 signaling.

Sevoflurane induces microRNA-18a to delay rat neurodevelopment via suppression of the RUNX1/Wnt/ß-catenin axis.

Sevoflurane anesthesia is reported to repress neurogenesis of neural stem cells (NSCs), thereby affecting the brain development, but the underlying mechanism of sevoflurane on the proliferation of NSCs remains unclear. Thus, this study aims to discern the relationship between sevoflurane and NSC proliferation. Bioinformatics tools were employed to predict the expression of microRNA-18a (miR-18a) in 9-day-old neonatal rat hippocampal tissues after sevoflurane treatment and the downstream genes of miR-18a, followed by a series of assays to explore the relationship among miR-18a, runt related transcription factor 1 (RUNX1), and ß-catenin in the hippocampal tissues. NSCs were isolated from the hippocampal tissues and subjected to gain-/loss-of-function assays to investigate the interactions among miR-18a, RUNX1, and ß-catenin in NSCs and their roles in NSC development. Bioinformatics analysis and experimental results confirmed high expression of miR-18a in rat hippocampal tissues and NSCs after sevoflurane treatment. Next, we found that miR-18a downregulated RUNX1 expression, while RUNX1 promoted NSC proliferation by activating the Wnt/ß-catenin signaling pathway. The behavioral experiments also showed that sevoflurane caused nerve injury in rats, whilst RUNX1 overexpression protected rat neurodevelopment. Our findings uncovered that sevoflurane attenuated NSC proliferation via the miR-18a-meidated RUNX1/Wnt/ß-catenin pathway, thereby impairing rat neurodevelopment.