Netrin-1 Is an Important Mediator in Microglia Migration.

Microglia migrate to the cerebral cortex during early embryonic stages. However, the precise mechanisms underlying microglia migration remain incompletely understood. As an extracellular matrix protein, Netrin-1 is involved in modulating the motility of diverse cells. In this paper, we found that Netrin-1 promoted microglial BV2 cell migration in vitro. Mechanism studies indicated that the activation of GSK3ß activity contributed to Netrin-1-mediated microglia migration. Furthermore, Integrin α6/ß1 might be the relevant receptor. Single-cell data analysis revealed the higher expression of Integrin α6 subunit and ß1 subunit in microglia in comparison with classical receptors, including Dcc, Neo1, Unc5a, Unc5b, Unc5c, Unc5d, and Dscam. Microscale thermophoresis (MST) measurement confirmed the high binding affinity between Integrin α6/ß1 and Netrin-1. Importantly, activation of Integrin α6/ß1 with IKVAV peptides mirrored the microglia migration and GSK3 activation induced by Netrin-1. Finally, conditional knockout (CKO) of Netrin-1 in radial glial cells and their progeny led to a reduction in microglia population in the cerebral cortex at early developmental stages. Together, our findings highlight the role of Netrin-1 in microglia migration and underscore its therapeutic potential in microglia-related brain diseases.

The Pre- and Post-column Derivatization on Monosaccharide Composition Analysis, a Review.

Polysaccharides, as common metabolic products in organisms, play a crucial role in the growth and development of living organisms. For humans, polysaccharides represent a class of compounds with diverse applications, particularly in the medical field. Therefore, the exploration of the monosaccharide composition and structural characteristics of polysaccharides holds significant importance in understanding their biological functions. This review provides a comprehensive overview of extraction methods and hydrolysis strategies for polysaccharides. It systematically analyzes strategies and technologies for determining polysaccharide composition and discusses common derivatization reagents employed in further polysaccharide studies. Derivatization is considered a fundamental strategy for determining monosaccharides, as it not only enhances the detectability of analytes but also increases detection sensitivity, especially in liquid chromatography (LC), capillary electrophoresis (CE), and gas chromatography (GC) techniques. The critical comparison of pre- and post-column derivatization is elaborated in this paper, aiming to serve as a reference for selecting appropriate modes based on the structural characteristics, biological activities of polysaccharides, and reaction systems.

Substance P in the medial amygdala regulates aggressive behaviors in male mice.

Behavioral and clinical studies have revealed a critical role of substance P (SP) in aggression; however, the neural circuit mechanisms underlying SP and aggression remain elusive. Here, we show that tachykinin-expressing neurons in the medial amygdala (MeATac1 neurons) are activated during aggressive behaviors in male mice. We identified MeATac1 neurons as a key mediator of aggression and found that MeATac1→ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) projections are critical to the regulation of aggression. Moreover, SP/neurokinin-1 receptor (NK-1R) signaling in the VMHvl modulates aggressive behaviors in male mice. SP/NK-1R signaling regulates aggression by influencing glutamate transmission in neurons in the VMHvl. In summary, these findings place SP as a key node in aggression circuits.

Inhibition Effect of Triphenylmethane Dyes for the Corrosion of Carbon Steel in CO2-Saturated NaCl Corrosion Medium.

Carbon dioxide corrosion presents a significant challenge in the oil and gas field. This study simulates the corrosive environment characteristics of oil and gas fields to investigate the corrosion inhibition properties of three triphenylmethane dyes. The inhibitive performance and mechanisms of these dyes were analyzed through weight loss and electrochemical testing, revealing that crystal violet (CV) exhibited a superior inhibition effectiveness over malachite green (MG) and Fuchsine basic (FB). At a concentration of 150 ppm in a CO2-saturated 5% NaCl solution at 25 °C, CV achieved an impressive maximum inhibition efficiency of 94.89%. With the increase in temperature, the corrosion rate slightly decreased, and the corrosion rate was 92.94% at 60 °C. The investigated CV acted as a mixed-type corrosion inhibitor and its protection obeyed the Langmuir adsorption isotherm. The corrosion morphology was characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and confocal laser scanning microscopy (CLMS). Quantum chemical calculations and molecular dynamics simulations were employed to validate the corrosion inhibition mechanisms, providing guidance for the further application of these dyes in corrosion control.

PRMT5-mediated homologous recombination repair is essential to maintain genomic integrity of neural progenitor cells.

Maintaining genomic stability is a prerequisite for proliferating NPCs to ensure genetic fidelity. Though histone arginine methylation has been shown to play important roles in safeguarding genomic stability, the underlying mechanism during brain development is not fully understood. Protein arginine N-methyltransferase 5 (PRMT5) is a type II protein arginine methyltransferase that plays a role in transcriptional regulation. Here, we identify PRMT5 as a key regulator of DNA repair in response to double-strand breaks (DSBs) during NPC proliferation. Prmt5F/F; Emx1-Cre (cKO-Emx1) mice show a distinctive microcephaly phenotype, with partial loss of the dorsal medial cerebral cortex and complete loss of the corpus callosum and hippocampus. This phenotype is resulted from DSBs accumulation in the medial dorsal cortex followed by cell apoptosis. Both RNA sequencing and in vitro DNA repair analyses reveal that PRMT5 is required for DNA homologous recombination (HR) repair. PRMT5 specifically catalyzes H3R2me2s in proliferating NPCs in the developing mouse brain to enhance HR-related gene expression during DNA repair. Finally, overexpression of BRCA1 significantly rescues DSBs accumulation and cell apoptosis in PRMT5-deficient NSCs. Taken together, our results show that PRMT5 maintains genomic stability by regulating histone arginine methylation in proliferating NPCs.

Experimental and DFT insights into the adsorption mechanism of methylene blue by alkali-modified corn straw biochar.

As an efficient and cost-effective adsorbent, biochar has been widely used in the adsorption and removal of dyes. In this study, a simple NaOH-modified biochar with the pyrolysis temperature of 300 °C (NaCBC300) was synthesized, characterized, and investigated for the adsorption performances and mechanisms of methylene blue (MB). NaCBC300 exhibited excellent MB adsorption performance with maximum removal efficiency and adsorption capacity of 99.98% and 290.71 mg g-1, which were three and four times higher than biochar without modification, respectively. This might be attributed to the increased content of -OH and the formation of irregular flakes after NaOH modification. The Freundlich isotherm suggested multilayer adsorption between NaCBC300 and MB. Spectroscopic characterizations demonstrated that multiple mechanisms including π-π interaction, H-bonding, and pore-filling were involved in the adsorption. According to density functional theory (DFT) calculations, electrostatic interaction between NaCBC300 and MB was verified. The highest possibility of the attraction between NaCBC300 and MB was between -COOH in NaCBC300 and R-N(CH3)2 in MB. This work improved our understanding of the mechanism for MB adsorption by modified biochar and provided practical and theoretical guidance for adsorbent preparation with high adsorption ability for dyes.

Effect of C Addition on the Microstructure and Fracture Properties of In Situ Laminated Nb/Nb5Si3 Composites.

//Nbss and α-Nb5Si3 phases were detected. Meanwhile, Nb2C was observed, and the crystal forms of Nb5Si3 changed in the C-doped composites. Furthermore, micron-sized and nano-sized Nb2C particles were found in the Nbss layer. The orientation relationship of Nb2C phase and the surrounding Nbss was [001]Nbss//[010]Nb2C, (200) Nbss//(101) Nb2C. Additionally, with the addition of C, the compressive strength of the composites, at 1400 °C, and the fracture toughness increased from 310 MPa and 11.9 MPa·m1/2 to 330 MPa and 14.2 MPa·m1/2, respectively; the addition of C mainly resulted in solid solution strengthening.

Microstructure and Mechanical Properties of Cast Al-Si-Cu-Mg-Ni-Cr Alloys: Effects of Time and Temperature on Two-Stage Solution Treatment and Ageing.

Ameliorating the high-temperature performance of cast Al-Si alloys used as engine components is essential. The effects of different T6 heat-treatment processes on the microstructure and mechanical properties of cast Al-Si-Cu-Mg-Ni-Cr alloys were investigated in the present study. The results demonstrate that, under the optimal solution treatment conditions of 500 °C for 2 h and 540 °C for 4 h, the T-Al9FeNi phase was present in the alloy, and the roundness of primary Si and the aspect ratio of eutectic Si in the alloy reached valley values of 1.46 and 2.56, respectively. With increasing ageing time at 180 °C, the tensile strength significantly improved, while the microhardness first increased and then decreased. When the ageing time was 4 h, microhardness reached a peak value of 155.82 HV. The fracture characteristics changed from quasi-cleavage to the coexistence of quasi-cleavage and dimples. After heat treatment, the high-temperature tensile properties of the alloy improved, which is a significant advantage compared to the as-cast alloy. The stable Al3Ni and Al9FeNi phases inhibited the cracking of the alloy at 350 °C.

A Nucleus Accumbens Tac1 Neural Circuit Regulates Avoidance Responses to Aversive Stimuli.

Neural circuits that control aversion are essential for motivational regulation and survival in animals. The nucleus accumbens (NAc) plays an important role in predicting aversive events and translating motivations into actions. However, the NAc circuits that mediate aversive behaviors remain elusive. Here, we report that tachykinin precursor 1 (Tac1) neurons in the NAc medial shell regulate avoidance responses to aversive stimuli. We show that NAcTac1 neurons project to the lateral hypothalamic area (LH) and that the NAcTac1→LH pathway contributes to avoidance responses. Moreover, the medial prefrontal cortex (mPFC) sends excitatory inputs to the NAc, and this circuit is involved in the regulation of avoidance responses to aversive stimuli. Overall, our study reveals a discrete NAc Tac1 circuit that senses aversive stimuli and drives avoidance behaviors.

Facile preparation of coprecipitates between iron oxides and dissolved organic matter for efficient Fenton-like degradation of norfloxacin.

As two important components of dissolved organic matter (DOM), dissolved black carbon (DBC) and humic acid (HA) possess different chemical and structural properties, which might influence their activities like metal complexation and mediating electron transfer. In this study, a series of coprecipitates of iron oxides (FeOx) and DOM (HA or DBC) having different C/Fe molar ratios (0.2-3.0) was prepared under ambient conditions, which exhibited excellent catalytic efficiencies upon Fenton-like degradation of norfloxacin (NOR). Pseudo-first-order rate constant of NOR oxidation catalyzed by DBC-FeOx (C/Fe=3.0, 1.13 h-1) was 30.5, 4.3-14.2, and 1.3-15.7 folds higher than those mediated by FeOx alone, HA-FeOx and DBC-FeOx coprecipitates having C/Fe molar ratios of 0.2 and 1.6, respectively. Due to the higher concentrations of surface-bound Fe(III)/Fe(II) in the DBC-FeOx mediated systems, improved Fe(III)/Fe(II) cycling rates, •OH accumulation and NOR degradation were observed as compared with those of counterpart systems mediated by HA-FeOx. Besides functioning in Fe-C complexation to accelerate FeOOH cleavage, carbonyl/carboxyl groups of the coprecipitates also serve as electron shuttles, both of which improved Fe(III)/Fe(II) cycling and •OH production. Our findings emphasized the influence of DOM source and compositions on Fe(III)/Fe(II) cycling and provided a facile approach of preparing Fe-C catalyst for contaminants elimination.

Dysregulation of AMPK-mTOR signaling leads to comorbid anxiety in Dip2a KO mice.

Autism is often comorbid with other psychiatric disorders. We have previously shown that Dip2a knockout (KO) induces autism-like behaviors in mice. However, the role of Dip2a in other psychiatric disorders remains unclear. In this paper, we revealed that Dip2a KO mice had comorbid anxiety. Dip2a KO led to a reduction in the dendritic length of cortical and hippocampal excitatory neurons. Molecular mechanism studies suggested that AMPK was overactivated and suppressed the mTOR cascade, contributing to defects in dendritic morphology. Deletion of Dip2a in adult-born hippocampal neurons (Dip2a conditional knockout (cKO)) increased susceptibility to anxiety upon acute stress exposure. Application of (2R,6R)-hydroxynorketamine (HNK), an inhibitor of mTOR, rescued anxiety-like behaviors in Dip2a KO and Dip2a cKO mice. In addition, 6 weeks of high-fat diet intake alleviated AMPK-mTOR signaling and attenuated the severity of anxiety in both Dip2a KO mice and Dip2a cKO mice. Taken together, these results reveal an unrecognized function of DIP2A in anxiety pathophysiology via regulation of AMPK-mTOR signaling.

Superhydrophobic Biological Fluid-Repellent Surfaces: Mechanisms and Applications.

Superhydrophobic biological fluid-repellent surfaces (SBFRSs) have attracted great attention in the treatment of blood and urine-related diseases because of their unique wettability and compatibility, which creates a new path for the development of medical apparatus and instruments, and are expected to create advances in various fields. Here, this review provides an up-to-date summary of research progress on the repellent mechanism and application of SBFRSs. The underlying physical and chemical principles for designing superhydrophobic surfaces are first introduced. Then, the dialectical influences of solid-liquid interactions between superhydrophobic surfaces and biological fluids on the wettability and compatibility are emphatically expounded. Subsequently, attention is drawn to the recent applications of SBFRSs in biomedical fields, such as surgical medical apparatus, implant materials, extracorporeal circulation devices, and biological fluid detection. Finally, the outlook and challenges in terms of employing SBFRSs are also discussed. This review is expected to provide a comprehensive guidance for the preparation of SBFRSs with compatibility and long-term superhydrophobic stability that is closely related to clinical applications.

A Novel Netrin-1-Derived Peptide Enhances Protection against Neuronal Death and Mitigates of Intracerebral Hemorrhage in Mice.

It has been reported that Netrin-1 is involved in neuroprotection following injury to the central nervous system. However, the minimal functional domain of Netrin-1 which can preserve the neuroprotection but avoid the major side effects of Netrin remains elusive. Here, we investigated the neuroprotective effect of a peptide E1 derived from Netrin-1's EGF3 domain (residues 407-422). We found that it interacts with deleted colorectal carcinoma (DCC) to activate focal adhesion kinase phosphorylation exhibiting neuroprotection. The administration of the peptide E1 was able to improve functional recovery through reduced apoptosis in an experimental murine model of intracerebral hemorrhage (ICH). In summary, we reveal a functional sequence of Netrin-1 that is involved in the recovery process after ICH and identify a candidate peptide for the treatment of ICH.

DIP2A is involved in SOD-mediated antioxidative reactions in murine brain.

Autism spectrum disorders (ASDs) are highly associated with oxidative stress. We have recently shown that Disconnected-interacting protein homolog 2 A (DIP2A) functions in ASD pathophysiology by regulating cortactin acetylation for spine development and synaptic transmission. However, its role is not fully understood in the context of its abundant expression in mitochondria. In this paper, we found that DIP2A was involved in superoxide dismutase (SOD)-mediated antioxidative reactions. In mice, DIP2A knockout inhibited SOD activity and increased reactive oxygen species (ROS) levels in the cerebral cortex. In vitro gain-of-function experiments further confirmed the positive role of DIP2A in scavenging ROS upon oxidative stress. Moreover, DIP2A knockout caused irregular mitochondrial morphology in the cerebral cortex and impaired mitochondrial metabolism with an over consumption of lipids for energy supply. Taken together, these results revealed unrecognized functions of DIP2A in antioxidative protection, providing another possible explanation for DIP2A-mediated ASD pathophysiology.

Synergistic catalytic Fenton-like degradation of sulfanilamide by biosynthesized goethite-reduced graphene oxide composite.

A series of goethite (Gt)-graphene (rGO) composites (Gt-rGO) having different rGO contents (2%-10%) was biologically prepared under mild conditions with Acidovorax sp. BoFeN1 and exhibited comparable or even higher catalytic efficiencies upon sulfonamides degradation than most known chemically synthesized catalysts. Pseudo-first-order rate constant of sulfanilamide degradation (60 µM, 0.971 h-1) in the system mediated by Gt-rGO with the optimal rGO content of 6% was 6.7, 15.4 and 168.1 folds higher than those in the control rGO/H2O2, Gt/H2O2 and H2O2 systems, respectively. Excellent synergistic catalytic effects between Gt and rGO in Gt-rGO were identified in four continuous cycles. The Gt-rGO systems exhibited more efficient •OH generation, H2O2 decomposition and Fe(II) accumulation rates than the control Gt or rGO systems. Fast Fe(III)/Fe(II) cycling was obtained in the Gt-rGO systems, which might be due to the strong Fe-C coordination and the decrease of rGO aggregation and Gt particle sizes. Additionally, Gt particles in Gt-rGO exposed more defects as active sites for H2O2 activation. High-performance liquid chromatography-mass spectrometer analysis suggested that sulfanilamide was gradually degraded through hydroxylation, C-N cleavage and benzene ring opening. The results provided a new approach for the tailored design of eco-friendly, cost-effective and efficient iron (oxyhydr)oxides-graphene catalysts for contaminants elimination.

Goethite-humic acid coprecipitate mediated Fenton-like degradation of sulfanilamide: The role of coprecipitated humic acid in accelerating Fe(III)/Fe(II) cycle and degradation efficiency.

While extensive studies found that dissociative and iron mineral-adsorbed humic acid (HA) could either stimulate or inhibit Fenton-like processes, little was known about the influence of iron mineral-coprecipitated HA on Fenton-like reactions. Here, goethite and HA (Gt-HA) coprecipitates having different C:Fe molar ratios (C:Fe = 0.16-0.99) were biologically prepared, and for the first time, investigated for their abilities of H2O2 activation and catalytic degradation of sulfanilamide. For system containing Gt-HA with the optimal C:Fe ratio of 0.30, over 91.1% of sulfanilamide (10 mg/L) was removed in 2 h, which was 46.2% higher than that of the control Gt system. Additionally, H2O2 decomposition, •OH production, and organic carbon removal in Gt-HA systems were all more efficient than those in Gt system. Higher carbon moieties stability and lower micropore surface area of Gt-HA decreased the competition for •OH and H2O2, thus helped to improve degradation efficiency. Electrochemical analysis, quenching experiments, and Fe species detection showed that the coprecipitated HA could serve as electron shuttle and complex with Fe(III) mainly via carboxyl groups at octahedral sites to improve Fe(III)/Fe(II) transformation. This study improved our understanding of Fe(III)/Fe(II) cycling in Fe‒C coprecipitates and demonstrated the potential of developing Fe‒C coprecipitates as efficient catalysts in Fenton-like processes.

Nucleus Accumbens Tac1-Expressing Neurons Mediate Stress-Induced Anhedonia-like Behavior in Mice.

Major depressive disorder (MDD) presents with two primary symptoms: depressed mood and anhedonia, which suggests that distinct neuronal circuits may regulate MDD. However, the underlying circuits of these individual symptoms linked to depression remain elusive. Herein, we identify a discrete circuit of tachykinin precursor 1 (Tac1)-expressing neurons in the nucleus accumbens (NAc) lateral shell, which project to ventral pallidum and contribute to stress-induced anhedonia-like behavior. Selective inhibition and activation of Tac1NAc neurons bidirectionally modulate stress susceptibility, revealing that Tac1 neurons in the NAc are critical for regulating anhedonia-like behaviors. We find that a subpopulation of VP neurons receives inhibitory inputs from Tac1NAc neurons and exhibits decreased excitability in susceptible mice. Furthermore, the inhibition of the neurokinin 1 receptor promotes susceptibility to social stress. Overall, our study reveals a discrete circuit regulating anhedonia-like behavior in mice.

Myosin X Interaction with KIF13B, a Crucial Pathway for Netrin-1-Induced Axonal Development.

Myosin X (Myo X) transports cargos to the tips of filopodia for cell adhesion, migration, and neuronal axon guidance. Deleted in Colorectal Cancer (DCC) is one of the Myo X cargos that is essential for Netrin-1-regulated axon pathfinding. The function of Myo X in axon development in vivo and the underlying mechanisms remain elusive. Here, we provide evidence for the role of Myo X in Netrin-1-DCC-regulated axon development in developing mouse neocortex. The knockout (KO) or knockdown (KD) of Myo X in cortical neurons of embryonic mouse brain impairs axon initiation and contralateral branching/targeting. Similar axon deficits are detected in Netrin-1-KO or DCC-KD cortical neurons. Further proteomic analysis of Myo X binding proteins identifies KIF13B (a kinesin family motor protein). The Myo X interaction with KIF13B is induced by Netrin-1. Netrin-1 promotes anterograde transportation of Myo X into axons in a KIF13B-dependent manner. KIF13B-KD cortical neurons exhibit similar axon deficits. Together, these results reveal Myo X-KIF13B as a critical pathway for Netrin-1-promoted axon initiation and branching/targeting.SIGNIFICANCE STATEMENT Netrin-1 increases Myosin X (Myo X) interaction with KIF13B, and thus promotes axonal delivery of Myo X and axon initiation and contralateral branching in developing cerebral neurons, revealing unrecognized functions and mechanisms underlying Netrin-1 regulation of axon development.

Acceleration of goethite-catalyzed Fenton-like oxidation of ofloxacin by biochar.

While carbon materials have been well studied to stimulate the homogeneous Fenton-like processes, little was known about their impacts on iron mineral-catalyzed heterogeneous Fenton-like reactions. Here, it was found that biochar prepared at 300 °C or 600 °C (BC300 or BC600) greatly stimulated the degradation of ofloxacin (OFX) in a goethite (Gt)-mediated Fenton-like system. In 4 h, while only 38.4 % and 48.4 % OFX were removed in Gt/H2O2 and BC600/H2O2 systems, the removal efficiency reached over 94.0 % in Gt/BC600/H2O2 system. And the pseudo-first-order rate constant of Gt/H2O2, BC600/H2O2 and Gt/BC600/H2O2 systems were 0.12, 0.16 and 0.72 h-1, respectively, indicating the occurrence of synergistically catalytic degradation. •OH was identified as the major oxidant. Both the •OH yield and the H2O2 utilization efficiency of Gt/BC600/H2O2 system were higher than those of Gt/H2O2 and BC600/H2O2 systems. BC600 showed better stimulation effects than BC300. The persistent free radicals (PFRs) of BC could activate H2O2 and partly contribute to •OH production in the Gt/BC/H2O2 system. While BC could not directly reduce Fe(III) in Gt, it improved the cycling of Fe(III)/Fe(II) through complexing Fe(III) with its carboxyl group. Potential pathways were proposed for OFX degradation in the Gt/BC/H2O2 system.

Bactericidal and antifouling electrospun PVA nanofibers modified with a quaternary ammonium salt and zwitterionic sulfopropylbetaine.

Bacterial adhesion and colonization on material surfaces have attracted great attention due to their potential threat to human health. Combining bactericidal and antifouling functions has been confirmed as an optimal strategy to prevent microbial infection. In this work, biodegradable electrospun polyvinyl alcohol (PVA) nanofibers were chosen due to its high specific area and abundant reactive hydroxyl groups. A quaternary ammonium salt (IQAS) and zwitterionic sulfopropylbetaine (ISB), both containing isocyanate (NCO) groups, were chemically bonded to the PVA nanofiber surface via a coupling reaction between the OH groups of the PVA nanofibers and the NCO groups of IQAS or ISB. The results indicated that the antimicrobial rates of PVA nanofibers modified by IQAS (0.5%) reached 99.9% against both gram-positive Staphylococcus aureus (S. aureus, ATCC 6538) and gram-negative Escherichia coli (E. coli, ATCC 25922). Additionally, the live/dead staining and cytotoxicity test indicated that the dual functional IQAS/ISB/PVA nanofibers exhibited excellent bactericidal and antifouling activities with low cytotoxicity. This work may provide practical guidelines to fabricate bactericidal and antifouling materials for healthcare applications, including but not limited to wound dressings, textile, food packaging and air filtration.