Dendritic Development Research Articles

Navigating highly reversible Zn metal anodes via a multifunctional corrosion inhibitor-inspired electrolyte additive

Uncontrolled dendrites growth and irreversible side reactions on the Zn anode have greatly shorten the lifespan of aqueous zinc-ion batteries (ZIBs), thereby hindering their application as promising energy storage devices. Herein, inspired by the use of corrosion and scale inhibitors in metal industry, sodium gluconate (SG) is proposed as a multifunctional electrolyte additive to improve the reversible plating/stripping behavior on Zn metal anodes by simultaneously modulating Zn anode-electrolyte interface and the Zn deposition behaviors. Combining theoretical calculations and experimental characterizations, it shows that SG can protect the Zn anode against the corrosion side reactions and suppress the random growth of dendritic Zn by absorbing on the Zn anode surface to form an artificial interface layer. Concomitantly, the gluconate anion reshapes the solvation shell of Zn2+, influencing the desolvation process of Zn2+ and disrupting the formation of active water. Furthermore, Na+ originating from SG suppresses the dendritic Zn development in the light of electrostatic shielding mechanism. Benefiting from these synergetic effects of SG additive, Zn metal anodes achieve exceptional reversibility with prolonged running lifetime and increased coulombic efficiency and the Zn||V2O5 full cell demonstrates outstanding cycle stability. This strategy is scalable and low-cost, developing a promising approach to advance high-performance ZIBs.

In vitro bioprinted 3D model enhancing osteoblast-to-osteocyte differentiation

Abstract In vitro bone models are pivotal for understanding tissue behavior and cellular responses, particularly in unravelling certain pathologies' mechanisms and assessing the impact of new therapeutic interventions. A desirable in vitro bone model should incorporate primary human cells within a 3D environment that mimics the mechanical properties characteristics of osteoid and faithfully replicate all stages of osteogenic differentiation from osteoblasts to osteocytes. However, to date, no bio-printed model using primary osteoblasts has demonstrated the expression of osteocytic protein markers. This study aimed to develop bio-printed in vitro model that accurately captures the differentiation process of human primary osteoblasts into osteocytes. Given the considerable impact of hydrogel stiffness and relaxation behavior on osteoblast activity, we employed three distinct cross-linking solutions to fabricate hydrogels. These hydrogels were designed to exhibit either similar elastic behavior with different elastic moduli, or similar elastic moduli with varying relaxation behavior. These hydrogels, composed of gelatin (5% w/v), alginate (1%w/v) and fibrinogen (2%w/v), were designed to be compatible with micro-extrusion bioprinting and proliferative. The modulation of their biomechanical properties, including stiffness and viscoelastic behavior, was achieved by applying various concentrations of cross-linkers targeting both gelatin covalent bonding (transglutaminase) and alginate chains’ ionic cross-linking (calcium). Among the conditions tested, the hydrogel with a low elastic modulus of 8 kPa and a viscoelastic behavior over time exhibited promising outcomes regarding osteoblast-to-osteocyte differentiation. The cessation of cell proliferation coincided with a significant increase in alkaline phosphatase (ALP) activity, the development of dendrites, and the expression of the osteocyte marker PHEX. Within this hydrogel, cells actively influenced their environment, as evidenced by hydrogel contraction and the secretion of collagen I. This bio-printed model, demonstrating primary human osteoblasts expressing an osteocyte-specific protein, marks a significant achievement. We envision its substantial utility in advancing research on bone pathologies, including osteoporosis and bone tumors.

Interactions of Polychlorinated Biphenyls and Their Metabolites with the Brain and Liver Transcriptome of Female Mice.

Exposure to polychlorinated biphenyls (PCBs) is linked to neurotoxic effects. This study aims to close knowledge gaps regarding the specific modes of action of PCBs in female C57BL/6J mice (>6 weeks) orally exposed for 7 weeks to a human-relevant PCB mixture (MARBLES mix) at 0, 0.1, 1, and 6 mg/kg body weight/day. PCB and hydroxylated PCB (OH-PCBs) levels were quantified in the brain, liver, and serum; RNA sequencing was performed in the striatum, prefrontal cortex, and liver, and metabolomic analyses were performed in the striatum. Profiles of PCBs but not their hydroxylated metabolites were similar in all tissues. In the prefrontal cortex, PCB exposure activated the oxidative phosphorylation respiration pathways, while suppressing the axon guidance pathway. PCB exposure significantly changed the expression of genes associated with neurodevelopmental and neurodegenerative diseases in the striatum, impacting pathways like growth hormone synthesis and dendrite development. PCBs did not affect the striatal metabolome. In contrast to the liver, which showed activation of metabolic processes following PCB exposure and the induction of cytochrome P450 enzymes, the expression of xenobiotic processing genes was not altered by PCB exposure in either brain region. Network analysis revealed complex interactions between individual PCBs (e.g., PCB28 [2,4,4'-trichlorobiphenyl]) and their hydroxylated metabolites and specific differentially expressed genes (DEGs), underscoring the need to characterize the association between specific PCBs and DEGs. These findings enhance the understanding of PCB neurotoxic mechanisms and their potential implications for human health.

Sex-biased human thymic architecture guides Tcell development through spatially defined niches.

Within the thymus, regulation of the cellular crosstalk directing Tcell development depends on spatial interactions within specialized niches. To create a spatially defined map of tissue niches guiding humanpostnatal Tcell development, we employed the multidimensional imaging platform co-detection by indexing (CODEX) as well as cellular indexing of transcriptomes and epitopes sequencing (CITE-seq) and assay for transposase accessible chromatin sequencing (ATAC-seq). We generated age-matched 4- to 5-month-old human postnatal thymus datasets for male and female donors, identifying significant sex differences in both Tcell and thymus biology. We demonstrate a possible role for JAG ligands in directing thymic-like dendritic cell development, identify important functions of a population ofextracellular matrix (ECM)- fibroblasts, and characterize the medullary niches surrounding Hassall's corpuscles. Together, these data represent an age-matched spatial multiomic resource to investigate how sex-based differences in thymus regulation and Tcell development arise, providing an essential resource to understand the mechanisms underlying immune function and dysfunction in males and females.

Reversal of neurodevelopmental impairment and cognitive enhancement by pharmacological intervention with the polyphenol polydatin in a Down syndrome model

Intellectual disability (ID) is the unavoidable hallmark of Down syndrome (DS), a genetic condition due to triplication of chromosome 21. ID in DS is largely attributable to neurogenesis and dendritogenesis alterations taking place in the prenatal/neonatal period, the most critical time window for brain development. There are currently no treatments for ID in DS. Considering the timeline of brain development, treatment aimed at improving the neurological phenotypes of DS should be initiated as early as possible and use safe agents. The goal of this study was to establish whether it is possible to improve DS-linked neurodevelopmental defects through early treatment with polydatin, a natural polyphenol. We used the Ts65Dn mouse model of DS and focused on the hippocampus, a brain region fundamental for long-term memory. We found that in Ts65Dn mice of both sexes treated with polydatin from postnatal (P) day 3 to P15 there was full restoration of neurogenesis, neuron number, and dendritic development. These effects were accompanied by normalization of Cyclin D1 and DSCAM levels, which may account for the rescue of neurogenesis and dendritogenesis, respectively. Importantly, in Ts65Dn mice treated with polydatin from P3 to adolescence (∼P50) there was full restoration of hippocampus-dependent memory, indicating a pro-cognitive outcome of treatment. No adverse effects were observed on the body and brain weight. The efficacy and safety of polydatin in a model of DS prospect the possibility of its use during early life stages for amelioration of DS-linked neurodevelopmental alterations.

Whole genome methylation sequencing in blood from persons with mild cognitive impairment and dementia due to Alzheimer's disease identifies cognitive status.

Whole genome methylation sequencing (WGMS) in blood identifies differential DNA methylation in persons with late-onset dementia due to Alzheimer's disease (AD) but has not been tested in persons with mild cognitive impairment (MCI). We used WGMS to compare DNA methylation levels at 25,244,219 CpG loci in 382 blood samples from 99 persons with MCI, 109 with AD, and 174 who are cognitively unimpaired (CU). WGMS identified 9,756 differentially methylated positions (DMPs) in persons with MCI, including 1,743 differentially methylated genes encoding proteins in biological pathways related to synapse organization, dendrite development, and ion transport. 447 DMPs exhibit progressively increasing or decreasing DNA methylation levels between CU, MCI, and AD that correspond to cognitive status. WGMS identifies DMPs in known and newly detected genes in blood from persons with MCI and AD that support blood DNA methylation levels as candidate biomarkers of cognitive status.

Dendritic morphological development of traumatic brain injury-induced new neurons in the dentate gyrus is important for post-injury cognitive recovery and is regulated by Notch1

Traumatic brain injury (TBI) is a prevalent problem with survivors suffering from chronic cognitive impairments. Following TBI there is a series of neuropathological changes including neurogenesis. It is well established that neurogenesis in the dentate gyrus (DG) of the hippocampus is important for hippocampal dependent learning and memory functions. Following TBI, injury-enhanced hippocampal neurogenesis is believed to contribute to post-injury cognitive recovery. Behavioral function is connected to synaptic plasticity and neuronal dendritic branching is critical for successful synapse formation. To ascertain the functional contribution of injury-induced DG new neurons in post-TBI cognitive recovery, it is necessary to study their dendritic morphological development and the molecular mechanisms controlling this process. Utilizing transgenic mice with tamoxifen-induced GFP expression and Notch1 knock-out in nestin+ neural stem cells, this study examined dendritic morphology, the role of Notch1 in regulating dendritic complexity of injury-induced DG new neurons, and their association to post-TBI cognitive recovery. We found that at 8 weeks after a moderate TBI, injury-induced DG new neurons in the injured control mice displayed a similar dendritic morphology as the cells in non-injured mice accompanied with cognitive recovery. In comparison, in Notch1 conditional knock-out mice, DG new neurons in the injured mice had a significant reduction in dendritic morphological development including dendritic arbors, volume span, and number of branches in comparison to the cells in non-injured mice concomitant with persistent cognitive dysfunction. The results of this study confirm the importance of post-injury generated new neurons in cognitive recovery following TBI and the role of Notch1 in regulating their maturation process.

GDNF facilitates cognitive function recovery following neonatal surgical-induced learning and memory impairment via activation of the RET pathway and modulation of downstream effectors PKMζ and Kalirin in rats

ObjectiveThe aim of this study is to elucidate the underlying mechanism through which glial cell line-derived neurotrophic factor (GDNF) improves cognitive deficits in adults resulting from neonatal surgical interventions. MethodsNewborn Sprague–Dawley rats, regardless of gender, were randomly allocated into seven groups on postnatal day 7 as follows (n=15): (1) Control group (not subjected to anesthesia, surgery, or any pharmaceutical interventions); (2) GDNF group (received intracerebroventricular injection of GDNF); (3) Surgery group (underwent right carotid artery exposure under anesthesia with 3 % sevoflurane); (4) Surgery plus GDNF group; (5) Surgery plus GDNF and type II JAK inhibitor NVP-BBT594 (BBT594) group (administered intraperitoneal injection of BBT594); (6) BBT group; and (7) Surgery plus BBT group. Starting from postnatal day 33, all rats underwent Barnes maze and fear conditioning tests, followed by decapitation under sevoflurane anesthesia for subsequent analyses. The left hemibrains underwent Golgi staining, while the right hemibrains were used for hippocampal protein extraction to assess Protein kinase Mζ (PKMζ) and Kalirin expression through western blotting. ResultsGDNF demonstrated a mitigating effect on spatial learning and memory impairment, as well as context-related fear memory impairment, reductions in dendritic total lengths, and spinal density within the hippocampus induced by surgical intervention. Notably, all of these ameliorative effects of GDNF were reversed upon administration of the RET inhibitor BBT594. Additionally, GDNF alleviated the downregulation of protein expression of PKMζ and Kalirin in the hippocampus of rats subjected to surgery, subsequently reversed by BBT594. ConclusionThe effective impact of GDNF on learning and memory impairment caused by surgical intervention appears to be mediated through the RET pathway. Moreover, GDNF may exert its influence by upregulating the expression of PKMζ and Kalirin, consequently enhancing the development of dendrites and dendritic spines.

Revealing the origin of dendritic deposition regulated solid electrolyte interphase enabled by cation receptor in Zn-ion batteries

Aqueous Zn-metal batteries open up promising prospects for large-scale energy storage due to the advantages of ample components, cost-effectiveness, and safety features. However, the notorious dendritic development and unavoidable hydrogen evolution reaction of Zn have grown to be one of the main barriers inhibiting its further commercialization. Despite substantial studies, the mechanism of nucleation and deposition of Zn2+ ions on zinc layer surfaces remains elusive. Here, inspired by additive, the SnCl2 additive is introduced to initiate the in-situ formation of the ZnS-rich solid electrolyte interphase (SEI) layer on the Zn anode, which creates a protective “shielding effect” that hinders direct contact between water and the zinc surface, suppressing the random growth of Zn dendrites in the whole process. The mechanism of Zn nucleation was revealed by employing high-resolution transmission electron microscopy, consecutive electron diffraction coupled with finite element method (FEM) simulations. Moreover, spontaneously formed 3D architecture consists of micorsized hemispherical Sn particles not only suppresses the Zn dendrite growth by reducing the local current density, but also enables the lateral growth of Zn crystals by increasing the average surface energy. Such an electrolyte enables a long cycle life of over 2000 h in the Zn||Zn cell. Importantly, the assembled Zn||MnVO full cells with SnCl2 electrolyte also delivers substantial capacity (171.1mA h g−1 at 1 A h g−1), presenting a promising application. These discoveries not only deepen the comprehension of fundamental scientific knowledge regarding the microscopic reaction mechanism of the Zn anode but also offer significant insights for optimizing performance.

Inhibiting Shuttle Effect and Dendrite Growth in Sodium-Sulfur Batteries Enabled by Applying External Acoustic Field.

The room-temperature sodium-sulfur (RT Na-S) battery is a promising alternative to traditional lithium-ion batteries owing to its abundant material availability and high specific energy density. However, the sodium polysulfide shuttle effect and dendritic growth pose significant challenges to their practical applications. In this study, we apply diverse disciplinary backgrounds to introduce a novel method to stimulate polarized BaTiO3 (BTO) nanoparticles on the separator. This approach generates more charges due to the piezoelectric effect under stronger driving forces produced by applying a controllable acoustic field at the outer edge of the cell. The acoustically stimulated BTO attracts more polysulfides, thus reducing the shuttling effect from the cathode to the anode and ultimately enhancing the battery performance. Meanwhile, the acoustic waves create additional streaming flows, improving the uniformity of the sodium ion dispersion, enhancing the sodium ion transport and reducing the possibility of sodium dendrite development. We believe that this work offers a new strategy for the development of high-performance Na-S batteries.

Beyond Glycolysis: Aldolase A Is a Novel Effector in Reelin-Mediated Dendritic Development.

Reelin, a secreted glycoprotein, plays a crucial role in guiding neocortical neuronal migration, dendritic outgrowth and arborization, and synaptic plasticity in the adult brain. Reelin primarily operates through the canonical lipoprotein receptors apolipoprotein E receptor 2 (Apoer2) and very low-density lipoprotein receptor (Vldlr). Reelin also engages with noncanonical receptors and unidentified coreceptors; however, the effects of which are less understood. Using high-throughput tandem mass tag (TMT) liquid chromatography tandem mass spectrometry (LC-MS/MS)-based proteomics and gene set enrichment analysis (GSEA), we identified both shared and unique intracellular pathways activated by Reelin through its canonical and noncanonical signaling in primary murine neurons of either sex during dendritic growth and arborization. We observed pathway cross talk related to regulation of cytoskeleton, neuron projection development, protein transport, and actin filament-based process. We also found enriched gene sets exclusively by the noncanonical Reelin pathway including protein translation, mRNA metabolic process, and ribonucleoprotein complex biogenesis suggesting Reelin fine-tunes neuronal structure through distinct signaling pathways. A key discovery is the identification of aldolase A, a glycolytic enzyme and actin-binding protein, as a novel effector of Reelin signaling. Reelin induced de novo translation and mobilization of aldolase A from the actin cytoskeleton. We demonstrated that aldolase A is necessary for Reelin-mediated dendrite growth and arborization in primary murine neurons and mouse brain cortical neurons. Interestingly, the function of aldolase A in dendrite development is independent of its known role in glycolysis. Altogether, our findings provide new insights into the Reelin-dependent signaling pathways and effector proteins that are crucial for dendritic development.

Influence of Phthalic Acid on the Process of Dendrite Development in Low-Density Polyethylene During Electrical Breakdown

The presented work presents the results of a study on the effect of small amounts of phthalic acid additives on dendrite formation in low-density polyethene (LDPE). Based on the results obtained, it is shown that the dendrite resistance of LDPE, as expected, increases with the introduction of 0.05 wt% phthalic acid. The established increase in dendrite resistance of LDPE with the introduction of phthalic acid can primarily be explained based on a decrease in inhomogeneities in the form of air pores as a result of accelerated structure formation and the emergence of a more homogeneous supramolecular structure. It was revealed that an increase in dendrite resistance correlates with an improvement in the dielectric characteristics of the composition. The influence of mechanical load on the development of dendrites in polymer dielectrics has been studied. As a result of studying the growth of dendrites in LDPE samples and its optimal composition subjected to unilateral stretching, it was found that under the influence of mechanical tensile stresses, the shape of the surface delimiting tree-like shoots changes, this surface is flattened in the direction of stretching. It has been shown that the rate of dendrite growth increases as mechanical tensile forces increase.

Neuroscience: The dynamic development of dendrites

Protocadherins are cell-surface proteins that endow developing neurons with the ability to distinguish self-contacts from non-self. This recognition is critical for dendrite patterning and neuronal function. New research demonstrates the cellular basis for dendrite self-avoidance following protocadherin-mediated self-recognition.

The impact of dexmedetomidine on ketamine-induced neurotoxicity and cognitive impairment in young mice.

The potential neuroprotective effects of dexmedetomidine against ketamine-induced neurotoxicity remain inconclusive. This study aims to investigate the influence of dexmedetomidine on ketamine-induced neuronal apoptosis and neurodevelopmental toxicity. In vitro experiments employed concentrations of 0.1uM for dexmedetomidine and 50 uM for ketamine individually as well as their combination. Changes in apoptotic proteins and dendritic development in neurons were assessed after a 6-h exposure to the drugs with evaluations conducted 24hs' post-treatment. In vivo experiments entailed intraperitoneal administration starting from postnatal Day 7 (P7) continuously for 3days (P7-P9) using dosages of 100 mg/kg for ketamine and 1mg/kg for dexmedetomidine alone or combined. Learning, memory and motor coordination abilities were evaluated via rotary rod tests and shuttle box experiments at P30 and P60, respectively. Dexmedetomidine effectively mitigated ketamine-induced apoptosis in hippocampal neurons but did not alleviate associated dendritic developmental abnormalities. Although causing reduced motor coordination in mice, no improvement was observed with regard to this effect or reaction speed when treated with dexmedetomidine alongside ketamine. This study demonstrates that while dexmedetomidine can mitigate ketamine-induced neuronal apoptosis, it has limited impact on its associated neurodevelopmental toxicities.

Heterozygous missense CSF1R variants hamper in vitro CD34+-derived dendritic cell generation but not in vivo dendritic cell development

Colony stimulating factor 1 receptor (CSF1R) is an essential receptor for both colony stimulating factor 1 (CSF1) and interleukin (IL) 34 signaling expressed on monocyte precursors and myeloid cells, including monocytes, dendritic cells (DC), and microglia. In humans, dominant heterozygous pathogenic variants in CSF1R cause a neurological condition known as CSF1R-related disorder (CSF1R-RD), typically with late onset, previously referred to as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). CSF1R-RD is characterized by microglia reduction and altered monocyte function; however, the impact of pathogenic CSF1R variants on the human DC lineage remains largely unknown.We previously reported that cord blood CD34+ stem cell-derived DCs generated in vitro originate specifically from CSF1R expressing precursors. In this study, we examined the DC lineage of four unrelated patients with late-onset CSF1R-RD who carried heterozygous missense CSF1R variants (c.2330G>A, c.2375C>A, c.2329C>T, and c.2381T>C) affecting different amino acids in the protein tyrosine kinase domain of CSF1R. CD34+ stem cells and CD14+ monocytes were isolated from peripheral blood and subjected to an in vitro culture protocol to differentiate towards conventional DCs and monocyte-derived DCs, respectively. Flow cytometric analysis revealed that monocytes from patients with late-onset CSF1R-RD were still able to differentiate into monocyte-derived DCs in vitro, whereas the ability of CD34+ stem cells to differentiate into conventional DCs was impaired. Strikingly, the peripheral blood of patients contained all naturally occurring DC subsets. We conclude that the in vitro abrogation of DC-development in patients with heterozygous pathogenic missense CSF1R variants does not translate to an impairment in DC development in vivo and speculate that CSF1R signalling in vivo is compensated, which needs further study.

Astrocyte extracellular matrix modulates neuronal dendritic development.

Major developmental events occurring in the hippocampus during the third trimester of human gestation and neonatally in altricial rodents include rapid and synchronized dendritic arborization and astrocyte proliferation and maturation. We tested the hypothesis that signals sent by developing astrocytes to developing neurons modulate dendritic development in vivo. We altered neuronal development by neonatal (third trimester-equivalent) ethanol exposure in mice; this treatment increased dendritic arborization in hippocampal pyramidal neurons. We next assessed concurrent changes in the mouse astrocyte translatome by translating ribosomal affinity purification (TRAP)-seq. We followed up on ethanol-inhibition of astrocyte Chpf2 and Chsy1 gene translation because these genes encode for biosynthetic enzymes of chondroitin sulfate glycosaminoglycan (CS-GAG) chains (extracellular matrix components that inhibit neuronal development and plasticity) and have not been explored before for their roles in dendritic arborization. We report that Chpf2 and Chsy1 are enriched in astrocytes and their translation is inhibited by ethanol, which also reduces the levels of CS-GAGs measured by Liquid Chromatography/Mass Spectrometry. Finally, astrocyte-conditioned medium derived from Chfp2-silenced astrocytes increased neurite branching of hippocampal neurons in vitro. These results demonstrate that CS-GAG biosynthetic enzymes in astrocytes regulates dendritic arborization in developing neurons.

Development of Aluminum Alloys 6061(AA6061) Silicon Carbide (SiC)-Graphite (GR) and Hybrid Composite for Automotive Applications

The microstructure and mechanical properties of composite materials made of Silicon carbide (SiC) and Graphite (GR) reinforcement, known as Aluminum Alloy 6061(AA6061) Matrix were developed. Using the stir casting method, the hybrid composites were prepared with 6 weight percent of the reinforcements in the ratio of 0:1,1:3,1:1,3:1,and 1:0. It was determined how the reinforcement particles affected the microstructures and mechanical characteristics of these materials. The microstructure displays a uniformly distributed fine particles of α-Al grains and Mg2Si phase with in the matrix alloy. The microstructure amply demonstrates the presence of the reinforcing particles (SiC and GR) and dendritic development was noted. There are very few indications of particles clusters, and the particles are very dispersed throughout the matrix. Sample A2 (AA6061 25% SiC/ 75% GR) had the highest recorded hardness value of 123.34 HRB4.8,9.33, while the base alloy had the lowest value of 70.36 HRB when compared to the base alloy, the developed hybrid composites showed improved tensile strength. In contrast to the base alloy, which displayed a strength of 115.67N/mm2, Sample A3 demonstrated a maximum strength of 143.88 N/mm2 as compared to the base alloy which showed strength of 115.67 N/mm2. The hard reinforcement particles sharp edges serve as a nucleation site, which is why the strength of samples A4 and A5 decreased when SiC reinforcement is added, the materials extension decreases when the developed hybrid composite materials with samples were compared with the base alloy. In comparison to the created hybrid composite materials, the base alloy displayed a maximum extension of 2.4mm, with sample A5 showing the lowest extension value of 1.23mm. Sample A2 displayed the highest structures rate of 0.060, while sample A5 displayed the lowest strain rate of 0.031. The impact strength values increases from 2.76 (Base alloy) to 4.77j (Sample A5) with the addition of the reinforcement particles. The obtained mechanical properties indicate that the reinforced alloy performed favorably well but not significantly better than the ones in the literature.

Intravesical Bacille Calmette-Guerin (BCG) Vaccine Affects Cognition.

The Montreal Cognitive Assessment (MoCA) is a valuable assessment of the patient's awareness of time and place. We show that bacille Calmette-Guerin (BCG) significantly affects MoCA testing when administered by the intravesical route. MoCA scores were lower with increasing age and higher in more formally educated individuals. Patients receiving BCG tended to maintain their MoCA scores, whereas almost half the control cases tended to show reduced scores. This benefit is supported by reduced pre-amyloid biomarkers in BCG-injected healthy volunteers and a favorable effect on neuronal dendritic development in animal models. Our results suggest that BCG has a beneficial impact on the cognitive status of older individuals.

EphA4 Induces the Phosphorylation of an Intracellular Adaptor Protein Dab1 via Src Family Kinases.

Dab1 is an intracellular adaptor protein essential for brain formation during development. Tyrosine phosphorylation in Dab1 plays important roles in neuronal migration, dendrite development, and synapse formation by affecting several downstream pathways. Reelin is the best-known extracellular protein that induces Dab1 phosphorylation. However, whether other upstream molecule(s) contribute to Dab1 phosphorylation remains largely unknown. Here, we found that EphA4, a member of the Eph family of receptor-type tyrosine kinases, induced Dab1 phosphorylation when co-expressed in cultured cells. Tyrosine residues phosphorylated by EphA4 were the same as those phosphorylated by Reelin in neurons. The autophosphorylation of EphA4 was necessary for Dab1 phosphorylation. We also found that EphA4-induced Dab1 phosphorylation was mediated by the activation of the Src family tyrosine kinases. Interestingly, Dab1 phosphorylation was not observed when EphA4 was activated by ephrin-A5 in cultured cortical neurons, suggesting that Dab1 is localized in a different compartment in them. EphA4-induced Dab1 phosphorylation may occur under limited and/or pathological conditions in the brain.

A functional MXene/cellulose nanofibers separator for high-performance dendrite-free zinc anode under harsh conditions

Aqueous zinc-ion batteries (AZIBs) show great potential for mass energy storage because of their intrinsic plentifulness and security. Nevertheless, the development of zinc dendrites is still a major challenge for the practical industrialisation of AZIB, especially under the demanding conditions of elevated current density and high temperatures. To combat this situation, we developed an ultrathin separator composed of cellulose nanofibers and MXene (noted as CM-15 separator) with a thickness of only 27 μm. The strong zincophilic characteristics and outstanding electrical/thermal conductivity of MXene make them suitable for use as an ion pump to expedite the transmission of Zn2+ through the electrolyte, which significantly increases the zinc ion transfer number and results in the deposition of homogeneous Zn nuclei and dendritic-free Zn. As a result, the symmetric battery equipped with a CM-15 separator enabled excellent dendrite free plating/stripping behavior, high coulomb efficiency (97.7 %) and cumulative plated capacity of 4.8 Ah/cm2 at 80 mA/cm2 at room temperature and as well as sustained operation for at least 300 h under 60 °C. More impressively, the Zn-MnO2/CNT battery equipped with a CM-15 separator achieved 72.6 % capacity retention after 10,000 cycles at 2 A/g under room temperature and 92.1 % capacity retention after 200 cycles at 1 A/g under 60 °C. Our research confirms the potential of functional separators to promote the application of AZIBs, especially under demanding conditions.