Enabling heterogeneous catalysis to achieve carbon neutrality: Directional catalytic conversion of CO_(2) into carboxylic acids

The increase in anthropogenic carbon dioxide(CO_(2))emissions has exacerbated the deterioration of the global environment,which should be controlled to achieve carbon neutrality.Central to the core goal of achieving carbon neutrality is the utilization of CO_(2) under economic and sustainable conditions.Recently,the strong need for carbon neutrality has led to a proliferation of studies on the direct conversion of CO_(2) into carboxylic acids,which can effectively alleviate CO_(2) emissions and create high-value chemicals.The purpose of this review is to present the application prospects of carboxylic acids and the basic principles of CO_(2) conversion into carboxylic acids through photo-,electric-,and thermal catalysis.Special attention is focused on the regulation strategy of the activity of abundant catalysts at the molecular level,inspiring the preparation of high-performance catalysts.In addition,theoretical calculations,advanced technologies,and numerous typical examples are introduced to elaborate on the corresponding process and influencing factors of catalytic activity.Finally,challenges and prospects are provided for the future development of this field.It is hoped that this review will contribute to a deeper understanding of the conversion of CO_(2) into carboxylic acids and inspire more innovative breakthroughs.

2D multifunctional devices:from material preparation to device fabrication and neuromorphic applications

Neuromorphic computing systems,which mimic the operation of neurons and synapses in the human brain,are seen as an appealing next-generation computing method due to their strong and efficient computing abilities.Two-dimensional (2D) materials with dangling bond-free surfaces and atomic-level thicknesses have emerged as promising candidates for neuromorphic computing hardware.As a result,2D neuromorphic devices may provide an ideal platform for developing multifunctional neuromorphic applications.Here,we review the recent neuromorphic devices based on 2D material and their multifunctional applications.The synthesis and next micro–nano fabrication methods of 2D materials and their heterostructures are first introduced.The recent advances of neuromorphic 2D devices are discussed in detail using different operating principles.More importantly,we present a review of emerging multifunctional neuromorphic applications,including neuromorphic visual,auditory,tactile,and nociceptive systems based on 2D devices.In the end,we discuss the problems and methods for 2D neuromorphic device developments in the future.This paper will give insights into designing 2D neuromorphic devices and applying them to the future neuromorphic systems.

Neutral and metallic vs.charged and semiconducting surface layer in acceptor doped CeO_(2)

The monomolecular surface layer of acceptor doped CeO_(2) may become neutral and metallic or charged and semiconducting.This is revealed in the theoretical analysis of the oxygen pressure dependence of the surface defects concentration in acceptor doped ceria with two different dopant types and operated under different oxygen pressures.Recently published experimental data for highly reduced Sm0.2Ce0.8O1.9-x(SDC)containing a fixed valence dopant Sm3+are very different from those published for Pr0.1Ce0.9O_(2)-x(PCO) with the variable valence dopant Pr4+/Pr3+being reduced under milder conditions.The theoretical analysis of these experimental results fits very well the experimental results of SDC and PCO.It leads to the following predictions:the highly reduced surface of SDC is metallic and neutral,the metallic surface electron density of state is gs=0.9×10^(38)J-1·m^(-2)(1.4×1015eV^(-1)·cm^(-2)),the electron effective mass is meff,s=3.3me,and the phase diagram of the reduced surface has theα(fcc)structure as in the bulk.In PCO a double layer is predicted to be formed between the surface and the bulk with the surface being negatively charged and semiconducting.The surface of PCO maintains high Pr^(3+) defect concentration as well as relative high oxygen vacancy concentration at oxygen pressures higher than in the bulk.The reasons for the difference between a metallic and semiconducting surface layer of acceptor doped CeO_(2) are reviewed,as well as the key theoretical considerations applied in coping with this problem.For that we make use of the experimental data and theoretical analysis available for acceptor doped ceria.

Neurogenic potential of NG2 in neurotrauma:a systematic review

Regenerative approaches towards neuronal loss following traumatic brain or spinal cord injury have long been considered a dogma in neuroscience and remain a cutting-edge area of research.This is reflected in a large disparity between the number of studies investigating primary and secondary injury as therapeutic to rgets in spinal co rd and traumatic brain injuries.Significant advances in biotechnology may have the potential to reshape the current state-of-the-art and bring focus to primary injury neurotrauma research.Recent studies using neural-glial factor/antigen 2(NG2)cells indicate that they may differentiate into neurons even in the developed brain.As these cells show great potential to play a regenerative role,studies have been conducted to test various manipulations in neurotrauma models aimed at eliciting a neurogenic response from them.In the present study,we systematically reviewed the experimental protocols and findings described in the scientific literature,which were peer-reviewed original research articles(1)describing preclinical experimental studies,(2)investigating NG2 cells,(3)associated with neurogenesis and neurotrauma,and(4)in vitro and/or in vivo,available in PubMed/MEDLINE,Web of Science or SCOPUS,from 1998 to 2022.Here,we have reviewed a total of 1504 papers,and summarized findings that ultimately suggest that NG2 cells possess an inducible neurogenic potential in animal models and in vitro.We also discriminate findings of NG2 neurogenesis promoted by different pharmacological and genetic approaches over functional and biochemical outcomes of traumatic brain injury and spinal co rd injury models,and provide mounting evidence for the potential benefits of manipulated NG2 cell ex vivo transplantation in primary injury treatment.These findings indicate the feasibility of NG2 cell neurogenesis strategies and add new players in the development of therapeutic alternatives for neurotrauma.

Effects of Curcumin on Neuroinflammation and the Nrf2/HO-1 Pathway in Rat Brains Following Gas Explosion

Gas explosions,a major occupational hazard in China’s coal industry,endanger the lives and health of miners.These explosions cause a specific type of traumatic brain injury with complex mechanisms,leading to disability and death.A study by Zhao et al.using magnetic resonance imaging on 49 gas explosion survivors revealed significant damage to brain regions like the hippocampus and cerebral cortex.

Neutrophil ALDH2 is a new therapeutic target for the effective treatment of sepsis-induced ARDS

Acetaldehyde dehydrogenase 2(ALDH2)mutations are commonly found in a subgroup of the Asian population.However,the role of ALDH2 in septic acute respiratory distress syndrome(ARDS)remains unknown.Here,we showed that human subjects carrying the ALDH2rs671 mutation were highly susceptible to developing septic ARDS.Intriguingly,ALDH2rs671-ARDS patients showed higher levels of blood cell-free DNA(cfDNA)and myeloperoxidase(MPO)-DNA than ALDH2WT-ARDS patients.To investigate the mechanisms underlying ALDH2 deficiency in the development of septic ARDS,we utilized Aldh2 gene knockout mice and Aldh2rs671 gene knock-in mice.In clinically relevant mouse sepsis models,Aldh2-/-mice and Aldh2rs671 mice exhibited pulmonary and circulating NETosis,a specific process that releases neutrophil extracellular traps(NETs)from neutrophils.Furthermore,we discovered that NETosis strongly promoted endothelial destruction,accelerated vascular leakage,and exacerbated septic ARDS.At the molecular level,ALDH2 increased K48-linked polyubiquitination and degradation of peptidylarginine deiminase 4(PAD4)to inhibit NETosis,which was achieved by promoting PAD4 binding to the E3 ubiquitin ligase CHIP.Pharmacological administration of the ALDH2-specific activator Alda-1 substantially alleviated septic ARDS by inhibiting NETosis.Together,our data reveal a novel ALDH2-based protective mechanism against septic ARDS,and the activation of ALDH2 may be an effective treatment strategy for sepsis.

CO_(2) electrolysis to formic acid for carbon neutralization

To avoid carbonate precipitation for CO_(2) electrolysis,developing CO_(2) conversion in an acid electrolyte is viewed as an ultimately challenging technology.In Nature,Xia et al.recently explored a proton-exchange membrane system for reducing CO_(2) to formic acid with a Pb±Pb SO_(4) composite catalyst derived from waste lead-acid batteries based on the lattice carbon activation mechanism.Up to 93%Faradaic efficiency was realized when formic acid was produced by this technology.

SARS-CoV2 Nsp3 protein triggers cell death and exacerbates amyloid β42-mediated neurodegeneration

Infection caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2)virus,responsible for the coronavirus disease 2019(COVID-19)pandemic,induces symptoms including increased inflammatory response,severe acute respiratory syndrome(SARS),cognitive dysfunction like brain fog,and cardiovascular defects.Long-term effects of SARS-CoV2 COVID-19 syndrome referred to as post-COVID-19 syndrome on age-related progressive neurodegenerative disorders such as Alzheimer's disease remain understudied.Using the targeted misexpression of individual SARS-CoV2 proteins in the retinal neurons of the Drosophila melanogaster eye,we found that misexpression of nonstructural protein 3(Nsp3),a papain-like protease,ablates the eye and generates dark necrotic spots.Targeted misexpression of Nsp3 in the eye triggers reactive oxygen species production and leads to apoptosis as shown by cell death reporters,terminal deoxynucleotidyl transferase(TdT)dUTP Nick-end labeling(TUNEL)assay,and dihydroethidium staining.Furthermore,Nsp3 misexpression activates both apoptosis and autophagy mechanism(s)to regulate tissue homeostasis.Transient expression of SARS-CoV2 Nsp3 in murine neuroblastoma,Neuro-2a cells,significantly reduced the metabolic activity of these cells and triggers cell death.Misexpression of SARS-CoV2 Nsp3 in an Alzheimer's disease transgenic fly eye model(glass multiple repeats[GMR]>amyloidβ42)further enhances the neurodegenerative rough eye phenotype due to increased cell death.These findings suggest that SARS-CoV2 utilizes Nsp3 protein to potentiate cell death response in a neurodegenerative disease background that has high pre-existing levels of neuroinflammation and cell death.

Neural Wiskott-Aldrich syndrome protein(N-WASP)promotes distant metastasis in pancreatic ductal adenocarcinoma via activation of LOXL2

Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been established.In this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of PDAC.We found that N-WASP is markedly expressed in clinical patients with PDAC.Clinical analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile studies.Knockdown of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and EMT.We also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were modulated.Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer.These results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer metastasis.These findings may aid in the development of therapeutic strategies against pancreatic cancer.

Targeting neuronal PAS domain protein 2 and KN motif/ankyrin repeat domains 1:Advances in type 2 diabetes therapy

This editorial summarizes the latest literature on the roles of neuronal PAS domain protein 2 and KN motif/ankyrin repeat domain 1 in type 2 diabetes(T2D).We highlight their involvement inβ-cell dysfunction,explore their potential as therapeutic targets,and discuss the implications for new treatment strategies.We offer valuable insights into relevant gene regulation and cellular mechanisms relevant for the targeted management of T2D.

Evaluating the role of interleukin-2 and interleukin-12 in pediatric patients with concurrent Mycoplasma pneumoniae and Epstein-Barr virus infections

BACKGROUND Mycoplasma pneumoniae(MP)frequently causes respiratory infections in children,whereas Epstein-Barr virus(EBV)typically presents subclinical manifestations in immunocompetent pediatric populations.The incidence of MP and EBV coinfections is often overlooked clinically,with the contributory role of EBV in pulmonary infections alongside MP remaining unclear.AIM To evaluate the serum concentrations of interleukin-2(IL-2)and interleukin-12(IL-12)in pediatric patients with MP pneumonia co-infected with EBV and assess their prognostic implications.METHODS We retrospectively analyzed clinical data from patients diagnosed with MP and EBV co-infection,isolated MP infection,and a control group of healthy children,spanning from January 1,2018 to December 31,2021.Serum IL-2 and IL-12 levels were quantified using enzyme-linked immunosorbent assay.Logistic regression was employed to identify factors influencing poor prognosis,while receiver operating characteristic(ROC)curves evaluated the prognostic utility of serum IL-2 and IL-12 levels in co-infected patients.RESULTS The co-infection group exhibited elevated serum IL-2 and C-reactive protein(CRP)levels compared to both the MP-only and control groups,with a reverse trend observed for IL-12(P<0.05).In the poor prognosis cohort,elevated CRP and IL-2 levels,alongside prolonged fever duration,contrasted with reduced IL-12 levels(P<0.05).Logistic regression identified elevated IL-2 as an independent risk factor and high IL-12 as a protective factor for adverse outcomes(P<0.05).ROC analysis indicated that the area under the curves for IL-2,IL-12,and their combination in predicting poor prognosis were 0.815,0.895,and 0.915,respectively.CONCLUSION Elevated serum IL-2 and diminished IL-12 levels in pediatric patients with MP and EBV co-infection correlate with poorer prognosis,with combined IL-2 and IL-12 levels offering enhanced predictive accuracy.

Triggering Receptor Expressed on Myeloid Cells 2 Alleviated Sevoflurane-Induced Developmental Neurotoxicity via Microglial Pruning of Dendritic Spines in the CA1 Region of the Hippocampus

Sevoflurane induces developmental neurotoxicity in mice;however,the underlying mechanisms remain unclear.Triggering receptor expressed on myeloid cells 2(TREM2)is essential for microglia-mediated synaptic refinement during the early stages of brain development.We explored the effects of TREM2 on dendritic spine pruning during sevoflurane-induced developmental neurotoxicity in mice.Mice were anaesthetized with sevoflurane on postnatal days 6,8,and 10.Behavioral performance was assessed using the open field test and Morris water maze test.Genetic knockdown of TREM2 and overexpression of TREM2 by stereotaxic injection were used for mechanistic experiments.Western blotting,immunofluorescence,electron microscopy,three-dimensional reconstruction,Golgi staining,and whole-cell patch-clamp recordings were performed.Sevoflurane exposures upregulated the protein expression of TREM2,increased microglia-mediated pruning of dendritic spines,and reduced synaptic multiplicity and excitability of CA1 neurons.TREM2 genetic knockdown significantly decreased dendritic spine pruning,and partially aggravated neuronal morphological abnormalities and cognitive impairments in sevoflurane-treated mice.In contrast,TREM2 overexpression enhanced microglia-mediated pruning of dendritic spines and rescued neuronal morphological abnormalities and cognitive dysfunction.TREM2 exerts a protective role against neurocognitive impairments in mice after neonatal exposures to sevoflurane by enhancing microglia-mediated pruning of dendritic spines in CA1 neurons.This provides a potential therapeutic target in the prevention of sevoflurane-induced developmental neurotoxicity.

Cross section determination of^(27)Al(n,2n)^(26)Al reaction induced by 14-MeV neutrons uniting with D-T neutron activation and AMS techniques

Aluminum is the primary structural material in nuclear engineering,and its cross section induced by 14-MeV neutrons is of great significance.To address the issue of insufficient accuracy for the^(27)Al(n,2n)^(26)Al reaction cross section,the activation method and accelerator mass spectrometry(AMS)technique were used to determine the^(27)Al(n,2n)^(26)Al cross section,which could be used as a D-T plasma ion temperature monitor in fusion reactors.At the China Academy of Engineering Physics,neutron activation was performed using a K-400 neutron generator produced by the T(d,n)4He reaction.The^(26)Al∕^(27)Al isotope ratios were measured using the newly installed GYIG 1 MV AMS at the Institute of Geochemistry,Chinese Academy of Sciences.The neutron flux was monitored by measuring the activity of 92mNb produced by the 93Nb(n,2n)92mNb reaction.The measured results were compared with available data in the experimental nuclear reaction database,and the measured values showed a reasonable degree of consistency with partially available literature data.The newly acquired cross-sectional data at 12 neutron energy points through systematic measurements clarified the divergence,which has two different growth trends from the existing experimental values.The obtained results are also compared with the corresponding evaluated database,and the newly calculated excitation functions with TALYS−1.95 and EMPIRE−3.2 codes,the agreement with CENDL−3.2,TENDL-2021 and EMPIRE−3.2 results are generally acceptable.A substantial improvement in the knowledge of the^(27)Al(n,2n)^(26)Al reaction excitation function was obtained in the present work,which will lay the foundation for the diagnosis of the fusion ion temperature,testing of the nuclear physics model,evaluation of nuclear data,etc.

Recent advances in nickel-based catalysts in eCO_(2)RR for carbon neutrality

The excessive use of nonrenewable energy has brought about serious greenhouse effect.Converting CO_(2) into high-value-added chemicals is undoubtedly the best choice to solve energy problems.Due to the excellent cost-effectiveness and dramatic catalytic performance,nickel-based catalysts have been considered as the most promising candidates for the electrocatalytic CO_(2) reduction reaction(eCO_(2)RR).In this work,the electrocatalytic reduction mechanism of CO_(2) over Ni-based materials is reviewed.The strategies to improve the eCO_(2)RR performance are emphasized.Moreover,the research on Ni-based materials for syngas generation is briefly summarized.Finally,the prospects of nickel-based materials in the eCO_(2)RR are provided with the hope of improving transition-metal-based electrocatalysts for eCO_(2)RR in the future.

Graph neural network-based scheduling for multi-UAV-enabled communications in D2D networks

In this paper,we jointly design the power control and position dispatch for Multi-Unmanned Aerial Vehicle(UAV)-enabled communication in Device-to-Device(D2D)networks.Our objective is to maximize the total transmission rate of Downlink Users(DUs).Meanwhile,the Quality of Service(QoS)of all D2D users must be satisfied.We comprehensively considered the interference among D2D communications and downlink transmissions.The original problem is strongly non-convex,which requires high computational complexity for traditional optimization methods.And to make matters worse,the results are not necessarily globally optimal.In this paper,we propose a novel Graph Neural Networks(GNN)based approach that can map the considered system into a specific graph structure and achieve the optimal solution in a low complexity manner.Particularly,we first construct a GNN-based model for the proposed network,in which the transmission links and interference links are formulated as vertexes and edges,respectively.Then,by taking the channel state information and the coordinates of ground users as the inputs,as well as the location of UAVs and the transmission power of all transmitters as outputs,we obtain the mapping from inputs to outputs through training the parameters of GNN.Simulation results verified that the way to maximize the total transmission rate of DUs can be extracted effectively via the training on samples.Moreover,it also shows that the performance of proposed GNN-based method is better than that of traditional means.

Neutrophil-to-lymphocyte ratio associated with renal function in type 2 diabetic patients

BACKGROUND Type 2 diabetes mellitus(T2DM)is a leading risk factor for the development and progression of chronic kidney disease(CKD).However,an accurate and con-venient marker for early detection and appropriate management of CKD in in-dividuals with T2DM is limited.Recent studies have demonstrated a strong correlation between the neutrophil-to-lymphocyte ratio(NLR)and CKD.None-theless,the predictive value of NLR for renal damage in type 2 diabetic patients remains understudied.This study included 1040 adults aged 65 or older with T2DM from Shanghai's Community Health Service Center.The total number of neutrophils and lym-phocytes was detected,and NLR levels were calculated.CKD was defined as an estimated glomerular filtration rate≤60 mL/min/1.73 m².Participants were di-vided into four groups based on NLR levels.The clinical data and biochemical characteristics were compared among groups.A multivariate logistic regression model was used to analyze the association between NLR levels and CKD.RESULTS Significant differences were found in terms of sex,serum creatinine,blood urea nitrogen,total cholesterol,and low-density lipoprotein cholesterol among patients with T2DM in different NLR groups(P<0.0007).T2DM patients in the highest NLR quartile had a higher prevalence of CKD(P for trend=0.0011).Multivariate logistic regression analysis indicated that a high NLR was an independent risk factor for CKD in T2DM patients even after adjustment for important clinical and pathological parameters(P=0.0001,odds ratio=1.41,95%confidence intervals:1.18-1.68).CONCLUSION An elevated NLR in patients with T2DM is associated with higher prevalence of CKD,suggesting that it could be a marker for the detection and evaluation of diabetic kidney disease.

2-O-β-D-Glucopyranosyl-L-ascorbic acid,an ascorbic acid derivative isolated from the fruits of Lycium barbarum L.,ameliorates high fructose-induced neuroinflammation in mice:involvement of gut microbiota and leaky gut

Western diet(rich in highly refined sugar and fat)can induce a range of metabolic dysfunctions in animals and humans,including neuroinflammation and cognitive function decline.Neuroinflammation and cognitive impairment,two critical pathological characteristics of Alzheimer’s disease,have been closely associated with microbial alteration via the gut-brain axis.Thus,the present study aimed to investigate the influence of 2-O-β-D-glucopyranosyl-L-ascorbic acid(AA-2βG)isolated from the fruits of Lycium barbarum on preventing the high-fructose diet(HFrD)induced neuroinflammation in mice.It was found that AA-2βG prevented HFr D-induced cognitive deficits.AA-2βG also predominantly enhanced the gut barrier integrity,decreased lipopolysaccharide entry into the circulation,which subsequently countered the activation of glial cells and neuroinflammatory response.These beneficial effects were transmissible by horizontal fecal microbiome transplantation,transferring from AA-2βG fed mice to HFr D fed mice.Additionally,AA-2βG exerted neuroprotective effects involving the enrichment of Lactobacillus and Akkermansia,potentially beneficial intestinal bacteria.The present study provided the evidence that AA-2βG could improve indices of cognition and neuroinflammmation via modulating gut dybiosis and preventing leaky gut.As a potential functional food ingredient,AA-2βG may be applied to attenuate neuroinflammation associated with Western-style diets.

A hybrid physics-informed data-driven neural network for CO_(2) storage in depleted shale reservoirs

To reduce CO_(2) emissions in response to global climate change,shale reservoirs could be ideal candidates for long-term carbon geo-sequestration involving multi-scale transport processes.However,most current CO_(2) sequestration models do not adequately consider multiple transport mechanisms.Moreover,the evaluation of CO_(2) storage processes usually involves laborious and time-consuming numerical simulations unsuitable for practical prediction and decision-making.In this paper,an integrated model involving gas diffusion,adsorption,dissolution,slip flow,and Darcy flow is proposed to accurately characterize CO_(2) storage in depleted shale reservoirs,supporting the establishment of a training database.On this basis,a hybrid physics-informed data-driven neural network(HPDNN)is developed as a deep learning surrogate for prediction and inversion.By incorporating multiple sources of scientific knowledge,the HPDNN can be configured with limited simulation resources,significantly accelerating the forward and inversion processes.Furthermore,the HPDNN can more intelligently predict injection performance,precisely perform reservoir parameter inversion,and reasonably evaluate the CO_(2) storage capacity under complicated scenarios.The validation and test results demonstrate that the HPDNN can ensure high accuracy and strong robustness across an extensive applicability range when dealing with field data with multiple noise sources.This study has tremendous potential to replace traditional modeling tools for predicting and making decisions about CO_(2) storage projects in depleted shale reservoirs.

Metal-N_(4) model single‐atom catalyst with electroneutral quadri‐pyridine macrocyclic ligand for CO_(2) electroreduction

Metal–N–C single‐atom catalysts,mostly prepared from pyrolysis of metalorganic precursors,are widely used in heterogeneous electrocatalysis.Since metal sites with diverse local structures coexist in this type of material and it is challenging to characterize the local structure,a reliable structure–property relationship is difficult to establish.Conjugated macrocyclic complexes adsorbed on carbon support are well‐defined models to mimic the singleatom catalysts.Metal–N_(4) site with four electroneutral pyridine‐type ligands embedded in a graphene layer is the most commonly proposed structure of the active site of single‐atom catalysts,but its molecular counterpart has not been reported.In this work,we synthesized the conjugated macrocyclic complexes with a metal center(Co,Fe,or Ni)coordinated with four electroneutral pyridinic ligands as model catalysts for CO_(2) electroreduction.For comparison,the complexes with anionic quadri‐pyridine macrocyclic ligand were also prepared.The Co complex with the electroneutral ligand expressed a turnover frequency of CO formation more than an order of magnitude higher than that of the Co complex with the anionic ligand.Constrained ab initio molecular dynamics simulations based on the well‐defined structures of the model catalysts indicate that the Co complex with the electroneutral ligand possesses a stronger ability to mediate electron transfer from carbon to CO_(2).

Characteristic changes in astrocyte properties during astrocyte-to-neuron conversion induced by NeuroD1/Ascl1/Dlx2

Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors––NeuroD1, Ascl1, and Dlx2––in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore,we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4(astrocyte endfeet signal), CX43(gap junction signal), and S100β. Importantly, none of these changes could be attributed to transgene leakage into preexisting neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.