Behavior Of Defects Research Articles

Non-Traditional Response to Intensive NBS and NBIS Treatments on IGZO TFTs

The traditional response to bias-stress treatments is consistent with the Fermi level position during the stress application. Positive-bias stress (PBS) supports trap state filling of electrons, presenting negative interface charge and causing a left-shift and/or distortion in the transfer characteristic. Negative-bias stress (NBS) supports trap state emptying of electrons, appearing as a net positive charge and causing a right-shift and/or distortion in the transfer characteristic. The extent of shifting, distortion, and hysteresis resulting from the bias-stress application depends on the magnitude of the bias-stress voltage and time duration, as well as the post-stress test conditions such as VGS sweep rate and temperature. Hysteresis occurs when the level of trapped charge is not in thermal equilibrium with the temperature and bias conditions, and provides insight into the magnitude of trap states involved in dynamic state changes.This work provides an interpretation of defect and trap state behavior following the application of intensive NBS and negative-bias illumination stress (NBIS). Staggered bottom-gate TFTs were fabricated with a 50 nm IGZO film sandwiched between a 50 nm gate oxide and a 50 nm passivation oxide layer. The working metal was molybdenum for the gate electrode and source/drain contacts. A passivation anneal was done and an alumina capping layer was deposited via ALD to promote electrical stability; full process details are provided in a previous report. Devices were tested with a Keysight B1500 parameter analyzer to establish initial device characteristics, with +20 V PBS and -10 V NBS stress applications for 20 ks having a negligible response. Intensive negative-bias stress testing was then done for 10 ks at either high bias (-20 V NBS) or with the addition of illumination (-10 V NBIS @ 410 nm). The responses to intensive NBS and NBIS applications were both non-traditional and distinctive.Pre- and post-NBS results are shown in Figure 1. ID-VGS transfer characteristics were measured over a VGS down-sweep from 10 V to -5 V at VDS values of 10 V (first) and 0.1 V (second), with a sweep rate of ~ 1 V/s. The measurement order, sweep direction and sweep rate were chosen to maintain consistent non-equilibrium conditions and suppress hysteresis. The intensive NBS shown in Figure 1a induces a significant distortion and spreading to the right, which can be explained by the creation of acceptor-like trap states during stress application. Figure 1b shows a comparison of hysteresis following NBS and subsequent PBS treatments, with the VGS up-sweep immediately followed by a down-sweep. Post-NBS hysteresis shows a separation of approximately 1 V, which translates to an equivalent interface state density difference of 4.3x1011 states/cm2. The separation in transfer characteristics reflects non-homogeneity in trap state formation. The application of +20V PBS following NBS was observed to partially reverse these effects, with hysteresis reduced significantly. The net shift around flatband is minimal, however pronounced distortion remains.Pre- and post-NBIS results are shown in Figure 2. The intensive NBIS shown in Figure 2a induces a significant right-shift of around 6 V, with minimal distortion. While this can also be explained by the creation of acceptor-like traps, the states created in response to NBIS have a slow response (i.e. remain unchanged over VGS sweep) appearing more like fixed charge. Note that this large shift is observed in the hysteresis loop shown in Figure 2b, however once VGS is increased to +10 V the traps remain filled and hysteresis is dramatically reduced. The application of +20 V PBS following NBIS was observed to partially reverse these effects, with a left-shift of approximately -4 V, or to within 2 V of the original pre-NBIS characteristics. The hysteresis loop observed following PBS treatment and relaxation is consistent with the position of the post-NBIS hysteresis measurement (up-sweep) and the final transfer characteristic (down-sweep).Remaining work in defect state characterization will utilize cryogenic measurements for temperature-dependent behavior. TCAD simulation will be used as a resource to model the defect state energy distribution resulting from the application of intensive NBS and NBIS treatments. Figure 1

(Invited) Silicon Carbide Technology Scaling: Challenges and Opportunities across the Value Chain

Silicon Carbide (SiC) technology has emerged as a promising solution to address the growing demand for high-performance power electronics in various applications, ranging from automotive to renewable energy systems. As the industry continues to push the boundaries of SiC technology, scaling opportunities and challenges arise across the entire value chain, from material to device fabrication and new package architectures. In addition, it should be noted that scientific understanding, especially in the areas of defect behaviour in the SiC epitaxy layer, threshold voltage instability, interface trap density, and integrity of the gate insulator, would be increasingly important and necessary for the further development of SiC power devices. To address the economics, and mass produce ultra-high-power electronics devices with improved performance and reliability, we partnered with ecosystem players across the value chain from substrate to power module packaging and set up a 200mm SiC specialty open innovation process line.This talk will provide an overview of the key challenges and opportunities associated with SiC technology. We will discuss the high grow rate (≥50µm/hr) SiC epitaxy process and share methodologies to achieve high-quality epitaxy layer with good doping control (≤10%), tight thickness uniformity (≤3%), low surface roughness (≤3Å) and low crystal defect densities (≤0.4 cm-2) on 200mm 4H-SiC substrate. Moving on to the metal oxide semiconductor (MOS) device interface engineering, we will discuss strategies for achieving low interface trap densities (~1011eV-1 cm-2) and improved threshold voltage instability. Beyond device fabrication, we will highlight the importance of the power module packaging technique in realizing the full potential of SiC technology. This includes the double-side liquid cooling system and the power dissipation capability with different designs and material options for the proposed 6-in-1 power module.Overall, by addressing these challenges collaboratively, we can accelerate the adoption of SiC technology and unlock its full potential to drive power semiconductor technology and beyond. Figure 1

Behavior of a defect in a flexible carbon nanotube

Abstract Carbon nanotubes (CNTs) play an indispensable role in the design and application of flexible devices due to their unique physical and chemical properties. ‌This study theoretically investigates the behavior of defects in bent CNTs. The results indicate that when the defect is under compressive strain, the conductance of the device decreases as the bending angle increases. Conversely, when the defect is under tensile strain, the conductance of the device increases with a larger bending angle.This phenomenon is primarily attributed to the enhancement of scattering states corresponding to the defect under tensile strain and the weakening of these states under compressive strain. Under bias voltage, similar patterns are observed for transmission peaks corresponding to the defect. These findings contribute to the device design process, enabling the exploitation of advantages and avoidance of disadvantages, ultimately leading to the development of flexible CNTs- devices.‌

Magneto‐Optical Control of Ordering Kinetics and Vacancy Behavior in Fe–Al Thin Films Quenched by Laser

One of the issues arising in materials science is the behavior of nonequilibrium point defects in the atomic lattice, which defines the rates of chemical reactions and relaxation processes as well as affects the physical properties of solids. It is previously theoretically predicted that melting and rapid solidification of metals and alloys provide a vacancy concentration in the quenched material, which can be comparable to that quantity at the point of melting. Here, the vacancy behavior is studied experimentally in thin films of the near equiatomic Fe–Al alloy subjected to nanosecond laser annealing with intensities up to film ablation. The effects of laser irradiation are studied by monitoring magneto‐optically the ordering kinetics in the alloy at the very ablation edge, within a narrow (micron‐scale) ring‐shaped region around the ablation zone. Quantitatively, the vacancy supersaturation in the quenched alloy has been estimated by fitting a simulated temporal evolution of the long‐range chemical order to the obtained experimental data. Laser quenching (LQ) of alloys and single‐element materials will be a tool for obtaining novel phase states within a small volume of the crystal.

Pore defect and corrosion behavior of HVAF-sprayed Co21Fe14Ni8Cr16Mo16C15B10 high entropy metallic glass coatings

Pore defect is a primary bottleneck limiting corrosion resistance of the coatings. The relationship between porosity and corrosion behaviors of HVAF-sprayed Co21Fe14Ni8Cr16Mo16C15B10 high entropy metallic glass (HE-MG) coatings was investigated by 3D XRT, XPS, SKPFM and SVET techniques. The potential difference between pores and surrounding regions expedites corrosion tendency. The corrosion current density of the coating and concentration of defects in passivation film increase as a function of porosity, thereby degrading corrosion resistance. The lowest porosity coating displays exceptional anti-corrosion due to compact films enriched with Cr2O3 and Mo4+ oxides. These findings provide valuable insights for designing corrosion-resistance coatings.

Defect recognition in Ti-6Al-4V fabrication by in situ monitoring of directed energy deposition using a laser beam

Purpose This paper aims to investigate the relationship between in situ monitoring characteristics and surface defects in laser-based directed energydeposited Ti-6Al-4V. Design/methodology/approach In situ monitoring was conducted to extract and quantify the monitoring characteristics of each frame. A two-dimensional contour map was generated using the quantified characteristics to determine the defect formation locations. Computational thermal-fluid dynamics software was used to determine which surface tension terms or shielding gas had a significant effect on the depression of the molten pool. Findings This study has made a significant contribution by revealing the direct correlation between the molten pool size and brightness with defect formation in laser-based DED of Ti-6Al-4V. It was found that in regions of reduced height, the molten pool exhibited increased size and brightness, leading to surface depressions due to vapor recoil pressure flattening the molten pool. Moreover, the results highlighted that the enhanced Marangoni forces, caused by a high-temperature gradient, hindered the proper accumulation of molten metal, exacerbating height reductions. This insight provides a deeper understanding of how molten pool dynamics directly influence surface quality, which is a critical factor in DED processes. Originality/value This study contributes to understanding of the relationship between in situ monitoring characteristics and surface defects in laser-based directed energy-deposited Ti-6Al-4V. Additionally, by using in situ monitoring and computational analysis, significant insights were gained into the factors influencing molten pool behavior and subsequent surface defects.

Defect dynamics modeling of mesoscale plasticity

The collective motion of defects and their interaction are the basic building blocks for plastic deformation and corresponding mechanical behaviors of crystalline metals. Especially, dislocations among various defects are the “carrier” of plastic deformation in many crystalline materials, particularly ductile materials. To get a fundamental understanding of plastic deformation mechanisms, it calls for an integrated computational platform to simultaneously capture detailed defects characteristics across several length scales together with corresponding macroscopic mechanical response. In this paper, we present a three-dimensional mesoscale defect dynamics model to directly couple the three dimensional discrete dislocation dynamics model with continuum finite element method, aiming at capturing both size dependent plasticity at micron-, and submicron scale and constitutive behaviors at larger scales where such size-dependence disappear. Using non-singular dislocation theories, our model could accurately consider both short- and long-range elastic interactions between multiple dislocation segments with even higher computational efficiency than traditional dislocation dynamics simulations, together with the careful consideration of crystal/material rotation in the coupled framework. In addition, our model could directly model dislocation nucleation from stress concentrators such as a void, crack and indentor tip, which could allow us to investigate various defects’ motion and their mutual interactions, predicting macroscopic mechanical response of complex structures. The developed concurrently coupled model could also consider multiphysical phenomena by solving coupled governing equations in finite element framework, which could shed light on complex defect behaviors under various physical environments.

Adjustment of link weights based on tolerance promotes cooperation in spatial prisoner's dilemma game

Understanding and explaining cooperative behavior in human society has become an open question. In this paper, we propose a dynamic adjustment of pair relationships in a spatial prisoner's dilemma game. Unlike previous studies that individuals dynamically adjust the intensity of interaction with their opponents at each step, this work consider tolerance, in which the intensity of interaction is adjusted when the time of successive defections by an individual exceeds a tolerance threshold T. We find that although the proposed mechanism can significantly improve cooperation compared to traditional versions, a higher tolerance for continuous defection behavior is not conducive to the evolution of cooperation. Furthermore, an environmental adaptor that dynamically adjusts the paired relationship with the opponent at all times is beneficial for the evolution of cooperation. And the higher the degree of adjustment in the paired relationship, the lower the probability of continuous exploitation by defector. We hope that our work can provide some insights into explaining the existence and maintenance of cooperation.

β-asarone relieves Parkinson’s disease through reducing intracellular Ca2+ in PINK1 mutant Drosophila melanogaster

β-asarone, an effective volatile oil component of Acorus chinensis, has been found to hold beneficial effects on Parkinson's disease (PD), but its mechanism remains incompletely understood. Drosophila melanogaster with PTEN induced kinase 1 (PINK1) mutations, a prototype PD model, was used in this study. We found that calcium chelation profoundly alleviated a spectrum of PD symptoms. Whereas, calcium supplementation made the case worse, suggesting accumulated calcium contributes to progression of PD. β-asarone administration decreased Ca2+ level in PD flies, accompanied by alleviated behavioral and neural defects. Further study demonstrated that β-asarone downregulated L-type Ca2+ channels (Dmca1D), which was increased in PD flies. Besides, β-asarone decreased expression of 1,4,5 - trisphosphate receptor (Itpr), which is responsible for calcium release from endoplasmic reticulum (ER). Knockdown of either Dmca1D or Itpr specifically in dopaminergic neurons alleviated behavioral and neural defects in PD flies. While overexpression of Itpr aggravated PD symptoms. The results indicated that increased intracellular calcium influx and release triggers dysregulation of calcium homeostasis in PD flies. And β-asarone prevents PD by restoring Ca2+ homeostasis. Overall, the study demonstrated that β-asarone can serve as a new prospective medication against PD or other diseases associated with dysregulation of Ca2+ homeostasis.

Amelioration of metabolic and behavioral defects through base editing in the PahR408W phenylketonuria mouse model

Phenylketonuria (PKU) is a liver metabolic disorders mainly caused by a deficiency of the hepatic phenylalanine hydroxylase (PAH) enzyme activity, often leading to severe brain function impairment in patients if untreated or if treatment is delayed. In this study, we utilized dual-AAV8 vectors to deliver a near PAM-less adenine base editor variant, known as ABE8e-SpRY, to treat the PahR408W PKU mouse model carrying a frequent R408W mutation in the Pah gene. Our findings revealed that a single intravenous injection in adult mice and a single intraperitoneal injection in neonatal mice resulted in 19.1% to 34.6% A-to-G editing efficiency at the pathogenic mutation site with minimal bystander edits. Furthermore, the dual-AAV8 treated mice exhibited reduced blood Phe levels to below the therapeutic threshold of 360 μmol L-1 and restored weight and fur color to normal levels. Importantly, the brain function of the mice was restored after the treatment, particularly when administered during the neonatal stage, as levels of monoamine neurotransmitters and metabolites in the brain returned to normal and near-normal levels. Our study demonstrated that ABE8e-SpRY-based base editing could effectively correct the point mutation in the PahR408W PKU mouse model, indicating potential clinical applications for PKU and other genetic diseases.

Deficiency of DDX3X results in neurogenesis defects and abnormal behaviors via dysfunction of the Notch signaling

The molecular mechanisms underlying the neurodevelopmental disorders (NDDs) caused by DDX3X variants remain poorly understood. In this study, we validated that de novo DDX3X variants are enriched in female developmental delay (DD) patients and mainly affect the evolutionarily conserved amino acids based on a meta-analysis of 46,612 NDD trios. We generated a ddx3x deficient zebrafish allele, which exhibited reduced survival rate, DD, microcephaly, adaptation defects, anxiolytic behaviors, social interaction deficits, and impaired spatial recognitive memory. As revealed by single-nucleus RNA sequencing and biological validations, ddx3x deficiency leads to reduced neural stem cell pool, decreased total neuron number, and imbalanced differentiation of excitatory and inhibitory neurons, which are responsible for the behavioral defects. Indeed, the supplementation of L-glutamate or glutamate receptor agonist ly404039 could partly rescue the adaptation and social deficits. Mechanistically, we reveal that the ddx3x deficiency attenuates the stability of the crebbp mRNA, which in turn causes downregulation of Notch signaling and defects in neurogenesis. Our study sheds light on the molecular pathology underlying the abnormal neurodevelopment and behavior of NDD patients with DDX3X mutations, as well as providing potential therapeutic targets for the precision treatment.

Anisotropy of radiation-induced defects in Yb-implanted β-Ga2O3

RE-doped β-Ga2O3 seems attractive for future high-power LEDs operating in high irradiation environments. In this work, we pay special attention to the issue of radiation-induced defect anisotropy in β-Ga2O3, which is crucial for device manufacturing. Using the RBS/c technique, we have carefully studied the structural changes caused by implantation and post-implantation annealing in two of the most commonly used crystallographic orientations of β-Ga2O3, namely the (-201) and (010). The analysis was supported by advanced computer simulations using the McChasy code. Our studies reveal a strong dependence of the structural damage induced by Yb-ion implantation on the crystal orientation, with a significantly higher level of extended defects observed in the (-201) direction than for the (010). In contrast, the concentration and behavior of simple defects seem similar for both oriented crystals, although their evolution suggests the co-existence of two different types of defects in the implanted zone with their different sensitivity to both, radiation and annealing. It has also been found that Yb ions mostly occupy the interstitial positions in β-Ga2O3 crystals that remain unchanged after annealing. The location is independent of the crystal orientations. We believe that these studies noticeably extend the knowledge of the radiation-induced defect structure, because they dispel doubts about the differences in the damage level depending on crystal orientation, and are important for further practical applications.

Neuronal connectivity, behavioral, and transcriptional alterations associated with the loss of MARK2.

Neuronal connectivity is essential for adaptive brain responses and can be modulated by dendritic spine plasticity and the intrinsic excitability of individual neurons. Dysregulation of these processes can lead to aberrant neuronal activity, which has been associated with numerous neurological disorders including autism, epilepsy, and Alzheimer's disease. Nonetheless, the molecular mechanisms underlying abnormal neuronal connectivity remain unclear. We previously found that the serine/threonine kinase Microtubule Affinity Regulating Kinase 2 (MARK2), also known as Partitioning Defective 1b (Par1b), is important for the formation of dendritic spines invitro. However, despite its genetic association with several neurological disorders, the invivo impact of MARK2 on neuronal connectivity and cognitive functions remains unclear. Here, we demonstrate that the loss of MARK2 invivo results in changes to dendritic spine morphology, which in turn leads to a decrease in excitatory synaptic transmission. Additionally, the loss of MARK2 produces substantial impairments in learning and memory, reduced anxiety, and defective social behavior. Notably, MARK2 deficiency results in heightened seizure susceptibility. Consistent with this observation, electrophysiological analysis of hippocampal slices indicates underlying neuronal hyperexcitability in MARK2-deficient neurons. Finally, RNAseq analysis reveals transcriptional changes in genes regulating synaptic transmission and ion homeostasis. These results underscore the invivo role of MARK2 in governing synaptic connectivity, neuronal excitability, and cognitive functions.

Blockade of brain alkaline phosphatase efficiently reduces amyloid-β plaque burden and associated cognitive impairment

BackgroundAlzheimer’s disease (AD) is the most prevalent neurodegenerative disease. Three new drugs for AD based on monoclonal antibodies against the amyloid-β peptide (Aβ) have recently been approved because they favor the reduction of the burden of senile plaque in the AD patient’s brain. Nonetheless, both drugs have very limited applicability and benefits and show several side effects. These limitations invite us to find alternative strategies for treating patients with AD. Here, we explored whether tissue-nonspecific alkaline phosphatase (TNAP), an ectoenzyme upregulated in the brain of AD patients and whose inhibition has beneficial effects on tau-induced pathology, is also efficient in reducing senile plaque burden.MethodsTo evaluate whether TNAP may reduce cerebral senile plaque loading and Aβ-related toxicity, we use both pharmacological and genetic approaches. We analyze postmortem samples from human AD patients, APP/PS1 mice (a mouse model that mimics amyloid pathology observed in AD patients) treated or not with TNAP inhibitors, and the newly generated transgenic mouse line, TNAP-deficient APP/PS1 mice.ResultsFor the first time, we describe that genetic or pharmacological blockade of TNAP effectively reduces senile plaque burden by promoting its clearance, which leads to amelioration of cognitive impairment caused by Aβ-induced toxicity. These beneficial effects of TNAP inhibition occur concomitantly with higher microglial recruitment toward the senile plaque and increased microglial phagocytic capacity of Aβ by a mechanism involving metalloprotease-depending osteopontin processing. In addition, we also found that TNAP blockade favors LRP1-mediated transport of Aβ through the BBB.ConclusionsHere, we have shown that TNAP inhibition effectively reduces brain senile plaque burden and associated behavioral defects. Furthermore, given that we had previously reported that TNAP blockade also ameliorates Tau-induced neurotoxicity and increases lifespan of P301S tauopathy mouse model, we can state that TNAP blockade may be a novel and efficient therapy for treating patients with AD.

Lifetime fatigue cracking behavior of weld defects in orthotropic steel bridge decks: Numerical and experimental study

Orthotropic steel decks (OSDs) are welded structures prone to weld defects, increasing the risk of fatigue fracture. It is crucial to clarify the fatigue evolution mechanism of weld defects throughout the entire lifecycle. In this study, the fatigue propagation behavior of weld defects is investigated from the hidden stage to final fracture. Firstly, a full-scale segmental OSD model with prefabricated defects was utilized to investigated fatigue propagation behavior of surface cracks. Secondly, stress intensity factors (SIFs) of welding defects throughout the entire process were simulated using a refined finite element model. Finally, the crack shape evolution and fatigue life were analyzed at different fatigue stages. The research identifies three stages in the fatigue evolution of hidden defects: the hidden defect stage, the initiation stage of surface crack, and the propagation stage of surface crack. Regardless of the initial aspect ratios, hidden defects evolve into a circular, while surface defects evolve into a flattened semi-ellipse. Compared to the propagation life of surface cracks, the hiding life of cracks account for a significantly larger proportion of the total life, and this proportion increases with both the initial aspect ratio and the hidden depth of the defects.

Extremely Low-Frequency Electromagnetic Field (ELF-EMF) Increases Mitochondrial Electron Transport Chain Activities and Ameliorates Depressive Behaviors in Mice.

Compromised mitochondrial electron transport chain (ETC) activities are associated with depression in humans and rodents. However, the effects of the enhancement of mitochondrial ETC activities on depression remain elusive. We recently reported that an extremely low-frequency electromagnetic field (ELF-EMF) of as low as 10 μT induced hormetic activation of mitochondrial ETC complexes in human/mouse cultured cells and mouse livers. Chronic social defeat stress (CSDS) for 10 consecutive days caused behavioral defects mimicking depression in mice, and using an ELF-EMF for two to six weeks ameliorated them. CSDS variably decreased the mitochondrial ETC proteins in the prefrontal cortex (PFC) in 10 days, which were increased by an ELF-EMF in six weeks. CSDS had no effect on the mitochondrial oxygen consumption rate in the PFC in 10 days, but using an ELF-EMF for six weeks enhanced it. CSDS inactivated SOD2 by enhancing its acetylation and increased lipid peroxidation in the PFC. In contrast, the ELF-EMF activated the Sirt3-FoxO3a-SOD2 pathway and suppressed lipid peroxidation. Furthermore, CSDS increased markers for mitophagy, which was suppressed by the ELF-EMF in six weeks. The ELF-EMF exerted beneficial hormetic effects on mitochondrial energy production, mitochondrial antioxidation, and mitochondrial dynamics in a mouse model of depression. We envisage that an ELF-EMF is a promising therapeutic option for depression.

Atomic-scale visualization of defect-induced localized vibrations in GaN.

Phonon engineering is crucial for thermal management in GaN-based power devices, where phonon-defect interactions limit performance. However, detecting nanoscale phonon transport constrained by III-nitride defects is challenging due to limited spatial resolution. Here, we used advanced scanning transmission electron microscopy and electron energy loss spectroscopy to examine vibrational modes in a prismatic stacking fault in GaN. By comparing experimental results with ab initio calculations, we identified three types of defect-derived modes: localized defect modes, a confined bulk mode, and a fully extended mode. Additionally, the PSF exhibits a smaller phonon energy gap and lower acoustic sound speeds than defect-free GaN, suggesting reduced thermal conductivity. Our study elucidates the vibrational behavior of a GaN defect via advanced characterization methods and highlights properties that may affect thermal behavior.

A Review of Wide Bandgap Semiconductors: Insights into SiC, IGZO, and Their Defect Characteristics.

Although the irreplaceable position of silicon (Si) semiconductor materials in the field of information has become a consensus, new materials continue to be sought to expand the application range of semiconductor devices. Among them, research on wide bandgap semiconductors has already achieved preliminary success, and the relevant achievements have been applied in the fields of energy conversion, display, and storage. However, similar to the history of Si, the immature material grown and device manufacturing processes at the current stage seriously hinder the popularization of wide bandgap semiconductor-based applications, and one of the crucial issues behind this is the defect problem. Here, we take amorphous indium gallium zinc oxide (a-IGZO) and 4H silicon carbide (4H-SiC) as two representatives to discuss physical/mechanical properties, electrical performance, and stability from the perspective of defects. Relevant experimental and theoretical works on defect formation, evolution, and annihilation are summarized, and the impacts on carrier transport behaviors are highlighted. State-of-the-art applications using the two materials are also briefly reviewed. This review aims to assist researchers in elucidating the complex impacts of defects on electrical behaviors of wide bandgap semiconductors, enabling them to make judgments on potential defect issues that may arise in their own processes. It aims to contribute to the effort of using various post-treatment methods to control defect behaviors and achieve the desired material and device performance.

Angiotensin-(1-7) relieves behavioral defects and α-synuclein expression through NEAT1/miR-153-3p axis in Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, whose characteristic pathology involves progressive deficiency of dopaminergic neurons and generation of Lewy bodies (LBs). Aggregated and misfolded α-synuclein (α-syn) is the major constituent of LBs. As the newly discovered pathway of renin-angiotensin system (RAS), Angiotensin-(1-7) (Ang-(1-7)) and receptor Mas have attracted increasing attentions for their correlation with PD, but underlying mechanisms remain not fully clear. Based on above, this study established PD models of mice and primary dopaminergic neurons with AAV-hα-syn(A53T), then discussed the effects of Ang-(1-7)/Mas on α-syn level and neuronal apoptosis for these models combined with downstream long non-coding RNA (lncRNA) and microRNA (miRNA). Results showed that Ang-(1-7) alleviated behavioral impairments, rescued dopaminergic neurons loss and lowered α-syn expression in substantia nigra of hα-syn(A53T) overexpressed PD mice. We also discovered that Ang-(1-7) decreased level of α-syn and apoptosis in the hα-syn(A53T) overexpressed dopaminergic neurons through lncRNA NEAT1/miR-153-3p axis. Moreover, miR-153-3p level in peripheral blood is found negatively correlated with that of α-syn. In conclusion, our work not only showed neuroprotective effect and underlying mechanisms for Ang-(1-7) on α-syn in vivo and vitro, but also brought new hope on miR-153-3p and NEAT1 for diagnosis and treatment in PD.

The Hunchback temporal transcription factor determines interneuron molecular identity, morphology, and presynapse targeting in the Drosophila NB5-2 lineage.

Interneuron diversity within the central nervous system (CNS) is essential for proper circuit assembly. Functional interneurons must integrate multiple features, including combinatorial transcription factor (TF) expression, axon/dendrite morphology, and connectivity to properly specify interneuronal identity. Yet, how these different interneuron properties are coordinately regulated remains unclear. Here we used the Drosophila neural progenitor, NB5-2, known to generate late-born interneurons in a proprioceptive circuit, to determine if the early-born temporal transcription factor (TTF), Hunchback (Hb), specifies early-born interneuron identity, including molecular profile, axon/dendrite morphology, and presynapse targeting. We found that prolonged Hb expression in NB5-2 increases the number of neurons expressing early-born TFs (Nervy, Nkx6, and Dbx) at the expense of late-born TFs (Runt and Zfh2); thus, Hb is sufficient to promote interneuron molecular identity. Hb is also sufficient to transform late-born neuronal morphology to early-born neuronal morphology. Furthermore, prolonged Hb promotes the relocation of late-born neuronal presynapses to early-born neuronal presynapse neuropil locations, consistent with a change in interneuron connectivity. Finally, we found that prolonged Hb expression led to defects in proprioceptive behavior, consistent with a failure to properly specify late-born interneurons in the proprioceptive circuit. We conclude that the Hb TTF is sufficient to specify multiple aspects of early-born interneuron identity, as well as disrupt late-born proprioceptive neuron function.