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Aging is characterized with a progressive decline in many cognitive functions, including behavioral flexibility, an important ability to respond appropriately to changing environmental contingencies. However, the underlying mechanisms of impaired behavioral flexibility in aging are not clear. In this study, we reported that necroptosis-induced reduction of neuronal activity in the basolateral amygdala (BLA) plays an important role in behavioral inflexibility in 5-month-old mice of the senescence-accelerated mice prone-8 (SAMP8) line, a well-established model with age-related phenotypes. Application of Nec-1s, a specific inhibitor of necroptosis, reversed the impairment of behavioral flexibility in SAMP8 mice. We further observed that the loss of glycogen synthase kinase 3α (GSK-3α) was strongly correlated with necroptosis in the BLA of aged mice and the amygdala of aged cynomolgus monkeys (Macaca fascicularis). Moreover, genetic deletion or knockdown of GSK-3α led to the activation of necroptosis and impaired behavioral flexibility in wild-type mice, while the restoration of GSK-3α expression in the BLA arrested necroptosis and behavioral inflexibility in aged mice. We further observed that GSK-3α loss resulted in the activation of mTORC1 signaling to promote RIPK3-dependent necroptosis. Importantly, we discovered that social isolation, a prevalent phenomenon in aged people, facilitated necroptosis and behavioral inflexibility in 4-month-old SAMP8 mice. Overall, our study not only revealed the molecular mechanisms of the dysfunction of behavioral flexibility in aged people but also identified a critical lifestyle risk factor and a possible intervention strategy.

The neuron-glia cross-talk is critical to brain homeostasis and is particularly affected by neurodegenerative diseases. How neurons manipulate the neuron-astrocyte interaction under pathological conditions, such as hyperphosphorylated tau, a pathological hallmark in Alzheimer’s disease (AD), remains elusive. In this study, we identified excessively elevated neuronal expression of adenosine receptor 1 (Adora1 or A1R) in 3×Tg mice, MAPT P301L (rTg4510) mice, patients with AD, and patient-derived neurons. The up-regulation of A1R was found to be tau pathology dependent and posttranscriptionally regulated by Mef2c via miR-133a-3p. Rebuilding the miR-133a-3p/A1R signal effectively rescued synaptic and memory impairments in AD mice. Furthermore, neuronal A1R promoted the release of lipocalin 2 (Lcn2) and resulted in astrocyte activation. Last, silencing neuronal Lcn2 in AD mice ameliorated astrocyte activation and restored synaptic plasticity and learning/memory. Our findings reveal that the tau pathology remodels neuron-glial cross-talk and promotes neurodegenerative progression. Approaches targeting A1R and modulating this signaling pathway might be a potential therapeutic strategy for AD.

Retrograde tracing is an important method for dissecting neuronal connections and mapping neural circuits. Over the past decades, several virus-based retrograde tracers have been developed and have contributed to displaying multiple neural circuits in the brain. However, most of the previously widely used viral tools have focused on mono-transsynaptic neural tracing within the central nervous system, with very limited options for achieving polysynaptic tracing between the central and peripheral nervous systems. In this study, we generated a novel mouse line, GT mice, in which both glycoprotein (G) and ASLV-A receptor (TVA) were expressed throughout the body. Using this mouse model, in combination with the well-developed rabies virus tools (RV-EnvA-ΔG) for monosynaptic retrograde tracing, polysynaptic retrograde tracing can be achieved. This allows functional forward mapping and long-term tracing. Furthermore, since the G-deleted rabies virus can travel upstream against the nervous system as the original strain, this mouse model can also be used for rabies pathological studies.

The table-like magnetocaloric effect is significant for the magnetic refrigeration applications above 20 K based on the Ericsson cycle. Herein, we prepared a series of Nd6Fe13Pd1–xCux (x=0.05, 0.1, 0.15) compounds by the arc-melting method. These compounds show the single crystalline phase in the tetragonal Nd6Fe13Si-type structure with the space group I4/mcm. A magnetic phase transition from ferromagnetism to antiferromagnetism and a metamagnetic transition from the antiferromagnetic state to the ferromagnetic state were observed in each of the compounds. The compounds exhibit table-like magnetocaloric effects with large refrigerant capacities. A constant ΔSM in a temperature span of 40 K in the Nd6Fe13Pd0.85Cu0.15 compound was observed. For a field change of 0–5 T, the peak values of –ΔSM for the Nd6Fe13Pd0.95Cu0.05, Nd6Fe13Pd0.90Cu0.10, and Nd6Fe13Pd0.85Cu0.15 compounds were estimated to be 4.8, 4.6 and 4.4 J/(kg·K) with corresponding refrigerant capacity values of 323, 331 and 316 J/kg, respectively. The obtained table-like magnetocaloric effects with large refrigerant capacities as well as fairly small thermal and magnetic hysteresis deem these series of compounds good candidates for single-phase magnetic refrigeration based on the Ericsson cycle.

Tau pathology, including aberrant tau hyperphosphorylation, aggregation, and mislocalization, is implicated in many neurodegenerative disorders, including Alzheimer’s disease (AD), which is the most prevalent dementia among the elderly. A better understanding of the molecular mechanisms underlying tau pathology should help advance therapies for neurodegenerative diseases. Perturbations in cyclic adenosine monophosphate (cAMP)-dependent signaling play an important role in the pathophysiology of numerous neurological diseases. EPAC2 is an intracellular cAMP receptor whose expression is downregulated in AD. However, the involvement and role of EPAC2 in tau pathology remain unclear. In this study, we report for the 1st time that EPAC2 is downregulated in the hippocampus of Tg2576 mice, a widely used transgenic mouse model of familial AD. Furthermore, genetic deletion of EPAC2 resulted in abnormal hyperphosphorylation at multiple sites on tau. Aberrant tau aggregation and abnormal neuronal morphology were also detected in these EPAC2−/− mice. Administration of inhibitors of CDK5 or calpain effectively rescued the tau pathology in EPAC2−/− mice. This suggests that the activation of CDK5 by calpain plays an important role in the development of tau pathology in these EPAC2−/− mice. Collectively, our findings demonstrate a direct link between EPAC2 and tau pathology, and suggest that the EPAC2 and calpain/CDK5 signaling pathways may have potential as therapeutic targets for AD.

LINC00662 plays a prominent role in the carcinogenesis and progression of diverse cancers. However, its biological functions in glioma are still unclear. LINC00662 expression in glioma tissue samples and cell lines was examined by quantitative real-time polymerase chain reaction. The correlation between LINC00662 expression and the clinical characteristics of 50 patients with glioma was analyzed. LINC00662 knockdown and overexpression cell lines were constructed, and the effects of LINC00662 on the proliferation, invasion, and apoptosis of glioma cells were evaluated by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, Transwell, and flow cytometry assays, respectively. Besides, the relationships among LINC00662, miR-483-3p, and sex-determining region Y-box 3 (SOX3) were assessed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Western blot was used to detect the regulatory effects of LINC00662 and miR-483-3p on SOX3 expression in glioma cells. LINC00662 expression level was elevated in glioma tissues and cell lines compared to that in normal tissues and cell lines. LINC00662 high expression was associated with the adverse prognosis of patients with glioma. Knockdown of LINC00662 repressed the proliferation and invasion of glioma cells, and promoted apoptosis. Additionally, it was revealed that LINC00662 acted as the molecular sponge of miR-483-3p, and SOX3 was verified as a direct target of miR-483-3p. The inhibition of miR-483-3p expression and SOX3 overexpression reversed the biological effects of LINC00662 knockdown on glioma cells. This study reports the key regulatory role of LINC00662/miR-483-3p/SOX3 axis in the tumorigenesis and progression of glioma, bringing novel insights into the underlying mechanisms of glioma.

Alzheimer’s disease (AD) is the most common neurodegenerative disease with limited therapeutic strategies. Cell cycle checkpoint protein kinase 1 (Chk1) is a Ser/Thr protein kinase which is activated in response to DNA damage, the latter which is an early event in AD. However, whether DNA damage-induced Chk1 activation participates in the development of AD and Chk1 inhibition ameliorates AD-like pathogenesis remain unclarified. Here, we demonstrate that Chk1 activity and the levels of protein phosphatase 2A (PP2A) inhibitory protein CIP2A are elevated in AD human brains, APP/PS1 transgenic mice, and primary neurons with Aβ treatment. Chk1 overexpression induces CIP2A upregulation, PP2A inhibition, tau and APP hyperphosphorylation, synaptic impairments, and cognitive memory deficit in mice. Moreover, Chk1 inhibitor (GDC0575) effectively increases PP2A activity, decreases tau phosphorylation, and inhibits Aβ overproduction in AD cell models. GDC0575 also reverses AD-like cognitive deficits and prevents neuron loss and synaptic impairments in APP/PS1 mice. In conclusion, our study uncovers a mechanism by which DNA damage-induced Chk1 activation promotes CIP2A-mediated tau and APP hyperphosphorylation and cognitive dysfunction in Alzheimer’s disease and highlights the therapeutic potential of Chk1 inhibitors in AD.

The third isoform of the Na+–Ca2+ exchanger (NCX3) is crucial for a physiological fine-tuning of the Ca2+ fluxes in excitable tissues. In this view, the NCX3 accounts for the aberrant Ca2+ influx seen during neuronal excitotoxicity, such as in Alzheimer’s disease (AD). However, little is known about NCX3 regulation and functional properties. Withania somnifera (L.) Dunal (W. somnifera), a traditional indigenous plant widely recognized for having numerous medicinal values, was undertaken to determine its potential therapeutic benefit against aggregated Aβ1–42-induced NCX3 dysregulation and the thereof cognition impairment in 5xFAD mice. The undertaken sourced dried roots of authenticated W. somnifera physicochemical compositional tests satisfied standards of pharmacognostic quality, and further phytochemical analysis of the roots methanol extract revealed the roots constitute several antioxidants. Following an intra-gastric gavage administration of synthesized W. somnifera roots methanolic extract from postnatal day 30 (P30) to P75, in vivo cognitional studies and then neurochemical examinations of the NCX3 expression level, Aβ plaque deposition, and antioxidant activities in the AD-associated brain regions of 4-month-old 5xFAD mice suggests that the oxidative stress normalizing effects of W. somnifera constituents, operating on the NCX3, may have a therapeutic role in the improvement of cognition in AD.

An Au@ZnO/rGO nanocomposite demonstrates a sensitive, selective, and ultra-low detection limit for NO2 sensing (5 ppb-1 ppm) at 60 °C.

Background Viral tracers are important tools for mapping brain connectomes. The feature of predominant anterograde transneuronal transmission offers herpes simplex virus-1 (HSV-1) strain H129 (HSV1-H129) as a promising candidate to be developed as anterograde viral tracers. In our earlier studies, we developed H129-derived anterograde polysynaptic tracers and TK deficient (H129-dTK) monosynaptic tracers. However, their broad application is limited by some intrinsic drawbacks of the H129-dTK tracers, such as low labeling intensity due to TK deficiency and potential retrograde labeling caused by axon terminal invasion. The glycoprotein K (gK) of HSV-1 plays important roles in virus entry, egress, and virus-induced cell fusion. Its deficiency severely disables virus egress and spread, while only slightly limits viral genome replication and expression of viral proteins. Therefore, we created a novel H129-derived anterograde monosynaptic tracer (H129-dgK) by targeting gK, which overcomes the limitations of H129-dTK. Methods Using our established platform and pipeline for developing viral tracers, we generated a novel tracer by deleting the gK gene from the H129-G4. The gK-deleted virus (H129-dgK-G4) was reconstituted and propagated in the Vero cell expressing wildtype H129 gK (gKwt) or the mutant gK (gKmut, A40V, C82S, M223I, L224V, V309M), respectively. Then the obtained viral tracers of gKmut pseudotyped and gKwt coated H129-dgK-G4 were tested in vitro and in vivo to characterize their tracing properties. Results H129-dgK-G4 expresses high levels of fluorescent proteins, eliminating the requirement of immunostaining for imaging detection. Compared to the TK deficient monosynaptic tracer H129-dTK-G4, H129-dgK-G4 labeled neurons with 1.76-fold stronger fluorescence intensity, and visualized 2.00-fold more postsynaptic neurons in the downstream brain regions. gKmut pseudotyping leads to a 77% decrease in retrograde labeling by reducing axon terminal invasion, and thus dramatically improves the anterograde-specific tracing of H129-dgK-G4. In addition, assisted by the AAV helper trans-complementarily expressing gKwt, H129-dgK-G4 allows for mapping monosynaptic connections and quantifying the circuit connectivity difference in the Alzheimer’s disease and control mouse brains. Conclusions gKmut pseudotyped H129-dgK-G4, a novel anterograde monosynaptic tracer, overcomes the limitations of H129-dTK tracers, and demonstrates desirable features of strong labeling intensity, high tracing efficiency, and improved anterograde specificity.

AlGaN/GaN Schottky barrier diode (SBD) temperature sensor with low turn-on voltage was fabricated by employing the recessed anode structure. This AlGaN/GaN SBD demonstrates good rectification in a broad temperature scope from 298 to 473 K. Compared with common planar diode, the recessed anode SBD shows a relatively lower turn-on voltage and better Schottky contact characteristics. The temperature-dependent forward voltage at a fixed current displays great linearity, contributing to a sensitivity of about 1.0 mV/K. The calculated sensitivities exhibit the downtrend by increasing current level, which is in agreement with the thermionic emission (TE) model. The recessed anode AlGaN/GaN SBDs show good potential in temperature sensor application.

Monosynaptic viral tracers are essential tools for dissecting neuronal connectomes and for targeted delivery of molecular sensors and effectors. Viral toxicity and complex multi-injection protocols are major limiting application barriers. To overcome these barriers, we developed an anterograde monosynaptic H129Amp tracer system based on HSV-1 strain H129. The H129Amp tracer system consists of two components: an H129-dTK-T2-pacFlox helper which assists H129Amp tracer’s propagation and transneuronal monosynaptic transmission. The shared viral features of tracer/helper allow for simultaneous single-injection and subsequent high expression efficiency from multiple-copy of expression cassettes in H129Amp tracer. These improvements of H129Amp tracer system shorten experiment duration from 28-day to 5-day for fast-bright monosynaptic tracing. The lack of toxic viral genes in the H129Amp tracer minimizes toxicity in postsynaptic neurons, thus offering the potential for functional anterograde mapping and long-term tracer delivery of genetic payloads. The H129Amp tracer system is a powerful tracing tool for revealing neuronal connectomes.

In this study, the high oxygen vacancy-rich ultrathin indium oxide (In2O3) nanosheets are synthesized by low-cost and environmental-friendly solvothermal method. The gas sensing properties of In2O3 nanosheets to low concentration of nitrogen dioxide (NO2) (concentration in 5 ppb to 5 ppm) at 50 °C are investigated. All In2O3 samples are successfully characterized using various techniques to obtain the information related to phase, morphological, oxygen vacancies, and surface area, etc. It is observed that among all the samples, the In2O3-350 exhibited benchmarked response of around 3223 at 2 ppm NO2 gas, with theoretical detection limit down to ppb level. The sensor has shown superior sensing characteristics, such as wide sensing bandwidth, excellent selectivity, high long-term stability, and good repeatability. It is considered that the high oxygen deficiency present on In2O3 nanosheets acts as favorable reaction sites for such remarkable sensing performance, and therefore, these improved gas-sensing properties make the In2O3 nanosheets suitable to detect NO2 at low-temperature.

Accumulating evidence suggests that gut microbiota as a critical mediator of gut-brain axis plays an important role in human health. Altered gut microbial profiles have been implicated in increasing the vulnerability of psychiatric disorders, such as autism, depression, and schizophrenia. However, the cellular and molecular mechanisms underlying the association remain unknown. Here, we modified the gut microbiome with antibiotics in newborn mice, and found that gut microbial alteration induced behavioral impairment by decreasing adult neurogenesis and long-term potentiation of synaptic transmission, and altering the gene expression profile in hippocampus. Reconstitution with normal gut flora produced therapeutic effects against both adult neurogenesis and behavioral deficits in the dysbiosis mice. Furthermore, our results show that circulating metabolites changes mediate the effect of gut dysbiosis on hippocampal plasticity and behavior outcomes. Elevating the serum 4-methylphenol, a small aromatic metabolite produced by gut bacteria, was found to induce autism spectrum disorder (ASD)-like behavior impairment and hippocampal dysfunction. Together our finding demonstrates that early-life gut dysbiosis and its correlated metabolites change contribute to hippocampal dysfunction and behavior impairment, hence highlight the potential microbiome-mediated therapies for treating psychiatric disorders.

The photocatalytic water splitting has a stupendous role to generate renewable hydrogen. However, the overall water splitting reaction is limited by the sluggish oxidation step. Bismuth vanadate (BiVO4) has been identified as one of the most promising n-type semiconductors for photocatalytic water oxidation due to its small energy gap and favorable band alignment. Thus, it is necessary to summarize the recent progress done on BiVO4 for the guidance of future research. In this review, we have discussed recent strategies that have been adopted to boost its photoconversion efficiency at three different levels: (1) facet control, (2) morphological control and, (3) interfacial control. The roles of high indexed facets, anisotropic morphologies, and mediator-based Z schemes are comprehensively discussed and the emphasis is given to find the suitable structural, morphological, and interfacial combination of BiVO4 for efficient water oxidation.

As an excitatory transmitter system, the glutamatergic transmitter system controls excitability and conductivity of neurons. Since both cardiomyocytes and neurons are excitable cells, we hypothesized that cardiomyocytes may also be regulated by a similar system. Here, we have demonstrated that atrial cardiomyocytes have an intrinsic glutamatergic transmitter system, which regulates the generation and propagation of action potentials. First, there are abundant vesicles containing glutamate beneath the plasma membrane of rat atrial cardiomyocytes. Second, rat atrial cardiomyocytes express key elements of the glutamatergic transmitter system, such as the glutamate metabolic enzyme, ionotropic glutamate receptors (iGluRs), and glutamate transporters. Third, iGluR agonists evoke iGluR-gated currents and decrease the threshold of electrical excitability in rat atrial cardiomyocytes. Fourth, iGluR antagonists strikingly attenuate the conduction velocity of electrical impulses in rat atrial myocardium both in vitro and in vivo. Knockdown of GRIA3 or GRIN1, two highly expressed iGluR subtypes in atria, drastically decreased the excitatory firing rate and slowed down the electrical conduction velocity in cultured human induced pluripotent stem cell (iPSC)-derived atrial cardiomyocyte monolayers. Finally, iGluR antagonists effectively prevent and terminate atrial fibrillation in a rat isolated heart model. In addition, the key elements of the glutamatergic transmitter system are also present and show electrophysiological functions in human atrial cardiomyocytes. In conclusion, our data reveal an intrinsic glutamatergic transmitter system directly modulating excitability and conductivity of atrial cardiomyocytes through controlling iGluR-gated currents. Manipulation of this system may open potential new avenues for therapeutic intervention of cardiac arrhythmias.

Aims: To compare Endoscopic Surgery and Robot CAS-R-2 drainage for surgical treatment of basal ganglia hypertensive intracerebral hemorrhage. Methods: Fifty consecutive basal ganglia hemorrhage patients were reviewed retrospectively. The primary and secondary outcomes were 6-months mortality and 6-months modified Rankin Scale score, which were assessed by a multivariate logistic regression mode.Results: Compared with the Robot CAS-R-2 group, the 6-month prognosis was significantly higher in the endoscopic evacuation group (OR 5.912, 95% CI 1.014-34.459). Preoperative hematoma volume (OR = 0.931, 95% CI 0.875-0.990) and IVH (OR = 0.578, 95% CI0.396-0.844) were independent predictors for 6-month prognosis. No significant difference in the mortality was found in the two groups (OR 0.501, 95% CI 0.192-1.308).Conclusion: Endoscopic hematoma removal significantly improved the 6-month prognosis compared with the drainage of hematoma under Robot CAS-R-2.

Dynamic change of mitochondrial morphology and distribution along neuronal branches are essential for neural circuitry formation and synaptic efficacy. However, the underlying mechanism remains elusive. We show here that Pink1 knockout (KO) mice display defective dendritic spine maturation, reduced axonal synaptic vesicles, abnormal synaptic connection, and attenuated long-term synaptic potentiation (LTP). Drp1 activation via S616 phosphorylation rescues deficits of spine maturation in Pink1 KO neurons. Notably, mice harboring a knockin (KI) phosphor-null Drp1S616A recapitulate spine immaturity and synaptic abnormality identified in Pink1 KO mice. Chemical LTP (cLTP) induces Drp1S616 phosphorylation in a PINK1-dependent manner. Moreover, phosphor-mimetic Drp1S616D restores reduced dendritic spine localization of mitochondria in Pink1 KO neurons. Together, this study provides the first in vivo evidence of functional regulation of Drp1 by phosphorylation and suggests that PINK1-Drp1S616 phosphorylation coupling is essential for convergence between mitochondrial dynamics and neural circuitry formation and refinement.

High-performance solar-blind UV detector with high response and fast speed is needed in multiple types of areas, which is hard to achieve in one device with a simple structure and device fabrication process. Here, the effects of Ag nanoparticles (NPs) with different sizes on UV response characteristics of the device are studied, the Ag NPs with different sizes that are made from a simple vacuum anneal method. Ag NPs with different sizes could modulate the peak response position of the mixed-phase MgZnO detector from near UV range (350 nm) to deep UV range (235 nm), and the enhancement effect of the Ag NPs on the UV response differs much with the crystal structure and the basic UV response of the MgZnO thin film. When high density 20-40 nm Ag NPs is induced, the deep UV (235 nm) response of the mixed-phase MgZnO detector is increased by 226 times, the I uv/I dark ratio of the modified device is increased by 17.5 times. The slight enhancement in UV light intensity from 20 to 40 nm Ag NPs induces multiple tunnel breakdown phenomena within the mixed-phase MgZnO thin film, which is the main reason for the abnormal great enhancement effect on deep UV response of the device, so the recovery speed of the modified device is not influenced. Therefore, Ag NPs with different sizes could effectively modulate the UV response peak position of mixed-phase MgZnO thin films, and the introduction of Ag NPs with high density and small size is a simple way to greatly increase the sensitivity of the mixed-phase MgZnO detector at deep UV light without decreasing the device speed. Published version This work was supported by the National Natural Science Foundation of China under grant nos. (51872187, 11774241, 51371120, 51302174, 61704111, 61504083, and 61574051), the Natural Science Foundation of Guangdong Province (2016A030313060 and 2017A030310524), the Public Welfare Capacity Building in Guangdong Province (2015A010103016), the Project of Department of Education of Guangdong Province (2014KTSCX110), the Science and Technology Research Items of Shenzhen (JCYJ20170818144255777, JCYJ20170818144212483, JCYJ20180507182248925, JCYJ201602261920, JCYJ20170818143417082, and JCYJ20160226192033020), the Science and Technology Foundation of Shenzhen, and the National Key Research and Development Program of China (2017YFB0404100 and 2017YFB0403000).

Aberrant regulation of microRNAs (miRNAs) has been implicated in the pathogenesis of Alzheimer’s disease (AD), but most abnormally expressed miRNAs found in AD are not regulated by synaptic activity. Here we report that dysfunction of miR-135a-5p/Rock2/Add1 results in memory/synaptic disorder in a mouse model of AD. miR-135a-5p levels are significantly reduced in excitatory hippocampal neurons of AD model mice. This decrease is tau dependent and mediated by Foxd3. Inhibition of miR-135a-5p leads to synaptic disorder and memory impairments. Furthermore, excess Rock2 levels caused by loss of miR-135a-5p plays an important role in the synaptic disorder of AD via phosphorylation of Ser726 on adducin 1 (Add1). Blocking the phosphorylation of Ser726 on Add1 with a membrane-permeable peptide effectively rescues the memory impairments in AD mice. Taken together, these findings demonstrate that synaptic-related miR-135a-5p mediates synaptic/memory deficits in AD via the Rock2/Add1 signaling pathway, illuminating a potential therapeutic strategy for AD., Several micro RNAs have been shown to be deregulated in brain tissue or sera from individuals with Alzheimer’s disease and in AD mouse models. The authors show that miR-135a-5p is downregulated in excitatory pyramidal neurons from AD mice and that dysfunction of miR-135a-5p/Rock2/Add1 results in memory/synaptic disorder in AD.

Urea electrolysis provides a promising approach for simultaneous energy-saving hydrogen production and wastewater utilization; however, the total reaction rate is severely restricted by the sluggish kinetics of the anodic urea oxidization reaction (UOR). Herein, we report a universal and highly controllable electrochemical defect-engineering approach to enrich the active sites on transition metal oxides toward promoted UOR catalysis. A large number of oxygen vacancies (Vo) were introduced on the surface of a Co3O4 nanowire model-material through negative potential tuning, leading to significantly increased UOR activity of the material. At a potential of 1.34 V vs. RHE, the defect-engineered catalyst delivers an optimal UOR current density of 100 mA cm−2, which is much higher than that (42 mA cm−2) offered by the original Co3O4 catalyst, and outperforms the best reported noble-metal-free UOR catalysts. Experimental results further reveal that the formation of Vo can effectively reduce the charge transport/transfer resistances both inside the nanowires and at the catalyst/electrolyte interface, giving rise to improved UOR activity. These findings suggest the great potential of this electrochemical defect-engineering strategy in the design of defect-enriched catalysts for advanced electrocatalysis.

Iron homeostasis disturbance has been implicated in Alzheimer’s disease (AD), and excess iron exacerbates oxidative damage and cognitive defects. Ferroptosis is a nonapoptotic form of cell death dependent upon intracellular iron. However, the involvement of ferroptosis in the pathogenesis of AD remains elusive. Here, we report that ferroportin1 (Fpn), the only identified mammalian nonheme iron exporter, was downregulated in the brains of APPswe/PS1dE9 mice as an Alzheimer’s mouse model and Alzheimer’s patients. Genetic deletion of Fpn in principal neurons of the neocortex and hippocampus by breeding Fpnfl/fl mice with NEX-Cre mice led to AD-like hippocampal atrophy and memory deficits. Interestingly, the canonical morphological and molecular characteristics of ferroptosis were observed in both Fpnfl/fl/NEXcre and AD mice. Gene set enrichment analysis (GSEA) of ferroptosis-related RNA-seq data showed that the differentially expressed genes were highly enriched in gene sets associated with AD. Furthermore, administration of specific inhibitors of ferroptosis effectively reduced the neuronal death and memory impairments induced by Aβ aggregation in vitro and in vivo. In addition, restoring Fpn ameliorated ferroptosis and memory impairment in APPswe/PS1dE9 mice. Our study demonstrates the critical role of Fpn and ferroptosis in the progression of AD, thus provides promising therapeutic approaches for this disease.

We demonstrate the growth of ultra-thin (~5 nm) indium ytterbium oxide (In-Yb-O) thin film using a simple vacuum-free aqueous solution approach for the first time. The influences of Yb addition on the microstructural, chemical, optical, and electrical properties of In2O3 are well investigated. The analyses indicate that Yb dopant could suppress oxygen vacancy defects effectively owing to the lower standard electrode potential, lower electronegativity, and stronger metal-oxide bond strength than that of In. The optimized In-Yb-O thin-film transistors (TFTs) exhibit excellent electrical performance (mobility of 8 cm2/Vs and on/off ratio of ~108) and enhanced stability. The triumph of In-Yb-O TFTs is owing to the high quality In2O3 matrix, the remarkable suppressor of Yb, and the nanometer-thin and atomically smooth nature (RMS: ~0.26 nm) of channel layer. Therefore, the eco-friendly water-induced ultra-thin In-Yb-O channel provides an excellent opportunity for future large-scale and cost-effective electronic applications.

Thin-film transistors (TFTs) made of solution-processable transparent metal oxide semiconductors show great potential for use in emerging large-scale optoelectronics. However, current solution-processed metal oxide TFTs still suffer from relatively poor device performance, hindering their further advancement. In this work, we create a novel ultrathin crystalline indium–boron–oxide (In-B-O) channel layer for high-performance TFTs. We show that high-quality ultrathin (~10 nm) crystalline In-B-O with an atomically smooth nature (RMS: ~0.15 nm) could be grown from an aqueous solution via facile one-step spin-coating. The impacts of B doping on the physical, chemical and electrical properties of the In2O3 film are systematically investigated. The results show that B has large metal–oxide bond dissociation energy and high Lewis acid strength, which can suppress oxygen vacancy-/hydroxyl-related defects and alleviate dopant-induced carrier scattering, resulting in electrical performance improvement. The optimized In-B-O (10% B) TFTs based on SiO2/Si substrate demonstrate a mobility of ~8 cm2/(V s), an on/off current ratio of ~106 and a subthreshold swing of 0.86 V/dec. Furthermore, by introducing the water-processed high-K ZrO2 dielectric, the fully aqueous solution-grown In-B-O/ZrO2 TFTs exhibit excellent device performance, with a mobility of ~11 cm2/(V s), an on/off current of ~105, a subthreshold swing of 0.19 V/dec, a low operating voltage of 5 V and superior bias stress stability. Our research opens up new avenues for low-cost, large-area green oxide electronic devices with superior performance.

Post-stroke depression (PSD) is a serious and common complication of stroke, which seriously affects the rehabilitation of stroke patients. To date, the pathogenesis of PSD is unclear and effective treatments remain unavailable. Here, we established a mouse model of PSD through photothrombosis-induced focal ischemia. By using a combination of brain imaging, transcriptome sequencing, and bioinformatics analysis, we found that the hippocampus of PSD mice had a significantly lower metabolic level than other brain regions. RNA sequencing revealed a significant reduction of miR34b-3p, which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E (eIF4E). Furthermore, silencing eIF4E inactivated microglia, inhibited neuroinflammation, and abolished the depression-like behaviors in PSD mice. Together, our data demonstrated that insufficient miR34b-3p after stroke cannot inhibit eIF4E translation, which causes PSD by the activation of microglia in the hippocampus. Therefore, miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.

Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neurodevelopmental disorders. However, the neuropathogenesis remains largely elusive due to a lack of informative animal models. In this study, we developed a congenital murine CMV (cMCMV) infection mouse model with high survival rate and long survival period that allowed long-term follow-up study of neurodevelopmental disorders. This model involves in utero intracranial injection and mimics many reported clinical manifestations of cCMV infection in infants, including growth restriction, hearing loss, and impaired cognitive and learning-memory abilities. We observed that abnormalities in MRI/CT neuroimaging were consistent with brain hemorrhage and loss of brain parenchyma, which was confirmed by pathological analysis. Neuropathological findings included ventriculomegaly and cortical atrophy associated with impaired proliferation and migration of neural progenitor cells in the developing brain at both embryonic and postnatal stages. Robust inflammatory responses during infection were shown by elevated inflammatory cytokine levels, leukocyte infiltration, and activation of microglia and astrocytes in the brain. Pathological analyses and CT neuroimaging revealed brain calcifications induced by cMCMV infection and cell death via pyroptosis. Furthermore, antiviral treatment with ganciclovir significantly improved neurological functions and mitigated brain damage as shown by CT neuroimaging. These results demonstrate that this model is suitable for investigation of mechanisms of infection-induced brain damage and long-term studies of neurodevelopmental disorders, including the development of interventions to limit CNS damage associated with cCMV infection.

Amorphous gallium tin oxide (GTO) thin films were prepared by a facile, and eco-friendly, aqueous solution process and their applications in thin-film transistors (TFTs) were investigated. The success of the aqueous route was realized by introducing tin fluoride (SnF2) instead of the traditional tin chloride (SnCl2) solute. The roles of adding Ga on the GTO’s microstructural, optical, chemical, and electrical performance were comprehensively studied. It was found that Ga can frustrate the crystallization while it augments the optical bandgap (Eg) value of pristine SnO2. More importantly, using Ga could effectively inhibit the formation of oxygen vacancies, thus greatly improving the electrical performance of the GTO TFTs. The amorphous GTO TFTs with a Ga content of 45% exhibited optimum performance, with a saturation mobility (μsat) of 4.26 cm2/V s, an on/off current ratio (Ion/Ioff) >107, and a decent bias stress durability.

In this study, pulsed laser deposition method (PLD) was employed to grow MgxZn1-xO films on quartz substrates. The optimal deposition temperature of 300 °C for MgxZn1-xO film was decided and Mg0.38Zn0.62O, Mg0.56Zn0.44O and Mg0.69Zn0.31O films were grown respectively using MgxZn1-xO targets with different Mg contents (x = 0.3, 0.5 and 0.7). As-deposited Mg0.38Zn0.62O film possessed the mixed-phase (hexagonal and cubic phase) structure, appropriate band gap of 4.68 eV and smaller surface roughness of 1.72 nm, and the solar-blind photodetector (PD) based on it was fabricated. The key features of our PD are the cutoff wavelength of 265 nm lying in solar-blind band, lower dark current (Idark) of 88 pA, higher peak responsivity of 0.10 A/W and bigger Ilight/Idark ratio of 1688, which provide the new idea for the application of solar-blind PDs based on MgxZn1-xO films.

In this paper, we report aqueous solution-processed boron-doped gallium oxide dielectric thin films for high-performance oxide thin-film transistors. The role of B incorporation on the microstructu...

Recently, metal surface plasma technology has been widely used to improve the quantum efficiency of optoelectronic devices, such as ZnO light-emitting diodes (LEDs). In this work, Ag films with the appropriate thickness were prepared by evaporation and annealed, and a layer of ZnCdO films with different Cd concentrations was grown on the Ag films by the pulsed laser deposition method. During this process, the changes in the Cd concentrations caused the near-band edge (NBE) emission of the ZnCdO films to be continuously adjusted in the ultraviolet to green wavelength range by controlling the oxygen pressure. The prepared Ag nanoparticles and ZnCdO composite films were used to study the metal localized surface plasmon (LSP) effect. The results show that the enhanced or reduced photoluminescence intensity of ZnCdO NBE depends on the probability of electrons transport to either the LSP level or the Fermi level of the metal. This discovery provides an important theoretical basis for the preparation of ZnCdO semiconductor LEDs in the future.

Tungsten oxide microflowers (WO3 MFs) were fabricated by a simple hydrothermal process through adjusting the pH of the solution by HCl. These MFs possess the outer diameters of about 2 μm and are composed of numerous nanoplates with the average pore size of 10.9 nm. Chemiresistive activity of as-fabricated WO3 MFs sensor was attempted towards oxidizing and reducing target gases, revealing a superior selectivity to NO2 with a maximum response of 22.95 (2 ppm NO2) @105 °C compared to other target gases. One of the key features of as-fabricatedWO3 MFs sensor is the lower detection limit of 125 ppb and operating temperature of 105 °C to NO2 with better reproducibility, signifying commercial prospective of the developed sensor materials. Finally, the gas sensing mechanism of WO3 MFs sensor has been proposed.

MoS2, as a typical representative of two-dimensional semiconductors, has been explored extensively in applications of optoelectronic devices because of its adjustable bandgap. However, to date, the performance of the fabricated photodetectors has been very sensitive to the surrounding environment owing to the large surface-to-volume ratio. In this work, we report on large-scale, high-performance monolayer MoS2 photodetectors covered with a 3-nm Al2O3 layer grown by atomic layer deposition. In comparison with the device without the Al2O3 stress liner, both the photocurrent and responsivity are improved by over 10 times under 460-nm light illumination, which is due to the tensile strain induced by the Al2O3 layer. Further characterization demonstrated state-of-the-art performance of the device with a responsivity of 16.103 A W−1, gain of 191.80, NEP of 7.96 × 10−15 W Hz−1/2, and detectivity of 2.73 × 1010 Jones. Meanwhile, the response rise time of the photodetector also reduced greatly because of the increased electron mobility and reduced surface defects due to the Al2O3 stress liner. Our results demonstrate the potential application of large-scale strained monolayer MoS2 photodetectors in next-generation imaging systems.

A p-GaN/i-MgO/n-ZnO nanorod array (NRA) heterojunction light-emitting diode has been fabricated. Its room-temperature electroluminescence spectra under different forward biases revealed a strong emission band across the whole visible region, which was blue-shifted when increasing the forward bias. The origin of this visible emission is considered to be related to oxygen vacancy (VO) defects in different valence states, where the blue emission (∼ 460 nm) comes from neutral oxygen vacancy (VOX ) defects and the green emission (∼ 520 nm) from singly charged oxygen vacancy (VO+ ) defects, while the yellow (∼ 580 nm) and red emission (∼ 670 nm) are attributed to doubly charge oxygen vacancy (VO++ ) defects. These VO defects in different states can convert into one another under different excitation conditions, resulting in the blue-shift of the emission peak as the forward voltage is increased.

As an n-type oxide semiconductor, Ga2O3 shows great promise in solar-blind ultraviolet (UV) photodetectors due to its adequate band gap, high absorption coefficient, high thermal and chemical stability, high breakdown voltage, and high sensitivity to UV light. In order to investigate the photoresponse of the Ga2O3 photodetector with different crystallization status, we fabricated a series of β-Ga2O3 thin films on a sapphire substrate via pulsed laser deposition with different deposition temperatures from 250°C to 650°C. X-ray diffraction and scanning electron microscopy result showed crystallization enhancement due to the increasing of deposition temperature, and the crystallization procedure started at ∼ 450°C. Optical analysis indicated a blue shift present at the absorption edge (from 4.6 eV to 5.1 eV) with temperature increasing from 450°C to 650°C, showing modulation feasibility in the band gap due to temperature dependence. In addition, all samples showed high transmittance (over 90%) over the entire visible spectrum. Film detectors fabricated by these samples showed high photoresponse and high light/dark current ratio (ILight/IDark) on Ga2O3 deposited at 450°C. Transmission electron microscopy result for film deposited at 450°C showed that the top and bottom regions of films contained both amorphous and crystalline Ga2O3, while there was no crystallization in the middle area of the film, indicating that a combined amorphous-crystalline Ga2O3 film with adequate ratio of crystalline state can significantly enhance the photoresponse while restraining the dark current.

Thin-film transistors (TFTs) based on solution-derived metal oxides hold great potential in emerging low-cost large-area printed electronics. Despite recent impressive progress, these device performances are far behind those of their corresponding vacuum-based counterparts, impeding their future commercialization. In this work, we designed and created high-performance TFTs based on a nanometer-thick (down to 5 nm) crystalline In–Sm–O channel via aqueous solution processing, with a performance comparable to those of existing vacuum-processed metal oxides. The microstructural, chemical, optical, and electrical properties of the ultra-thin In–Sm–O samples as a function of Sm doping content (0–10%) were comprehensively investigated. The In–Sm–O TFTs (5% Sm) on SiO2/Si dielectrics demonstrated state-of-the-art performance, including a high mobility of 21.51 ± 1.33 cm2 V−1 s−1, subthreshold swing of 0.66 ± 0.06 V per decade, threshold voltage of 2.14 ± 0.44 V, on/off current ratio >108, and remarkable bias stress stability. The success of In–Sm–O was attributed to the high quality of the crystalline In2O3 matrix, the ideal nature of Sm dopant in suppressing oxygen vacancies, as well as the ultrathin and atomically smooth nature of the channel layer. Therefore, the aqueous solution-processed ultra-thin In–Sm–O channel is expected to enable the realization of future low-cost, large-area, and high-performance green electronics.

Au/MgZnO/nanolayered ZnO (Ga-doped)/In MIS (metal–insulator–semiconductor) structure UV detectors are fabricated by the PLD (pulsed laser deposition) method, and the effect of different thickness G...

Transparent amorphous oxide semiconductor (TAOS) represented by a-InGaZnO (IGZO) has achieved their commercial success in the display industry due to its superior material properties (e.g. high mobility (>10 cm 2 V −1 s −1 ), good transparency and excellent uniformity). However, TAOSs with excellent electrical properties are all n-type due to the particular electronic structures of oxide materials. The absence of high performance p-type TAOS limits the device application such as complimentary circuit and is now the largest drawback for oxide electronics. Here, we propose a low-temperature solution method to fabricate p-type transparent amorphous nickel oxide (NiO). The influence of processing parameters such as annealing temperature, precursor concentration, source/drain electrode, and dielectric layer is systematically investigated to maximum the NiO device performance. The optimized NiO TFT exhibits outstanding p-channel behavior, including a high hole mobility of 6.0 cm 2 V −1 s −1 , remarkable on/off current modulation ratio of ∼10 7 , and good subthreshold swing of 0.13 V/decade. The high performance NiO device is attributed to the synergistic optimization of annealing temperature, channel thickness, source/drain electrodes, and dielectric materials. The properties of our p-type TAOS are comparable with that of traditional n-type TAOS.

Background Aldh1a1 neurons are a subtype of gamma-aminobutyric acid (GABA) inhibitory neurons that use Aldh1a1 rather than glutamate decarboxylase (GAD) as an enzyme for synthesizing GABA transmitters. However, the behaviors and circuits of this newly identified subtype of inhibitory interneurons remain unknown. Methods We generated a mutant mouse line in which cyclization recombination enzyme (CRE) was expressed under the control of the Aldh1a1 promotor (Aldh1a1-CRE mice). Using this mutant strain of mice together with the heterozygous male Alzheimer’s disease (AD) related model mice (APPswe/PSEN1dE9, or AD mice) and a genetically modified retrograde and anterograde synaptic tracing strategy, we have studied a specific synaptic circuit of Aldh1a1 neurons with system-level function and disease progression in AD mice. Results We demonstrate that Aldh1a1 neurons encode delay of gratification that measures self-control skills in decision making by projecting inhibitory synapses directly onto excitatory glutamate neurons in the intermediate lateral septum (EGNIS) and receiving synaptic inputs from layer 5b pyramidal neurons in the medial prefrontal cortex (L5PN). L5PN → Aldh1a1 synaptic transmission undergoes long-term potentiation (LTP). Pathway specific inhibition by either genetic silencing presynaptic terminals or antagonizing postsynaptic receptors impairs delay of gratification, resulting in the impulsive behaviors. Further studies show that reconstitution of Aldh1a1-deficient neurons with the expression of exogenous Aldh1a1 (eAldh1a1) restores Aldh1a1 → EGNIS synaptic transmission and rescues the impulsive behaviors in AD mice. Conclusions These results not only identify a specific function and circuit of Aldh1a1 neurons but also provide a cellular point of entry to an important but understudied synaptic mechanism for the induction of impulsive behaviors at an early stage of AD.

Cholinergic neurons in the medial septum (MS) constitute a major source of cholinergic input to the forebrain and modulate diverse functions, including sensory processing, memory, and attention. Most studies to date have treated cholinergic neurons as a single population; as such, the organizational principles underling their functional diversity remain unknown. Here, we identified two subsets (D28K

Dynamic change of mitochondrial morphology and distribution along neuronal branches are essential for neural circuitry formation and synaptic efficacy. However, the underlying mechanism remains elusive. We show here that Pink1 knockout (KO) mice display defective dendritic spine maturation, reduced axonal synaptic vesicles, abnormal synaptic connection, and attenuated long-term synaptic potentiation (LTP). Drp1 activation via S616 phosphorylation rescues deficits of spine maturation in Pink1 KO neurons. Notably, mice harboring a knockin (KI) phosphor-null Drp1

Background Communicating hydrocephalus (CH) is a common neurological disorder caused by a blockage of cerebrospinal fluid. In this study, we aimed to explore the potential molecular mechanism underlying CH development. Methods Quantitative proteomic analysis was performed to screen the differentially expressed proteins (DEPs) between patients with and without CH. A CH rat model was verified by Hoechst staining, and the co-localization of the target protein and neuron was detected using immunofluorescence staining. Loss-of-function experiments were performed to examine the effect of KLK6 on the synapse structure. Results A total of 11 DEPs were identified, and kallikrein 6 (KLK6) expression was found to be significantly upregulated in patients with CH compared with that in patients without CH. The CH rat model was successfully constructed, and KLK6 was found to be co-localized with neuronal nuclei in brain tissue. The expression level of IL-1β, TNF-α, and KLK6 in the CH group was higher than that in the control group. After knockdown of KLK6 expression using small-interfering RNA (siRNA), the expression levels of synapsin-1 and PSD95 in neuronal cells were increased, and the length, number, and structure of synapses were significantly improved. Following siRNA interference KLK6 expression, 5681 differentially expressed genes (DEGs) were identified in transcriptome profile. The upregulated DEGs of Appl2, Nav2, and Nrn1 may be involved in the recovery of synaptic structures after the interference of KLK6 expression. Conclusions Collectively, KLK6 participates in the development of CH and might provide a new target for CH treatment.