ABSTRACT
BACKGROUND: Sleep fragmentation is a persistent problem throughout the course of Parkinson's disease (PD). However, the related neurophysiological patterns and the underlying mechanisms remained unclear. METHOD: We recorded subthalamic nucleus (STN) local field potentials (LFPs) using deep brain stimulation (DBS) with real-time wireless recording capacity from 13 patients with PD undergoing a one-night polysomnography recording, 1 month after DBS surgery before initial programming and when the patients were off-medication. The STN LFP features that characterised different sleep stages, correlated with arousal and sleep fragmentation index, and preceded stage transitions during N2 and REM sleep were analysed. RESULTS: Both beta and low gamma oscillations in non-rapid eye movement (NREM) sleep increased with the severity of sleep disturbance (arousal index (ArI)-betaNREM: r=0.9, p=0.0001, sleep fragmentation index (SFI)-betaNREM: r=0.6, p=0.0301; SFI-gammaNREM: r=0.6, p=0.0324). We next examined the low-to-high power ratio (LHPR), which was the power ratio of theta oscillations to beta and low gamma oscillations, and found it to be an indicator of sleep fragmentation (ArI-LHPRNREM: r=-0.8, p=0.0053; ArI-LHPRREM: r=-0.6, p=0.0373; SFI-LHPRNREM: r=-0.7, p=0.0204; SFI-LHPRREM: r=-0.6, p=0.0428). In addition, long beta bursts (>0.25 s) during NREM stage 2 were found preceding the completion of transition to stages with more cortical activities (towards Wake/N1/REM compared with towards N3 (p<0.01)) and negatively correlated with STN spindles, which were detected in STN LFPs with peak frequency distinguishable from long beta bursts (STN spindle: 11.5 Hz, STN long beta bursts: 23.8 Hz), in occupation during NREM sleep (ß=-0.24, p<0.001). CONCLUSION: Features of STN LFPs help explain neurophysiological mechanisms underlying sleep fragmentations in PD, which can inform new intervention for sleep dysfunction. TRIAL REGISTRATION NUMBER: NCT02937727.
ABSTRACT
Sleep disturbances profoundly affect the quality of life in individuals with neurological disorders. Closed-loop deep brain stimulation (DBS) holds promise for alleviating sleep symptoms, however, this technique necessitates automated sleep stage decoding from intracranial signals. We leveraged overnight data from 121 patients with movement disorders (Parkinson's disease, Essential Tremor, Dystonia, Essential Tremor, Huntington's disease, and Tourette's syndrome) in whom synchronized polysomnograms and basal ganglia local field potentials were recorded, to develop a generalized, multi-class, sleep specific decoder - BGOOSE. This generalized model achieved 85% average accuracy across patients and across disease conditions, even in the presence of recordings from different basal ganglia targets. Furthermore, we also investigated the role of electrocorticography on decoding performances and proposed an optimal decoding map, which was shown to facilitate channel selection for optimal model performances. BGOOSE emerges as a powerful tool for generalized sleep decoding, offering exciting potentials for the precision stimulation delivery of DBS and better management of sleep disturbances in movement disorders.
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Background: Anxiety and social withdrawal are highly prevalent among patients with Alzheimer's disease (AD). However, the neural circuit mechanisms underlying these symptoms remain elusive, and there is a need for effective prevention strategies. Objective: This study aims to elucidate the neural circuitry mechanisms underlying social anxiety in AD. Methods: We utilized 5xFAD mice and conducted a series of experiments including optogenetic manipulation, Tandem Mass Tag-labeled proteome analysis, behavioral assessments, and immunofluorescence staining. Results: In 5xFAD mice, we observed significant amyloid-ß (Aß) accumulation in the anterior part of basolateral amygdala (aBLA). Behaviorally, 6-month-old 5xFAD mice displayed excessive social avoidance during social interaction. Concurrently, the pathway from aBLA to ventral hippocampal CA1 (vCA1) was significantly activated and exhibited a disorganized firing patterns during social interaction. By optogenetically inhibiting the aBLA-vCA1 pathway, we effectively improved the social ability of 5xFAD mice. In the presence of Aß accumulation, we identified distinct changes in the protein network within the aBLA. Following one month of administration of Urolithin A (UA), we observed significant restoration of the abnormal protein network within the aBLA. UA treatment also attenuated the disorganized firings of the aBLA-vCA1 pathway, leading to an improvement in social ability. Conclusions: The aBLA-vCA1 circuit is a vulnerable pathway in response to Aß accumulation during the progression of AD and plays a crucial role in Aß-induced social anxiety. Targeting the aBLA-vCA1 circuit and UA administration are both effective strategies for improving the Aß-impaired social ability.
Subject(s)
Amyloid beta-Peptides , Basolateral Nuclear Complex , CA1 Region, Hippocampal , Coumarins , Mice, Transgenic , Animals , Mice , Amyloid beta-Peptides/metabolism , CA1 Region, Hippocampal/metabolism , CA1 Region, Hippocampal/drug effects , Basolateral Nuclear Complex/metabolism , Basolateral Nuclear Complex/drug effects , Coumarins/pharmacology , Alzheimer Disease/metabolism , Male , Social Behavior , Disease Models, Animal , Anxiety/metabolism , Social Interaction/drug effects , Neural Pathways/drug effects , OptogeneticsABSTRACT
BACKGROUND: Episodic memory loss is a prominent clinical manifestation of Alzheimer's disease (AD), which is closely related to tau pathology and hippocampal impairment. Due to the heterogeneity of brain neurons, the specific roles of different brain neurons in terms of their sensitivity to tau accumulation and their contribution to AD-like social memory loss remain unclear. Therefore, further investigation is necessary. METHODS: We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic analysis, social behavioural tests, hippocampal electrophysiology, immunofluorescence staining and in vivo optical fibre recording of GCaMP6f and iGABASnFR. Additionally, we utilized optogenetics and administered ursolic acid (UA) via oral gavage to examine the effects of these agents on social memory in mice. RESULTS: The results of proteomic and phosphoproteomic analyses revealed the characteristics of ventral hippocampal CA1 (vCA1) under both physiological conditions and AD-like tau pathology. As tau progressively accumulated, vCA1, especially its excitatory and parvalbumin (PV) neurons, were fully filled with mislocated and phosphorylated tau (p-Tau). This finding was not observed for dorsal hippocampal CA1 (dCA1). The overexpression of human tau (hTau) in excitatory and PV neurons mimicked AD-like tau accumulation, significantly inhibited neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within vCA1. Photoactivating excitatory and PV neurons in vCA1 at specific rhythms and time windows efficiently ameliorated tau-impaired social memory. Notably, 1 month of UA administration efficiently decreased tau accumulation via autophagy in a transcription factor EB (TFEB)-dependent manner and restored the vCA1 microcircuit to ameliorate tau-impaired social memory. CONCLUSION: This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1 and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau accumulation. Notably, our novel findings regarding the efficacy of UA in reducing tau load and targeting the vCA1 microcircuit may provide a promising strategy for treating AD in the future.
Subject(s)
Alzheimer Disease , Humans , Male , Mice , Animals , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Mice, Transgenic , Proteomics , Hippocampus/metabolism , Hippocampus/pathology , Memory Disorders/metabolismABSTRACT
OBJECTIVE: An emergency cesarean section (CS), which is extremely life-threatening to the mother or fetus, seems to be performed within an adequate time horizon to avoid negative fetal-maternal denouement. An effective and vigilant technique for anesthesia remains vital for emergency cesarean delivery. Therefore, this study aimed to validate the impact of various anesthesia tactics on maternal and neonatal outcomes. METHOD: This was a retrospective cohort study of parturient patients who were selected for emergency CS with the assistance of general or neuraxial anesthesia between January 2015 and July 2021 at our institution. The 5-min Apgar score was documented as the primary outcome. Secondary outcomes, including the 1 min Apgar score, decision-to-delivery interval (DDI), onset of anesthesia to incision interval (OAII), decision to incision interval (DII), duration of operation, length of hospitalization, height and weight of the newborn, use of vasopressors, blood loss, neonatal resuscitation rate, admission to neonatal intensive care unit (NICU), duration of NICU and complications, were also measured. RESULTS: Of the 539 patients included in the analysis, 337 CSs were performed under general anesthesia (GA), 137 under epidural anesthesia (EA) and 65 under combined spinal-epidural anesthesia (CSEA). The Apgar scores at 1 min and 5 min in newborns receiving GA were lower than those receiving intraspinal anesthesia, and no difference was found between those receiving EA and those receiving CSEA. The DDI of parturients under GA, EA, and CSE were 7[6,7], 6[6,7], and 14[11.5,20.5], respectively. The DDI and DII of GA and EA were shorter than those of CSE, and the DDI and DII were similar between GA and EA. Compared to that in the GA group, the OAII in the intraspinal anesthesia group was significantly greater. GA administration correlated with more frequent resuscitative interventions, increased admission rates to NICU, and a greater incidence of neonatal respiratory distress syndrome (NRDS). Nevertheless, the duration of NICU stay and the incidence rates of neonatal hypoxic ischemic encephalopathy (HIE) and pneumonia did not significantly differ based on the type of anesthesia performed. CONCLUSION: Compared with general anesthesia, epidural anesthesia may not be associated with a negative impact on neonatal or maternal outcomes and could be utilized as an alternative to general anesthesia in our selected patient population following emergency cesarean section; In addition, a comparably short DDI was achieved for emergency cesarean delivery under epidural anesthesia when compared to general anesthesia in our study. However, the possibility that selection bias related to the retrospective study design may have influenced the results cannot be excluded.
Subject(s)
Anesthesia, Epidural , Anesthesia, Obstetrical , Infant, Newborn , Humans , Pregnancy , Female , Cesarean Section/methods , Retrospective Studies , Resuscitation , Anesthesia, General/adverse effectsABSTRACT
Pulmonary hypertension (PH) is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated. The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary vascular remodeling in pulmonary hypertension, which is closely linked to the downregulation of fork-head box transcriptional factor O1 (FoxO1) and apoptotic protein caspase 3 (Cas-3). Here, PA-targeted co-delivery of a FoxO1 stimulus (paclitaxel, PTX) and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension. The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles, followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs. The co-loaded system (170 nm) circulates in the blood over time, accumulates in the lung, effectively targets the PAs, and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics, leading to a decrease in pulmonary arterial pressure and Fulton's index. Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis. Taken together, this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.
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In this study, magnetic resonance imaging (MRI) based on a deep learning algorithm was used to evaluate the clinical effect of the small-incision approach in treating proximal tibial fractures. Super-resolution reconstruction (SRR) algorithm was used to reconstruct MRI images for analysis and comparison. The research objects were 40 patients with proximal tibial fractures. According to the random number method, patients were divided into a small-incision approach group (22 cases) and an ordinary approach group (18 cases). The peak signal-to-noise ratio (PSNR) and the structural similarity index (SSIM) of the MRI images before and after the reconstruction of the two groups were analyzed. The operative time, intraoperative blood loss, complete weight-bearing time, complete healing time, knee range of motion, and knee function of the two treatments were compared. The results showed that after SRR, the PSNR and SSIM of MRI images were 35.28 and 0.826 dB, respectively, so the MRI image display effect was better. The operation time in the small-incision approach group was 84.93 min, which was significantly shorter than that in the common approach group, and the intraoperative blood loss was 219.95 mL, which was significantly shorter than that in the common approach group (P < 0.05). The complete weight-bearing time and complete healing time in the small-incision approach group were 14.75 and 16.79 weeks, respectively, which were significantly shorter than those in the ordinary approach group (P < 0.05). The half-year knee range of motion and 1-year knee range of motion in the small-incision approach group were 118.27° and 128.72°, respectively, which were significantly higher than those in the conventional approach group (P < 0.05). After 6 months of treatment, the rate of good treatment was 86.36% in the small-incision approach group and 77.78% in the ordinary approach group. After 1 year of treatment, the rate of excellent and good treatment was 90.91% in the small-incision approach group and 83.33% in the ordinary approach group. The rate of good treatment for half a year and 1 year in the small incision group was significantly higher than that in the common approach group (P < 0.05). In conclusion, MRI image based on deep learning algorithm has a high resolution, good display effect, and high application value. The small-incision approach can be applied to the treatment of proximal tibial fractures, which showed good therapeutic effects and a high positive clinical application value.
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Liming acidic paddy soils to near-neutral pH is the most cost-effective strategy to minimize cadmium (Cd) accumulation by rice. However, the liming-induced effect on arsenic (As) (im)mobilization remains controversial and is called upon for further investigation, particularly for the safe utilization of paddy soils co-contaminated with As and Cd. Here, we explored As and Cd dissolution along pH gradients in flooded paddy soils and extracted key factors accounting for their release discrepancy with liming. The minimum As and Cd dissolution occurred concurrently at pH 6.5-7.0 in an acidic paddy soil (LY). In contrast, As release was minimized at pH < 6 in the other two acidic soils (CZ and XX), while the minimum Cd release still appeared at pH 6.5-7.0. Such a discrepancy was determined largely by the relative availability of Fe under overwhelming competition from dissolved organic carbon (DOC). A mole ratio of porewater Fe/DOC at pH 6.5-7.0 is suggested as a key indicator of whether co-immobilization of As and Cd can occur in flooded paddy soils with liming. In general, a high mole ratio of porewater Fe/DOC (≥ 0.23 in LY) at pH 6.5-7.0 can endow co-immobilization of As and Cd, regardless of Fe supplement, whereas such a case is not in the other two soils with lower Fe/DOC mole ratios (0.01-0.03 in CZ and XX). Taking the example of LY, the introduction of ferrihydrite promoted the transformation of metastable As and Cd fractions to more stable ones in the soil during 35 days of flooded incubation, thus meeting a class I soil for safe rice production. This study demonstrates that the porewater Fe/DOC mole ratio can indicate a liming-induced effect on co-(im)mobilization of As and Cd in typical acidic paddy soils, providing new insights into the applicability of liming practice for the paddy soils.
Subject(s)
Arsenic , Oryza , Soil Pollutants , Cadmium/analysis , Arsenic/analysis , Soil , Soil Pollutants/analysis , Acids/pharmacologyABSTRACT
Display and power supply have been two essential and independent cornerstones of modern electronics. Here, we report a lithium-plasmon-based low-powered dynamic color display with intrinsic dual functionality (plasmonic display and energy recycling unit) which is a result of the electric-field-driven transformation of nanostructured lithium metals. Dynamic color displays are enabled by plasmonic transformation through electrodeposition (electrostripping) of lithium metals during the charging (discharging) process, while the consumed energy for coloring can be retrieved in the inverse process respectively. Energy recycling of lithium metals brings energy consumption down to 0.390 mW cm-2 (0.105 mW cm-2) for the active (static) coloration state of a proof-of-concept display/battery device, which approaches nearly-zero-energy-consumption in the near-100%-energy-efficiency limit of commercial lithium batteries. Combining the subwavelength feature of plasmonics with effective energy recycling, the lithium-plasmon-based dynamic display offers a promising route towards next-generation integrated photonic devices, with the intriguing advantages of low energy consumption, a small footprint and high resolution.
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Aiming at the problems of complex structure parameters and low feature extraction ability of U-Net used in vegetation classification, a deep network with improved U-Net and dual-way branch input is proposed. Firstly, The principal component analysis (PCA) is used to reduce the dimension of hyperspectral remote sensing images, and the effective bands are obtained. Secondly, the depthwise separable convolution and residual connections are combined to replace the common convolution layers of U-Net for depth feature extraction to ensure classification accuracy and reduce the complexity of network parameters. Finally, normalized difference vegetation index (NDVI), gray level co-occurrence matrix (GLCM) and edge features of hyperspectral remote sensing images are extracted respectively. The above three artificial features are fused as one input, and PCA dimension reduction features are used as another input. Based on the improved U-net, a dual-way vegetation classification model is generated. Taking the hyperspectral remote sensing image of Matiwan Village, Xiong'an, Beijing as the experimental object, the experimental results show that the precision and recall of the improved U-Net are significantly improved with the residual structure and depthwise separable convolution, reaching 97.13% and 92.36% respectively. In addition, in order to verify the effectiveness of artificial features and dual-way branch design, the accuracy of single channel and the dual-way branch are compared. The experimental results show that artificial features in single channel network interfere with the original hyperspectral data, resulting in reduction of the recognition accuracy. However, the accuracy of the dual-way branch network has been improved, reaching 98.67%. It shows that artificial features are effective complements of network features.
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Pine cones are important forest products, and the picking process is complex. Aiming at the multi-objective and dispersed characteristics of pine cones in the forest, a machine vision detection model (EBE-YOLOV4) is designed to solve the problems of many parameters and poor computing ability of the general YOLOv4, so as to realize rapid and accurate recognition of pine cones in the forest. Taking YOLOv4 as the basic framework, this method can realize a lightweight and accurate recognition model for pine cones in forest through optimized design of the backbone and the neck networks. EfficientNet-b0 (E) is chosen as the backbone network for feature extraction to reduce parameters and improve the running speed of the model. Channel transformation BiFPN structure (B), which improves the detection rate and ensures the detection accuracy of the model, is introduced to the neck network for feature fusion. The neck network also adds a lightweight channel attention ECA-Net (E) to solve the problem of accuracy decline caused by lightweight improvement. Meanwhile, the H-Swish activation function is used to optimize the model performance to further improve the model accuracy at a small computational cost. 768 images of pine cones in forest were used as experimental data, and 1536 images were obtained after data expansion, which were divided into training set and test set at the ratio of 8:2. The CPU used in the experiment was Inter Core i9-10885@2.40Ghz, and the GPU was NVIDIA Quadro RTX 5000. The performance of YOLOv4 lightweight design was observed based on the indicators of precision (P), recall (R) and detection frames per second (FPS). The results showed that the measurement accuracy (P) of the EBE-YOLOv4 was 96.25%, the recall rate (F) was 82.72% and the detection speed (FPS) was 64.09F/S. Compared with the original YOLOv4, the precision of detection had no significant change, but the speed increased by 70%, which demonstrated the effectiveness of YOLOv4 lightweight design.
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Generalization is a fundamental cognitive ability of organisms to deal with the uncertainty in real-world situations. Excessive fear generalization and impaired reward generalization are closely related to many psychiatric disorders. However, the neural circuit mechanism for reward generalization and its role in anxiety-like behaviours remain elusive. Here, we found a robust activation of calbindin 1-neurons (Calb 1) in the posterior basolateral amygdala (pBLA), simultaneous with reward generalization to an ambiguous cue after reward conditioning in mice. We identify the infralimbic medial prefrontal cortex (IL) to the pBLACalb1 (Calb 1 neurons in the pBLA) pathway as being involved in reward generalization for the ambiguity. Activating IL-pBLA inputs strengthens reward generalization and reduces chronic unpredictable mild stress-induced anxiety- and depression-like behaviours in a manner dependent on pBLACalb1 neuron activation. These findings suggest that the IL-pBLACalb1 circuit could be a target to promote stress resilience via reward generalization and consequently ameliorate anxiety- and depression-like behaviours.
Subject(s)
Anxiety , Basolateral Nuclear Complex , Calbindin 1 , Depression , Neurons , Prefrontal Cortex , Animals , Anxiety/genetics , Anxiety/metabolism , Basolateral Nuclear Complex/metabolism , Calbindin 1/genetics , Calbindin 1/metabolism , Depression/genetics , Depression/metabolism , Mice , Neurons/metabolism , Neurons/physiology , Prefrontal Cortex/metabolism , Prefrontal Cortex/physiologyABSTRACT
BACKGROUND: Esophageal granular cell tumor (eGCT) is a relatively rare, usually benign neoplasm of the neuroectoderm. It is derived from Schwann cells. Clinical symptoms of this disease are non-specific. However, the most common presenting symptom is dysphagia, which is mostly misdiagnosed as esophageal polyps under gastroscopy, yet it has a 2% chance of forming cancers. We report the case of a 52-year-old woman with solitary eGCT, then analysed retrospectivelyanalyze the clinical features and elucidate on the reduction of misdiagnosis and missed diagnosis. CASE SUMMARY: A 52-year-old woman was diagnosed with "esophageal granulossoma" after esophagoscopy, which was mistaken for eGCT. CONCLUSION: eGCT diagnosis depends on characteristic pathomorphologies and detection of the S-100 protein. Endoscopic mucosal resection is the preferred therapeutic method.
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BACKGROUND: To explore the correlation and consistency of non-invasive pleth variability index (PVI) combined with ultrasonic measurement of inferior vena cava-collapsibility index (IVC-CI) in parturients with twin pregnancies undergoing cesarean section under spinal anesthesia. METHODS: Forty-seven twin pregnancies women undergoing elective cesarean section were selected. The ASA score was rated as I-II, aged from 18 to 45 years. Spinal anesthesia was performed at L3-4. PVI and IVC-CI, general data (BMI, gestational weeks, operation duration, blood loss), MAP, temperature sensory block level and adverse reactions were recorded at baseline (T1) and completion of testing the level of spinal anesthesia (T2). RESULTS: The correlation coefficient analysis of baseline IVC-CI% and PVI revealed that the Pearson's coefficient was 0.927, > 0.4. Thus, pre-anesthesia IVC-CI% had a strong correlation with PVI, with R2 of 85.69%. The correlation coefficient analysis of post-anesthesia IVC-CI% and PVI revealed that the Pearson's coefficient was 0.904, > 0.4. Thus, post-anesthesia IVC-CI% had a strong correlation with PVI, with R2 of 81.26%. CONCLUSION: PVI is strongly consistent with ultrasound measurement of IVC-CI twin pregnancies, which can be used as a valuable index for predicting the volume in parturients with twin pregnancies undergoing cesarean section under spinal anesthesia. Trial registration This study was registered on ClinicalTrials.gov with clinical trial registration number of ChiCTR2200055364 (08/01/2022).
Subject(s)
Anesthesia, Spinal , Anesthesia, Spinal/adverse effects , Cesarean Section/adverse effects , Female , Humans , Pregnancy , Pregnancy, Twin , Ultrasonics , Vena Cava, Inferior/diagnostic imagingABSTRACT
BACKGROUND: Human Tau (hTau) accumulation and synapse loss are two pathological hallmarks of tauopathies. However, whether and how hTau exerts toxic effects on synapses remain elusive. METHODS: Mutated hTau (P301S) was overexpressed in the N2a cell line, primary hippocampal neurons and hippocampal CA3. Western blotting and quantitative polymerase chain reaction were applied to examine the protein and mRNA levels of synaptic proteins. The protein interaction was tested by co-immunoprecipitation and proximity ligation assays. Memory and emotion status were evaluated by a series of behavioural tests. The transcriptional activity of nuclear factor-erythroid 2-related factor 2 (NRF2) was detected by dual luciferase reporter assay. Electrophoresis mobility shift assay and chromosome immunoprecipitation were conducted to examine the combination of NRF2 to specific anti-oxidative response element (ARE) sequences. Neuronal morphology was analysed after Golgi staining. RESULTS: Overexpressing P301S decreased the protein levels of post-synaptic density protein 93 (PSD93), PSD95 and synapsin 1 (SYN1). Simultaneously, NRF2 was decreased, whereas Kelch-like ECH-associated protein 1 (KEAP1) was elevated. Further, we found that NRF2 could bind to the specific AREs of DLG2, DLG4 and SYN1 genes, which encode PSD93, PSD95 and SYN1, respectively, to promote their expression. Overexpressing NRF2 ameliorated P301S-reduced synaptic proteins and synapse. By means of acetylation at K312, P301S increased the protein level of KEAP1 via inhibiting KEAP1 degradation from ubiquitin-proteasome pathway, thereby decreasing NRF2 and reducing synapse. Blocking the P301S-KEAP1 interaction at K312 rescued the P301S-suppressed expression of synaptic proteins and memory deficits with anxiety efficiently. CONCLUSIONS: P301S-hTau could acetylate KEAP1 to trigger synaptic toxicity via inhibiting the NRF2/ARE pathway. These findings provide a novel and potential target for the therapeutic intervention of tauopathies.
Subject(s)
NF-E2-Related Factor 2 , Tauopathies , Carboxylic Ester Hydrolases/metabolism , Genes, Regulator , Humans , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Response Elements , Tauopathies/geneticsABSTRACT
Reductive dissolution of iron oxides in flooded paddy soils is the most important cause of arsenic (As) release into soil aqueous solution and thus entry into rice. From the perspective of soil cleanup, however, As release under flooded condition could facilitate labile As removal. In this study, a porous column pre-loaded with ferrihydrite (Fh) was constructed, and its efficiency of soil As extraction was investigated using a purpose-designed mesocosm coupled with diffusive gradients in thin films (DGT) for in situ visualization. With Fh-column deployed in aqueous solution, >90% removal of As(III) was achieved within 5 days at initial As (100 mg L-1) of two orders of magnitude higher than in most paddy soil solutions (1-1538 µg L-1). By applying Fh-column in a seriously contaminated paddy soil (102 mg As kg-1), porewater As showed stepwise decreases from 2727 µg L-1 to 129-1455 µg L-1 at a distance-dependent manner over four intermittent extractions during 91 days. Soil DGT-As exhibited similar spatiotemporal changes to porewater As. After four extractions, 17.8% of total soil As was removed by Fh-column in a 10 cm radius range on average and â¼1/3 of As bound to amorphous and crystalline Fe/Al oxides was depleted, which accounted for 88.7% of decline in total soil As. With the post-extracted soil, a 48% lower As accumulation in rice seedlings and a 65% decline in bulk soil DGT-As were attained. This study provides a conceptual foundation for rapid removal of high soluble As by Fh-columns from flooded soils, improving seriously As-contaminated paddies to sustainable resources for safe food production.
Subject(s)
Arsenic , Oryza , Soil Pollutants , Arsenic/analysis , Ferric Compounds , Iron/analysis , Oryza/chemistry , Oxides/metabolism , Sand , Soil/chemistry , Soil Pollutants/analysisABSTRACT
Maternal immune activation (MIA) during pregnancy is considered a risk factor for neurodevelopment in the offspring, resulting in behavioral abnormalities. Furthermore, adolescence is a vulnerable period for developing different psycho-cognitive deficits. Here, we aimed to observe the cognitive consequences of prenatal MIA exposure in adolescents and explored the underlying mechanisms. We divided dams into CON and MIA groups after inducing a mouse model of MIA using lipopolysaccharide (120 µg/kg) on gestational day 15. Open field (OF), elevated plus maze (EPM), and novel object recognition (NOR) tests were performed on postnatal day (PD) 35-37. The expression of hippocampal Wisteria floribunda agglutinin (WFA)+ perineuronal net (PNN), parvalbumin (PV), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule-1(Iba-1) were evaluated using immunofluorescence, and the expression of matrix metalloprotein-9 (MMP-9) in the hippocampus was assessed using the western blot. Following the infusion of chondroitinase ABC (ChABC) into CA1 in the offspring from the CON group on PD 30, they were divided into ChABC and Sham groups. OF, EPM, and NOR were performed on PD 35-37. Compared to the CON group, decreased exploration time of the novel object and preference ratio were observed in the MIA group. Meanwhile, the MIA group presented significantly decreased WFA+ PNN in CA1, increased Iba-1+ microglia, and MMP-9 in the hippocampus. Additionally, the density of PV+ neurons and GFAP+ astrocytes was comparable between both groups. After digesting the PNN, the exploration time of novel object and preference ratio decreased in the ChABC group compared to the Sham group. Conclusively, the PNN deficit in CA1 caused by prenatal MIA might, at least partially, induce cognitive impairment in adolescents. Microglia and MMP-9 may also be potential candidates for PNN deficit after MIA.
Subject(s)
Cognitive Dysfunction , Matrix Metalloproteinase 9 , Animals , Female , Hippocampus , Mice , Microglia , Parvalbumins , PregnancyABSTRACT
Bamboo delignification is a common method for studying its functional value-added applications. In this study, bamboo samples were delignified by treatment with sodium chlorite. The effects of this treatment on the bamboo's microstructure, surface chemical composition, and pyrolysis behaviour were evaluated. Field-emission scanning electron microscopy (FE-SEM), Fourier-transform infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) were conducted to evaluate these parameters. The FTIR results demonstrated that the lignin peak decreased or disappeared, and some hemicellulose peaks decreased, indicating that sodium chlorite treatment effectively removed lignin and partly decomposed hemicellulose, although cellulose was less affected. The XPS results showed that, after treatment, the oxygen-to-carbon atomic ratio of delignified bamboo increased from 0.34 to 0.45, indicating a lack of lignin. XRD revealed increased crystallinity in delignified bamboo. Further pyrolysis analysis of treated and untreated bamboo showed that, although the pyrolysis stage of the delignified bamboo did not change, the maximum thermal degradation rate (Rmax) and its corresponding temperature (from 353.78 to 315.62 °C) decreased significantly, indicating that the pyrolysis intensity of the bamboo was weakened after delignification. Overall, this study showed that delignified bamboo develops loose surfaces, increased pores, and noticeable fibres, indicating that alkali-treated bamboo has promising application potential due to its novel and specific functionalities.
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BACKGROUND: MXenes with interesting optical and electrical properties have been attractive in biomedical applications such as antibacterial and anticancer agents, but their low photogeneration efficiency of reactive oxygen species (ROS) and poor stability are major concerns against microbial resistance. METHODS: Water-dispersible single layer Ti3C2Tx-based MXene through etching tightly stacked MAX phase precursor using a minimally intensive layer delamination method. After addition of Cu(II) ions, the adsorbed Cu(II) ions underwent self-redox reactions with the surface oxygenated moieties of MXene, leading to in situ formation of Cu2O species to yield Cu2O/Ti3C2Tx nanosheets (heterostructures). RESULTS: Under NIR irradiation, the Cu2O enhanced generation of electron-hole pairs, which boosted the photocatalytic production of superoxide and subsequent transformation into hydrogen peroxide. Broad-spectrum antimicrobial performance of Cu2O/Ti3C2Tx nanosheets with sharp edges is attributed to the direct contact-induced membrane disruption, localized photothermal therapy, and in situ generated cytotoxic free radicals. The minimum inhibitory concentration of Cu2O/Ti3C2Tx nanosheets reduced at least tenfold upon NIR laser irradiation compared to pristine Cu2O/Ti3C2Tx nanosheets. The Cu2O/Ti3C2Tx nanosheets were topically administrated on the methicillin-resistant Staphylococcus aureus (MRSA) infected wounds on diabetic mice. CONCLUSION: Upon NIR illumination, Cu2O/Ti3C2Tx nanosheets eradicated MRSA and their associated biofilm to promote wound healing. The Cu2O/Ti3C2Tx nanosheets with superior catalytic and photothermal properties have a great scope as an effective antimicrobial modality for the treatment of infected wounds.
Subject(s)
Diabetes Mellitus, Experimental , Methicillin-Resistant Staphylococcus aureus , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Mice , Oxidation-Reduction , Titanium/pharmacologyABSTRACT
Different from conventional brain-machine interfaces that focus more on decoding the cerebral cortex, deep brain-machine interfaces enable interactions between external machines and deep brain structures. They sense and modulate deep brain neural activities, aiming at function restoration, device control and therapeutic improvements. In this article, we provide an overview of multiple deep brain recording and stimulation techniques that can serve as deep brain-machine interfaces. We highlight two widely used interface technologies, namely deep brain stimulation and stereotactic electroencephalography, for technical trends, clinical applications and brain connectivity research. We discuss the potential to develop closed-loop deep brain-machine interfaces and achieve more effective and applicable systems for the treatment of neurological and psychiatric disorders.