c-Src regulates δ-secretase activation and truncated Tau production by phosphorylating the E3 ligase Traf6.

The accumulation of abnormal Tau protein is a common feature of various neurodegenerative diseases. Truncated Tau, resulting from cleavage by asparaginyl endopeptidase (AEP, δ-secretase), promotes its own phosphorylation and aggregation. Our study focused on understanding the regulatory mechanisms of AEP activation and its interaction with other proteins. We discovered that c-Src plays a critical role in mediating the activation and polyubiquitination of AEP in response to epidermal growth factor stimulation. In addition, we investigated the involvement of tumor necrosis factor receptor-associated factor 6 (Traf6), an E3 ligase, in the regulation of AEP levels and its interaction with c-Src. Knockdown of Traf6 effectively inhibited c-Src-induced AEP activation. To gain further insights into the molecular mechanisms, we employed mass spectrometry to identify the specific tyrosine residues of Traf6 that are phosphorylated by c-Src. By mutating these phosphorylation sites to phenylalanine, we disrupted Traf6-mediated polyubiquitination and subsequently observed the inactivation of AEP. This finding suggests that the phosphorylation of Traf6 by c-Src is crucial for AEP activation. Pharmacological inhibition of c-Src reduced the phosphorylation of Traf6 and inhibited AEP activation in neurons derived from human-induced pluripotent stem cells. Conditional knockout of Traf6 in neurons prevented c-Src-induced AEP activation and subsequent Tau truncation in vivo. Moreover, phosphorylation of Traf6 is highly correlated with AEP activation, Tau368 and pathological Tau (AT8) in Alzheimer's disease brain. Overall, our study elucidates the role of c-Src in regulating AEP-cleaved Tau through phosphorylating Traf6. Targeting the c-Src-Traf6 pathway may hold potential for the treatment of Alzheimer's disease and other tauopathies.

Homocysteine-potentiated Kelch-like ECH-associated protein 1 promotes senescence of neuroblastoma 2a cells via inhibiting ubiquitination of ß-catenin.

Elevated serum homocysteine (Hcy) level is a risk factor for Alzheimer's disease (AD) and accelerates cell aging. However, the mechanism by which Hcy induces neuronal senescence remains largely unknown. In this study, we observed that Hcy significantly promoted senescence in neuroblastoma 2a (N2a) cells with elevated ß-catenin and Kelch-like ECH-associated protein 1 (KEAP1) levels. Intriguingly, Hcy promoted the interaction between KEAP1 and the Wilms tumor gene on the X chromosome (WTX) while hampering the ß-catenin-WTX interaction. Mechanistically, Hcy attenuated the methylation level of the KEAP1 promoter CpG island and activated KEAP1 transcription. However, a slow degradation rate rather than transcriptional activation contributed to the high level of ß-catenin. Hcy-upregulated KEAP1 competed with ß-catenin to bind to WTX. Knockdown of both ß-catenin and KEAP1 attenuated Hcy-induced senescence in N2a cells. Our data highlight a crucial role of the KEAP1-ß-catenin pathway in Hcy-induced neuronal-like senescence and uncover a promising target for AD treatment.

Altered brain functional network dynamics in classic trigeminal neuralgia: a resting-state functional magnetic resonance imaging study.

BACKGROUND: Accumulating studies have indicated a wide range of brain alterations with respect to the structure and function of classic trigeminal neuralgia (CTN). Given the dynamic nature of pain experience, the exploration of temporal fluctuations in interregional activity covariance may enhance the understanding of pain processes in the brain. The present study aimed to characterize the temporal features of functional connectivity (FC) states as well as topological alteration in CTN. METHODS: Resting-state functional magnetic resonance imaging and three-dimensional T1-weighted images were obtained from 41 CTN patients and 43 matched healthy controls (HCs). After group independent component analysis, sliding window based dynamic functional network connectivity (dFNC) analysis was applied to investigate specific FC states and related temporal properties. Then, the dynamics of the whole brain topological organization were estimated by calculating the coefficient of variation of graph-theoretical properties. Further correlation analyses were performed between all these measurements and clinical data. RESULTS: Two distinct states were identified. Of these, the state 2, characterized by complicated coupling between default mode network (DMN) and cognitive control network (CC) and tight connections within DMN, was expressed more in CTN patients and presented as increased fractional windows and dwell time. Moreover, patients switched less frequently between states than HCs. Regarding the dynamic topological analysis, disruptions in global graph-theoretical properties (including network efficiency and small-worldness) were observed in patients, coupled with decreased variability in nodal efficiency of anterior cingulate cortex (ACC) in the salience network (SN) and the thalamus and caudate nucleus in the subcortical network (SC). The variation of topological properties showed negative correlation with disease duration and attack frequency. CONCLUSIONS: The present study indicated disrupted flexibility of brain topological organization under persistent noxious stimulation and further highlighted the important role of "dynamic pain connectome" regions (including DMN/CC/SN) in the pathophysiology of CTN from the temporal fluctuation aspect. Additionally, the findings provided supplementary evidence for current knowledge about the aberrant cortical-subcortical interaction in pain development.

GhYGL1d, a pentatricopeptide repeat protein, is required for chloroplast development in cotton.

BACKGROUND: The pentatricopeptide repeat (PPR) gene family, which contains multiple 35-amino acid repeats, constitutes one of the largest gene families in plants. PPR proteins function in organelles to target specific transcripts and are involved in plant development and growth. However, the function of PPR proteins in cotton is still unknown. RESULTS: In this study, we characterized a PPR gene YELLOW-GREEN LEAF (GhYGL1d) that is required for cotton plastid development. The GhYGL1d gene has a DYW domain in C-terminal and is highly express in leaves, localized to the chloroplast fractions. GhYGL1d share high amino acid-sequence homology with AtECB2. In atecb2 mutant, overexpression of GhYGL1d rescued the seedling lethal phenotype and restored the editing of accD and ndhF transcripts. Silencing of GhYGL1d led to the reduction of chlorophyll and phenotypically yellow-green leaves in cotton. Compared with wild type, GhYGL1d-silenced cotton showed significant deformations of thylakoid structures. Furthermore, the transcription levels of plastid-encoded polymerase (PEP) and nuclear-encoded polymerase (NEP) dependent genes were decreased in GhYGL1d-silenced cotton. CONCLUSIONS: Our data indicate that GhYGL1d not only contributes to the editing of accD and ndhF genes, but also affects the expression of NEP- and PEP-dependent genes to regulate the development of thylakoids, and therefore regulates leaf variegation in cotton.

Liver fibrosis automatic diagnosis utilizing dense-fusion attention contrastive learning network.

BACKGROUND: Liver fibrosis poses a significant public health challenge given its elevated incidence and associated mortality rates. Diffusion-Weighted Imaging (DWI) serves as a non-invasive diagnostic tool for supporting the identification of liver fibrosis. Deep learning, as a computer-aided diagnostic technology, can assist in recognizing the stage of liver fibrosis by extracting abstract features from DWI images. However, gathering samples is often challenging, posing a common dilemma in previous research. Moreover, previous studies frequently overlooked the cross-comparison information and latent connections among different DWI parameters. Thus, it is becoming a challenge to identify effective DWI parameters and dig potential features from multiple categories in a dataset with limited samples. PURPOSE: A self-defined Multi-view Contrastive Learning Network is developed to automatically classify multi-parameter DWI images and explore synergies between different DWI parameters. METHODS: A Dense-fusion Attention Contrastive Learning Network (DACLN) is designed and used to recognize DWI images. Concretely, a multi-view contrastive learning framework is constructed to train and extract features from raw multi-parameter DWI. Besides, a Dense-fusion module is designed to integrate feature and output predicted labels. RESULTS: We evaluated the performance of the proposed model on a set of real clinical data and analyzed the interpretability by Grad-CAM and annotation analysis, achieving average scores of 0.8825, 0.8702, 0.8933, 0.8727, and 0.8779 for accuracy, precision, recall, specificity and F-1 score. Of note, the experimental results revealed that IVIM-f, CTRW-ß, and MONO-ADC exhibited significant recognition ability and complementarity. CONCLUSION: Our method achieves competitive accuracy in liver fibrosis diagnosis using the limited multi-parameter DWI dataset and finds three types of DWI parameters with high sensitivity for diagnosing liver fibrosis, which suggests potential directions for future research.

A robust triphenylamine-based monolithic polymer network for selective sieving of CO2 and PM from flue gas.

The increasingly urgent issue of climate change is driving the development of carbon dioxide (CO2) capture and separation technologies in flue gas after combustion. The monolithic adsorbent stands out in practical adsorption applications for its simplified powder compaction process while maintaining the inherent balance between energy consumption for regeneration and selectivity for adsorption. However, optimizing the adsorption capacity and selectivity of CO2 separation materials remains a significant challenge. Herein, we synthesized monolithic polymer networks (N-CMPs) with triphenylamine adsorption sites, acid-base environment tolerance, and precise narrow microchannel pore systems for the selective sieving of CO2 and particulate matter (PM) in flue gas. The inherent continuous covalent bonding of N-CMPs, along with their highly delocalized π-π conjugated porous framework, ensures the stability of the monolithic polymer network's adsorption and separation capabilities under wet and acid-base conditions. Specifically, under the conditions of 1 bar at 273 K, the CO2 adsorption capacity of N-CMP-1 is 3.35 mmol/g. Attributed to the highly polar environment generated by triphenylamine and the inherent high micropore/mesopore ratio, N-CMPs exhibit an excellent ideal adsorbed solution theory (IAST) selectivity for CO2/N2 under simulated flue gas conditions (CO2/N2 = 15:85). Dynamic breakthrough experiments further visualize the high separation efficiency of N-CMPs in practical adsorption applications. Moreover, under acid-base conditions, N-CMPs achieve a capture efficiency exceeding 99.76 % for PM0.3, enabling the selective separation of CO2 and PM in flue gas. In fact, the combined capture of hazardous PM and CO2 from the exhaust gases produced by the combustion of fossil fuels will play a pivotal role in mitigating climate change and environmental issues until low-carbon and alternative energy technologies are widely adopted.

Staging liver fibrosis with various diffusion-weighted magnetic resonance imaging models.

BACKGROUND: Diffusion-weighted imaging (DWI) has been developed to stage liver fibrosis. However, its diagnostic performance is inconsistent among studies. Therefore, it is worth studying the diagnostic value of various diffusion models for liver fibrosis in one cohort. AIM: To evaluate the clinical potential of six diffusion-weighted models in liver fibrosis staging and compare their diagnostic performances. METHODS: This prospective study enrolled 59 patients suspected of liver disease and scheduled for liver biopsy and 17 healthy participants. All participants underwent multi-b value DWI. The main DWI-derived parameters included Mono-apparent diffusion coefficient (ADC) from mono-exponential DWI, intravoxel incoherent motion model-derived true diffusion coefficient (IVIM-D), diffusion kurtosis imaging-derived apparent diffusivity (DKI-MD), stretched exponential model-derived distributed diffusion coefficient (SEM-DDC), fractional order calculus (FROC) model-derived diffusion coefficient (FROC-D) and FROC model-derived microstructural quantity (FROC-µ), and continuous-time random-walk (CTRW) model-derived anomalous diffusion coefficient (CTRW-D) and CTRW model-derived temporal diffusion heterogeneity index (CTRW-α). The correlations between DWI-derived parameters and fibrosis stages and the parameters' diagnostic efficacy in detecting significant fibrosis (SF) were assessed and compared. RESULTS: CTRW-D (r = -0.356), CTRW-α (r = -0.297), DKI-MD (r = -0.297), FROC-D (r = -0.350), FROC-µ (r = -0.321), IVIM-D (r = -0.251), Mono-ADC (r = -0.362), and SEM-DDC (r = -0.263) were significantly correlated with fibrosis stages. The areas under the ROC curves (AUCs) of the combined index of the six models for distinguishing SF (0.697-0.747) were higher than each of the parameters alone (0.524-0.719). The DWI models' ability to detect SF was similar. The combined index of CTRW model parameters had the highest AUC (0.747). CONCLUSION: The DWI models were similarly valuable in distinguishing SF in patients with liver disease. The combined index of CTRW parameters had the highest AUC.

Ultra-stable hollow nanotube conjugated microporous polymer incorporating fluorenyl moieties for Co-capture of PM and CO2.

Conjugated microporous polymers have a highly delocalized π-π conjugated porous skeleton connected by covalent bonds, which can combine their excellent stability with high adsorption, in order to be applied to the study of co-capture of harmful particulate matter (PM) and carbon dioxide (CO2) under high temperature and high humidity conditions. In this paper, fluorene-based coupled conjugated microporous polymers (D-CMPs) with functionalized hollow nanotubes and abundant microporous structures were proposed. Through mechanism exploration and molecular electrostatic potential (MESP) calculation, the capture efficiency, adsorption capacity and selectivity of PM and CO2 in the waste gas stream of carbon-based combustion were analyzed. The results indicate that D-CMPs, with their rigid carbon-based π-conjugated framework, exhibit excellent tolerance under prolonged high-humidity conditions, with a capture efficiency exceeding 99.87% for PM0.3 and exceeding 99.99% for PM2.5. Meanwhile, based on its chemical/thermal stability, it can realize the recycling of adsorption-regeneration. On this basis, the "slip effect" induced by the open three-dimensional hierarchical porous structure of D-CMPs significantly enhances airflow dispersion and improves gas throughput (with a minimal permeation resistance of only 15 Pa). At a pressure of 1 bar and a temperature of 273.15 K, D-CMP-2 exhibited a CO2 adsorption capacity of up to 2.69 mmol g-1. The fitting results of three isothermal adsorption models demonstrate that D-CMPs exhibit an outstanding equilibrium selectivity towards CO2. Therefore, prior to the widespread adoption of low-carbon and clean energy technologies, porous solid materials exhibiting excellent structural stability, equilibrium selectivity, environmental tolerance, and high adsorption capacity emerge as optimal candidates for the treatment of industrial waste gases.

Staging liver fibrosis by a continuous-time random-walk diffusion model.

PURPOSE: Noninvasive assessment of liver fibrosis holds significant clinical importance. We aimed to evaluate the clinical potential of using a continuous-time random-walk diffusion model (CTRW) for staging liver fibrosis. METHODS: This prospective study included 52 patients suspected of liver disease and scheduled for liver biopsy. All patients underwent multi-b value diffusion-weighted imaging (DWI) using a 1.5 T MR scanner to derive the anomalous diffusion coefficient (D) and temporal (α) and spatial (ß) diffusion heterogeneity indexes sourced from the CTRW. The mono-exponential DWI-derived apparent diffusion coefficient (ADC), transient elastography-derived liver stiffness measurement (LSM), aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) index were calculated. We assessed and compared the correlations of these parameters with fibrosis stages and their efficacy in staging liver fibrosis. RESULTS: Significant correlations with fibrosis stages were found for APRI (r = 0.336), FIB-4 (r = 0.351), LSM (r = 0.523), D (r = -0.458), and ADC (r = -0.473). Significant differences were observed between APRI, LSM, D, and ADC of different fibrosis stages. The diagnostic performance of an index that combined D, α, ß, ADC, and LSM was superior to that of ADC or LSM alone for fibrosis stage F ≥ 2 and better than the index that combined D, α, ß for fibrosis stage F ≥ 4. CONCLUSIONS: Accurate liver fibrosis staging was achieved with a model that combined CTRW-derived parameters (D, α, and ß), ADC, and LSM. The model could serve as a reliable tool for noninvasive fibrosis evaluation.

Comparison of the Mechanical Properties and Crack Expansion Mechanism of Different Content and Shapes of Brass-Coated Steel Fiber-Reinforced Ultra-High-Performance Concrete.

Steel fiber-reinforced ultra-high-performance concrete (UHPC) is becoming an important type of concrete reinforcement. After mixing with the reinforced steel fibers, the UHPC has perfect flex resistance, shear strength, crack resistance, shock resistance, and anti-seepage. In this study, the influence of straight, corrugated, and hooked brass-coated steel fibers (BCSFs) on the microstructure, mechanical properties, and crack expansion mechanism of ultra-high-performance concrete (UHPC) with varying content of 1-6 wt.% under different curing times were investigated. Field emission scanning electron microscopy and energy dispersive X-ray spectrometry were employed to characterize the microstructure of the BCSF-reinforced UHPC mix specimens. X-ray computed tomography was employed to determine the porosity of the BCSF-reinforced UHPC mix specimens. The obtained results indicate the flexural strength and compressive strength of BCSF-reinforced UHPC mix specimens are enhanced, along with increasing the content of BCSFs reinforcement with different shapes (straight, corrugated, and hooked). The embedded BCSFs play a major role in the adhesive property and stress transfer of the BCSFs-UHPC matrix interface. Different from many studies, the flexural strength of mix UHPC with straight BCSFs is higher than those with corrugated and hooked BCSFs. However, the compressive strength of UHPC with corrugated BCSFs is higher than those with straight and hooked BCSFs. The flexural strength of mix UHPC with 6 wt.% straight BCSFs at 28 days reaches the maximum value of 26.2 MPa, and the compressive strength of UHPC with 6 wt.% corrugated BCSFs at 28 days reaches the maximum value of 142.3 MPa. With the increase in straight BCSF content from 1 wt.% to 6 wt.%, the porosity in mix UHPC reduces gradually from 18.4% to 8.3%. The length of average crack spacing is dependent on the straight BCSF content. With the increase in straight BCSF content from 1 wt.% to 6 wt.%, the average crack length reduces gradually from 34.2 mm to 12.1 mm, and the average crack width reduces gradually from 0.78 mm to less than 0.1 mm. During crack extension, part of the energy in the UHPC mixture specimen with the 6 wt.% BCSF content flows into the crack tip region converted into the work dissipated during the bridging process. The crack propagation resistance of the UHPC mixture with straight BCSFs was improved compared with those with corrugated and hooked BCSFs. The bond strength between the BCSFs and UHPC matrix was enhanced by using vibrational mixing, and the brass film coated on the BCSFs contributes to increase the flexural and compressive strength of the UHPC mixture.

Evaluating Mediastinal Lymph Node Metastasis of Non-Small Cell Lung Cancer Using Mono-exponential, Bi-exponential, and Stretched-exponential Models of Diffusion-weighted Imaging.

PURPOSE: To explore and compare the diagnostic values of mono-exponential, bi-exponential, and stretched-exponential diffusion-weighted imaging (DWI) parameters of primary lesions and lymph nodes (LNs) to predict mediastinal LN metastasis in patients with non-small cell lung cancer. PATIENTS AND METHODS: Sixty-one patients with non-small cell lung cancer underwent preoperative magnetic resonance imaging, including multiple b-value DWI. The DWI parameters, including apparent diffusion coefficient (ADC) from a mono-exponential model, true diffusion (D) coefficient, pseudo-diffusion (D*) coefficient, and perfusion fraction (f) from a bi-exponential model, distributed diffusion coefficient (DDC) and intravoxel diffusion heterogeneity index (α) from a stretched-exponential model of primary tumors and LNs and the size characteristics of LNs, were measured and compared. Multivariate logistic regression analysis was used to establish models for predicting mediastinal LN metastasis. Receiver operating characteristic analysis was applied to evaluate diagnostic performances. RESULTS: The DWI parameters of primary tumors showed no statistical significance between LN metastasis-positive and LN metastasis-negative groups. Nonmetastatic LNs had significantly higher ADC, D, DDC, and α values compared with metastatic LNs (all P < 0.05). The short-dimension, long-dimension, and short-long dimension ratio of metastatic LNs was significantly larger than those of nonmetastatic ones (all P < 0.05). The D value showed the best diagnostic performance among all DWI-derived single parameters, and the short dimension of LNs performed the same among all the size variables. Furthermore, the combination of DWI parameters (ADC and D) and the short dimension of LNs can significantly improve diagnostic efficiency. CONCLUSIONS: The ADC, D, DDC, and α from the mono-exponential, bi-exponential, and stretched-exponential models were demonstrated efficient in differentiating benign from metastatic LNs, and the combination of ADC, D, and short dimension of LNs may have a better diagnostic performance than DWI or size-derived parameters either in combination or individually.

Passive immunization inhibits tau phosphorylation and improves recognition learning and memory in 3xTg-AD mice.

Tau pathology is essential in the pathogenesis of Alzheimer's disease (AD) and related tauopathies. Tau immunotherapy aimed at reducing the progression of tau pathology provides a potential therapeutic strategy for treating these diseases. By screening monoclonal antibodies 43D, 63B, 39E10, and 77G7 that recognize epitopes ranging from tau's N-terminus to C-terminus, we found the 77G7, which targets the microtubule-binding domain promoted tau clearance in a dose-dependent manner by entering neuronal cells in vitro. Intra-cerebroventricular injection of 77G7 antibody reduced tau levels in the wild-type FVB mouse brain. Without influencing the levels of detergent-insoluble and aggregated tau, intravenous injection of 77G7 reduced tau hyperphosphorylation in the brain and improved novel object recognition but not spatial learning and memory in 15-18-month-old 3xTg-AD mice. These studies suggest that epitopes recognized by tau antibodies are crucial for the efficacy of immunotherapy. Immunization with antibody 77G7 provides a novel potential opportunity for tau-directed immunotherapy of AD and related tauopathies.

Application of multi-echo Dixon and MRS in quantifying hepatic fat content and staging liver fibrosis.

This study associated the liver proton density fat fraction (PDFF), measured by multi-echo Dixon (ME-Dixon) and breath-hold single-voxel high-speed T2-corrected multi-echo 1H magnetic resonance spectroscopy (HISTO) at 1.5 T, with serum biomarkers and liver fibrosis stages. This prospective study enrolled 75 patients suspected of liver fibrosis and scheduled for liver biopsy and 23 healthy participants with normal liver function. The participant underwent ME-Dixon and HISTO scanning. The agreement of PDFF measured by ME-Dixon (PDFF-D) and HISTO (PDFF-H) were compared. Correlations between PDFF and serum fat biomarkers (total cholesterol, triglyceride, and high- and low-density lipoproteins) and the liver fibrosis stages were assessed. PDFF were compared among the liver fibrosis stages (F0-F4) based on clinical liver biopsies. The Bland-Altman plot showed agreement between PDFF-D and PDFF-H(LoA, - 4.44 to 6.75), which have high consistency (ICC 0.752, P < 0.001). The correlations with the blood serum markers were mild to moderate (PDFF-H: r = 0.261-0.410, P < 0.01; PDFF-D: r = 0.265-0.367, P < 0.01). PDFF-D, PDFF-H, and steatosis were distributed similarly among the liver fibrosis stages. PDFF-H showed a slight negative correlation with the liver fibrosis stages (r = - 0.220, P = 0.04). Both ME-Dixon and HISTO sequences measured liver fat content noninvasively. Liver fat content was not directly associated with liver fibrosis stages.

The Preparation, Microstructure, and Wet Wear Properties of an Fe55-Based Welding Layer with the Co-Addition of 0.01 wt% CeO2 and 1.5 wt% SiC Particles Using the Plasma Beam Spraying Method.

Severe erosion wear is found on valve spools, which threatens the safety and reliability of these units. The use of the plasma beam spraying surfacing method can significantly improve the corrosion resistance and sealing performance of hydraulic valve spools, reduce material waste, and reduce maintenance costs. The effects of the co-addition of CeO2 and SiC particles on the morphology, surface cracks, microstructure, precipitated phases, and wear property of plasma-beam-sprayed Fe55-based coatings on 1025 steel were investigated using OM, EDS, ultra-deep field microscopy, and a wet sand rubber wheel friction tester, respectively. The dendrite exhibited a directional growth pattern perpendicular to the substrate and the transitional states of the microstructure with the co-addition of CeO2 and SiC particles. CeO2 or SiC reduced the liquid phase diffusion coefficient DL of Cr and C and resulted in a decrease in the G/R ratio. The dendrites changed into equiaxed grains. The main phase composition of the Fe55 welding layer was Cr7C3, γ-Fe. The martensite in the surfacing layer and the carbides formed Cr7C3, which can improve the hardness of the surfacing layer. The grain boundaries consisted mainly of a reticular eutectic structure. The uniform distribution of the Cr7C3 hard phase in the Fe55+1.5 wt% SiC+0.01 wt% CeO2 resulted in a uniformly worn surface. The sub-wear mechanisms during the friction process were micro-ploughing and micro-cutting. The hardness and toughness of Fe55+1.5 wt% SiC+0.01 wt% CeO2 were well-matched, avoiding excessive micro-cutting and microplastic deformation. A low content of CeO2 could lead to the formation of equiaxed grain and effectively improve the uniformity of the microstructure. The wear-resistant layer of Fe55+1.5 wt% SiC+0.01 wt% CeO2 can effectively improve the service life and long-term sealing performance of the valve spools.

Simulation and Experimental of Infiltration and Solidification Process for Al2O3(3D)/5083Al Interpenetrating Phase Composite for High Speed Train Prepared by Low-Pressure Infiltration.

Understanding the infiltration and solidification processes of liquid 5083Al alloy into Al2O3 three-dimensional reticulated porous ceramic (Al2O3(3D) RPC) is essential for optimizing the microstructure and properties of Al2O3(3D)/5083Al interpenetrating phase composites (IPCs) prepared by low-pressure infiltration process (LPIP). This study employs ProCAST software to simulate the infiltration and solidification processes of liquid 5083Al with pouring velocities (PV) of 0.4 m/s infiltrating into Al2O3(3D) RPC preforms with varying porosities at different pouring temperatures (PT) to prepare Al2O3(3D)/5083Al IPCs using LPIP. The results demonstrate that pore diameter of Al2O3(3D) RPC preforms and PT of liquid 5083Al significantly influence the of the infiltration. Solidification process analysis reveals that the Al2O3(3D) RPC preform with smaller pore diameters allows the lower pouring velocity of 5083Al to solidify faster compared to the preform with larger pore diameters. Al2O3(3D)/5083Al IPCs were prepared successfully from Al2O3(3D) RPC porosity of 15 PPI with liquid 5083Al at PV 0.4 m/s and PT 800 °C using LPIP, resulting in nearly fully dense composites, where both Al2O3(3D) RPCs and 5083Al interpenetrate throughout the microstructure. The infiltration and solidification defects were reduced under air pressure of 0.3 MPa (corresponding to PV of 0.4 m/s) during LPIP. Finite volume method simulations are in good agreement with experimental data, validating the suitability of the simplified model for Al2O3(3D) RPCs in the infiltration simulation.

miR-124 is upregulated in diabetic mice and inhibits proliferation and promotes apoptosis of high-glucose-induced ß-cells by targeting EZH2.

BACKGROUND: Diabetes is a chronic metabolic disease, and a variety of miRNA are involved in the occurrence and development of diabetes. In clinical studies, miR-124 is highly expressed in the serum of patients with diabetes and in pancreatic islet ß-cells. However, few reports exist concerning the role and mechanism of action of miR-124 in diabetes. AIM: To investigate the expression of miR-124 in diabetic mice and the potential mechanism of action in islet ß-cells. METHODS: The expression levels of miR-124 and enhancer of zeste homolog 2 (EZH2) in pancreatic tissues of diabetic mice were detected. The targeted relationship between miR-124 and EZH2 was predicted by Targetscan software and verified by a double luciferase reporter assay. Mouse islet ß-cells Min6 were grown in a high glucose (HG) medium to mimic a diabetes model. The insulin secretion, proliferation, cell cycle and apoptosis of HG-induced Min6 cells were detected after interference of miR-124a and/or EZH2. RESULTS: The expression of miR-124 was upregulated and EZH2 was downregulated in the pancreatic tissue of diabetic mice compared with control mice, and the expression of miR-124 was negatively correlated with that of EZH2. miR-124 was highly expressed in HG-induced Min6 cells. Inhibition of miR-124 promoted insulin secretion and cell proliferation, induced the transition from the G0/G1 phase to the S phase of the cell cycle, and inhibited cell apoptosis in HG-induced Min6 cells. EZH2 was one of the targets of miR-124. Co-transfection of miR-124 inhibitor and siRNA-EZH2 could reverse the effects of the miR-124 inhibitor in HG-induced Min6 cells. CONCLUSION: miR-124 is highly expressed in diabetic mice and HG-induced Min6 cells and regulates insulin secretion, proliferation and apoptosis of islet ß-cells by targeting EZH2.

Early Changes in the White Matter Microstructure and Connectome Underlie Cognitive Deficit and Depression Symptoms After Mild Traumatic Brain Injury.

Cognitive and emotional impairments are frequent among patients with mild traumatic brain injury (mTBI) and may reflect alterations in the brain structural properties. The relationship between microstructural changes and cognitive and emotional deficits remains unclear in patients with mTBI at the acute stage. The purpose of this study was to analyze the alterations in white matter microstructure and connectome of patients with mTBI within 7 days after injury and investigate whether they are related to the clinical questionnaires. A total of 79 subjects (42 mTBI and 37 healthy controls) underwent neuropsychological assessment and diffusion-tensor MRI scan. The microstructure and connectome of white matter were characterized by tract-based spatial statistics (TBSSs) and graph theory approaches, respectively. Mini-mental state examination (MMSE) and self-rating depression scale (SDS) were used to evaluate the cognitive function and depressive symptoms of all the subjects. Patients with mTBI revealed early increases of fractional anisotropy in most areas compared with the healthy controls. Graph theory analyses showed that patients with mTBI had increased nodal shortest path length, along with decreased nodal degree centrality and nodal efficiency, mainly located in the bilateral temporal lobe and right middle occipital gyrus. Moreover, lower nodal shortest path length and higher nodal efficiency of the right middle occipital gyrus were associated with higher SDS scores. Significantly, the strength of the rich club connection in the mTBI group decreased and was associated with the MMSE. Our study demonstrated that the neuroanatomical alterations of mTBI in the acute stage might be an initial step of damage leading to cognitive deficits and depression symptoms, and arguably, these occur due to distinct mechanisms.

Comparing the Corrosion Resistance of 5083 Al and Al2O33D/5083 Al Composite in a Chloride Environment.

In this study, an Al2O33D/5083 Al composite was fabricated by infiltrating a molten 5083 Al alloy into a three-dimensional alumina reticulated porosity ceramics skeleton preform (Al2O33D) using a pressureless infiltration method. The corrosion resistance of 5083 Al alloy and Al2O33D/5083 Al in NaCl solution were compared via electrochemical impedance spectroscopy (EIS), dynamic polarization potential (PDP), and neutral salt spray (NSS) tests. The microstructure of the two materials were investigated by 3D X-ray microscope and scanning electron microscopy aiming at understanding the corrosion mechanisms. Results show that an Al2O33D/5083 Al composite consists of interpenetrating structure of 3D-continuous matrices of continuous networks 5083 Al alloy and Al2O33D phase. A large area of strong interfaces of 5083 Al and Al2O33D exist in the Al2O33D/5083 Al composite. The corrosion development process can be divided into the initial period, the development period, and the stability period. Al2O33D used as reinforcement in Al2O33D/5083 Al composite improves the corrosion resistance of Al2O33D/5083 Al composite via electrochemistry tests. Thus, the corrosion resistance of Al2O33D/5083 Al is higher than that of 5083 Al alloy. The NSS test results indicate that the corrosion resistance of Al2O33D/5083 Al was lower than that of 5083 Al alloy during the initial period, higher than that of 5083 Al alloy during the development period, and there was no obvious difference in corrosion resistance during the stability period. It is considered that the elements in 5083 Al alloy infiltrated into the Al2O33D/5083 Al composite are segregated, and the uniform distribution of the segregated elements leads to galvanic corrosion during the corrosion initial period. The perfect combination of interfaces of Al2O33D and the 5083 Al alloy matrix promotes excellent corrosion resistance during the stability period.

Expression of Modified Snowdrop Lectin (Galanthus nivalis Agglutinin) Protein Confers Aphids and Plutella xylostella Resistance in Arabidopsis and Cotton.

Cotton is a major fiber crop in the world that can be severely infested by pests in agricultural fields. Identifying new insect-resistance genes and increasing the expression of known insect-resistance genes are imperative in cultivated cotton. Galanthus nivalis agglutinin (GNA), a lectin that is toxic to both chewing and sucking pests, is mainly expressed in monocotyledons. It is necessary to improve the expression of the GNA protein and to test whether the lectin confers insect resistance to dicotyledons plants. We report a modified GNA gene (ASGNA) via codon optimization, its insertion into Arabidopsis thaliana, and transient expression in cotton to test its efficacy as an insect-resistance gene against cotton aphids and Plutella xylostella. The amount of ASGNA in transgenic plants reached approximately 6.5 µg/g of fresh weight. A feeding bioassay showed that the survival rate of aphids feeding on the leaves of ASGNA transgenic plants was lower than those of aphids feeding on the leaves of non-optimized GNA (NOGNA) transgenic plants and wild-type plants. Meanwhile, the fertility rate was 36% when fed on the ASGNA transgenic plants, while the fertility was 70% and 95% in NOGNA transgenic plants and wild-type plants. Correspondingly, the highest mortality of 55% was found in ASGNA transgenic lines, while only 35% and 20% mortality was observed in NOGNA transgenic plants and wild-type plants, respectively. Similar results were recorded for aphids feeding on cotton cotyledons with transient expression of ASGNA. Taken together, the results show that ASGNA exhibited high insecticidal activity towards sap-sucking insects and thus is a promising candidate gene for improving insect resistance in cotton and other dicotyledonous plants.

Altered Cerebro-Cerebellar Effective Connectivity in New-Onset Juvenile Myoclonic Epilepsy.

(1) Objective: Resting-state fMRI studies have indicated that juvenile myoclonic epilepsy (JME) could cause widespread functional connectivity disruptions between the cerebrum and cerebellum. However, the directed influences or effective connectivities (ECs) between these brain regions are poorly understood. In the current study, we aimed to evaluate the ECs between the cerebrum and cerebellum in patients with new-onset JME. (2) Methods: Thirty-four new-onset JME patients and thirty-four age-, sex-, and education-matched healthy controls (HCs) were included in this study. We compared the degree centrality (DC) between the two groups to identify intergroup differences in whole-brain functional connectivity. Then, we used a Granger causality analysis (GCA) to explore JME-caused changes in EC between cerebrum regions and cerebellum regions. Furthermore, we applied a correlation analysis to identify associations between aberrant EC and disease severity in patients with JME. (3) Results: Compared to HCs, patients with JME showed significantly increased DC in the left cerebellum posterior lobe (CePL.L), the right inferior temporal gyrus (ITG.R) and the right superior frontal gyrus (SFG.R), and decreased DC in the left inferior frontal gyrus (IFG.L) and the left superior temporal gyrus (STG.L). The patients also showed unidirectionally increased ECs from cerebellum regions to the cerebrum regions, including from the CePL.L to the right precuneus (PreCU.R), from the left cerebellum anterior lobe (CeAL.L) to the ITG.R, from the right cerebellum posterior lobe (CePL.R) to the IFG.L, and from the left inferior semi-lunar lobule of the cerebellum (CeISL.L) to the SFG.R. Additionally, the EC from the CeISL.L to the SFG.R was negatively correlated with the disease severity. (4) Conclusions: JME patients showed unidirectional EC disruptions from the cerebellum to the cerebrum, and the negative correlation between EC and disease severity provides a new perspective for understanding the cerebro-cerebellar neural circuit mechanisms in JME.