Serum proteomic biomarker investigation of vascular depression using data-independent acquisition: a pilot study.

Background: Vascular depression (VaD) is a depressive disorder closely associated with cerebrovascular disease and vascular risk factors. It remains underestimated owing to challenging diagnostics and limited information regarding the pathophysiological mechanisms of VaD. The purpose of this study was to analyze the proteomic signatures and identify the potential biomarkers with diagnostic significance in VaD. Methods: Deep profiling of the serum proteome of 35 patients with VaD and 36 controls was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Functional enrichment analysis of the quantified proteins was based on Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Reactome databases. Machine learning algorithms were used to screen candidate proteins and develop a protein-based model to effectively distinguish patients with VaD. Results: There were 29 up-regulated and 31 down-regulated proteins in the VaD group compared to the controls (|log2FC| ≥ 0.26, p ≤ 0.05). Enrichment pathways analyses showed that neurobiological processes related to synaptic vesicle cycle and axon guidance may be dysregulated in VaD. Extrinsic component of synaptic vesicle membrane was the most enriched term in the cellular components (CC) terms. 19 candidate proteins were filtered for further modeling. A nomogram was developed with the combination of HECT domain E3 ubiquitin protein ligase 3 (HECTD3), Nidogen-2 (NID2), FTO alpha-ketoglutarate-dependent dioxygenase (FTO), Golgi membrane protein 1 (GOLM1), and N-acetylneuraminate lyase (NPL), which could be used to predict VaD risk with favorable efficacy. Conclusion: This study offers a comprehensive and integrated view of serum proteomics and contributes to a valuable proteomics-based diagnostic model for VaD.

A tuning fork gyroscope with drive-sense orthogonal thin-walled holes for high sensitivity.

A tuning fork gyroscope (TFG) with orthogonal thin-walled round holes in the driving and sensing directions is proposed to improve sensitivity. The thin walls formed by through holes produce stress concentration, transforming the small displacement of tuning fork vibration into a large concentrated strain. When piezoelectric excitation or detection is carried out here, the driving vibration displacement and detection output voltage can be increased, thereby improving sensitivity. Besides, quadrature coupling can be suppressed because the orthogonal holes make the optimal excitation and detection positions in different planes. The finite element method is used to verify the benefits of the holes, and the parameters are optimized for better performance. The experimental results show that the sensitivity of the prototype gyroscope with a driving frequency of 890.68 Hz is 100.32 mV/(°/s) under open-loop driving and detection, and the rotation rate can be resolved at least 0.016 (°/s)/Hz, which is about 6.7 times better than that of the conventional TFG. In addition, the quadrature error is reduced by 2.7 times. The gyroscope has a simple structure, high reliability, and effectively improves sensitivity, which is helpful to guide the optimization of piezoelectric gyroscopes and derived MEMS gyroscopes.

Prognosis and Prediction of Asymptomatic Intracranial Hemorrhage After Endovascular Thrombectomy: A Multi-Center Study.

PURPOSE: The impact of asymptomatic intracranial hemorrhage (aICH) on functional outcomes after endovascular thrombectomy (EVT) remains unclear, and tools for forecasting this complication are lacking. We aim to evaluate the clinical relevance of aICH and establish a prediction model. METHODS: Data of patients who received EVT for acute anterior-circulation large vessel occlusion in 3 comprehensive hospitals were retrospectively analyzed. Asymptomatic intracranial hemorrhage was defined as any hemorrhage detected after EVT that did not fulfill the definition of symptomatic intracranial hemorrhage in the European Cooperative Acute Stroke Study. Logistic regression models were performed to assess the impact of aICH on 90-day functional outcomes and identify the predictors of aICH, which were then used to establish a prediction model. The discrimination, calibration, and clinical utility of the model were evaluated. RESULTS: This study included 460 patients, among whom 152 (33.0%) developed aICH after EVT. Asymptomatic intracranial hemorrhage was negatively associated with 90-day excellent outcomes (adjusted odds ratio [OR]: 0.414, 95% confidence interval [CI]: 0.230-0.745, p=0.003) and good outcome (adjusted OR: 0.603, 95% CI: 0.374-0.971, p=0.037), but not with mortality (adjusted OR: 1.110, 95% CI: 0.611-2.017, p=0.732) after adjusted for other predictors of functional outcome. Pre-stroke anticoagulant therapy (OR: 2.233, 95% CI: 1.073-4.647, p=0.032), Alberta stroke program early CT score (OR: 0.842, 95% CI: 0.754-0.939, p=0.002), site of occlusion (internal carotid artery occlusion as the reference; M1 segment of middle cerebral artery occlusion, OR: 2.827, 95% CI: 1.409-5.674, p=0.003; tandem occlusion, OR: 3.928, 95% CI: 1.752-8.806, p=0.001), intravenous thrombolysis (OR: 2.091, 95% CI: 1.362-3.209, p=0.001), and successful recanalization (OR: 0.383, 95% CI: 0.213-0.689, p=0.001) were identified as the predictors of aICH, which were incorporated into a nomogram model. The area under the receiver operating characteristic curve of the model was 0.707 (95% CI: 0.657-0.757), and the calibration plot demonstrated good consistency between actual observed and predicted probability of aICH. Decision curve analysis showed that patients might benefit from the model. CONCLUSION: Asymptomatic intracranial hemorrhage was negatively associated with favorable functional outcome after EVT. We established a nomogram model for predicting aICH, which requires external clinical validation. CLINICAL IMPACT: The impact of asymptomatic intracranial hemorrhage after endovascular thrombectomy on mid-term functional outcome has been controversial. We found that asymptomatic intracranial hemorrhage may also decreased the likelihood of 90-day favourable functional outcome after endovascular thrombectomy, supporting the notion that asymptomatic intracranial hemorrhage at the acute stage may not be benign. Moreover, we established a prediction model for this complication, which may improve clinical evaluation and management of patients who would receive endovascular thrombectomy for large vessel occlusion.

Case report: Retrograde endovascular recanalization of vertebral artery occlusion with non-tapered stump via the deep cervical collateral.

Introduction: Vertebral artery (VA) occlusive disease is the major cause of posterior circulation ischemic stroke. Endovascular recanalization has been reported as a feasible treatment for patients with symptomatic VA occlusion refractory to optimal medical therapy. However, VA occlusion with non-tapered stump exhibits a low technique success rate when treated by antegrade endovascular therapy because of increased difficulty in passing the guidewire into the occluded segment. Herein, we presented a novel endovascular approach to recanalize chronically occluded VA with a non-tapered stump using a retrograde method via the deep cervical collateral, which has not been reported before. Case presentation: The present case was a patient with VA ostial occlusion with non-tapered stump and distal severe stenosis of the left VA who had recurrent posterior circulation transit ischemic attacks under optimal medical therapy. CT angiography demonstrated proximal non-tapered occlusion and distal severe stenosis of the left VA, and that the right VA did not converge with the left VA into basilar artery. Endovascular treatment was recommended and performed on this patient. However, antegrade endovascular recanalization of the left VA origin occlusion failed because the micro guidewire was unable to traverse the occluded segment. Fortunately, robust collateral from the deep cervical artery to the V3 segment of the left VA developed, in which we advanced the micro guidewire to the V3 segment of the left VA and reversely passed the micro guidewire through the occluded segment. Then, the occlusion and stenosis of the left VA were successfully resolved with angioplasty and stenting. After the procedure, the patient reported no neurological symptoms under medical therapy during 3-month follow-up. Conclusion: Antegrade endovascular recanalization of VA occlusion with a non-tapered stump is a challenge. The retrograde endovascular method via the cervical collateral may be an alternative for this type of VA occlusion, which requires further exploration.

Reduced biophotonic activities and spectral blueshift in Alzheimer's disease and vascular dementia models with cognitive impairment.

Background: Although clinically, Alzheimer's disease (AD) and vascular dementia (VaD) are the two major types of dementia, it is unclear whether the biophotonic activities associated with cognitive impairments in these diseases share common pathological features. Methods: We used the ultraweak biophoton imaging system (UBIS) and synaptosomes prepared by modified percoll method to directly evaluate the functional changes in synapses and neural circuits in AD and VaD model animals. Results: We found that biophotonic activities induced by glutamate were significantly reduced and spectral blueshifted in synaptosomes and brain slices. These changes could be partially reversed by pre-perfusion of the ifenprodil, a specific antagonist of the GluN2B subunit of N-methyl-D-aspartate receptors (NMDARs). Conclusion: Our findings suggest that AD and VaD pathology present similar but complex changes in biophotonic activities and transmission at synapses and neural circuits, implying that communications and information processing of biophotonic signals in the brain are crucial for advanced cognitive functions.

Pore Structure Characterizations of Shale Oil Reservoirs with Heat Treatment: A Case Study from Dongying Sag, Bohai Bay Basin, China.

Heat treatment plays a significant role in determining the petrophysical properties of shale reservoirs; however, the existing studies on the evolution of pore structures are still insufficient. This study conducts a series of tests, including Rock-Eval, low-temperature nitrogen adsorption-desorption, nuclear magnetic resonance (NMR) T2, and T1-T2 tests on samples from Shahejie Formation, Dongying Sag, Bohai Bay Basin. The tests aim to determine the changes in the shale pore structures under increasing heat treatments (ranging from 110 to 500 °C) and identify the factors that control pore structures. The results show that the gradual decomposition of organic matter leads to an eventual decrease in the total organic carbon (TOC) content. The decrease in TOC is more prominent when the temperature exceeds 300 °C. For shales with lower TOC contents (<2%), the Brunauer-Emmett-Teller specific surface area (BET SSA) first decreases, then increases, but eventually decreases again. However, the average pore diameter demonstrates an opposite trend when the temperature increases. In contrast, for organic-rich shales (TOC > 2%), the BET SSA increases at temperatures above 200 °C. The similarity between the D1 values implies that the complexity and heterogeneity of shale pore surface only undergo minor changes during heat treatment. Porosity shows an increasing trend, and the higher the contents of clay minerals and organic matter in shales are, the greater the change in porosity is. The NMR T2 spectra suggest that micropores (<0.1 µm) in shales first decrease and then increase, whereas the contents of meso- (0.1-1 µm) and macropores (>1 µm) increase, corresponding to the increase in free shale oil. Moreover, shale pore structures are primarily controlled by clay minerals and organic matter contents during heat treatments, with higher contents resulting in better pore structures. Overall, this study contributes to detailing the shale pore structure characteristics during the in situ conversion process (ICP).

Enriched environment attenuates hippocampal theta and gamma rhythms dysfunction in chronic cerebral hypoperfusion via improving imbalanced neural afferent levels.

Chronic cerebral hypoperfusion (CCH) is increasingly recognized as a common cognitive impairment-causing mechanism. However, no clinically effective drugs to treat cognitive impairment due to CCH have been identified. An abnormal distribution of neural oscillations was found in the hippocampus of CCH rats. By releasing various neurotransmitters, distinct afferent fibers in the hippocampus influence neuronal oscillations in the hippocampus. Enriched environments (EE) are known to improve cognitive levels by modulating neurotransmitter homeostasis. Using EE as an intervention, we examined the levels of three classical neurotransmitters and the dynamics of neural oscillations in the hippocampus of the CCH rat model. The results showed that EE significantly improved the balance of three classical neurotransmitters (acetylcholine, glutamate, and GABA) in the hippocampus, enhanced the strength of theta and slow-gamma (SG) rhythms, and dramatically improved neural coupling across frequency bands in CCH rats. Furthermore, the expression of the three neurotransmitter vesicular transporters-vesicular acetylcholine transporters (VAChT) and vesicular GABA transporters (VGAT)-was significantly reduced in CCH rats, whereas the expression of vesicular glutamate transporter 1 (VGLUT1) was abnormally elevated. EE partially restored the expression of the three protein levels to maintain the balance of hippocampal afferent neurotransmitters. More importantly, causal mediation analysis showed EE increased the power of theta rhythm by increasing the level of VAChT and VGAT, which then enhanced the phase amplitude coupling of theta-SG and finally led to an improvement in the cognitive level of CCH. These findings shed light on the role of CCH in the disruption of hippocampal afferent neurotransmitter balance and neural oscillations. This study has implications for our knowledge of disease pathways.

Vesicular acetylcholine transporter in the basal forebrain improves cognitive impairment in chronic cerebral hypoperfusion rats by modulating theta oscillations in the hippocampus.

The cholinergic transmission in the medial septum and ventral limb of the diagonal band of broca (MS/VDB)-hippocampal circuit and its associated theta oscillations play a crucial role in chronic cerebral hypoperfusion (CCH)-related cognitive impairment. However, the contribution and mechanism of the vesicular acetylcholine transporter (VAChT), a vital protein that regulates acetylcholine (ACh) release, in CCH-related cognitive impairment are not well understood. To investigate this, we established a rat model of CCH by performing 2-vessel occlusion (2-VO) and overexpressed VAChT in the MS/VDB via stereotaxic injection of adeno-associated virus (AAV). We evaluated the cognitive function of the rats using the Morris Water Maze (MWM) and Novel Object Recognition Test (NOR). We employed enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and immunohistochemistry (IHC) to assess hippocampal cholinergic levels. We also conducted in vivo local field potentials (LFPs) recording experiments to evaluate changes in hippocampal theta oscillations and synchrony. Our findings showed that VAChT overexpression shortened the escape latency in the hidden platform test, increased swimming time in the platform quadrant in probe trains, and increased the recognition index (RI) in NOR. Moreover, VAChT overexpression increased hippocampal cholinergic levels, improved theta oscillations, and improved the synchrony of theta oscillations between CA1 and CA3 in CCH rats. These results suggest that VAChT plays a protective role in CCH-induced cognitive deficits by regulating cholinergic transmission in the MS/VDB-hippocampal circuit and promoting hippocampal theta oscillations. Therefore, VAChT could be a promising therapeutic target for treating CCH-related cognitive impairments.

Honokiol prevents chronic cerebral hypoperfusion induced astrocyte A1 polarization to alleviate neurotoxicity by targeting SIRT3-STAT3 axis.

Alzheimer's Dementia (AD) and Vascular Dementia (VaD) are two main types of dementias for which no specific treatment is available. Chronic Cerebral Hypoperfusion (CCH) is a pathogenesis underlying AD and VaD that promotes neuroinflammatory responses and oxidative stress. Honokiol (HNK) is a natural compound isolated from magnolia leaves that can easily cross blood brain barrier and has anti-inflammatory and antioxidant effects. In the present study, the effects of HNK on astrocyte polarization and neurological damage in in vivo and in vitro models of chronic cerebral hypoperfusion were explored. We found that HNK was able to inhibit the phosphorylation and nuclear translocation of STAT3, A1 polarization, and reduce conditioned medium's neuronal toxicity of astrocyte under chronic hypoxia induced by cobalt chloride; STAT3 phosphorylation inhibitor C188-9 was able to mimic the above effects of HNK, suggesting that HNK may inhibit chronic hypoxia-induced A1 polarization in astrocytes via STAT3. SIRT3 inhibitor 3-TYP reversed, while Sirt3 overexpression mimicked the inhibitory effects of HNK on oxidative stress, STAT3 phosphorylation and nuclear translocation, A1 polarization and neuronal toxicity of astrocyte under chronic hypoxic conditions. For in vivo research, continuous intraperitoneal injection of HNK (1 mg/kg) for 21 days ameliorated the decrease in SIRT3 activity and oxidative stress, inhibited astrocytic STAT3 nuclear translocation and A1 polarization, and prevented neuron and synaptic loss in the hippocampal of CCH rats. Besides, HNK application improved the spatial memory impairment of CCH rats, as assessed with Morris Water Maze. In conclusion, these results suggest that the phytochemical HNK can inhibit astrocyte A1 polarization via regulating SIRT3-STAT3 axis, thus improving CCH-induced neurological damage. These results highlight HNK as novel treatment for dementia with underlying vascular mechanisms.

ß-hydroxybutyrate improves cognitive impairment caused by chronic cerebral hypoperfusion via amelioration of neuroinflammation and blood-brain barrier damage.

BACKGROUND: Vascular cognitive impairment (VCI) is the second most common type of dementia after Alzheimer's disease (AD) in elderly people. Chronic cerebral hypoperfusion (CCH) is the early pathophysiological basis of VCI. ß-Hydroxybutyrate (BHB) is one of the important components of ketone bodies, an intermediate product of endogenous energy metabolism, which can mitigate neuroinflammation in stroke and neurodegenerative diseases. The present study aimed to investigate whether BHB can improve cognitive impairment caused by CCH and the underlying mechanism. METHODS: The CCH model was established by permanent bilateral common carotid artery occlusion (2VO). CCH rats were intraperitoneally injected with BHB (1.5 mmol/kg/d) every day for 8 consecutive weeks from 2 weeks before surgery. The hippocampal blood flow of rats was measured by using a laser Doppler velocimetry. Used the Morris water maze test (MWM) to assess spatial learning and memory of rats, and harvested brain tissues for molecular, biochemical, and pathological tests. RESULTS: We found that BHB intervention for 8 weeks could effectively restore hippocampal blood flow and improve spatial learning and memory in CCH rats. BHB can protect the blood-brain barrier (BBB), as manifested by reducing the ultrastructural damage and leakage of the BBB, restoring the expression of tight junction-related proteins and reducing the expression of Matrix Metalloproteinases-9 (MMP-9). Additionally, after BHB intervention, microglia activation was reduced, oligodendrocyte motility was active, and the expression levels of pro-inflammatory factors such as tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), nuclear factor-κB (NF-κB) and advanced glycation end-products (RAGE) were lower, which also indicated that BHB had a beneficial effect in mitigating neuroinflammation. CONCLUSION: BHB can improve the cognitive impairment caused by CCH. The potential mechanisms of BHB may be through reducing neuroinflammation and protecting BBB.

Proximal hyperdense middle cerebral artery sign is associated with increased risk of asymptomatic hemorrhagic transformation after endovascular thrombectomy: a multicenter retrospective study.

OBJECTIVE: To investigate whether hyperdense middle cerebral artery sign (HMCAS) on pretreatment no-contrast CT (NCCT) is associated with hemorrhagic transformation (HT) after endovascular thrombectomy (EVT). METHODS: Patients with acute middle cerebral artery (MCA) occlusion who received EVT in three comprehensive hospitals were retrospectively evaluated. They were divided into four groups based on the presence or absence of HMCAS and corresponding CTA findings, among whom differences were compared. Univariate and multivariate logistic regression analyses were performed to investigate the association between HMCAS and HT and its subtypes. RESULTS: 318 patients were included, among whom 149 (46.9%) had HMCAS. Patients in the proximal positive HMCAS group had higher National Institute of Health Stroke Scale scores and lower Alberta Stroke Program Early CT Scores (ASPECTS) than those in the proximal negative HMCAS group. The rate of HT was higher in the proximal positive HMCAS group than that in the proximal negative HMCAS group. In multivariate logistic regression analysis, the proximal HMCAS were independently associated with HT (adjusted OR = 2.073, 95% CI 1.211-3.551, p = 0.008) and aHT (adjusted OR = 2.271, 95% CI 1.294-3.986, p = 0.004), but not with sHT. Patients who developed HT, including aHT and sHT, had a lower rate of good outcome. CONCLUSION: Proximal HMCAS on initial NCCT was independently associated with aHT in patients who received EVT for acute MCA occlusion. Both aHT and sHT had a detrimental effect on clinical outcome.

Structural network efficiency mediates the association between glymphatic function and cognition in mild VCI: a DTI-ALPS study.

Background and objective: Vascular cognitive impairment (VCI) can be caused by multiple types of cerebrovascular pathology and is considered a network disconnection disorder. The heterogeneity hinders research progress in VCI. Glymphatic failure has been considered as a key common pathway to dementia recently. The emergence of a new method, Diffusion Tensor Image Analysis Along the Perivascular Space (DTI-ALPS), makes it possible to investigate the changes of the glymphatic function in humans non-invasively. We aimed to investigate alterations of glymphatic function in VCI and its potential impact on network connectivity. Methods: We recruited 79 patients with mild VCI, including 40 with cerebral small vessel disease cognitive impairment (SVCI) and 39 with post-stroke cognitive impairment (PSCI); and, 77 normal cognitive (NC) subjects were recruited. All subjects received neuropsychological assessments and multimodal magnetic resonance imaging scans. ALPS-index was calculated and structural networks were constructed by deterministic tractography, and then, the topological metrics of these structural connectivity were evaluated. Results: The ALPS-index of VCI patients was significantly lower than that of NC subjects (P < 0.001). Multiple linear regression analysis showed that ALPS-index affects cognitive function independently (ß = 0.411, P < 0.001). The results of correlation analysis showed that the ALPS-index was correlated with overall vascular risk factor burden (r = -0.263, P = 0.001) and multiple cerebrovascular pathologies (P < 0.05). In addition, global efficiency (Eg) of network was correlated with ALPS-index in both SVCI (r = 0.348, P = 0.028) and PSCI (r = 0.732, P < 0.001) patients. Finally, the results of mediation analysis showed that Eg partially mediated in the impact of glymphatic dysfunction on cognitive impairment (indirect effect = 7.46, 95% CI 4.08-11.48). Conclusion: In both major subtypes of VCI, the ALPS-index was decreased, indicating impaired glymphatic function in VCI. Glymphatic dysfunction may affect cognitive function in VCI by disrupting network connectivity, and, may be a potential common pathological mechanism of VCI. ALPS-index is expected to become an emerging imaging marker for VCI.

Diagenetic Control of Reservoir Performance and Its Implications for Reservoir Prediction in Jinci Sandstone of Upper Carboniferous in the Middle East Ordos Basin.

The Upper Carboniferous sandstone reservoir is a vital replacement area for natural gas exploration in Ordos Basin. In this study, 157 Jinci sandstone samples were selected to conduct a series of experiments and analyses. The reservoir material composition and pore structure analysis shows that the lithology of the reservoir is mainly quartz arenite, followed by sublithic arenite. The detrital particles are mainly quartz (69-97.5%), followed by rock fragments (0.1-24.5%), and the content of feldspar is less than 0.01%. The cement consists of siliceous material, clay minerals, and carbonate, with averages of 2.34, 5.96, and 1.81%, respectively. Three types of pore-throat structures (HPMI curve: types 1, 2, and 3) are identified in the Jinci sandstone reservoir, corresponding to different pore-throat radius distributions (RCP curves: types A, B, and C). The study of the factors affecting reservoir pore structure and its internal mechanism shows that the reservoir pore-throat combination, affecting the reservoir performance, is mainly controlled by deposit composition and the subsquent diagenetic modification. A higher rigid particle content and an appropriate amount of siliceous cementation (2-10%) would lead to resistance of the compaction, in favor of the preservation of primary intergranular pores. When the content of ductile particles is more than 3%, the original intergranular pores tend to be substantially reduced. The deposit composition of sandstone controls the preservation of residual intergranular pores by affecting the intensity of compaction and dissolution controlling the amount and type of cementation. Compared with dissolution-subjected quartz arenites, the sublithic arenites are characterized by a common occurrence of altered kaolinite and recrystallized illite, which would destroy the reservoir property. The early diagenetic carbonate cementation, as well as the strong siliceous cementation in "sedimentary quartz arenite", are unfavorable to the formation of high-quality reservoirs. Then, on the basis of the characteristics of various diagenesis and their interaction and internal relationship, the diagenetic sequence and diagenetic-pore evolution patterns of different types of reservoirs were established. Finally, according to the lithological characteristics and the diagenetic-controlled pore-throat evolution patterns of different types of reservoirs, the reservoir quality in the study area was predicted.

Review on the Application of Low-Field Nuclear Magnetic Resonance Technology in Coalbed Methane Production Simulation.

Low-field nuclear magnetic resonance has become one of the main methods to characterize static parameters and dynamic changes in unconventional reservoirs. The research focus of this paper is process simulation of coalbed methane (CBM) production. The dynamic variation of pore volume with different pore sizes during pressure drop, methane desorption-diffusion process, and methane-water interaction during migration is discussed. Moreover, the calculation principles of NMR single and multifractal models are systematically described, and the applicability of NMR fractal models within different research contexts is discussed. Four aspects need urgent attention in the application of this technology in CBM production: (1) overburden NMR technology has limitations in characterizing the stress sensitivity of shale and high-rank coal reservoirs with micropores developed, and we should aim to enable an accurate description of micropore pore stress sensitivity; (2) dynamic NMR physical simulation of reservoir gas and water production based on in-situ and actual geological development conditions should become one of the key aspects of follow-up research; (3) low-temperature freeze-thaw NMR technology, as a new pore-fracture characterization method, needs to be further applied in characterizing the distribution characteristics of pores and fractures; and (4) NMR fractal model should be used as the main theoretical method to expand the simulation results. The applicability of different fractal models in characterizing pore-fracture structure (static) and CBM production process (dynamic) needs to be clarified.

Development of a resonant piezohydraulic hybrid actuator.

This paper proposes a piezohydraulic hybrid actuator driven by a resonant vibrator based on two rhombic micro-displacement amplifiers. The resonant piezohydraulic hybrid actuator consists of a resonant piezoelectric vibrator, a pump body, a manifold, a return valve, and an output cylinder. The vibration mode of the piezoelectric vibrator is simulated, and the working principle of the resonant piezohydraulic hybrid actuator is depicted. Then, the performance of the piezohydraulic hybrid actuator is experimentally investigated, and the effects of exciting frequency, exciting voltage, and bias pressure are analyzed. The results demonstrate that the hybrid actuator performs the best when the exciting frequency is near the resonant frequency; meanwhile, the higher the exciting voltage, the better the performance. Moreover, it indicates that a larger bias pressure will bring a larger reaction force to the vibrator and reduce the performance of the actuator system. The maximum blocked force and no-load velocity are 378 N and 4.8 mm/s, respectively, when the bias pressure is 1.5 MPa and the exciting voltage is 500 Vpp.

Green tea improves cognitive function through reducing AD-pathology and improving anti-oxidative stress capacity in Chinese middle-aged and elderly people.

Background: Numerous benefits of green tea have been reported. However, the effects of green tea on cognitive function remain disputable and the mechanism is still unclear. Objective: To investigate the relationship of green tea consumption with cognitive function and related blood biomarkers among Chinese middle-aged and elderly people. Methods: A total of 264 participants aged 50-70 years old were enrolled from Zhongnan Hospital of Wuhan University. They were interviewed about green tea consumption patterns and underwent neuropsychological tests covering five main cognitive domains to assess cognition including Montreal Cognitive Assessment (MoCA) and the other 10 scales. Then we detected serum oxidative stress biomarkers including Superoxide Dismutase (SOD), Malondialdehyde (MDA), Glutathione Peroxidase (GPx), Glutathione Reductase (GR), and Alzheimer's disease (AD) markers including ß-amyloid (Aß)40, Aß42, and phosphorylated tau-181 (pTau181). Results: In the tea-consuming group, the MoCA scores (P = 0.000), Hopkins Verbal Learning Test (HVLT) immediate recall (P = 0.012) and delayed recall (P = 0.013) were significantly higher while Trail Making Test-B (P = 0.005) and Victoria Stroop test interference (P = 0.000) were lower. In terms of oxidative stress markers, the tea-consuming group had lower serum MDA levels (P = 0.002) and higher serum SOD (P = 0.005) and GPx (P = 0.007) levels. In terms of AD markers, serum pTau181 (P < 0.000), Aß42 (P = 0.019) and total Aß levels (P = 0.034) but not serum Aß40 levels, were lower in the tea-consuming group. In the logistic regression analysis, there was a significant negative correlation between green tea consumption and cognitive impairment (OR = 0.26, 95 % CI 0.13 0.52 for high group). Conclusion: Regular green tea consumption is associated with better cognitive function among Chinese middle-aged and elderly people, mainly reflected in memory and executive function. It may achieve protective effects by reducing AD-related pathology and improving anti-oxidative stress capacity and higher levels of tea consumption have a stronger protective effect.

The environmental enrichment ameliorates chronic unpredictable mild stress-induced depressive-like behaviors and cognitive decline by inducing autophagy-mediated inflammation inhibition.

BACKGROUND: People exposed to prolonged chronic unpredictable mild stress (CUMS) are easy to suffer from depression and cognitive impairment. Environmental enrichment (EE) had a beneficial effect on depressive-like and cognition-like behaviors by inhibiting inflammation. However, the specific mechanism involved in the inflammation inhibition that occurs after EE treatment for the depression and cognitive decline induced by CUMS remains unclear. In this study, we evaluated the possible mechanism of the beneficial effects on depression and cognition by EE. METHODS: Rats were randomly divided into 5 groups as follows: (1) Control + standard environment (SE), (2) CUMS + SE, (3) CUMS + EE, (4) CUMS + EE+ 3-methiladenine (3-MA), (5) CUMS + SE + 3-MA. They were exposed to CUMS procedure for 5 weeks except the control group. After CUMS procedure, rats were housed in the EE or SE for 3 weeks. During EE or SE treatment, rats were injected with normal saline or 3-MA every day. 3-MA as an autophagy inhibitor suppresses autophagy via inhibition of class III PI3K. Behavioral tests were used to investigate depressive-like and cognition-like behaviors after EE treatment. Then, autophagy-related proteins, inflammation-related molecules, transmission electron microscopy (TEM) and immunofluoresence were determined. RESULTS: We found that CUMS induced depressive-like behaviors and cognitive impairment, reflected in worse behavioral test, such as reduced sucrose preference ratio, decreased locomotor and exploratory activity, prolonged immobility and spatial learning and memory impairment. In addition, CUMS rats exhibited the reduced expression of autophagy related proteins including LC3 and Beclin-1 and the increased inflammation activation including microglia cells, NLRP3 inflammasome and proinflammatory cytokines (IL-1ß, IL-6 and TNF-α). After EE treatment, these changes were reversed. However, 3-MA, the inhibitor of autophagy, eliminated the neuroprotective effects of EE on depressive-like behaviors and cognitive decline. CONCLUSION: This study demonstrates that EE can play neuroprotective effects on depression and cognitive impairment by inducing autophagy-mediated inflammation inhibition, which accounts for the reduction of proinflammatory cytokines, including IL-1ß, IL-6 and TNF-α.

Contrast agent retention sign in angiography predicts acute internal carotid artery embolic occlusion.

BACKGROUND: Identification of acute internal carotid artery embolism (ICAE) and internal carotid artery atherosclerotic stenosis (ICAAS) in acute ischemic stroke patients is important for selection of treatment. The presence of contrast agent retention on pre-procedural angiographic images is more common in patients with ICA occlusion caused by embolism compared to patients with ICA atherosclerotic stenosis. This study aimed to evaluate effectiveness of contrast agent retention sign for predicting ICAE. METHODS: Sixty-five patients with ICA occlusion who underwent emergency endovascular treatment from September 2014 to September 2020 were included in this retrospective analysis. Patients were divided into ICAE (n = 46) and ICAAS (n = 19) groups. Clinical characteristics, imaging data and ICA contrast agent retention signs of patients were collected. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnosis accuracy of contrast agent retention sign were conducted. RESULTS: The positive ICA contrast agent retention sign was significantly more common in patients with ICAE (60.87% vs 0.00%, P < 0.001) than that of patients with ICAAS, but significantly lower in male patients (53.57% vs 81.08%, P = 0.017). There were significantly more patients with positive sign had occlusion in C6 segment (64.29% vs 13.51%, P < 0.001) and no outflow tract (85.71% vs 5.41%, P < 0.001) compared with negative sign group. There were significantly fewer patients with postive sign had occlusion in C1 segment (0.00% vs 40.54%, P < 0.001) compared with negative sign group. The sensitivity, specificity, PPV, NPV and diagnosis accuracy of contrast agent retention sign for predicting ICAE occlusion were 60.87%, 100%, 100%, 51.35% and 72.31%, respectively. CONCLUSION: The ICA contrast agent retention sign has very high specificity and moderate sensitivity for detection of acute ICAE.

White Matter and Alzheimer's Disease: A Bidirectional Mendelian Randomization Study.

INTRODUCTION: Observational studies have indicated widespread comorbidity of white matter (WM) lesions and Alzheimer's disease (AD) in the elderly, but the causality and direction of their relationship remained unclear. Our study aims to examine the bidirectional causal relationship between WM change and AD using a genetically informed method. METHODS: We performed a bidirectional two-sample mendelian randomization (MR) study to investigate the correlation of three WM phenotypes-white matter hyperintensities (WMH, N = 18,381), fractional anisotropy (FA, N = 17,673), and mean diffusivity (MD, N = 17,467)-with AD (N = 63,926) using summary statistics from genome-wide association studies (GWAS). The inverse variance weighted method (IVW) was used to evaluate the causal estimate and alternative methods to test the heterogeneity, horizontal pleiotropy, and outliers. RESULTS: There was no significant causal evidence of WM MRI markers on AD across all MR methods. We identified significant evidence of causal effects of AD on the risk of WMH (OR 1.06, 95% CI 1.03-1.10, p < 0.01). The same direction of effects was observed in MR-Egger, weighted median, and weighted mode analysis. Besides, we also observed a risk causal relationship between AD with MD in MR-Egger, weighted median, and weighted mode-based methods (MR-Egger OR 1.38, 95% CI 1.07-1.79, p = 0.02; weighted median OR 1.21, 95% CI 1.02-1.45, p = 0.03; weighted mode-based OR 1.32, 95% CI 1.14-1.53, p < 0.01). However, the general significance of the causal effect of AD on WMH and MD disappeared when we removed the single nucleotide polymorphisms (SNPs) near the APOE regions, revealing that the ability of AD to increase the risk of white matter damage might be mediated by APOE to some extent. Unfortunately, we did not observe significant causal evidence of AD on FA across all MR analyses. CONCLUSIONS: In this bidirectional MR study, we did not observe that WM injuries were associated with a higher risk of AD. Likewise, genetically predicted AD did not result in a causal effect on white matter damage. However, our research revealed that underlying mechanisms linking AD and white matter lesions might be related to the SNPs near APOE regions.