•A deep long short-term memory (LSTM) network is developed for nonlinear structural response modeling.•Two input-output schemes (LSTM-s and LSTM-f) are presented.•The deep learning model is capable ...of modeling both elastic and inelastic response of buildings.•An unsupervised learning algorithm is used to cluster the seismic inputs for training enhancement.•The approach was successfully verified by both numerical and experimental examples.
This paper presents a comprehensive study on developing advanced deep learning approaches for nonlinear structural response modeling and prediction. Two schemes of the long short-term memory (LSTM) network are proposed for data-driven structural seismic response modeling. The proposed deep learning model, trained on available datasets, is capable of accurately predicting both elastic and inelastic response of building structures in a data-driven fashion as opposed to the classical physics-based nonlinear time history analysis using numerical methods. In addition, an unsupervised learning algorithm based on a proposed dynamic K-means clustering approach is established to cluster the seismic inputs in order to (1) generate the least but the most informative datasets for training the LSTM and (2) improve the prediction accuracy and robustness of the model trained with limited data. The performance of the proposed approach is successfully demonstrated through three proof-of-concept studies that include a nonlinear hysteretic system, a real-world building with field sensing data, and a steel moment resisting frame. The results show that the proposed LSTM network is a promising, reliable and computationally efficient approach for nonlinear structural response prediction, and offers significant potential in seismic fragility analysis of buildings for reliability assessment.
Neuroinflammation and oxidative stress play important roles in early brain injury following subarachnoid hemorrhage (SAH). This study is the first to show that activation of apelin receptor (APJ) by ...apelin-13 could reduce endoplasmic reticulum (ER)-stress-associated inflammation and oxidative stress after SAH.
Apelin-13, apelin siRNA, APJ siRNA, and adenosine monophosphate-activated protein kinase (AMPK) inhibitor-dorsomorphin were used to investigate if the activation of APJ could provide neuroprotective effects after SAH. Brain water content, neurological functions, blood-brain barrier (BBB) integrity, and inflammatory molecules were evaluated at 24 h after SAH. Western blotting and immunofluorescence staining were applied to assess the expression of target proteins.
The results showed that endogenous apelin, APJ, and p-AMPK levels were significantly increased and peaked in the brain 24 h after SAH. In addition, administration of exogenous apelin-13 significantly alleviated neurological functions, attenuated brain edema, preserved BBB integrity, and also improved long-term spatial learning and memory abilities after SAH. The underlying mechanism of the neuroprotective effects of apelin-13 is that it suppresses microglia activation, prevents ER stress from overactivation, and reduces the levels of thioredoxin-interacting protein (TXNIP), NOD-like receptor pyrin domain-containing 3 protein (NLRP3), Bip, cleaved caspase-1, IL-1β, TNFα, myeloperoxidase (MPO), and reactive oxygen species (ROS). Furthermore, the use of APJ siRNA and dorsomorphin abolished the neuroprotective effects of apelin-13 on neuroinflammation and oxidative stress.
Exogenous apelin-13 binding to APJ attenuates early brain injury by reducing ER stress-mediated oxidative stress and neuroinflammation, which is at least partly mediated by the AMPK/TXNIP/NLRP3 signaling pathway.
Stroke is one of the most devastating diseases worldwide. In recent years, a great number of studies have focused on the effects of microRNAs (miRNAs) on stroke and the results demonstrated that the ...expressions of miRNAs are associated with the prognosis of stroke. In the present study, we review relevant articles regarding miRNAs and stroke and will explain the complex link between both. The miRNAs participate extensively in the pathophysiology following the stroke, including apoptosis, neuroinflammation, oxidative stress, blood–brain barrier (BBB) disruption and brain edema. The information about the stroke–miRNA system may be helpful for therapeutic and diagnostic methods in stroke treatment.
•Actual DHF experiments with sandstone were conducted for the first time.•The crack propagation law of DHF was compared by CT scans.•Sample failure characteristic was described and explained.•The ...crack control mechanism of DHF was analyzed in detail.
Hydraulic fracturing is mainly used for increasing large-scale coal seam permeability in coal mines to exploit coalbed methane and prevent coal and gas outbursts. However, conventional hydraulic fracturing cracks tend to propagate along the direction of maximum principal stress, which is inconsistent with reinforcement direction engineering and/or project area needs and makes identification of the orientation or specified location of increased coal seam permeability difficult. To address these problems, we have conducted physical similarity simulation experiments and numerical analysis of directional hydraulic fracturing (DHF) and obtained the crack propagation law of DHF technology. By analyzing the variation law of the maximum principal stress inside the rock mass, the crack propagation control mechanism of DHF technique is revealed. The influence of horizontal stress difference coefficients and angles between the hydraulic slotting direction and maximum principal stress direction (i.e., the hydraulic slotting deviation angle) on the crack propagation deflection is investigated. The results show that the DHF technique can achieve crack-oriented propagation along the desired direction. The maximum principal stress range in the rock mass is redistributed after slotting. A directional fracturing induction region is formed between the slots. In addition, DHF hydraulic pressure curves show a secondary fracturing stage when cracks connect the hydraulic fracturing and hydraulic slotting boreholes. Initiation pressures and values of maximum principle stress in the directional fracturing zone increase with increasing horizontal stress difference coefficients and slotting deviation angles. However, increasing the horizontal stress difference coefficient does not significantly influence the directional fracturing zone range. The results provide a reliable basis for subsequent theoretical research and engineering applications.
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial/macrophage activation and neuroinflammation are key cellular events following TBI, but the regulatory and ...functional mechanisms are still not well understood. Myeloid-epithelial-reproductive tyrosine kinase (Mer), a member of the Tyro-Axl-Mer (TAM) family of receptor tyrosine kinases, regulates multiple features of microglial/macrophage physiology. However, its function in regulating the innate immune response and microglial/macrophage M1/M2 polarization in TBI has not been addressed. The present study aimed to evaluate the role of Mer in regulating microglial/macrophage M1/M2 polarization and neuroinflammation following TBI.
The controlled cortical impact (CCI) mouse model was employed. Mer siRNA was intracerebroventricularly administered, and recombinant protein S (PS) was intravenously applied for intervention. The neurobehavioral assessments, RT-PCR, Western blot, magnetic-activated cell sorting, immunohistochemistry and confocal microscopy analysis, Nissl and Fluoro-Jade B staining, brain water content measurement, and contusion volume assessment were performed.
Mer is upregulated and regulates microglial/macrophage M1/M2 polarization and neuroinflammation in the acute stage of TBI. Mechanistically, Mer activates the signal transducer and activator of transcription 1 (STAT1)/suppressor of cytokine signaling 1/3 (SOCS1/3) pathway. Inhibition of Mer markedly decreases microglial/macrophage M2-like polarization while increases M1-like polarization, which exacerbates the secondary brain damage and sensorimotor deficits after TBI. Recombinant PS exerts beneficial effects in TBI mice through Mer activation.
Mer is an important regulator of microglial/macrophage M1/M2 polarization and neuroinflammation, and may be considered as a potential target for therapeutic intervention in TBI.
•Fecal SARS-CoV-2 was relevant to milder condition and better radiological recovery.•The first attempt of using a survival analysis for SARS-CoV-2 RNA duration.•SARS-CoV-2 RNA survival in feces was ...significantly longer than in oropharyngeal swabs.•In spite of the negative oropharyngeal swabs, Fecal viral load easily rebounded.
To investigate the clinical significance, viral shedding duration and viral load dynamics of positive fecal SARS-CoV-2 signals in COVID-19.
COVID-19 patients were included. SARS-CoV-2 RNA was tested in stool and respiratory specimens until two sequential negative results were obtained. Clinical, laboratory and imaging data were recorded.
Of the 69 COVID-19 patients, 20 (28.99 %) had positive fecal viral tests who were younger, had lower C-reactive protein (CRP) and fibrinogen (FIB) levels on admission (all P < 0.05), and showed more improvement and less progression on chest CT during recovery. The median duration of positive viral signals was significantly longer in stool samples than in respiratory samples (P < 0.05). In spite of the negative oropharyngeal swabs, eleven patients were tested positive for viral RNA in stool specimens, with their fecal SARS-CoV-2 RNA Ct (cycle threshold) values reaching 25–27. 6 of these 11 patients' Ct values rebounded.
SARS-CoV-2 RNA in stool specimens was associated with a milder condition and better recovery of chest CT results while the median duration of SARS-CoV-2 RNA persistence was significantly longer in fecal samples than in oropharyngeal swabs. The fecal viral load easily reached a high level and rebounded even though respiratory signals became negative.
Sirtuin3 (sirt3) plays a pivotal role in improving oxidative stress and mitochondrial dysfunction which directly induced neuronal apoptosis after intracerebral hemorrhage (ICH). Reactive oxygen ...species (ROS) is also a critical activator in triggering NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasomes activation which can regulate inflammatory responses in brain. Moreover, hyperglycemia can aggravate the ICH-induced damage. Hence, this study was designed to investigate the mechanisms of neuroprotection of sirt3 in hyperglycemic ICH.
ICH model was established by autologous blood injection. Hyperglycemia was induced by intraperitoneal injection with streptozotocin. Honokiol (HKL, a pharmacological agonist of sirt3) was injected intraperitoneally at doses of 2.5, 5, or 10 mg/kg. Sirt3 small interfering RNA transfection was implemented through intracerebroventricular injection. The expression of sirt3 and its downstream signaling molecules were detected using Western blotting or immunofluorescence staining. Morphological changes of mitochondria were detected by electron microscopy. SH-SY5Y cells were incubated with 10 μM oxyhemoglobin for 48 h to establish an
ICH model, and then JC-1 staining was used to determine mitochondrial membrane potential (Δψ
).
Hyperglycemia could suppress sirt3 expression after ICH when compared with non-diabetic rats. Sirt3 protein expression was decreased to the minimum at 24 h in perihematoma tissues. Electron microscope analysis indicated that hyperglycemic ICH induced extensive mitochondrial vacuolization. HKL attenuated ROS accumulation, adenosine triphosphate reduction, and Δψ
through Sirt3-superoxide dismutase 2 (SOD2) and Sirt3-NRF1-TFAM pathway. Sirt3 knockdown could exacerbate the neuronal apoptosis and reverse the positive effects of HKL. Sirt3 activation could decrease NLRP3 and interleukin-1β levels through deacetylating SOD2 and scavenging ROS.
HKL protects against hyperglycemic ICH-induced neuronal injury via a sirt3-dependent manner.
Intracerebral hemorrhage (ICH) can induce excessive accumulation of reactive oxygen species (ROS) that may subsequently cause severe white matter injury. The process of oligodendrocyte progenitor ...cell (OPC) differentiation is orchestrated by microglia and astrocytes, and ROS also drives the activation of microglia and astrocytes. In light of the potent ROS scavenging capacity of ceria nanoparticles (CeNP), we aimed to investigate whether treatment with CeNP ameliorates white matter injury by modulating ROS-induced microglial polarization and astrocyte alteration.
ICH was induced in vivo by collagenase VII injection. Mice were administered with PLX3397 for depleting microglia. Primary microglia and astrocytes were used for in vitro experiments. Transmission electron microscopy analysis and immunostaining were performed to verify the positive effects of CeNP in remyelination and OPC differentiation. Flow cytometry, real-time polymerase chain reaction, immunofluorescence and western blotting were used to detect microglia polarization, astrocyte alteration, and the underlying molecular mechanisms.
CeNP treatment strongly inhibited ROS-induced NF-κB p65 translocation in both microglia and astrocytes, and significantly decreased the expression of M1 microglia and A1 astrocyte. Furthermore, we found that CeNP treatment promoted remyelination and OPC differentiation after ICH, and such effects were alleviated after microglial depletion. Interestingly, we also found that the number of mature oligodendrocytes was moderately increased in ICH + CeNP + PLX3397-treated mice compared to the ICH + vehicle + PLX3397 group. Therefore, astrocytes might participate in the pathophysiological process. The subsequent phagocytosis assay indicated that A1 astrocyte highly expressed C3, which could bind with microglia C3aR and hinder microglial engulfment of myelin debris. This result further replenished the feedback mechanism from astrocytes to microglia.
The present study reveals a new mechanism in white matter injury after ICH: ICH induces M1 microglia and A1 astrocyte through ROS-induced NF-κB p65 translocation that hinders OPC maturation. Subsequently, A1 astrocytes inhibit microglial phagocytosis of myelin debris via an astrocytic C3-microglial C3aR axis. Polyethylene glycol-CeNP treatment inhibits this pathological process and ultimately promotes remyelination. Such findings enlighten us that astrocytes and microglia should be regarded as a functional unit in future works.
Despite the advancement of neuroimaging techniques, it often remains a diagnostic challenge to distinguish recurrent glioma from lesions representing treatment effect. Preliminary reports suggest ...that 11C-methionine Positron emission tomography (PET) can assist in diagnosing true glioma recurrence. We present here a meta-analysis to assess the accuracy of 11C-methionine PET in identifying recurrent glioma in patients who had undergone prior therapy. A comprehensive search of the PubMed, Embase and Chinese Biomedical (CBM) databases yielded 23 eligible articles comprising 29 studies listed prior to November 20, 2016, representing 891 patients. In this report, we assess the methodological quality of each article individually and perform a meta-analysis to obtain the summary diagnostic accuracy of 11C-methionine PET in correctly identifying recurrent glioma. The pooled sensitivity and specificity are 0.88 (95% CI: 0.85, 0.91) and 0.85 (95% CI: 0.80, 0.89), respectively, with an area under the curve (AUC) for the summary receiver-operating characteristic curve (SROC) of 0.9352. We conclude that 11C-methionine PET has excellent diagnostic performance for differentiating glioma recurrence from treatment effect.
When hydraulic fractures do not expand in the direction required by a project, it is difficult to enhance coal seam permeability effectively. Slotting–directional hydraulic fracturing (SDHF) has been ...proposed as a possible alternative, but there is not enough theoretical mechanism to guide the construction. Based on preliminary study of the directional mechanism of single slotted hole, we established a new slotting–directional hydraulic fracturing (NSDHF) mechanical model by using the complex function theory of elasticity, and the influence of stress interference between adjacent slotted holes and non-uniform pore water pressure was considered. We carried out true triaxial double slotted holes SDHF experiments and used large-scale nondestructive computer tomography to scan the fractured samples to ensure accurate measurement of directional distance. The measured directional distance was used to verify the NSDHF model; the maximum deviation was 5.1%. Taking the experimental data in this paper as example, the stress interference between adjacent slotted holes decreased the fracture directional distance by 20.3%, and the non-uniform pore water pressure increased the fracture directional distance by 47.6%. NSDHF mechanical model realized the quantitative description of the influence of non-uniform pore water pressure on directional distance. The contribution of non-uniform pore water pressure to directional distance accounted for more than 25% of the total directional distance; the effect of non-uniform pore water pressure on fracture direction distance was almost twice the stress interference between adjacent slotted holes. The verified NSDHF model was used to study further the influence of horizontal stress difference, azimuth of slotted hole, slotting size and fluid injection pressure on directional distance with different slotting spacing. The work discussed in this paper will contribute to promoting and apply SDHF on a large scale in low-permeability coal mines.
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