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Decision-making is a crucial intelligence shared by animals and humans and it helps them to act in an intricate environment to seek rewards and avoid punishments. Psychologists first became interested in this ability and studied the conditional behavioral problems associated with it, then these studies have further led to the need for unified quantitative explanation models, among which Reinforcement learning is still the most convincing and data-backed model today. The model itself, in turn, facilitates research in neuroscience. In this paper, the researcher first introduces the original framework of reinforcement learning and the potential neural correlates to it. Then the paper reviews new developments in reinforcement learning algorithms that address the limitations of the original model as well as variants further inspired by neuroscience. Finally, the study highlights some new directions for future research. This study focuses on the evolution of reinforcement learning algorithms inspired by neuroscience, shows the relationship of mutual promotion and common development between reinforcement Learning and neuroscience, and clarifies some concerns for future exploration.

In order to reduce expensive cost and downtimes, visual inspection method based on unmanned aerial vehicles has become a promising method for surface damage detection in wind turbine blades. Due to the fact that the linear velocity of points on the blade varies along its longitudinal dimension while the blade is in-operation, the captured blade image suers degradation caused by motionblur, and the degradation process of the image is nonlinear. To address this issue, an area-based deblurring method is rstly developed. The points on each divided region can be assumed to follow a uniform motion with the same linear velocity and blurring eect, which indicates that the nonlinear problem can be resolved by linear methods. Point spread function estimation is then conducted to each region to obtain the blur kernels, and image restoration of each region is carried out by using Wiener lter algorithm. Ultimately, image fusion is implemented to merge all the restored regions to realize blade image restoration. Experimental results and evaluation have demonstrated that the proposed areabased method can mitigate blurring effects of rotating blade images, thus further improve the detection accuracy for the on-line inspection.

To accelerate the practical application of Li–O2 batteries. A catalyst with outstanding oxygen reduction reaction and oxygen evolution reaction catalytic activity is required. Here, in-situ growth ZIF-67 within three-dimensional nitrogen-doped reduced graphene oxide (3D-N/rGO) layers was used to investigate a bifunctional catalyst. The inner space is supported by ZIF-67 particles, while 3D-N/rGO extends a suitable three-phase reaction interface and enhances O2 adsorbability. When assembled battery with normal electrolyte, it delivered a high specific capacity of 12028 mAh g−1, and stabilised for 203 cycles at 200 mA g−1 with a limited capacity of 500 mAh g−1. When LiBr-gel polymer electrolyte (GPE) was used instead of electrolyte the lithium metal anode, the polarisation value of LiBr-GPE in Li/Li batteries was only about 0.0384 V after continuous working for 1600 h. When used as a cathode catalyst in Li–O2 batteries, the electrode performance was doubled compared with using the normal electrolyte. These findings pave the way for developing of all-encompassing battery materials with high capacity and long cycle life.

Objective: At present, intramural block anesthesia is mostly used clinically for vaginal delivery, but it is unclear whether intraocular block anesthesia has an effect on postpartum pelvic floor muscles and immune function after vaginal delivery. Therefore, this study investigated the effect of intraspinal block anesthesia on vaginal delivery parturients and its effect on postpartum pelvic floor muscle strength and immune function.Patients and Methods:A total of 182 parturients with vaginal delivery were selected as the study subjects. They were admitted in our hospital from March 2015 to January 2017. Among them, 92 parturients receiving intraspinal block anesthesia were enrolled in the study group and 90 parturients without intraspinal block anesthesia in the control group. The pelvic floor muscle damage and muscle strength recovery in the two groups were measured 3 months after delivery. The peripheral blood T lymphocyte subsets of parturients at different time points in the two groups was detected to investigate the effect of intraspinal block anesthesia on pelvic floor muscle strength and immune function after vaginal delivery. Results: The pain degree during delivery in the study group was significantly lower than that in the control group (p

N6-methyladenosine (m6A) is the addition of a methyl group on the N6 position of adenosine and is the most prevalent and abundant epigenetic modification in eukaryote mRNA. m6A marks are added to mRNA by the m6A methyltransferase complex ("writers"), removed by m6A demethylases ("erasers"), and recognized by m6A-binding proteins ("readers"). Recent evidence has shown that the m6A modification plays a crucial role in the pathogenic mechanism and malignant progression of pancreatic cancer, with roles in cell survival, proliferation, migration, invasion, tumor metastasis, and drug resistance.Literature was searched in Pubmed and Web of Science for the following keywords: "N6-methyladenosine", "pancreatic cancer", "epigenetic modification", "immunotherapy".Among classical m6A regulators, while METTL3, METTL14, WTAP, FTO, YTHDF2, IGF2BP1-3, hnRNPC, and NKAP are upregulated in pancreatic cancer, METTL16 and ALKBH5 are downregulated in pancreatic cancer. m6A modification has been investigated in pancreatic cancer therapy.Dysregulated m6A and its related factors in pancreatic cancer cells and patients indicate their potential values as novel biomarkers in pancreatic cancer diagnosis and targeted therapy.

Accumulation of amyloid-β (Aβ) in the brain is a central component of pathology in Alzheimer’s disease. A growing volume of evidence demonstrates close associations between periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aβ remain to be unclear. In this study, we demonstrated that T. denticola was able to enter the brain and act directly on nerve cells resulting in intra- and extracellular Aβ1–40 and Aβ1–42 accumulation in the hippocampus of C57BL/6 mice by selectively activating both β-secretase and γ-secretase. Furthermore, both KMI1303, an inhibitor of β-secretase, as well as DAPT, an inhibitor of γ- secretase, were found to be able to inhibit the effect of T. denticola on Aβ accumulation in N2a neuronal cells. Overall, it is concluded that T. denticola increases the expression of Aβ1–42 and Aβ1–40 by its regulation on beta-site amyloid precursor protein cleaving enzyme-1 and presenilin 1.

Evidence has shown that m-THPC and verteporfin (VP) are promising sensitizers in photodynamic therapy (PDT). In addition, autophagy can act as a tumor suppressor or a tumor promoter depending on the photosensitizer (PS) and the cancer cell type. However, the role of autophagy in m-THPC- and VP-mediated PDT in in vitro and in vivo models of human colorectal cancer (CRC) has not been reported. In this study, m-THPC-PDT or VP-PDT exhibited significant phototoxicity, inhibited proliferation, and induced the generation of large amounts of reactive oxygen species (ROS) in CRC cells. From immunoblotting, fluorescence image analysis, and transmission electron microscopy, we found extensive autophagic activation induced by ROS in cells. In addition, m-THPC-PDT or VP-PDT treatment significantly induced apoptosis in CRC cells. Interestingly, the inhibition of m-THPC-PDT-induced autophagy by knockdown of ATG5 or ATG7 substantially inhibited the apoptosis of CRC cells. Moreover, m-THPC-PDT treatment inhibited tumorigenesis of subcutaneous HCT116 xenografts. Meanwhile, antioxidant treatment markedly inhibited autophagy and apoptosis induced by PDT in CRC cells by inactivating JNK signaling. In conclusion, inhibition of autophagy can remarkably alleviate PDT-mediated anticancer efficiency in CRC cells via inactivation of the ROS/JNK signaling pathway. Our study provides evidence for the therapeutic application of m-THPC and VP in CRC.

Hyperphosphorylated tau is the main component of neurofibrillary tangles and involved in the pathogenesis of Alzheimer's disease (AD). Increasing evidences suggest close associations between Porphyromonas gingivalis (P. gingivalis) and AD, but the relationship between P. gingivalis and tau hyperphosphorylation is still unclear. In this study, we investigated whether peripheral infection with P. gingivalis caused tau hyperphosphorylation by using wild Sprague-Dawley (SD) rats and HT-22 cells. The rats were injected with P. gingivalis suspension or phosphate-buffered saline 3 times per week. After 4 weeks or 12 weeks, the rats were sacrificed for analyzing systemic inflammation, neuroinflammation, and tau hyperphosphorylation. The results showed that the severity of phosphorylated tau at the AD-related sites Thr181 and Thr231 and the number of activated astrocytes were notably greater in the hippocampus of rats with P. gingivalis injection. And the levels of the inflammatory cytokines interleukin (IL)-1β and IL-6 and tumor necrosis factor-α in serum and hippocampus were also increased in the rats with P. gingivalis injection. In addition, the activity of protein phosphatase 2A (PP2A) was significantly inhibited in the hippocampus of rats with P. gingivalis injection. In vitro, IL-1β induced tau hyperphosphorylation by inhibiting the activity of PP2A in HT-22 cells and application of the PP2A promoter efficiently attenuated IL-1β-induced tau hyperphosphorylation in HT-22 cells. These results indicated that P. gingivalis could induce tau hyperphosphorylation via, in part, attenuating the activity of PP2A through triggering systemic inflammation and neuroinflammation in wild-type SD rats.

Multiple myeloma (MM) is an incurable plasma cell malignancy with poor survival. Autophagy, a stress-responsive catabolic process mediated by lysosomal activity, plays a crucial role in the pathophysiology of MM. Growing evidence has indicated that dysregulated microRNAs (miRNAs) are associated with the aberrant autophagy in various human cancers. However, to date, few miRNAs have been reported to directly modulate autophagy in the pathobiology of MM. In this study, we investigated the role of MIR145-3p (microRNA 145-3p) in MM, with focus on cellular processes autophagy and cell death. Our results provided evidence that downregulation of MIR145-3p expression was associated with disease progression in human MM. MIR145-3p triggered autophagic flux through direct targeting of HDAC4 (histone deacetylase 4) in MM cells, leading to enhanced apoptosis. Silencing HDAC4 recapitulated the effects of MIR145-3p, whereas enforced expression of HDAC4 abrogated the effects of MIR145-3p. Furthermore, we showed that suppression of HDAC4 by MIR145-3p resulted in upregulation of the pro-apoptotic protein BCL2L11 and caused MTORC1 inactivation, which in turn led to enhanced autophagy and cell death. Importantly, we demonstrated that MIR145-3p mimic could potentiate the anti-MM activity of bortezomib in both in vitro and in vivo experiments. Overall, our findings indicate that MIR145-3p exerted a tumor suppression function in MM by inducing autophagic cell death and suggest that MIR145-3p-based targeted therapy would represent a novel strategy for MM treatment. Abbreviations: 3-MA: 3-methyladenine; 3ʹ-UTR: 3ʹ-untranslated region; 7-AAD: 7-aminoactinomycin D; ACTB: actin beta; ANXA5: annexin A5; ATG5: autophagy related 5; ATG7: autophagy related 7; B2M: beta-2-microglobulin; BAF: bafilomycin A(1); BCL2L11: BCL2 like 11; Bort: bortezomib; CASP3: caspase 3; CCK-8: Cell Counting Kit-8; CQ: chloroquine; Ct: threshold cycle; ctrl: control; DAPI: 4ʹ,6-diamidino-2-phenylindole; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HDAC4: histone deacetylase 4; ISS: International Staging System; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; miRNAs: microRNAs; MIR145-3p: microRNA 145-3p; MM: multiple myeloma; mRNA: messenger RNA; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1; PCs: plasma cells; PFS: progression-free survival; qRT-PCR: quantitative reverse transcription PCR; RPS6KB1: ribosomal protein S6 kinase B1; SD: standard deviation; siRNA: small interfering RNA; SQSTM1: sequestosome 1; STV: starvation; TUBB: tubulin beta class I.

Wear debris analysis is used for machine condition monitoring because it is capable of identifying wear related faults in machinery components. In particular, wear mechanisms can be explored based on debris shape and texture features. As current wear monitoring practices prefer rapid data interpretation, on-line ferrograph is favored where debris images are collected and processed on-site with an imaging apparatus. However, such images are often blurred due to lubricant contamination and limited optical field depth. This drawback makes the subsequent investigation of wear debris features a challenging task. To address this issue, a restoration method is developed to reduce the influence of out-of-focus blurring in on-line ferrograph images. Firstly, in order to model the out-of-focus blurring process, a degradation model is constructed with a convolutional neural network. Different from general deep learning structures, larger convolutional kernels are embedded in the network to more comprehensively characterize the blurring process. Next, training samples of different types of debris are collected in the laboratory. The neural network structure then is optimized to minimize the difference between restored images and their corresponding ground truths. The final restoration is conducted based on the trained network via a pixel-wise regression process. To evaluate the performance of the developed method, experiments are carried out with debris images collected from a gear-box test rig. Results have demonstrated that: (1) the proposed restoration strategy allows robust extractions of debris features in greater detail; (2) the developed method is more computationally efficient than traditional deblurring techniques, which enables it to be applicable in on-line machine health monitoring.

Circular RNAs (circRNAs) are RNA molecules with a stable closed-loop structure that are found in a variety of organisms. CircRNAs are highly stable and conserved, and they play important roles in transcriptional regulation and splicing. Multiple Myeloma (MM) is a malignant proliferative disease for which there are currently no effective and comprehensive treatments. Numerous circRNAs may contribute to the development and progression of MM by acting as oncogenes or regulators. Due to the unique function of circRNAs, they have a high potential for regulating the biological functions (including proliferation and apoptosis) of MM cells, and their expression levels and molecular mechanism are closely related to their diagnostic value, therapeutic sensitivity, and clinical prognosis of MM patients. In this review, we aim to provide a detailed overview of the structure and function of circRNAs and demonstrate the potential therapeutic value and potential mechanism of circRNAs in MM via experiments and clinical trials.

Background. Circular RNA Transformation/Transcription Domain Associated Protein (circTRRAP, hsa_circ_0081241) was abnormally upregulated in acute myocardial infarction (AMI) patients. However, its biological role and functional mechanism in AMI remain to be researched. Methods. Human cardiomyocyte AC16 was exposed to hypoxia to induce cell injury. Cell viability was detected through Cell Counting Kit-8. CircTRRAP, microRNA-370-3p (miR-370-3p), and Pro-Apoptotic WT1 Regulator (PAWR) levels were assayed by reverse transcription-quantitative polymerase chain reaction. Cell proliferation analysis was performed via 5-ethynyl-2 ′ -deoxyuridine (EdU) assay. Cell apoptosis was assessed using flow cytometry and caspase-3 activity assay. The protein levels were measured through western blot. Enzyme-linked immunosorbent assay was used to examine the release of inflammatory cytokines. Oxidative stress was assessed by the commercial kits. Dual-luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assays were performed for the validation of target interaction. Results. CircTRRAP was highly expressed following hypoxia treatment in AC16 cells. Downregulation of circTRRAP promoted cell growth but inhibited apoptosis, inflammation, and oxidative stress in hypoxic cells. CircTRRAP could target miR-370-3p, and the regulatory effects of circTRRAP on the hypoxic cells were associated with the sponge function of miR-370-3p. PAWR served as the target for miR-370-3p, and it was regulated by circTRRAP/miR-370-3p axis. The protective role of miR-370-3p was achieved by downregulating the PAWR expression in hypoxia-treated AC16 cells. Conclusion. These findings demonstrated that silence of circTRRAP exerted the protection against the hypoxia-induced damages in cardiomyocytes through regulating the miR-370-3p and PAWR levels.

Gearbox is a vulnerable component of a turbine's drivetrain and plays a vital role in the power transmission in wind turbines. Wind turbines usually operate under harsh working environments, such as in deserts, oceans, and on hills. The adverse operating conditions (such as inevitable fluctuating wind loads and speeds) make the gearbox transmission prone to reliability degradation and premature failure. Gear wear is a common and unavoidable surface degradation phenomenon during the lifespan of the gear transmission system. The gear wear propagation can result in severe failures, such as gear surface spalling, gear root crack, and gear tooth breakage, all of which could lead to the failure of the drivetrain system of wind turbines and bring unexpected economic loss, even serious accidents. Thus, it is crucial to monitor the gear wear propagation progression in order to enable reliable and safe operation. To this end, this paper develops a novel vibration-based health indicator to monitor the gear surface degradation induced by gear wear progression. With the help of the novel indicator developed, the health status of the gearbox can be well evaluated and thus predictive maintenance-based decisions can be made to reduce maintenance costs and minimize gearbox failures in wind turbines. A series of endurance tests under different lubrication conditions and operational conditions are carried out to verify the effectiveness of the gear wear monitoring indicator.

Accumulation of amyloid-β (Aβ) in the brain is a central component of pathology in Alzheimer’s disease. A growing number of evidences demonstrate close associations between periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aβ remain to be unclear. In this study, we demonstrated that T. denticola was able to enter brain and act directly on nerve cells resulting in intra and extracellular Aβ1−40 and Aβ1−42 accumulation in the hippocampus of C57BL/6 mice by selectively activating both β-secretase and γ-secretase. Furthermore, both KMI1303, an inhibitor of β- secretase, as well as DAPT, an inhibitor of γ- secretase were found to be able to inhibit the effect of T. denticola on Aβ accumulation in N2a neuronal cells. Overall, it is concluded that T. denticola increases the expression of Aβ1−42 and Aβ1−40 by its regulation on beta-site amyloid precursor protein cleaving enzyme-1 and Presenilin 1.

Objectives Wnt/β-catenin signaling pathway plays an important role in regulation of macrophage activation implicated in the development of atherosclerosis. However, as a negative regulator of Wnt/β-catenin, the potential role of Dickkopf-2 (Dkk2) on macrophage activation remains unexplored. Materials and methods Bone marrow-derived macrophages (BMDMs) and mouse peritoneal macrophages (MPMs) collected from ApoE knockout mice upon oxidation low lipoprotein (Ox-LDL) administration were performed to test the expression of Dkk2. The loss-of-function strategy using siRNA-Dkk2 was further utilized for the function of Dkk2. Inhibition of β-catenin with XAV939 (a β-catenin specific inhibitor) was further used for testing its effect on macrophage activation mediated by Dkk2 knockdown. Results and conclusion In the current study, real time-polymerase chain reaction analysis demonstrated that an up-regulated Dkk2 expression was observed in BMDMs and MPMs of ApoE knockout mice upon Ox-LDL administration, which was confirmed by western blot. The double immunofluorescence staining further exhibited that Dkk2 showed a strong immunoreactivity in BMDMs and primarily located in cytoplasm of macrophages. Dkk2 knockdown significantly decreased the genes related to classic M1 polarized macrophage but increased alternative M2 polarized macrophage markers. Moreover, Dkk2 silencing dramatically attenuated foam cell formation which was contributed by promoted markers’ expression associated with cholesterol efflux but attenuated markers to cholesterol influx. Mechanistically, we observed that Dkk2 knockdown activated Wnt/β-catenin signaling by promoting β-catenin to translocate into the nuclei of macrophages, and XAV939 reversed the ameliorated effect of Dkk2 silencing macrophage activation. Taken together, these results suggested that downregulated Dkk2 expression in macrophages was responsible for the inactivation of macrophage through targeting Wnt/β-catenin pathway.

Accumulation of amyloid-β (Aβ) in the brain is a central component of pathology in Alzheimer's disease. A growing volume of evidence demonstrates close associations between periodontal pathogens including Porphyromonas gingivalis (P. gingivalis) and Treponema denticola (T. denticola) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aβ remain to be unclear. In this study, we demonstrated that T. denticola was able to enter the brain and act directly on nerve cells resulting in intra- and extracellular Aβ

Background and Purpose: Most patients cannot receive intravenous thrombolytic therapy in the early stage of stroke onset, and the application of mobile stroke unit (MSU) in prehospital intravenous thrombolytic therapy of acute stroke may change this situation. The first MSU in China was put into use in 2017. Herein, we aimed to explore the preliminary experience of MSU in prehospital thrombolysis of acute stroke. Methods: Patients who received prehospital intravenous thrombolytic therapy using MSU were classified to the MSU thrombolysis group, and the control group consisted of stroke patients admitted by regular ambulances, who were transferred to hospital for intravenous thrombolytic therapy. The feasibility, safety, and duration of procedures were compared. Results: There were 14 patients received prehospital intravenous thrombolysis on the MSU, and 24 patients underwent intravenous thrombolysis in the emergency center, who were transferred by the ordinary ambulance during the same period. The median call-to-needle time was 59.5 min in the MSU thrombolysis group, while it was 89 min in the control group; the difference between the 2 groups was statistically significant (p = 0.001). The median time from onset to thrombolysis was 70 and 102.5 min, respectively, in the 2 groups (p = 0.002). The percentages of good clinical outcome (modified Rankin Scale score ≤ 2) at 90-day follow-up were 79 and 67%, respectively (p = 0.488). The rate of symptomatic intracranial hemorrhage and mortality during the perioperative period did not differ significantly between 2 groups. Conclusion: Despite the small sample size, our preliminary experience of the application of MSU in the prehospital thrombosis therapy seems to indicate a significant reduction in time from call to needle, the efficacy of MSU in the treatment of acute stroke needs further experiment and larger sample size to confirm.

Images captured under low-illumination environments often impose difficulties in revealing objects of interest. An effective approach, Optimum Shift-and-Weighted Brightness Mapping, is here propose...

The Bare Bones Particle Swarm Optimization (BBPSO), because of its implementation simplicity, has been a popular swarm-based metaheuristic algorithm for solving optimization problems. However, as found in its many variants, their search behaviors were not considered in the design. Instead of employing heuristics, we formulate a low complexity particle swarm optimizer, called the First-Order Bare Bones Particle Swarm Optimizer (FODBB), whose behavior obeys the principle of first-order difference equations. The search trajectory can be constructed in a prescribed manner together with decreasing random searches that enable particles to explore the search space more completely. This characteristic thus allows for a wider search coverage at initial iterations and consequently improves the search performance. A comparative evaluation with recently reported BBPSO algorithms was conducted and experimental results indicate that the proposed optimizer outperforms others in a majority of benchmark optimization functions.