A giant virus genome is densely packaged by stable nucleosomes within virions.

The two doublet histones of Marseillevirus are distantly related to the four eukaryotic core histones and wrap 121 base pairs of DNA to form remarkably similar nucleosomes. By permeabilizing Marseillevirus virions and performing genome-wide nuclease digestion, chemical cleavage, and mass spectrometry assays, we find that the higher-order organization of Marseillevirus chromatin fundamentally differs from that of eukaryotes. Marseillevirus nucleosomes fully protect DNA within virions as closely abutted 121-bp DNA-wrapped cores without linker DNA or phasing along genes. Likewise, we observed that nucleosomes reconstituted onto multi-copy tandem repeats of a nucleosome-positioning sequence are tightly packed. Dense promiscuous packing of fully wrapped nucleosomes rather than "beads on a string" with genic punctuation represents a distinct mode of DNA packaging by histones. We suggest that doublet histones have evolved for viral genome protection and may resemble an early stage of histone differentiation leading to the eukaryotic octameric nucleosome.

Malignant pleural effusion: current understanding and therapeutic approach.

Malignant pleural effusion (MPE) is a common complication of thoracic and extrathoracic malignancies and is associated with high mortality and elevated costs to healthcare systems. Over the last decades the understanding of pathophysiology mechanisms, diagnostic techniques and optimal treatment intervention in MPE have been greatly advanced by recent high-quality research, leading to an ever less invasive diagnostic approach and more personalized management. Despite a number of management options, including talc pleurodesis, indwelling pleural catheters and combinations of the two, treatment for MPE remains symptom directed and centered around drainage strategy. In the next future, because of a better understanding of underlying tumor biology together with more sensitive molecular diagnostic techniques, it is likely that combined diagnostic and therapeutic procedures allowing near total outpatient management of MPE will become popular. This article provides a review of the current advances, new discoveries and future directions in the pathophysiology, diagnosis and management of MPE.

Research on a Fault Diagnosis Method for Crankshafts Based on Improved Multi-Scale Permutation Entropy.

As the crucial part of a transmission assembly, the monitoring of the status of the crankshaft is essential for the normal working of a reciprocating machinery system. In consideration of the interaction between crankshaft system components, the fault vibration feature is typically non-stationary and nonlinear, and the single-scale feature extraction method cannot adequately assess the fault features, therefore a novel impact feature extraction method based on genetic algorithms to optimize multi-scale permutation entropy is proposed. Compared with other traditional feature extraction methods, the proposed method illustrates good robustness and high adaptability in the signal processing of crankshaft vibrations. Firstly, the improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN) method is developed on the signal to obtain several intrinsic mode function (IMF) components, and the IMF components with a large kurtosis are selected for array reorganization. Then, the parameters of multi-scale permutation entropy (MPE) are optimized based on genetic algorithm (GA), the multi-scale permutation entropy is calculated and the feature vector set is constructed. The feature vector set is input into the support vector machine (SVM) and optimized by a particle swarm optimization (PSO) model for training and final pattern recognition, where the Variational Mode Decomposition(VMD)-GA-MPE with a PSO-SVM recognition model and the ICEEMDAN-MPE with PSO-SVM recognition model without GA optimization are constructed for a comparison with the proposed method. The research result illustrates that the proposed method, which inputs the genetic algorithm optimized multi-scale permutation entropy extracted from the ICEEMDAN decomposition into the PSO-SVM, performs well in impact feature extraction and the pattern recognition of crankshaft vibrations.

Research Progress on Magneto-Refractive Magnetic Field Fiber Sensors.

The magnetic field is a vital physical quantity in nature that is closely related to human production life. Magnetic field sensors (namely magnetometers) have significant application value in scientific research, engineering applications, industrial productions, and so forth. Accompanied by the continuous development of magnetic materials and fiber-sensing technology, fiber sensors based on the Magneto-Refractive Effect (MRE) not only take advantage in compact structure, superior performance, and strong environmental adaptability but also further meet the requirement of the quasi-distributed/distributed magnetic field sensing; they manifest potential and great application value in space detection, marine environmental monitoring, etc. Consequently, the present and prevalent Magneto-Refractive Magnetic Field Fiber Sensors (MR-MFSs) are briefly summarized by this paper, proceeding from the perspective of physicochemical properties; design methods, basic performance and properties are introduced systematically as well. Furthermore, this paper also summarizes key fabrication techniques and future development trends of MR-MFSs, expecting to provide ideas and technical references for staff engaging in relevant research.

Does metatarsus primus elevatus really exist in hallux rigidus? A weightbearing CT case-control study.

BACKGROUND: Elevated first metatarsal, Metatarsus primus elevatus (MPE), has been a topic of controversy. Recent studies have supported a significantly elevated first metatarsal in hallux rigidus on weight-bearing radiographs (WBR). However, conventional radiographs have limitations for accurate measurement. Our objective was to comparatively assess MPE and other variables which can affect the spatial relationship of the forefoot in the HR group compared to controls using weight-bearing CT (WBCT). METHODS: In this single-center, retrospective, case-control study, 25 patients (30 feet) with symptomatic HR and 30 controls were selected. WBCT parameters were measured by two independent investigators. Inter-observer reliabilities were assessed using intra-class correlation coefficients (ICCs). MPE was evaluated by measuring the direct distance between 1st and 2nd metatarsals. Independent t tests were performed to compare the two groups. A threshold of MPE to diagnose HR was calculated using the Receiver Operating Characteristic (ROC) curve. RESULTS: HR groups had increased hallux valgus angle (HVA) (8.52° in control vs 11.98° in HR) and MPE (2.92 vs 5.09 mm), decreased 1st metatarsal declination angle (21.09° vs 19.07°) 1st/2nd metatarsal declination ratio (87.45 vs 79.71) indicating elevated first metatarsal compared to controls. Dorsal translation of the first metatarsal at the first tarsometatarsal joint was observed in 21 (70%) patients of the HR group when defined as a step-off or discontinuation of the curvature along the first TMT joint. The threshold of MPE for diagnosis of HR was 4.19 mm with 77% sensitivity and 77% specificity. CONCLUSION: Our results confirmed a significantly elevated first metatarsal in the HR group compared to controls on WBCT. A MPE greater than 4.19 mm was found to be diagnostic for symptomatic HR. Significant number of patients in the HR group (70%) had dorsal translation of the first metatarsal at the first TMT joint which can contribute to increased MPE. CLINICAL RELEVANCE: The present study demonstrated significantly increased MPE in HR on WBCT and MPE greater than 4.19 mm on WBCT can be used as a diagnostic threshold for HR.

Intraperitoneal infusion of recombinant human endostatin improves prognosis in gastric cancer ascites.

Objective: To investigate the efficacy and safety of intraperitoneal administration of recombinant human endostatin in gastric cancer with malignant ascites. Methods: Clinical data of 90 patients (37 in an Endostar® combined with cisplatin group and 53 in a cisplatin group) were retrospectively analyzed. The primary end point was overall survival, and the secondary end points were objective response rate (ORR), disease control rate (DCR) and so on. Results: Median overall survival was longer in the combination group (9.7 vs 8.1 months; p = 0.01). ORR and DCR were higher in the combination group (ORR: 75.7% vs 54.7%; p = 0.04; DCR: 94.6% vs 75.5%; p = 0.02). There were no significant differences in adverse effects between the two groups. Conclusion: Intraperitoneal administration of recombinant human endostatin improved efficacy and survival for gastric cancer with ascites.

Ascites (a buildup of fluid in the abdomen) resulting from the spread of gastric cancer (GC) results in extremely poor clinical outcomes, and current treatments have shown little effectiveness. Previous results showed that abdominal injection with chemotherapeutic agents enabled an increase in the dose of chemotherapeutic agents and reduced side effects or undesirable effects in the abdominal cavity. This study aimed to investigate the effectiveness and safety of abdominal injection with the anticancer drug recombinant human endostatin in GC with ascites. Clinical data of 90 patients were inspected and analyzed in this study. Thirty-seven patients who received abdominal infusion with both cisplatin (CDDP) and recombinant human endostatin were included in an Endostar^® combined with CDDP group, and 53 patients who received abdominal infusion with CDDP alone were included in a CDDP group. The results showed that median survival time was longer in the combination group than in the CDDP group (9.7 months vs 8.1 months). Besides, therapeutic outcomes, including objective response rate and disease control rate, were better in the combination group. Side effects or undesirable effects were similar in the two groups. To conclude, abdominal injection with recombinant human endostatin improved survival time and therapeutic outcomes for GC patients with ascites.

Mulberry polyphenols ameliorate atherogenic migration and proliferation by degradation of K-Ras and downregulation of its signals in vascular smooth muscle cell.

Extra-proliferation and increased migration of vascular smooth cells con-tribute to the formation of atherosclerosis. Ras small G proteins play a critical role in the prolif-eration and migration of a wide range of cells. Mulberry, an economic fruit in Asia, exhibits anti-inflammation, anti-migration, and anti-oxidant properties. The mechanisms of action of mulberry extracts on K-Ras small G protein-induced proliferation and migration of vascular smooth muscle cell have not been extensively investigated. In this study, we explored the effects of mulberry polyphenol extracts (MPE) on the proliferation and migration of K-Ras-overexpressing A7r5 smooth muscle cells. The overexpression of K-Ras enhanced the ex-pression and activity of matrix metalloproteinase (MMP)-2, promoted vascular endothelial growth factor (VEGF) production, and eventually triggered the migration of A7r5 cells. Treatment with MPE attenuated K-Ras-induced phenomenon. In addition, MPE blocked K-Ras-induced actin fibril stress. MPE dose-dependently diminished K-Ras-induced Rho A, Rac1, CDC42, and phosphorylated focal adhesion kinase (FAK) expression. MPE elevated Rho B ex-pression. Phosphorylated AKT and glycogen synthase kinase (GSK) induced by K-Ras were also repressed by MPE treatment. MPE enhanced the interaction of IκB with NFκB. MPE restored the G0/G1 population and p21 and p27 expressions, which were repressed by K-Ras. Finally, MPE triggered the degradation of K-Ras by ubiquitination. MPE inhibited the migration and proliferation of vascular smooth cell through K-Ras-induced pathways and eventually pre-vented atherosclerosis.

Molecular Insights into mRNA Polyadenylation and Deadenylation.

Poly(A) tails are present on almost all eukaryotic mRNAs, and play critical roles in mRNA stability, nuclear export, and translation efficiency. The biosynthesis and shortening of a poly(A) tail are regulated by large multiprotein complexes. However, the molecular mechanisms of these protein machineries still remain unclear. Recent studies regarding the structural and biochemical characteristics of those protein complexes have shed light on the potential mechanisms of polyadenylation and deadenylation. This review summarizes the recent structural studies on pre-mRNA 3'-end processing complexes that initiate the polyadenylation and discusses the similarities and differences between yeast and human machineries. Specifically, we highlight recent biochemical efforts in the reconstitution of the active human canonical pre-mRNA 3'-end processing systems, as well as the roles of RBBP6/Mpe1 in activating the entire machinery. We also describe how poly(A) tails are removed by the PAN2-PAN3 and CCR4-NOT deadenylation complexes and discuss the emerging role of the cytoplasmic poly(A)-binding protein (PABPC) in promoting deadenylation. Together, these recent discoveries show that the dynamic features of these machineries play important roles in regulating polyadenylation and deadenylation.

Coal and Rock Hardness Identification Based on EEMD and Multi-Scale Permutation Entropy.

This study offers an efficient hardness identification approach to address the problem of poor real-time performance and accuracy in coal and rock hardness detection. To begin, Ensemble Empirical Mode Decomposition (EEMD) was performed on the current signal of the cutting motor to obtain a number of Intrinsic Mode Functions (IMFs). Further, the target signal was selected among the IMFs to reconstruct the current signal according to the energy density and correlation coefficient criteria. After that, the Multi-scale Permutation Entropy (MPE) of the reconstructed signal was trained by the Adaboost improved Back Propagation (BP) neural network, in order to establish the hardness recognition model. Finally, the cutting arm's swing speed and the cutting head's rotation speed were adjusted based on the coal and rock hardness. The simulation results indicated that using the energy density and correlation criterion to reconstruct the signal can successfully filter out noise interference. Compared to the BP model, the relative root-mean-square error of the Adaboost-BP model decreased by 0.0633, and the prediction results were more accurate. Additionally, the speed control strategy based on coal and rock hardness can ensure the efficient cutting of the roadheader.

A Comprehensive Diagnosis Method of Rolling Bearing Fault Based on CEEMDAN-DFA-Improved Wavelet Threshold Function and QPSO-MPE-SVM.

A comprehensive fault diagnosis method of rolling bearing about noise interference, fault feature extraction, and identification was proposed. Based on complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), detrended fluctuation analysis (DFA), and improved wavelet thresholding, a denoising method of CEEMDAN-DFA-improved wavelet threshold function was presented to reduce the distortion of the noised signal. Based on quantum-behaved particle swarm optimization (QPSO), multiscale permutation entropy (MPE), and support vector machine (SVM), the QPSO-MPE-SVM method was presented to construct the fault-features sets and realize fault identification. Simulation and experimental platform verification showed that the proposed comprehensive diagnosis method not only can better remove the noise interference and maintain the original characteristics of the signal by CEEMDAN-DFA-improved wavelet threshold function, but also overcome overlapping MPE values by the QPSO-optimizing MPE parameters to separate the features of different fault types. The experimental results showed that the fault identification accuracy of the fault diagnosis can reach 95%, which is a great improvement compared with the existing methods.

A Rolling Bearing Fault Classification Scheme Based on k-Optimized Adaptive Local Iterative Filtering and Improved Multiscale Permutation Entropy.

The health condition of the rolling bearing seriously affects the operation of the whole mechanical system. When the rolling bearing parts fail, the time series collected in the field generally shows strong nonlinearity and non-stationarity. To obtain the faulty characteristics of mechanical equipment accurately, a rolling bearing fault detection technique based on k-optimized adaptive local iterative filtering (ALIF), improved multiscale permutation entropy (improved MPE), and BP neural network was proposed. In the ALIF algorithm, a k-optimized ALIF method based on permutation entropy (PE) is presented to select the number of ALIF decomposition layers adaptively. The completely average coarse-graining method was proposed to excavate more hidden information. The performance analysis of the simulation signal shows that the improved MPE can more accurately dig out the depth information of the time series, and the entropy value obtained is more consistent and stable. In the research application, rolling bearing time series are decomposed by k-optimized ALIF to obtain a certain number of intrinsic mode functions (IMFs). Then the improved MPE value of effective IMF is calculated and input into backpropagation (BP) neural network as the feature vector for automatic fault identification. The comparative analysis of simulation signals shows that this method can extract fault information effectively. At the same time, the experimental part shows that this scheme not only effectively extracts the fault features, but also realizes the classification and identification of different fault modes and faults of different degrees, which has a certain application prospect in the research and application direction of rolling bearing fault identification.

A New Fuzzy Logic Classifier Based on Multiscale Permutation Entropy and Its Application in Bearing Fault Diagnosis.

The self-organizing fuzzy (SOF) logic classifier is an efficient and non-parametric classifier. Its classification process is divided into an offline training stage, an online training stage, and a testing stage. Representative samples of different categories are obtained through the first two stages, and these representative samples are called prototypes. However, in the testing stage, the classification of testing samples is completely dependent on the prototype with the maximum similarity, without considering the influence of other prototypes on the classification decision of testing samples. Aiming at the testing stage, this paper proposed a new SOF classifier based on the harmonic mean difference (HMDSOF). In the testing stage of HMDSOF, firstly, each prototype was sorted in descending order according to the similarity between each prototype in the same category and the testing sample. Secondly, multiple local mean vectors of the prototypes after sorting were calculated. Finally, the testing sample was classified into the category with the smallest harmonic mean difference. Based on the above new method, in this paper, the multiscale permutation entropy (MPE) was used to extract fault features, linear discriminant analysis (LDA) was used to reduce the dimension of fault features, and the proposed HMDSOF was further used to classify the features. At the end of this paper, the proposed fault diagnosis method was applied to the diagnosis examples of two groups of different rolling bearings. The results verify the superiority and generalization of the proposed fault diagnosis method.

Evaluation of efficacy and safety for Brucea javanica oil emulsion in the control of the malignant pleural effusions via thoracic perfusion.

BACKGROUND: Brucea javanica oil emulsion (BJOE) is traditional Chinese medicine with implicated anti-tumor activity, which has been used for treating lung cancer in China. The aim of this investigation was to evaluate the effects and safety of intrapleural injection of BJOE in treating malignant pleural effusion (MPE). METHODS: The randomised controlled trials (RCTs) on the effects and safety of BJOE in treating MPE were searched from electronic medical database including MEDLINE, SCI, EMBASE, Cochrance Library and CNKI. A total of 14 RCTs with 1085 patients were involved in this meta-analysis. RESULTS: The overall response rate (ORR) of traditional chemotherapy drugs plus BJOE was higher than that of traditional chemotherapy drugs alone (p = 0.001; odds ratio = 1.39). Meanwhile, the combination of BJOE and traditional chemotherapy drugs improved the quality of life (QOL) of patients with MPE (p < 0.001; odds ratio = 1.56) compared with traditional chemotherapy drugs alone. Moreover, the participation of BJOE reduced the myelotoxicity and digestive reactions caused by traditional chemotherapy drugs (p < 0.05). CONCLUSIONS: The efficacy and safety of traditional chemotherapy drugs plus BJOE was superior to traditional chemotherapy drugs alone via intrapleural injection in controlling MPE, which suggested that BJOE can be used to treat MPE.

Multiscale Persistent Functions for Biomolecular Structure Characterization.

In this paper, we introduce multiscale persistent functions for biomolecular structure characterization. The essential idea is to combine our multiscale rigidity functions (MRFs) with persistent homology analysis, so as to construct a series of multiscale persistent functions, particularly multiscale persistent entropies, for structure characterization. To clarify the fundamental idea of our method, the multiscale persistent entropy (MPE) model is discussed in great detail. Mathematically, unlike the previous persistent entropy (Chintakunta et al. in Pattern Recognit 48(2):391-401, 2015; Merelli et al. in Entropy 17(10):6872-6892, 2015; Rucco et al. in: Proceedings of ECCS 2014, Springer, pp 117-128, 2016), a special resolution parameter is incorporated into our model. Various scales can be achieved by tuning its value. Physically, our MPE can be used in conformational entropy evaluation. More specifically, it is found that our method incorporates in it a natural classification scheme. This is achieved through a density filtration of an MRF built from angular distributions. To further validate our model, a systematical comparison with the traditional entropy evaluation model is done. It is found that our model is able to preserve the intrinsic topological features of biomolecular data much better than traditional approaches, particularly for resolutions in the intermediate range. Moreover, by comparing with traditional entropies from various grid sizes, bond angle-based methods and a persistent homology-based support vector machine method (Cang et al. in Mol Based Math Biol 3:140-162, 2015), we find that our MPE method gives the best results in terms of average true positive rate in a classic protein structure classification test. More interestingly, all-alpha and all-beta protein classes can be clearly separated from each other with zero error only in our model. Finally, a special protein structure index (PSI) is proposed, for the first time, to describe the "regularity" of protein structures. Basically, a protein structure is deemed as regular if it has a consistent and orderly configuration. Our PSI model is tested on a database of 110 proteins; we find that structures with larger portions of loops and intrinsically disorder regions are always associated with larger PSI, meaning an irregular configuration, while proteins with larger portions of secondary structures, i.e., alpha-helix or beta-sheet, have smaller PSI. Essentially, PSI can be used to describe the "regularity" information in any systems.

Design, data monitoring, and analysis of clinical trials with co-primary endpoints: A review.

We review the design, data monitoring, and analyses of clinical trials with co-primary endpoints. Recently developed methods for fixed-sample and group-sequential settings are described. Practical considerations are discussed, and guidance for the application of these methods is provided.

Elevated Hsp90-beta contributes to differential diagnosis of pleural effusion caused by lung cancer and correlates with malignant biological behavior of lung cancer.

BACKGROUND: Hsp90-beta has been investigated to be correlated with the occurrence and development of tumor. The intention of this research was to test the level of Hsp90-beta in malignant pleural effusion (MPE) of patients with lung cancer and disclose the clinical significance of Hsp90-beta as a potential tumor marker for differential diagnosis of pleural effusion caused by lung cancer. METHODS: The level of Hsp90-beta was determined using enzyme-linked immunosorbent assay. Calculations of the Hsp90-beta threshold, the sensitivity and specificity for distinguishing MPE from benign pleural effusion were performed using receiver operator characteristic curve. RESULTS: The level of Hsp90-beta in MPE of lung cancer patients was higher than that in control individuals (P < 0.05) and increased MPE Hsp90-beta was correlated with the pathological differentiation, tumor size and lymphatic metastasis (P < 0.05). The cutoff value of Hsp90-beta produced by receiver operator characteristic curve for distinguishing lung cancer from control individuals were 1.659 ng/mL and the sensitivity and specificity were 93.46 and 79%. CONCLUSIONS: Increased Hsp90-beta in MPE was correlated with malignant biological behavior of lung cancer patients, indicating that the level of Hsp90-beta could be a tool of referential value for differential diagnosis of pleural effusion caused by lung cancer.

MPE-seq, a new method for the genome-wide analysis of chromatin structure.

The analysis of chromatin structure is essential for the understanding of transcriptional regulation in eukaryotes. Here we describe methidiumpropyl-EDTA sequencing (MPE-seq), a method for the genome-wide characterization of chromatin that involves the digestion of nuclei withMPE-Fe(II) followed by massively parallel sequencing. Like micrococcal nuclease (MNase), MPE-Fe(II) preferentially cleaves the linker DNA between nucleosomes. However, there are differences in the cleavage of nuclear chromatin by MPE-Fe(II) relative to MNase. Most notably, immediately upstream of the transcription start site of active promoters, we frequently observed nucleosome-sized (141-190 bp) and subnucleosome-sized (such as 101-140 bp) peaks of digested chromatin fragments with MPE-seq but not with MNase-seq. These peaks also correlate with the presence of core histones and could thus be due, at least in part, to noncanonical chromatin structures such as labile nucleosome-like particles that have been observed in other contexts. The subnucleosome-sized MPE-seq peaks exhibit a particularly distinct association with active promoters. In addition, unlike MNase, MPE-Fe(II) cleaves nuclear DNA with little sequence bias. In this regard, we found that DNA sequences at RNA splice sites are hypersensitive to digestion by MNase but not by MPE-Fe(II). This phenomenon may have affected the analysis of nucleosome occupancy over exons. These findings collectively indicate that MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias. In particular, the combined use of MPE-seq and MNase-seq enables the identification of noncanonical chromatin structures that are likely to be important for the regulation of gene expression.

Cutaneous drug reactions to antiepileptic drugs and relation with HLA alleles in the Turkish population.

Summary: Background and objective. Many studies have shown associations between HLAB*15:02, HLA-A*31:01 and carbamazepine (CBZ)-induced delayed cutaneous hypersensitivity reactions. The aim of this study is to evaluate a possible association between delayed cutaneous reactions to antiepileptic drugs (AEDs) and certain HLA-A and HLA-B alleles in the Turkish population. Methods. The study consisted of 3 groups: Group I (reactive group) included the patients who had documented delayed cutaneous reactions to any antiepileptic drug. Group II (non-reactive group) included the patients who have been on antiepileptic treatment at least for three months without any adverse reactions. Group III consisted of healthy subjects. The HLA-A and B alleles were analyzed in all groups. Results. Forty patients (29 female) had experienced different hypersensitivity reactions due to AEDs: maculopapular exanthema (26 patients), Stevens-Johnson syndrome (6 patients), drug rash with eosinophilia and systemic symptoms (7 patients), toxic epidermal necrolysis (1 patient). Lamotrigine (11) and CBZ (10) were the most common culprit drugs involved in the reactions. The HLA-B*15:02 was not present in any of the study groups. However, HLA-B*35:02 was found in 4 patients from the reactive group, while it was not observed in non-reactive patients and was detected in only one healthy subject (p = 0.021). Conclusion. Although our preliminary results did not indicate a strong allele association with AED hypersensitivity, HLA-B*35:02 appears to be a candidate allele for MPE / DRESS / DIHSS induced by AED's in Turkish population. Further studies with a larger sample size may result in more comprehensive data about the genetic tendency for AED hypersensitivity in the Turkish population.

Data Decomposition Techniques with Multi-Scale Permutation Entropy Calculations for Bearing Fault Diagnosis.

This paper presents the local mean decomposition (LMD) integrated with multi-scale permutation entropy (MPE), also known as LMD-MPE, to investigate the rolling element bearing (REB) fault diagnosis from measured vibration signals. First, the LMD decomposed the vibration data or acceleration measurement into separate product functions that are composed of both amplitude and frequency modulation. MPE then calculated the statistical permutation entropy from the product functions to extract the nonlinear features to assess and classify the condition of the healthy and damaged REB system. The comparative experimental results of the conventional LMD-based multi-scale entropy and MPE were presented to verify the authenticity of the proposed technique. The study found that LMD-MPE’s integrated approach provides reliable, damage-sensitive features when analyzing the bearing condition. The results of REB experimental datasets show that the proposed approach yields more vigorous outcomes than existing methods.

The possible mechanisms of protocatechuic acid-induced central analgesia.

It is aimed to investigate the central antinociceptive effect of protocatechuic acid and the involvement of stimulation of opioidergic, serotonin 5-HT2A/2C, α2-adrenergic and muscarinic receptors in protocatechuic acid-induced central analgesia in mice. Time-dependent antinociceptive effects of protocatechuic acid at the oral doses of 75, 150 and 300 mg/kg were tested in hot-plate (integrated supraspinal response) and tail-immersion (spinal reflex) tests in mice. To investigate the mechanisms of action; the mice administered 300 mg/kg protocatechuic acid (p.o.) were pre-treated with non-specific opioid antagonist naloxone (5 mg/kg, i.p.), serotonin 5-HT2A/2C receptor antagonist ketanserin (1 mg/kg, i.p.), α2-adrenoceptor antagonist yohimbine (1 mg/kg, i.p.) and non-specific muscarinic antagonist atropine (5 mg/kg, i.p.), respectively. The antinociceptive effect of protocatechuic acid was observed at the doses of 75, 150 and 300 mg/kg in tail-immersion test, at the doses of 150 and 300 mg/kg in hot-plate test at different time interval. The enhancement in the latency of protocatechuic acid-induced response to thermal stimuli was antagonized by yohimbine, naloxone and atropine in tail-immersion test, while it was antagonized only by yohimbine and naloxone pretreatments in hot-plate test. These results indicated that protocatechuic acid has the central antinociceptive action that is probably organized by spinal mediated cholinergic and opiodiergic, also spinal and supraspinal mediated noradrenergic modulation. However, further studies are required to understand how protocatechuic acid organizes the interactions of these modulatory systems. As a whole, these findings reinforce that protocatechuic acid is a potential agent that might be used for pain relief. Additionally, the clarification of the effect and mechanisms of action of protocatechuic acid will contribute to new therapeutic approaches and provide guidance for new drug development studies.