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Abnormal activation of hepatic gluconeogenesis is a major contributor to fasting hyperglycemia in type 2 diabetes; however, the potential role of microRNAs in gluconeogenesis remains unclear. Here, we showed that hepatic expression levels of microRNA-21 (miR-21) were decreased in db/db and high-fat diet (HFD)-induced diabetic mice. Adenovirus-mediated overexpression of miR-21 decreased the expression of phosphoenolpyruvate carboxykinase ( PEPCK ) and glucose-6-phosphatase ( G6Pase ) and inhibited glucose production in primary mouse hepatocytes. Silencing of miR-21 reversed this effect. Overexpression of miR-21 in the livers of db/db and HFD-induced mice was able to suppress hepatic gluconeogenesis, subsequently decreasing blood glucose levels and improving glucose and insulin intolerance. Furthermore, overexpression of miR-21 in primary mouse hepatocytes and mouse livers decreased the protein levels of FOXO1 and increased hepatic insulin sensitivity. By contrast, silencing of miR-21 increased the protein levels of FOXO1, subsequently leading to a decrease in insulin sensitivity and impaired glucose intolerance in C57BL/6 mice fed with high-fat diet for 4 weeks. Finally, we confirmed that FOXO1 was a potential target of miR-21. These results suggest that miR-21 is a critical regulator in hepatic gluconeogenesis and may provide a novel therapeutic target for treating insulin resistance and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Adenosine deaminase acting on RNA1 (ADAR1), catalyzing post-transcriptional adenosine-to-inosine RNA editing, promotes cancer progression and therapeutic resistance. However, very little is known about the association of ADAR1 variants with acute lymphoblastic leukemia (ALL). Here we first explored the potential association of three polymorphisms (rs9616, rs2229857, and rs1127313) of ADAR1 with susceptibility in Chinese children ALL, then functionally characterized ADAR1 in ALL. Our results demonstrated that rs9616 T and rs2229857 T were associated with increased expression of ADAR1 mRNA and higher risk to ALL. Of note, a stronger risk effect of rs2229857 T genotypes was found among relapse children. Furthermore, ADAR1 knockdown specifically inhibited proliferation and promoted apoptosis in ALL cells. These findings give insights into a mechanism by which the risk variant at rs9616 and rs2229857 modulate ADAR1 expression and confers a predisposition and relapse risk to ALL, and representing a potential novel biomarker for pediatric ALL. [ABSTRACT FROM AUTHOR]

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. IKZF3 (IKAROS family zinc finger 3) is a hematopoietic‐specific transcription factor, and it has been validated that it is involved in leukemia. However, the role of IKZF3 single‐nucleotide polymorphisms (SNPs) remains unclear. In this case–control study, the authors investigated the association of IKZF3 SNPs with ALL in children. Methods: Six IKZF3 reference SNPs (rs9635726, rs2060941, rs907092, rs12946510, rs1453559, and rs62066988) were genotyped in 692 patients who had ALL (cases) and in 926 controls. The associations between IKZF3 polymorphisms and ALL risk were determined using odds ratios (ORs) and 95% confidence intervals (CIs). The associations of rs9635726 and rs2060941 with the risk of ALL were further estimated by using false‐positive report probability (FPRP) analysis. Functional analysis in silico was performed to evaluate the probability that rs9635726 and rs2060941 might influence the regulation of IKZF3. Results: The authors observed that rs9635726C>T (adjusted OR, 1.49; 95% CI, 1.06–2.11; p =.023) and rs2060941G>T (adjusted OR, 1.51; 95% CI, 1.24–1.84; p =.001) were related to and increased risk of ALL in the recessive and dominant models, respectively. Furthermore, the associations of both rs9635726 (FPRP =.177) and rs2060941 (FPRP <.001) with ALL were noteworthy in the FPRP analysis. Functional analysis indicated that rs9635726 and rs2060941 might repress the transcription of IKZF3 by disrupting its binding to MLLT1, TAF1, POLR2A, and/or RAD21. Conclusions: This study revealed that IKZF3 polymorphisms were associated with increased ALL susceptibility in children and might influence the expression of IKZF3 by disrupting its binding to MLLT1, TAF1, POLR2A, and/or RAD21. IKZF3 polymorphisms were suggested as a biomarker for childhood ALL. [ABSTRACT FROM AUTHOR]

Background: Myocardial ischemia reperfusion injury (MIRI), the tissue damage which is caused by the returning of blood supply to tissue after a period of ischemia, greatly reduces the therapeutic effect of treatment of myocardial infarction. But the underlying functional mechanisms of MIRI are still unclear. Methods: We constructed mouse models of MIRI, extracted injured and healthy myocardial tissues, and performed transcriptome sequencing experiments (RNA-seq) to systematically investigate the dysregulated transcriptome of MIRI, especially the alternative splicing (AS) regulation and RNA binding proteins (RBPs). Selected RBPs and MIRI-associated AS events were then validated by RT-qPCR experiments. Results: The differentially expressed gene (DEG) analyses indicated that transcriptome profiles were changed by MIRI and that DEGs' enriched functions were consistent with MIRI's dysregulated pathways. Furthermore, the AS profile was synergistically regulated and showed clear differences between the mouse model and the healthy samples. The exon skipping events significantly increased in MIRI model samples, while the opposite cassette exon events significantly decreased. According to the functional analysis, regulated alternative splicing genes (RASGs) were enriched in protein transport, cell division /cell cycle, RNA splicing, and endocytosis pathways, which were associated with the development of MIRI. Meanwhile, 493 differentially expressed RBPs (DE RBPs) were detected, most of which were correlated with the changed ratios of AS events. In addition, nine DE RBP genes were validated, including Eif5, Pdia6, Tagln2, Vasp, Zfp36l2, Grsf1, Idh2, Ndrg2, and Uqcrc1. These nine DE RBPs were correlated with RASGs enriched in translation process, cell growth and division, and endocytosis pathways, highly consistent with the functions of all RASGs. Finally, we validated the AS ratio changes of five regulated alternative splicing events (RASEs) derived from important regulatory genes, including Mtmr3, Cdc42, Cd47, Fbln2, Vegfa, and Fhl2. Conclusion: Our study emphasized the critical roles of the dysregulated AS profiles in MIRI development, investigated the potential functions of MIRI-associated RASGs, and identified regulatory RBPs involved in AS regulation. We propose that the identified RASEs and RBPs could serve as important regulators and potential therapeutic targets in MIRI treatment in the future. [ABSTRACT FROM AUTHOR]

Vibration analysis has been proved to be an effective and powerful tool for the condition monitoring and fault diagnosis of rolling bearings. During the past decades, the conventional envelope analysis has been one of the main approaches in vibration signal processing. However, the envelope analysis is based on stationary assumption, thus it is not applicable to the fault diagnosis of bearings under rotating speed variation conditions. This constraint limits the bearing diagnosis in industrial applications. In recent years, order tracking methods based on time–frequency representation have been proposed for bearing fault detection under speed variation operating conditions. However, the methods are only applicable for offline bearing fault detection. Aiming at the shortcomings of the current tacholess order tracking techniques, an online tacholess order tracking method is proposed in this paper. The proposed method is on the basis of extracting the instantaneous tachometer information from the collected vibration signal itself continuously, and resampling the original signal with equal angle increment. The envelope order spectrum is used for bearing fault identification. The effectiveness of the proposed method has been validated by both simulated and experimental bearing vibration signals. [ABSTRACT FROM AUTHOR]

Discusses the isolation of choline monooxygenase of spinach leaves. Experimental procedure; Production of the intermediate betaine aldehyde; Adsorption peak.

Background: Hematopoietic stem cell transplantation (HSCT) is a standard therapy strategy for most malignant disorders in children. However, transplant-related pneumonia remains a major therapy challenge and mesenchymal stromal cells (MSCs) are rarely reported in HSCT-related pneumonia. The aim of our study was to assess the efficacy of MSC for HSCT-related pneumonia in children. Methods: We retrospectively retrieved HSCT-related (severe and non-severe) pneumonia cases (aged < 18 years), which underwent MSC treatment (MSC group) or non-MSC treatment (non-MSC group) in Guangzhou Women and Children's Medical Center, from December 2017 to December 2019. We investigated outcomes of the two different treatments among severe cases and non-severe cases, respectively. The primary endpoints were differences in overall cure rate and time to cure between MSC and non-MSC groups. The secondary endpoints were 180-day overall survival and cumulative cure rate. Results: Finally, 31 severe pneumonia cases (16 in MSC group, 15 in non-MSC group) and 76 non-severe cases (31 in MSC group, 45 in non-MSC group) were enrolled in this study. Among severe pneumonia cases, overall cure rate in MSC group was significant higher than that in non-MSC group (12[75.0%] vs. 5[33.3%]; OR = 6.00, 95% CI [1.26–28.5]; p = 0.020); the time (days) to cure in MSC group was dramatically reduced compared with that in non-MSC group (36 [19–52] vs. 62 [42–81]; OR = 0.32, 95% CI [0.12–0.88]; p = 0.009); the 180-day overall survival in MSC group was better than that in non-MSC group (74.5% [45.4–89.6] vs. 33.3% [12.2–56.4]; p = 0.013). Among non-severe pneumonia cases, the time (days) to cure in MSC group was notably decreased compared with that in non-MSC group (28 [24–31] vs. 33 [26–39]; OR = 0.31, 95% CI [0.18–0.56]; p = 0.003). Compared with non-MSC group, MSC-treated patients achieved significant improvements of cumulative cure rate not only in severe pneumonia cases (p = 0.027), but also in non-severe cases (p < 0.001). Conclusions: This study revealed that MSC treatment could contribute to improving outcomes in children with pneumonia post-HSCT, especially in severe cases. These findings suggest MSC treatment as a promising therapy for HSCT-related pneumonia in children. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and have been confirmed to be critical in tumorigenesis and to be potential biomarkers or therapeutic targets. However, only a few circRNAs have been functionally characterized in pediatric acute myeloid leukemia (AML). Methods: Here, we investigated the expression pattern of circRNAs in pediatric AML using a circRNA microarray. The characteristics, potential diagnostic value, and prognostic significance of circRNF220 were evaluated. A series of functional experiments were performed to investigate the role of circRNF220 in primary pediatric AML cells. Then we investigated the aberrant transcriptional networks regulated by circRNF220 in primary AML cells by RNA-seq. Furthermore, biotin RNA pulldown assays were implemented to verify the relationship between circRNF220 and miR-30a. Results: We identified a circRNA, circRNF220, which was specifically abundant in and accumulated in the peripheral blood and bone marrow of pediatric patients with AML. It could distinguish AML from ALL and other hematological malignancies with high sensitivity and specificity. Significantly, circRNF220 expression independently predicted prognosis, while high expression of circRNF220 was an unfavorable prognostic marker for relapse. Furthermore, we characterized the function of circRNF220 and found that circRNF220 knockdown specifically inhibited proliferation and promoted apoptosis in AML cell lines and primary cells. Mechanistically, circRNF220 may act as an endogenous sponge of miR-30a to sequester miR-30a and inhibit its activity, which increases the expression of its targets MYSM1 and IER2 and implicated in AML relapse. Conclusions: Collectively, these findings demonstrated that circRNF220 could be highly efficient and specific for the accurate diagnosis of pediatric AML, with implications for relapse prediction. [ABSTRACT FROM AUTHOR]

Species differences in the metabolism of xenobiotics by cytochrome P450 are critical in evaluating the use of experimental animals in studying toxic compounds relevant to human diseases. 2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), which is produced by high‐temperature cooking of fish and meat, is activated to become a carcinogen by cytochrome P4501A2 (CYP1A2) through N2‐hydroxylation in humans, but is detoxified by Cyp1a2 through 4′‐hydroxylation in mice. CYP1A‐humanized (hCYP1A) mice, in which mouse Cyp1a is replaced with human CYP1A, show constitutive human xenobiotic metabolism by hCYP1A, thereby serving as a suitable model for studying PhIP. Previous studies have demonstrated that oral administration of PhIP induces colon tumors in hCYP1A mice; however, these studies used a super‐high dose, raising concerns regarding the relevance of the mechanism to human cancer. Herein, we systematically investigated PhIP‐induced colon carcinogenesis in hCYP1A mice treated with lower doses. We found that a dose 2000 times lower than that used previously, which is comparable to human daily intake levels, could induce colon tumors, albeit at a lower incidence rate. We further investigated the transcriptome changes in the colon of hCYP1A mice treated with PhIP and identified that PhIP treatment increased the expression of Bax, Btg2, Ccng1, Cdkn1a, and Trp53inp1 and decreased the expression of Igf1 and Ccnd1. Since these genes are key components of the p53‐dependent DNA damage response, the altered expression patterns indicated PhIP‐induced DNA damage in hCYP1A mice. Together, these results prove that hCYP1A mice are suitable for studying PhIP‐induced carcinogenesis and show that PhIP is an important colorectal cancer carcinogen in human diet. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma is the most frequently diagnosed extracranial solid tumor in children. Previous studies have shown that single-nucleotide polymorphisms in some genes are associated with the risk of multiple cancers, including neuroblastoma. Although Hox transcript antisense intergenic RNA (HOTAIR) gene polymorphisms have been investigated in a variety of cancers, to the authors' knowledge the relationships between HOTAIR gene polymorphisms and neuroblastoma susceptibility have not been reported to date. The objective of the current study was to evaluate the correlation between HOTAIR gene polymorphisms and neuroblastoma risk in Chinese children.Methods: The authors genotyped 6 polymorphisms (rs920778 A>G, rs12826786 C>T, rs4759314 A>G, rs7958904 G>C, rs874945 C>T, and rs1899663 C>A) of the HOTAIR gene in 2 Chinese populations including 393 neuroblastoma cases and 812 healthy controls. The strength of the associations was evaluated using odds ratios and 95% confidence intervals. Further stratification analyses were conducted to explore the association between the HOTAIR gene polymorphisms rs12826786 C>T, rs874945 C>T, and rs1899663 C>A with neuroblastoma susceptibility in terms of age, sex, clinical stage of disease, and sites of origin.Results: The authors found that the rs12826786 C>T (P =.013), rs874945 C>T (P =.020), and rs1899663 C>A (P =.029) polymorphisms were significantly associated with increased neuroblastoma risk. In stratification analyses, these associations were more predominant in females and among patients with tumor in the retroperitoneal region or mediastinum. The remaining 3 polymorphisms were not found to be related to neuroblastoma susceptibility.Conclusions: The results of the current study verified that HOTAIR gene polymorphisms are associated with increased neuroblastoma risk and suggest that HOTAIR gene polymorphisms might be a potential biomarker for neuroblastoma susceptibility. Cancer 2018;124:2599-606. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Human Waardenburg syndrome 2A (WS2A) is a dominant hearing loss (HL) syndrome caused by mutations in the microphthalmia-associated transcription factor ( MITF) gene. In mouse models with MITF mutations, WS2A is transmitted in a recessive pattern, which limits the study of hearing loss (HL) pathology. In the current study, we performed ENU (ethylnitrosourea) mutagenesis that resulted in substituting a conserved lysine with a serine (p. L247S) in the DNA-binding domain of the MITF gene to generate a novel miniature pig model of WS2A. The heterozygous mutant pig ( MITF ) exhibits a dominant form of profound HL and hypopigmentation in skin, hair, and iris, accompanied by degeneration of stria vascularis (SV), fused hair cells, and the absence of endocochlear potential, which indicate the pathology of human WS2A. Besides hypopigmentation and bilateral HL, the homozygous mutant pig ( MITF ) and CRISPR/Cas9-mediated MITF bi-allelic knockout pigs both exhibited anophthalmia. Three WS2 patients carrying MITF mutations adjacent to the corresponding region were also identified. The pig models resemble the clinical symptom and molecular pathology of human WS2A patients perfectly, which will provide new clues for better understanding the etiology and development of novel treatment strategies for human HL. [ABSTRACT FROM AUTHOR]

Human action recognition using 3D pose data has gained a growing interest in the field of computer robotic interfaces and pattern recognition since the availability of hardware to capture human pose. In this paper, we propose a fast, simple, and powerful method of human action recognition based on human kinematic similarity. The key to this method is that the action descriptor consists of joints position, angular velocity and angular acceleration, which can meet the different individual sizes and eliminate the complex normalization. The angular parameters of joints within a short sliding time window (approximately 5 frames) around the current frame are used to express each pose frame of human action sequence. Moreover, three modified KNN (k-nearest-neighbors algorithm) classifiers are employed in our method: one for achieving the confidence of every frame in the training step, one for estimating the frame label of each descriptor, and one for classifying actions. Additional estimating of the frame’s time label makes it possible to address single input frames. This approach can be used on difficult, unsegmented sequences. The proposed method is efficient and can be run in real time. The research shows that many public datasets are irregularly segmented, and a simple method is provided to regularize the datasets. The approach is tested on some challenging datasets such as MSR-Action3D, MSRDailyActivity3D, and UTD-MHAD. The results indicate our method achieves a higher accuracy. [ABSTRACT FROM AUTHOR]

It is well known that electroencephalogram (EEG) signals collected from scalps are highly contaminated by various types of artifacts and background noise. The perturbations induced by artifacts and random noise are particularly difficult to correct because of their high amplitude, wide spectral distribution, and variable topographical distribution. Therefore, de-noising of EEG is a very challenging pre-processing step prior to qualitative or quantitative EEG signal analysis. To address this issue, some de-noising approaches have been proposed for noise suppression. However, most of these methods are only available for multi-electrode EEG signal processing, besides, the co-channel interference are always left unprocessed. Aiming at the obstacles encountered by the conventional approaches in single electrode EEG signal co-channel interference suppression, a method based on time-frequency image dimensionality reduction is proposed in this paper. The innovative idea of the proposed method is that it is applicable for single electrode EEG signal enhancement and the background noise can be suppressed in entire time-frequency space. The proposed method is experimentally validated by a group of real EEG data. The experimental results indicate that the proposed method is effective in EEG single electrode co-channel interference suppression. [ABSTRACT FROM AUTHOR]

Steady-state visual evoked potential (SSVEP) is one of the typical stimulation paradigms of brain-computer interface (BCI). It has become a research approach to improve the performance of human-computer interaction, because of its advantages including multiple objectives, less recording electrodes for electroencephalogram (EEG) signals, and strong anti-interference capacity. Traditional SSVEP using light flicker stimulation may cause visual fatigue with a consequent reduction of recognition accuracy. To avoid the negative impacts on the brain response caused by prolonged strong visual stimulation for SSVEP, steady-state motion visual evoked potential (SSMVEP) stimulation method was used in this study by an equal-luminance colored ring-shaped checkerboard paradigm. The movement patterns of the checkerboard included contraction and expansion, which produced less discomfort to subjects. Feature recognition algorithms based on power spectrum density (PSD) peak was used to identify the peak frequency on PSD in response to visual stimuli. Results demonstrated that the equal-luminance red-green stimulating paradigm within the low frequency spectrum (lower than 15 Hz) produced higher power of SSMVEP and recognition accuracy than black-white stimulating paradigm. PSD-based SSMVEP recognition accuracy was 88.15±6.56%. There was no statistical difference between canonical correlation analysis (CCA) (86.57±5.37%) and PSD on recognition accuracy. This study demonstrated that equal-luminance colored ring-shaped checkerboard visual stimulation evoked SSMVEP with better SNR on low frequency spectrum of power density and improved the interactive performance of BCI. [ABSTRACT FROM AUTHOR]

This paper presents the theory and implementation of a novel sensor system for measuring the angular speed (AS) of a shaft rotating at a very low speed range, nearly zero speed. The sensor system consists mainly of an eccentric sleeve rotating with the shaft on which the angular speed to be measured, and an eddy current displacement sensor to obtain the profile of the sleeve for AS calculation. When the shaft rotates at constant speed the profile will be a pure sinusoidal trace. However, the profile will be a phase modulated signal when the shaft speed is varied. By applying a demodulating procedure, the AS can be obtained in a straightforward manner. The sensor system was validated experimentally based on a gearbox test rig and the result shows that the AS obtained are consistent with that obtained by a conventional encoder. However, the new sensor gives very smooth and stable traces of the AS, demonstrating its higher accuracy and reliability in obtaining the AS of the low speed operations with speed-up and down transients. In addition, the experiment also shows that it is easy and cost-effective to be realised in different applications such as condition monitoring and process control. [ABSTRACT FROM AUTHOR]

Abstract: The performance of ball bearings is greatly affected by the applied preload. This paper suggests a preload analytical method that accurately determines the optimum preload for different speed ranges. Mathematical models of ball bearings were used to calculate the proper preload. According to Hirano's criterion, the critical preload between the skidding and rolling of ball bearings is calculated as the optimum preload. Experimental results confirmed that the optimum suggested preload instilled the ball bearings with excellent temperature behaviour. This paper provides a foundation for the future development of an optimum preload technique for high-speed ball bearings. [Copyright &y& Elsevier]

Abstract: An experimental study was conducted to investigate the possibility and the effect of frost release from a finned-tube evaporator by using ultrasonic vibrations in natural convection. A compressor was adopted as cold source, and a finned-tube evaporator was placed horizontal on the frames inside a chamber. The aluminum fins surface was covered with hydrophilic coatings whose contact angle of the water drop of the surface is 37.7°, and the fins had wing-cases to enlarge the heat-exchange area. The thickness of a fin was approximately 0.1mm, and the gap distance between any two fins of the evaporator was about 1.55mm in average. An ultrasonic transducer with resonance 28.2kHz and rating power 60W was adopted as a vibrator to excite the evaporator. A microscopic image system was used to observe and record the whole frosting process with/without ultrasonic vibrations, a method of frost thickness measurement on the double sides of a fin was present and realized through digital image processing technology. From microscopic view, the deposited frost nearly block the fins gaps when the compressor worked for 32min without ultrasonic vibration, while almost 2/3 of the gaps between two neighbor fins were unblocked when the compressor worked for 92min with ultrasonic vibration, which shows that the frost deposited on the fins surfaces could be suppressed with high frequency ultrasonic vibrations. From macroscopic view, the frost growing on the fins are being vibrated to fall off and accumulated under the evaporator to form frost piles. Although the fins above the braze tubes were deposited with frost, the fins between any two neighboring tubes were unblocked. Experiments show that the basic ice layer on the fins cannot be removed with ultrasonic vibrations, but frost crystals and frost branches on the ice layer can be fractured and removed effectively, the frost growing on the evaporator can be suppressed by using ultrasonic vibrations. The main mechanism of ultrasonic frost suppression maybe mainly attributed to the high frequency ultrasonic mechanical vibrations that can break up frost crystals and frost layers, then frost will fall off with the gravity, not to ultrasonic cavitation effect or heat effect. [Copyright &y& Elsevier]

A letter to the editor is presented about a case of a unilateral sensorimotor deficit caused by delayed lumbar epidural hematoma in a parturient after cesarean section under epidural anesthesia.