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Background: Our previous study proved that Shen Qi Li Xin formula (SQLXF) improved the heart function of chronic heart failure (CHF) patients, while the action mechanism remains unclear. Methods: H&E staining and TUNEL staining were performed to measure myocardial damages. Western blot was used to examine the expression of proteins. Moreover, CCK-8 assay and flow cytometry were used to measure cell viability and cell apoptosis, respectively. Concentrations of ATP and ROS in cells, and mitochondrial membrane potential (MMP) were detected to estimate oxidative stress. Results: In vivo, we found that SQLXF improved cardiac hemodynamic parameters, reduced LDH, CK-MB and BNP production, and attenuated myocardial damages in CHF rats. Besides, SQLXF promoted mitochondrial fusion-related proteins expression and inhibited fission-related proteins expression in CHF rats and oxygen glucose deprivation/reoxygenation (OGD/R)-induced cardiac myocytes (CMs). In vitro, our data show that certain dose of SQLXF inhibited OGD/R-induced CMs apoptosis, cell viability decreasing and oxidative stress. Conclusion: Overall, certain dose of SQLXF could effectively improve the cardiac function of CHF rats through inhibition of CMs apoptosis via balancing mitochondrial fission and fusion. Our data proved a novel action mechanism of SQLXF in CHF improvement, and provided a reference for clinical. [ABSTRACT FROM AUTHOR]

Gout, a common type of inflammatory arthritis resulting from chronic elevation of uric acid (UA) level, is usually accompanied with hyperuricemia. The current clinical drugs for the treatment of gout and hyperuricemia are greatly restricted by their limited therapeutic efficacy, off-target toxicity and severe side effects. Here, a neutrophil membrane (NM)-coated and cascade catalytic nanoenzyme was devised with excellent inflammation targeting, inflammatory cytokines neutralizing and UA degrading characteristics for the treatment of gout and hyperuricemia with high efficacy and safety. This nanoenzyme was fabricated by encapsulating uricase (UOx) and catalase (CAT) into zeolitic imidazolate framework-8 (ZIF-8) and further coating it with NM. The NM-coated nanoenzyme inherits the antigenic exterior and cell membrane functions of neutrophils for inflammation targeting and cytokine neutralization. UOx and CAT encapsulated in ZIF-8 could efficiently degrade UA and eliminate hydrogen peroxide (H2O2) via a biocatalytic cascade, thus successfully blocking the inflammation amplification during gout development. Both in vitro and in vivo experiments demonstrated the preferable potentials of the nanoenzyme for gout targeting, inflammation elimination and UA degradation, exhibiting great promise for the treatment of gout and hyperuricemia in an effective and safe manner. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) has been associated with increased risk for physical comorbidity. This study used a twin cohort to investigate the association between physical diseases and phenotypic variations of ADHD. A twin cohort enriched for ADHD and other neurodevelopmental conditions were analysed. The Attention Problems subscale of the Child Behavior Checklist/Adult Behavior Checklist (CBCL/ABCL-AP) was used to measure the participants' severity of ADHD symptoms. Physical health issues were obtained with a validated questionnaire and were tested in relation to ADHD symptom severity in a co-twin control model. Neurological problems were significantly associated with a diagnosis of ADHD. A conditional model for the analysis of within-twin pair effects revealed an inverse association between digestive problems and the severity of ADHD symptoms, after adjusting for co-existing autism spectrum disorder and ADHD medications. Our findings suggest that individuals with ADHD are susceptible to neurological problems, why a thorough neurological check-up is indicated in clinical practice for this population. In addition, health conditions of digestive system could be considered as a non-shared environmental factor for behavioral phenotypes in ADHD. It supports the possible role of gut-brain axis in the underpinnings of ADHD symptoms, at least for a subgroup of individuals with certain genetic predisposition. [ABSTRACT FROM AUTHOR]

This study used a twin cohort to investigate the association of autism spectrum disorder (ASD) and autistic traits with somatic health. A total of 344 twins (172 pairs; mean age 15.56 ± 5.62 years) enriched for ASD and other neurodevelopmental conditions were examined. Medical history and current physical problems were collected with a validated questionnaire to determine twin's somatic health. The Social Responsiveness Scale (SRS-2) was used to measure the participant's severity of autistic traits. Identified somatic health issues with significant within-twin pair differences were tested in relation to both ASD diagnosis and autistic traits in a co-twin control model. Twins with ASD exhibited more neurological and immunological health problems compared to those without ASD (p = 0.005 and p = 0.004, respectively). The intra-pair differences of neurological conditions and SRS-2 score were significantly correlated in monozygotic twins differing for autism traits (r = 0.40, p = 0.001), while the correlation was not found for immunological problems. In addition, a conditional model for analysis of within-twin pair effects revealed an association between neurological problems and clinical ASD diagnosis (Odds ratio per neurological problem 3.15, p = 0.02), as well as autistic traits (β = 10.44, p = 0.006), after adjusting for possible effects of co-existing attention deficit hyperactivity disorder and general intellectual abilities. Our findings suggest that neurological problems are associated with autism, and that non-shared environmental factors contribute to the overlap for both clinical ASD and autistic traits. Further population-based twin studies are warranted to validate our results and examine in detailed the shared genetic and environmental contributions of neurological problems and ASD. [ABSTRACT FROM AUTHOR]

The development of methods to synthesize electrode materials can improve the performance of lithium ion storage. In this study, a facile and low-cost approach is employed to synthesize LiFePO (LFP/NC) hybrid materials decorated with nitrogen-doped carbon nanomaterials (NC). Melamine was used as nitrogen and carbon source with an NC to LFP ratio of 3.19%. As electrode materials for lithium ion batteries (LIBs), the LFP/NC composites exhibit an optimum performance with a high rate capacity of 144.6 mAh·g at 1 C after 500 cycles without apparent loss. The outstanding cycling stability may be attributed to the synergetic effects of well-crystallized particles and NC layers. [ABSTRACT FROM AUTHOR]

Adolescents with attention-deficit/hyperactivity disorder (ADHD) often exhibit functional impairment even those having less visible symptoms. Therefore, it is of great clinical importance to identify ADHD symptoms among adolescents in the community. Furthermore, little is known regarding the role of internalizing symptoms in their quality of life. Thus, this study aimed to screen ADHD in a sample of high school students using the Adult ADHD Self-report Scale (ASRS) and to investigate the impact of internalizing symptoms on their well-being. In the first year, adolescents aged 15-17 years old from a senior high school ( N = 1947) completed the Adult ADHD Self-rating Scale (ASRS), Wender Utah Rating Scale, Impulsiveness Scale, Beck's Depression Inventory and Beck's Anxiety Inventory. In the second year, the World Health Organization Quality of Life-BREF was applied for the measurement of their psychosocial outcomes. Results showed that adolescents with higher ASRS scores manifested more severe concurrent depressive and anxiety symptoms. ADHD symptoms among these adolescents were significantly associated with poorer quality of life 1 year later ( p < 0.001). And both depressive and anxiety symptoms were mediators in the relationship between ADHD symptoms and quality of life. The finding of this study supports that the concurrent internalizing symptoms may underlie the negative relations between ADHD symptoms and quality of life in adolescents in the community. The application of ASRS in adolescents may help clinicians in early intervention for their ADHD problems as well as emotional symptoms. [ABSTRACT FROM AUTHOR]

A sensitive and rapid ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to determine methadone, EDDP, fluoxetine, norfluoxetine, venlafaxine and O-desmethylvenlafaxine in rat plasma using diazepam as the internal standard (IS). Sample preparation was accomplished through a simple one-step protein precipitation with 200 µL acetonitrile added to 100 µL rat plasma. The analytes were separated on an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) and the mobile phase was acetonitrile and 0.1 % formic acid in water in gradient elution at a flow rate of 0.40 mL min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with positive electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions. The linearity of this method was found to be within the concentration range of 0.5-250.0 ng mL for methadone, EDDP, fluoxetine and norfluoxetine and 0.4-200.0 ng mL for venlafaxine and O-desmethylvenlafaxine, respectively. The limit of quantification (LOQ) was 0.5 ng mL for methadone, EDDP, fluoxetine and norfluoxetine and 0.4 ng mL for venlafaxine and O-desmethylvenlafaxine, respectively. A time period of 3 min was needed for an analytical run. The method described above was successfully applied to the subsequent pharmacokinetic study. [ABSTRACT FROM AUTHOR]

We aimed at investigating the role of CYP2C9 in carvedilol O-desmethylation and identifying the effect of 35 CYP2C9 allelic variants we found in Chinese Han population on the in vitro metabolism of carvedilol. Recombinant CYP2C9 and CYP2D6 microsomes of the wild type were used to test and verify the enzymes involved in carvedilol O-desmethylation. Recombinant CYP2C9 microsomes of distinguished genotypes were used to characterize the corresponding enzyme activity toward carvedilol. 2-100 μM carvedilol was incubated for 30 min at 37 °C. The products were detected using high-performance liquid chromatography. CYP2C9 plays a certain role in carvedilol metabolism. Compared with wild-type CYP2C9*1, the intrinsic clearance ( V/ K) values of all variants toward carvedilol O-desmethylation were significantly altered. The variants exhibited significantly decreased values (from 30 to 99.8 %) due to increased K and/or decreased V values. We conclude that recombinant system could be used to investigate the enzymes involved in drug metabolism and these findings complement the database where CYP2C9 polymorphism interacts with biotransformation of exogenous substances like drugs and toxins. [ABSTRACT FROM AUTHOR]

Over the course of the past 35 years, assisted reproductive technologies (ARTs) have been increasingly used worldwide, while debates on their safety have been generated. Birth defects and imprinting disorders were reported in previous research. Thus, the psychological development of children born following ARTs has become a major concern nowadays. This review gives a systematic view of psychological well-being of children conceived by different types of ART, including in vitro fertilization, intracytoplasmic sperm injection (ICSI), preimplantation genetic diagnosis/screening, and in vitro maturation. The previous studies are analyzed in three sections: (1) cognitive, motor, and language developments, (2) behavior problems and socio-emotional development, and (3) parent-child relationship. We conclude that although the majority of the studies on cognitive, motor, and language developments reported comparable achievements in the ART group vs. the naturally conceived group, lower intelligence quotient (IQ) scores, worse visual-motor ability or locomotor development, and delayed receptive language competence were found in the ART group. The results on the socio-emotional development were reassuring. As for the behavior problems, a higher prevalence of behavior problems existed in ART children; moreover, ICSI children were found to be at a higher risk of autism than the general population. Meanwhile, ART parents tended to have positive parental attitudes and be more protective of their children. Some suggestions for further research are also given in this review. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of clearing the Governor Vessel and refreshing the mind needling in neural development and remediation of children with cerebral palsy. Methods: A total of 200 cases of children with cerebral palsy were randomly assigned to the treatment group (100 patients) and the control group (100 patients). The treatment group was given the combined therapy of acupuncture and rehabilitation training, and the chosen acupoints were 13 points of the Governor Vessel, Shenshu (BL 23), Taixi (KI 3), Yanglingquan (GB 34), Zusanli (ST 36) and Sanyinjiao (SP 6), and points of refreshing the mind were also selected, which included puncturing Shenting (GV 24) toward Qianding (GV 21), puncturing Qianding (GV 21) toward Baihui (GV 20), puncturing Baihui (GV 20) toward Naohu (GV 17) and Sishencong (Ex-HN 1). The control group was only treated with rehabilitation training. A contrastive analysis of the therapeutic effect between acupuncture combined with rehabilitation training and rehabilitation training alone was made after a treatment course of 3 months. The Gross Motor Function Measure (GMFM) and Beijing Gesell Developmental Scale were adopted to assess the neural development and rehabilitation outcomes of the two groups. In addition, skull CT/MRI was adopted to evaluate the plerosis of injured cerebral nerve after treatment. Results: The total effective rate in treatment group was 87% (87/100), significantly higher than the 55% (55/100) in the control group. The children's development quotient (DQ) tested by Gesell Developmental Scale and scores tested by GMFM in the treatment group were obviously higher than those in the control group ( P<0.01). The improving and curing rates presented by skull CT/MRI in the treatment group were higher than those in the control group ( P<0.01). Conclusions: Clearing the Governor Vessel and refreshing the mind needling could accelerate the recovery of injured brain nerve and the reconstruction of brain function. The acupuncture therapy could ameliorate both the motor development and cognitive development. On the other hand, the forward curative effect of acupuncture combined with rehabilitation training was significantly better than the rehabilitation training alone. [ABSTRACT FROM AUTHOR]

Preliminary observations have suggested mild behavioral changes and a morphological disruption of brain histology in 1.5-year-old carbonic anhydrase IX (CA IX)-deficient ( Car9) mice. These findings led us to design a 1-year follow-up study in which the behavior and brain histology of Car9 and wild-type mice were monitored. Morphological analysis revealed vacuolar degenerative changes in the brains of Car9 mice. The changes became visible at the age of eight to ten months. Behavioral tests showed that the Car9 mice exhibited abnormal locomotor activity and poor performance in a memory test. To further identify the transcriptomic responses to CA IX deficiency in the brain, genome-wide cDNA microarray analyses were performed. Thirty-one and 37 genes were significantly up- or down-regulated, respectively, in the brain of Car9 mice compared to the wild-type mice. Functional annotation revealed that the genes with increased expression were involved in several processes, such as RNA metabolism, and the genes with reduced expression were implicated in other important processes, including the regulation of cellular ion homeostasis. Notably, the biological processes 'behavior' and 'locomotory behavior' were the two prominent terms overrepresented among the down-regulated genes, which is consistent with the behavioral phenotype. These results suggest that CA IX may directly or indirectly play novel functions in brain tissue. Furthermore, the brain phenotype of Car9 mice seems to be age-dependent. The results indicate that the functional changes precede the microscopic alterations in the brains of Car9 mice. [ABSTRACT FROM AUTHOR]

The harderian gland is located within the orbit of the eye of most terrestrial vertebrates. It is especially noticeable in rodents, in which it synthesises lipids, porphyrins, and indoles. Various functions have been ascribed to the harderian gland, such as lubrication of the eyes, a site of immune response, and a source of growth factors. Carbonic anhydrases (CAs) are zinc-containing metalloenzymes that catalyse the reaction $$ {\text{CO}}_{2} + {\text{H}}_{2} {\text{O}} \Leftrightarrow {\text{H}}^{ + } + {\text{HCO}}_{3}^{ - } $$ . They are involved in the adjustment of pH in the secretions of different glands. Thirteen enzymatically active isozymes have been described in the mammalian α-CA family. Here, we first investigated the mRNA expression of all 13 active CAs in the mouse harderian gland by quantitative real-time PCR. Nine CA mRNAs were detectable in the gland. Car5b and Car13 showed the highest signals. Car4, Car6, and Car12 showed moderate expression levels, whereas Car2, Car3, Car7, and Car15 mRNAs were barely within the detection limits. Immunohistochemical staining was performed to study the expression of Car2, Car4, Car5b, Car12, and Car13 at the protein level. The epithelial cells were intensively stained for CAVB, whereas only weak signal was detected for CAXIII. Positive signals for CAIV and CAXII were observed in the capillary endothelial cells and the basolateral plasma membrane of the epithelial cells, respectively. This study provides an expression profile of all CAs in the mouse harderian gland. These results should improve our understanding of the distribution of CA isozymes and their potential roles in the function of harderian gland. The high expression of mitochondrial CAVB at both mRNA and protein levels suggests a role in lipid synthesis, a key physiological process of the harderian gland. [ABSTRACT FROM AUTHOR]

This paper presents a new algorithm of path planning for mobile robots, which utilises the characteristics of the obstacle border and fuzzy logical reasoning. The environment topology or working space is described by the time-variable grid method that can be further described by the moving obstacles and the variation of path safety. Based on the algorithm, a new path planning approach for mobile robots in an unknown environment has been developed. The path planning approach can let a mobile robot find a safe path from the current position to the goal based on a sensor system. The two types of machine learning: advancing learning and exploitation learning or trial learning are explored, and both are applied to the learning of mobile robot path planning algorithm. Comparison with A* path planning approach and various simulation results are given to demonstrate the efficiency of the algorithm. This path planning approach can also be applied to computer games. [ABSTRACT FROM AUTHOR]

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Global alterations in the metabolic network provide substances and energy to support tumor progression. To fuel these metabolic processes, extracellular matrix (ECM) plays a dominant role in supporting the mass transport and providing essential nutrients. Here, we report a fibrinogen and thrombin based coagulation system to construct an artificial ECM (aECM) for selectively cutting-off the tumor metabolic flux. Once a micro-wound is induced, a cascaded gelation of aECM can be triggered to besiege the tumor. Studies on cell behaviors and metabolomics reveal that aECM cuts off the mass transport and leads to a tumor specific starvation to inhibit tumor growth. In orthotopic and spontaneous murine tumor models, this physical barrier also hinders cancer cells from distant metastasis. The in vivo gelation provides an efficient approach to selectively alter the tumor mass transport. This strategy results in a 77% suppression of tumor growth. Most importantly, the gelation of aECM can be induced by clinical operations such as ultrasonic treatment, surgery or radiotherapy, implying this strategy is potential to be translated into a clinical combination regimen. The extracellular matrix (ECM) can influence tumor growth and its response to therapy. Here, the authors develop a fibrinogen and thrombin based artificial ECM that can starve tumours and prevent dissemination of cancer cells. [ABSTRACT FROM AUTHOR]