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The brain receives sensory information about food, evaluates its desirability and value, and responds with approach or withdrawal. The evaluation process of food in the brain with obesity may involve a variety of neurocircuit abnormalities in the integration of internal and external information processing. There is a lack of consistency of the results extant reported for aberrant changes in the brain with obesity that prohibits key brain alterations to be identified. Moreover, most studies focus on the observation of neural plasticity of function or structure, and the evidence for functional and structural correlations in the neuronal plasticity process of obesity is still insufficient. The aims of this article are to explore the key neural structural regions and the hierarchical activity pattern of key structural nodes and evaluate the correlation between changes in functional modulation and eating behavior. Forty-two participants with obesity and 33 normal-weight volunteers were recruited. Gray matter volume (GMV) and Granger causality analysis (GCA) were performed using the DPARSF, CAT12, and DynamicBC toolbox. Compared with the normal weight group, the obesity group exhibited significantly increased GMV in the left parahippocampal gyrus (PG). The obesity group showed decreased causal inflow to the left PG from the left orbitofrontal cortex (OFC), right calcarine, and bilateral supplementary motor area (SMA). Decreased causal outflow to the left OFC, right precuneus, and right SMA from the left PG, as well as increased causal outflow to the left middle occipital gyrus (MOG) were observed in the obesity group. Negative correlations were found between DEBQ-External scores and causal outflow from the left PG to the left OFC, and DEBQ-Restraint scores and causal inflow from the left OFC to the left PG in the obesity group. Positive correlation was found between DEBQ-External scores and causal outflow from the left PG to the left MOG. These results show that the increased GMV in the PG may play an important role in obesity, which may be related to devalued reward system, altered behavioral inhibition, and the disengagement of attentional and visual function for external signals. These findings have important implications for understanding neural mechanisms in obesity and developing individual-tailored strategies for obesity prevention.

Melanoma is a highly metastatic disease with an increasing rate of incidence worldwide. It is treatment refractory and has poor clinical prognosis; therefore, the development of new therapeutic agents for metastatic melanoma are urgently required. In this study, we created a lung-seeking A375LM5IF4g/Luc BRAFV600E mutant melanoma cell clone and investigated the bioefficacy of a plant sesquiterpene lactone deoxyelephantopin (DET) and its novel semi-synthetic derivative, DETD-35, in suppressing metastatic A375LM5IF4g/Luc melanoma growth in vitro and in a xenograft mouse model. DET and DETD-35 treatment inhibited A375LM5IF4g/Luc cell proliferation, and induced G2/M cell-cycle arrest and apoptosis. Furthermore, A375LM5IF4g/Luc exhibited clonogenic, metastatic and invasive abilities, and several A375LM5IF4g/Luc metastasis markers, N-cadherin, MMP2, vimentin and integrin α4 were significantly suppressed by treatment with either compound. Interestingly, DET- and DETD-35-induced Reactive Oxygen Species (ROS) generation and glutathione (GSH) depletion were found to be upstream events important for the in vitro activities, because exogenous GSH supplementation blunted DET and DETD-35 effects on A375LM5IF4g/Luc cells. DET and DETD-35 also induced mitochondrial DNA mutation, superoxide production, mitochondrial bioenergetics dysfunction, and mitochondrial protein deregulation. Most importantly, DET and DETD-35 inhibited lung metastasis of A375LM5IF4g/Luc in NOD/SCID mice through inhibiting pulmonary vascular permeability and melanoma cell (Mel-A+) proliferation, angiogenesis (VEGF+, CD31+) and EMT (N-cadherin) in the tumor microenvironment in the lungs. These findings indicate that DET and DETD-35 may be useful in the intervention of lung metastatic BRAFV600E mutant melanoma.

The rapid development of intelligent manufacturing provides strong support for the intelligent medical service ecosystem. Researchers are committed to building Wise Information Technology of 120 (WIT 120) for residents and medical personnel with the concept of simple smart medical care and through core technologies such as Internet of Things, Big Data Analytics, Artificial Intelligence, and microservice framework, to improve patient safety, medical quality, clinical efficiency, and operational benefits. Among them, how to use computers and deep learning technology to assist in the diagnosis of tongue images and realize intelligent tongue diagnosis has become a major trend. Tongue crack is an important feature of tongue states. Not only does change of tongue crack states reflect objectively and accurately changed circumstances of some typical diseases and TCM syndrome but also semantic segmentation of fissured tongue can combine the other features of tongue states to further improve tongue diagnosis systems’ identification accuracy. Although computer tongue diagnosis technology has made great progress, there are few studies on the fissured tongue, and most of them focus on the analysis of tongue coating and body. In this paper, we do systematic and in-depth researches and propose an improved U-Net network for image semantic segmentation of fissured tongue. By introducing the Global Convolution Network module into the encoder part of U-Net, it solves the problem that the encoder part is relatively simple and cannot extract relatively abstract high-level semantic features. Finally, the method is verified by experiments. The improved U-Net network has a better segmentation effect and higher segmentation accuracy for fissured tongue image dataset. It can be used to design a computer-aided tongue diagnosis system.

Fufang Xueshuantong (FXT) is a well-known Chinese herbal formula which has been used to treat cardiovascular and ophthalmic diseases, especially diabetic retinopathy. Panax notoginseng (Burkill) F.H. Chen (PN) is the main herb of FXT, whose major bioactive constituents are ginsenosides. However, the scientific basis of the compatibility of FXT is still ambiguous. The present study investigated the scientific basis of the compatibility of FXT by comparing the pharmacokinetics of marker compounds after oral administrations of PN and FXT. A high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed for simultaneous detection of notoginsenoside R1 (NR1), ginsenoside Rg1 (GRg1), and ginsenoside Rb1 (GRb1) in rat plasma. The pharmacokinetic studies of FXT and PN were performed using the established method with the pharmacokinetic parameters being determined by non-compartmental analysis. The results showed that the pharmacokinetic parameters (maximum concentration, area under the curve (AUC0–t ), clearance, and mean residence time) of NR1, GRg1, and GRb1 were significantly different after oral administration of FXT (P

Small heat shock proteins (shsps) are conserved across invertebrate species. They are implicated in the modulation of various biological processes, such as immune responses, abiotic stress tolerance metamorphosis, and embryonic development. Herein, we identified a heat shock protein 20 from the red swamp crayfish, Procambarus clarkii (named as Pc-Hsp20), and performed in vivo studies to elucidate its physiological functions in the innate immunity. The open reading frame of Pc-Hsp20 was 609 base pair, encoding a protein of 202 amino acid residues with a hsp20/alpha crystallin family domain. Pc-Hsp20 was ubiquitously expressed in various tissues; however, it was highest in the hepatopancreas. The challenge with immune elicitors remarkably enhanced the transcript level of Pc-Hsp20 in the hepatopancreas when compared with the control. Administration of double-stranded RNA could significantly reduce expression of the Pc-Hsp20 mRNAs, and most of the immune-related genes expression enhanced with a variable concentration in the hepatopancreas. Altogether, these results suggest that Pc-Hsp20 may participate in innate immunity against microbial pathogens.

Melanoma is a highly metastatic disease with an increasing rate of incidence worldwide. It is treatment refractory and has poor clinical prognosis, therefore, the development of new therapeutic agents for metastatic melanoma are urgently required. In this study, we created a lung-seeking A375LM5IF4g/Luc BRAFV600E mutant melanoma cell clone and investigated the bioefficacy of a plant sesquiterpene lactone deoxyelephantopin (DET) and its novel semi-synthetic derivative, DETD-35, in suppressing metastatic A375LM5IF4g/Luc melanoma growth in vitro and in a xenograft mouse model. DET and DETD-35 treatment inhibited A375LM5IF4g/Luc cell proliferation, and induced G2/M cell-cycle arrest and apoptosis. Furthermore, A375LM5IF4g/Luc exhibited clonogenic, metastatic and invasive abilities, and several A375LM5IF4g/Luc metastasis markers, N-cadherin, MMP2, vimentin and integrin α4 were significantly suppressed by treatment with either compound. Interestingly, DET- and DETD-35-induced Reactive Oxygen Species (ROS) generation and glutathione (GSH) depletion were found to be upstream events important for the in vitro activities, because exogenous GSH supplementation blunted DET and DETD-35 effects on A375LM5IF4g/Luc cells. DET and DETD-35 also induced mitochondrial DNA mutation, superoxide production, mitochondrial bioenergetics dysfunction, and mitochondrial protein deregulation. Most importantly, DET and DETD-35 inhibited lung metastasis of A375LM5IF4g/Luc in NOD/SCID mice through inhibiting pulmonary vascular permeability and melanoma cell (Mel-A+) proliferation, angiogenesis (VEGF+, CD31+) and EMT (N-cadherin) in the tumor microenvironment in the lungs. These findings indicate that DET and DETD-35 may be useful in the intervention of lung metastatic BRAFV600E mutant melanoma.

The reward-related regions have been considered a crucial component in the regulation of eating behavior. Furthermore, appetite-related regions associated with reward can influence eating behaviors through altered functional activity related to food in brain areas associated with emotion, memory, sensory processing, motor function, and cognitive control.To investigate the key nodes in obese females of reward-related regions and, based on key nodes, to evaluate the directionality of functional connectivity between key nodes and appetite-related regions.Prospective.Twenty-eight obese and 28 normal-weight female controls of similar age.3.0 T MRI and echo planar imaging (EPI) sequence, 3D BRAVO sequence.The fMRI data preprocessing was based on the Data ProcessingAnalysis of Brain Imaging and Statistical Parametric Mapping 12. Degree centrality calculation was based on the GRETNA toolkit and granger causality analysis were based on the DynamicBC toolbox. Statistical Tests: Independent two-sample t-tests were used to assess the differences in demographic and clinical data between two groups. Two-sample t-tests were conducted to test the difference in degree centrality and effective connectivity of key nodes between two groups.Compared with normal-weight controls, obese females showed an increased degree centrality in the left ventral striatum/caudate (t = 2.96808, P0.05) and decreased degree centrality in right orbitofrontal cortex (OFC) (t = -3.3558, P0.05). The obese females showed directional effective connectivity between left ventral striatum/caudate and several regions (left inferior temporal gyrus, fusiform gyrus, postcentral gyrus, and right precentral gyrus) (P0.05). Directional effective connectivity was also observed between the right OFC and several regions (left middle temporal gyrus, cuneus, OFC, superior temporal gyrus, middle frontal gyrus, and right inferior parietal lobule) (P0.05).The left ventral striatum/caudate and right OFC are key nodes in reward-related regions. The key nodes with reward processing mainly enhance visual processing of information and further participate in cognitive, attention, and sensorimotor processing.1. Technical Efficacy: Stage 4. J. Magn. Reson. Imaging 2019;50:541-551.

With the prevalence of credit system, the stipulation of “academic warning” is written into the teaching management constitution by more colleges and universities. However, the present research in this stipulation is only limited to the simulation of multivariate normal distribution. This paper aims to improve the current setting of academic warning through Monte Carlo simulation of multivariate Copula functions, and to calculate more reasonable academic warning credit line. The result demonstrates that the accuracy is significantly improved, therefore, this approach can provide a new train of thought and universal method for colleges and universities to set specific standards.

With the prevalence of credit system, the stipulation of “academic warning” is written into the teaching management constitution by more colleges and universities. However, the establishment of this stipulation hasn’t formed unified and scientific standards at present. This paper aims at studying the credit setting of academic warning through the method of Monte Carlo simulation, and at applying multivariate normal distribution and variance reduction techniques to calculate relatively reasonable academic warning credit line, which provides a new train of thought and a universal method for colleges and universities to set specific standards.

Aim Bitter taste is sensed by the bitter taste receptor (TAS2R), which is mainly expressed in the tongue as well as in extra-oral organs, such as the gastrointestinal tract, respiratory tract, brain, heart and testis. This study aimed to investigate whether TAS2R is expressed in the mesenteric, cerebral and omental arteries. Main methods The expression levels of TAS2R mRNA and protein were determined by reverse-transcription polymerase chain reaction and Western blotting, respectively. The location of TAS2R was determined by immunofluorescence imaging. TAS2R agonists were used in a sensitive myograph to study the function of TAS2R in arteries. Key findings The mRNA of rat TAS2Rs, including rTAS2R39, rTAS2R40, rTAS2R108, rTAS2R114, rTAS2R130, rTAS2R137, and rTAS2R140, was expressed in rat mesenteric and cerebral arteries, but rTAS2R114 was not expressed in the cerebral arteries. The mRNA of human TAS2Rs, including hTAS2R3, hTAS2R4, hTAS2R7, hTAS2R10, hTAS2R14, hTAS2R39 and hTAS2R40, was expressed in human omental arteries. The TAS2R7 protein was expressed in rat mesenteric and cerebral arteries, as well as in human omental arteries. Immunofluorescence imaging confirmed that TAS2R7 was located in vascular smooth muscle cells and endothelial cells. The TAS2R agonists, chloroquine and quinine relaxed rat mesenteric arteries and cerebral arteries and human omental arteries in a concentration-dependent manner. Significance TAS2R is expressed in the arteries of systemic circulation, including rat mesenteric and cerebral arteries and human omental arteries. This study provides evidence that TAS2R do exist in the arteries and may be involved in the mediation of vessel functions.

To explore genotype distributions at MTHFR C677T, MS A2756G, MTHFD G1958A and CBS 844 ins68bp loci in healthy Chinese living in northern area, and to assess the association of single or combined gene mutations with folic acid, Vit.B(12), Hcy levels and CHD.192 patients having CHD and their biological parents in Liaoning province registered as birth defects were included in this study as case group, and 124 healthy subjects (age and gender matched) and their biological parents were simultaneously selected from the same geographic area as control. To all subjects, the gene polymorphism at MTHFR C677T, MS A2756G, MTHFD G1958A and CBS 844 ins68bp loci was examined with PCR-RFLP. The serum folic acid and homocysteine (Hcy) level were analyzed with Radioimmunoassay or fluorescence polarization immunoassay (FPIA).In healthy Chinese living in northern China, the mutant allele frequencies of these four loci were MTHFR 51.18%, MS 7.58%, MTHFD 24.32%, and CBS insertion 2.36%, respectively. The heterozygosity of CBS 844 ins68bp was more prevalent in case than in control (12.57% vs 2.97% in children, 10.88% vs 3.09% in father and 11.54% vs 1.02% in mother, respectively), and yielded an odds ratio (OR) of 4.70 (95% CI 1.34-25.15) in children, 3.83 (95% CI 1.05-20.98) in fathers and 12.65 (95% CI 1.92-532.47) in mothers. There is no existed significant difference at the other three loci. The percents of mothers with MTHFR, CBS and MTHFD gene polymorphisms, of mothers with MTHFR and CBS being polymorphisms (OR=8.44, 95aCI 1.23-362.26), of mothers with MTHFD and CBS being polymorphisms in case were higher than those in control. Serum folic acid levels of mothers and fathers in case were significantly higher than those of counterparts in control. Serum Hcy level of mothers in case was higher than that of counterparts in control without significant difference. Homozygous mutation at MTHFR and MTHFD loci made serum folic acid and Vit.B(12) levels slightly decreased and serum Hcy level increased.The study showed presence of ethnic and district difference of gene polymorphisms at these four loci. 68 bp insertion at exon 8 of CBS gene base 844 could be a risk factor for CHD, and the insertion in parents (especially in mothers) could increase CHD risk in offspring.