Behavior-related potentials from single-trial interindividual correlation between event related potentials and behavioral performance reveals right lateralized processing of numerosity.

Accumulated functional magnetic resonance imaging (fMRI) and electroencephalography evidence indicate that numerosity is first processed in the occipito-parietal cortex. fMRI evidence also indicates right-lateralized processing of numerosity, but there is no consistent evidence from event-related potential (ERP) studies. This study investigated the ERP of numerosity processing in the left, right, and bilateral visual fields. The single-trial ERP-behavioral correlation was applied to show how the ERP was associated with behavioral responses. The results showed a significant early behavioral-ERP correlation on the right N1 component when stimuli were presented in the left visual field rather than in the right visual field. The behavioral ERP correlation was termed BN1. There was bilateral BN1 based on the reaction time or error rate, but the right BN1 was larger than that the left BN1 when the stimulus was present in the bilateral visual field. Therefore, this study provided a new neural marker for individual differences in processing numerosity and suggested that processing numerosity was supported by the right occipito-parietal cortex.

Form perception is a cognitive correlate of the relation between subitizing ability and math performance.

"Subitizing" defines a phenomenon whereby approximately four items can be quickly and accurately processed. Studies have shown the close association between subitizing and math performance, however, the mechanism for the association remains unclear. The present study was conducted to investigate whether form perception assessed on a serial figure matching task is a potential non-numerical mechanism between subitizing ability and math performance. Three-hundred and seventy-three Chinese primary school students completed four kinds of dot comparison tasks, serial figure matching task, math performance tasks (including three arithmetic computation tasks and math word problem task), and other cognitive tasks as their general cognitive abilities were observed as covariates. A series of hierarchical regression analyses showed that after controlling for age, gender, nonverbal matrix reasoning, and visual tracking, subitizing comparison (subitizing vs. subitizing, subitizing vs. estimation) still contributed to simple addition or simple subtraction but not to complex subtraction ability or math word problem. After taking form perception as an additional control variable, the predictive power of different dot comparison conditions disappeared. A path model also showed that form perception fully mediates the relation between numerosity comparison (within and beyond the subitizing range) and arithmetic performance. These findings support the claim that form perception is a non-numerical cognitive correlate of the relation between subitizing ability and math performance (especially arithmetic computation).

A More Female-Characterized Resting-State Brain: Graph Similarity Analyses of Sex Influence on the Human Brain Intrinsic Functional Network.

It remains unclear whether human species exhibits sexual dimorphism in brain activities, and how the dimorphisms associated with sex-characterized behaviors. Here, in a large dataset from Human Connectome Project, we investigated sex differences of resting-state network structure by using local and global network graph similarity analysis. The "typical male" and "typical female" resting-state networks were highly similar. However, we found significant inter-sex difference in all local brain networks compared with sex-label permutations. The global and many local network topologies showed significant higher intra-female similarity, while males' network topologies were more dissimilar to each other. Additionally, by using global graph similarity analysis, we found that female individuals whose brain network were more similar to the average pattern present lower social-related anger, lower social distress and better companionships, while similar effects were not detected for males. Our study confirms the existence of sex-related resting-state network topology. Female's intrinsic brain is closer to a typical pattern than male's, and they may more fulfill the "similarity breeds connection" principle in building social ties.

The database for extracting numerical and visual properties of numerosity processing in the Chinese population.

The ability to handle non-symbolic numerosity has been recurrently linked to mathematical abilities. The accumulated data provide a rich resource that can reflect the underlying properties (i.e., dot ratio, area, convex hull, perimeters, distance, and hash) of numerosity processing. This article reports a database of numerosity processing in the Chinese population. The database contains five independent datasets with 7459, 4902, 415, 671, 414 participants respectively. For each dataset, all data were collected in the same online computerized test, examination room, professorial tester, and using the same protocols. Computational modeling method could be used to extract the dot ratio and visual properties of numerosity from five types of dot stimuli. This database enables researchers to test the theoretical hypotheses regarding numerosity processing using a large sample population. The database can also indicate the individual difference of non-symbolic numerosity in mathematical abilities.

PLA2R1 Inhibits Differentiated Thyroid Cancer Proliferation and Migration via the FN1-Mediated ITGB1/FAK Axis.

PLA2R1 is a novel gene that is aberrantly expressed in a variety of malignancies. However, the role and mechanism of PLA2R1 in thyroid cancer has not been elucidated. We aimed to uncover the underlying mechanism of PLA2R1 in thyroid cancer. We collected 115 clinical specimens, including 54 tumor tissues and 61 para-cancerous tissues, who underwent surgical treatment at Shanghai Tenth Hospital. Immunohistochemical staining was used to evaluate PLA2R1 expression in differentiated thyroid cancer (DTC) tissues. The thyroid cancer cell lines 8505c and FTC133 transfected with PLA2R1 overexpression or knockdown plasmids were used for CCK8 assays and a wound healing assay. Next, we conducted coimmunoprecipitation (Co-IP) experiments and western blotting to explore the underlying mechanism of PLA2R1 in regulating the growth of thyroid cancer. We discovered that the expression of PLA2R1 was lower in the tumor tissues than in para-cancerous tissues (χ2 = 37.0, p < 0.01). The overexpression of PLA2R1 significantly suppressed thyroid cancer cell proliferation and migration, and both of these effects were partially attenuated by the knockdown of PLA2R1. Furthermore, the in vivo growth of DTC could be alleviated by the knockdown of PLA2R1. The mechanistic study revealed that PLA2R1 competed with FN1 for binding to ITGB1, inhibiting the FAK axis and epithelial-mesenchymal transition (EMT). We speculate that PLA2R1 might be a promising marker and a novel therapeutic target for thyroid cancer.

Relatively Lower FT3 Levels Are Associated with Impaired Quality of Life in Levothyroxine-Treated Patients with Hashimoto Thyroiditis.

Objective: Patients with Hashimoto thyroiditis (HT) frequently have some complaints despite achieving euthyroidism after levothyroxine (LT4) treatment. This study aimed to investigate the relevant factors affecting the quality of life (QoL) in euthyroid HT patients after LT4 treatment. Methods: In this case-control study, 133 participants with HT were included. They were divided into two groups: 64 euthyroid HT subjects (control group) and 69 HT patients were rendered euthyroid by LT4 treatment (well-controlled group). QoL was measured with the Thyroid-Related Patient-Reported Outcome (ThyPRO-39) questionnaire. Results: Both study groups were well matched with respect to gender, age, BMI, euthyroidism, and thyroid antibodies (TPOAb and TGAb). Compared with the control group, the well-controlled group had lower FT3 (P < 0.01) levels. Of note, QoL was impaired on all scales in the well-controlled group. Moreover, ThyPRO-39 scores among the well-controlled group were significantly higher (worse) than the control group in all scales. Regarding the composite scale, its score was related to FT3 (r = -0.176, P=0.043) but not to FT4 and TSH levels. Further logistic regression analysis revealed FT3 was significantly associated with elevated composite QoL [0.128 (0.029-0.577), P < 0.01] after adjustment of potential confounders. Conclusion: Relatively lower FT3 concentrations, even within the normal reference range, were related to impaired QoL in HT patients treated with LT4. This finding supports the great value of FT3 in clinical decision-making on dose adequacy.

Evaluation of bone mineral density and body compositions interrelation in young and middle-aged male patients with Crohn's disease by quantitative computed tomography.

Background: The aim of this study was to investigate the characteristics of bone mineral density (BMD) and body compositions, and the impact of body compositions on BMD in young and middle-aged male patients with Crohn's disease (CD). Methods: Patients with CD (n = 198) and normal controls (n = 123) underwent quantitative computed tomography (QCT) examination of lumbar vertebrae 1-3 (L1-3). The BMD and bone geometric parameters were measured and outputted by QCT post-process software. Meanwhile, body composition parameters, including subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), lean mass (LM), and muscles mass around lumbar vertebrae were also acquired by QCT. Blood indicators [interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), Ca, and P] were collected from clinical medical records. Independent t-test was used to compare these variables between the CD group and the normal control group. Results: There was no significant difference in age, height, and weight between the CD group and the control group (p > 0.05), indicating that the sample size was relatively balanced. Mean BMD in the CD group were lower than those in the control group, but the difference was not statistically significant (p > 0.05). The bone geometric parameters of the CD group, including cortical area/density (Ct. Ar, Ct. BMD) and trabecular area/density (Tb. Ar and Tb. BMD), were significantly lower than those of the control group (p < 0.05), so were the body composition parameters including total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), lean mass (LM), and muscles mass (p < 0.05). In addition, the level of plasma IL-6, IL-8, CRP, and TNF-α of the CD group were higher than those of the control group (p < 0.05). On the contrary, the body mass index (BMI) and serum Ca and P levels of the CD group were lower than those of the control group (p < 0.05). Through multiple linear regression analysis, Tb. BMD, VAT, Ct. Ar, LM, Ca, and IL-8 entered the regression model and revealed a significant contribution to BMD. Conclusions: Patients with CD could suffer from reduction in BMD. However, the parameters of bone geometric parameters are more sensitive and accurate than BMD changes. Among them, Tb. BMD, VAT, Ct. Ar, and LM have significant effects on BMD reduction.

Targeting adipocytic discoidin domain receptor 2 impedes fat gain while increasing bone mass.

Obesity is closely associated with low-bone-mass disorder. Discoidin domain receptor 2 (DDR2) plays essential roles in skeletal metabolism, and is probably involved in fat metabolism. To test the potential role of DDR2 in fat and fat-bone crosstalk, Ddr2 conditional knockout mice (Ddr2Adipo) were generated in which Ddr2 gene is exclusively deleted in adipocytes by Adipoq Cre. We found that Ddr2Adipo mice are protected from fat gain on high-fat diet, with significantly decreased adipocyte size. Ddr2Adipo mice exhibit significantly increased bone mass and mechanical properties, with enhanced osteoblastogenesis and osteoclastogenesis. Marrow adipocyte is diminished in the bone marrow of Ddr2Adipo mice, due to activation of lipolysis. Fatty acid in the bone marrow was reduced in Ddr2Adipo mice. RNA-Seq analysis identified adenylate cyclase 5 (Adcy5) as downstream molecule of Ddr2. Mechanically, adipocytic Ddr2 modulates Adcy5-cAMP-PKA signaling, and Ddr2 deficiency stimulates lipolysis and supplies fatty acid for oxidation in osteoblasts, leading to the enhanced osteoblast differentiation and bone mass. Treatment of Adcy5 specific inhibitor abolishes the increased bone mass gain in Ddr2Adipo mice. These observations establish, for the first time, that Ddr2 plays an essential role in the crosstalk between fat and bone. Targeting adipocytic Ddr2 may be a potential strategy for treating obesity and pathological bone loss simultaneously.

Deep learning for intelligent diagnosis in thyroid scintigraphy.

OBJECTIVE: To construct deep learning (DL) models to improve the accuracy and efficiency of thyroid disease diagnosis by thyroid scintigraphy. METHODS: We constructed DL models with AlexNet, VGGNet, and ResNet. The models were trained separately with transfer learning. We measured each model's performance with six indicators: recall, precision, negative predictive value (NPV), specificity, accuracy, and F1-score. We also compared the diagnostic performances of first- and third-year nuclear medicine (NM) residents with assistance from the best-performing DL-based model. The Kappa coefficient and average classification time of each model were compared with those of two NM residents. RESULTS: The recall, precision, NPV, specificity, accuracy, and F1-score of the three models ranged from 73.33% to 97.00%. The Kappa coefficient of all three models was >0.710. All models performed better than the first-year NM resident but not as well as the third-year NM resident in terms of diagnostic ability. However, the ResNet model provided "diagnostic assistance" to the NM residents. The models provided results at speeds 400 to 600 times faster than the NM residents. CONCLUSION: DL-based models perform well in diagnostic assessment by thyroid scintigraphy. These models may serve as tools for NM residents in the diagnosis of Graves' disease and subacute thyroiditis.

Local and whole-network topologies reveal that pulvinar and semantic hub interactions correlate with picture vocabulary.

Evidence from cognitive neuroscience indicates that subcortical regions, especially the pulvinar region of the thalamus, are involved in semantic processing. In the current study, graph-based methods were used to investigate whether a cortical-subcortical network is involved in vocabulary processing. In addition to traditional resting-state functional connectivity (rsFC) analysis between local brain areas, we applied a novel method to validate the interaction between semantic network hubs and the pulvinar. Unlike the traditional rsFC, the new metrics assessed rsFC pattern similarity (rsFCS), which was calculated with a cosine similarity algorithm based on whole-network topological information. We also applied a support vector regression program based on left pulvinar connectivity patterns. A brain-behavior analysis was conducted based on 100 randomly selected unrelated participants from the Human Connectome Project S1200 database. After controlling for the visuospatial and attention test scores, the rsFC between the left middle temporal gyrus, left inferior parietal lobule, and left pulvinar was significantly positively correlated with age-adjusted picture vocabulary scores. Similar results were confirmed based on the new rsFCS analysis. The support vector regression procedures also showed a clearly relationship between picture vocabulary scores and left pulvinar-related rsFCs. Our study verified a role for a subcortical-cortical network in vocabulary processing that is based on local and whole-network topologies.

Hierarchically Assembled Theranostic Nanopolyplexes Enable Robust Tumor Gene Therapy and Magnetic Resonance Imaging In Vivo.

Theranostic nanosystems encompassing imaging reagents and therapeutic genes are promising for concurrent tumor diagnosis and gene therapy. In this work, we developed bioresponsive gadolinium (Gd)-based nanopolyplexes (denoted as Gdplexes) for in vivo tumor theranostic applications. Gdplexes were generated by a hierarchical assembly method involving the neutralization of DNA with a Gd-chelated bioreducible cationic polyurethane (termed as GdCPUA), which was followed by condensation of DNA with a cationic dextran conjugate (DP800). By adjusting GdCPUA/DP800 ratios, the resultant Gdplexes had GdCPUA/DNA complex as an inner core and a dextran outer shell; thus, Gdplexes exhibit an improved colloidal stability under physiological conditions and perform active gene release in an intracellular reductive environment. In vitro tests against cancer cells revealed that optimized Gdplexes afforded comparable transfection efficiency to that of the 25 kDa branched polyethylenimine used as a positive control. Additionally, the Gdplexes could robustly transfer small hairpin RNA plasmids to silence vascular endothelial growth factor expression in SKOV-3 cells. In vivo, the Gdplexes loaded with plasmid were practical for systemic gene delivery via intravenous administration, yielding marked growth repression of an SKOV-3 tumor xenograft in a BALB/c nude mouse model. The tumor could be visualized by T1-weighted magnetic resonance (MR) imaging. Such efficient gene therapy had no adverse effects on hepatorenal functions and weight gain in the mouse. This work highlights Gdplexes as biosafe and robust nanocarriers for tumor theranostic applications in vivo.

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We examined the physiological response of 1-year-old branches of 37 Xinjiang wild walnut germplasm resources in Gongliu wild walnut forest under cold temperatures (-20 ℃ and 4 ℃) for 12 hours, compared the responses with that of Juglans mandshurica. The relative conductivity (REC), free proline (PRO), soluble sugar (SS), malondialdehyde (MDA) content and peroxidase (POD) activity were measured in an artificial climate chamber by simulating spring low temperature. Subordinate function and principal component analysis were used to evaluate the physiological response of walnut germplasm to low temperature. The results showed that the REC, PRO, SS, MDA content and POD activity of Xinjiang wild walnut were increased. By evaluating the relationship between low temperature resistance and habitat, we found that cold tolerance level was middle valley > east valley > west valley > general valley. Xinjiang wild walnut showed stronger cold tolerance than J. mandshurica. Seven germplasm with cold resistance were selected from the total 37 wild walnut germplasm in Xinjiang, which provided a reference for improving walnut varieties and their responses to sudden weather change in late spring and other growing stages.

Intestinal microbiota changes in Graves' disease: a prospective clinical study.

Graves' disease (GD) occurs due to an autoimmune dysfunction of thyroid gland cells, leading to manifestations consistent with hyperthyroidism. Various studies have confirmed the link between autoimmune conditions and changes in the composition of intestinal microbial organisms. However, few studies have assessed the relationship between the GD and the changes in intestinal microbiota. Therefore, the present study aimed to investigate changes in intestinal flora that may occur in the setting of GD. Thirty-nine patients with GD and 17 healthy controls were enrolled for fecal sample collection. 16S rRNA sequencing was used to analyze the diversity and composition of the intestinal microbiota. High-throughput sequencing of 16S rRNA genes of intestinal flora was performed on Illumina Hiseq2500 platform. Comparing to healthy individuals, the number of Bacilli, Lactobacillales, Prevotella, Megamonas and Veillonella strains were increased, whereas the number of Ruminococcus, Rikenellaceae and Alistipes strains were decreased among patients with GD. Furthermore, patients with GD showed a decrease in intestinal microbial diversity. Therefore, it indicates that the diversity of microbial strains is significantly reduced in GD patients, and patients with GD will undergo significant changes in intestinal microbiota, by comparing the intestinal flora of GD and healthy controls. These conclusions are expected to provide a preliminary reference for further researches on the interaction mechanism between intestinal flora and GD.

Trends in contraceptive patterns and behaviors during a period of fertility transition in China: 1988-2006.

BACKGROUND: This paper explores how contraceptive patterns and behaviors changed during the course of China's population transition and a period of low fertility from 1988 to 2006. STUDY DESIGN: Based on data from Chinese nationwide surveys of family planning and reproductive health undertaken in 1988, 1997, 2001 and 2006, this study uses a multinomial logit model to analyze changes in, regional differences in and determinants of contraceptive behaviors during this period. RESULTS: The overall prevalence of contraceptive use among married women aged 15-49 years changed little during these 20 years, holding steady at about 90%. However, there were notable changes in the method mix: the predominant methods used were the long-term methods of the intrauterine device (IUD) and female sterilization, and contraceptive use gradually shifted from sterilization to IUDs and condoms. There existed a close relationship between contraceptive methods used and sociodemographic characteristics. Hans, rural, old and less educated women are more likely to use sterilization, while minorities, urban, young and educated women are more likely to use IUDs. CONCLUSION: There are marked changes in the method mix among different demographic groups during the course of China's population transition and a period of low fertility. The findings indicate that future works aimed at promoting reproductive health should be diverse among different populations.