The effects of maternal competence and situational stress level on children's help-seeking expectations across 4 to 6 years of age.

Help-seeking is a crucial problem-solving strategy for young children. However, it is not yet clear how children weigh different cues to make help-seeking decisions across preschool years, especially in caregiver-child interactions. The current study used a social expectation task to examine the effects of maternal competence and situational stress level on 4- to 6-year-old children's help-seeking expectations from a third-party perspective. Children's expectations of whether to seek help were measured. A total fo 135 Han Chinese children aged 4 to 6 years from an eastern city of China participated in this study. We found that 4- to 6-year-olds expected to seek more help from a competent mother than from an incompetent mother in low-stress conditions. When the stress level was high, however, they expected to seek help regardless of maternal competence levels. These results suggest that the interaction between the situational stress level and maternal competence determines young children's help-seeking expectations across preschool years. They further suggest that young children seek help from mothers in an active and discriminatory way.

Angular Gyrus Responses Show Joint Statistical Dependence with Brain Regions Selective for Different Categories.

Category selectivity is a fundamental principle of organization of perceptual brain regions. Human occipitotemporal cortex is subdivided into areas that respond preferentially to faces, bodies, artifacts, and scenes. However, observers need to combine information about objects from different categories to form a coherent understanding of the world. How is this multicategory information encoded in the brain? Studying the multivariate interactions between brain regions of male and female human subjects with fMRI and artificial neural networks, we found that the angular gyrus shows joint statistical dependence with multiple category-selective regions. Adjacent regions show effects for the combination of scenes and each other category, suggesting that scenes provide a context to combine information about the world. Additional analyses revealed a cortical map of areas that encode information across different subsets of categories, indicating that multicategory information is not encoded in a single centralized location, but in multiple distinct brain regions.SIGNIFICANCE STATEMENT Many cognitive tasks require combining information about entities from different categories. However, visual information about different categorical objects is processed by separate, specialized brain regions. How is the joint representation from multiple category-selective regions implemented in the brain? Using fMRI movie data and state-of-the-art multivariate statistical dependence based on artificial neural networks, we identified the angular gyrus encoding responses across face-, body-, artifact-, and scene-selective regions. Further, we showed a cortical map of areas that encode information across different subsets of categories. These findings suggest that multicategory information is not encoded in a single centralized location, but at multiple cortical sites which might contribute to distinct cognitive functions, offering insights to understand integration in a variety of domains.

Anomalous kinetics of galactose-deficient IgA incurring nephropathy revealed by cross-scale optical imaging.

IgA nephropathy (IgAN) is the most common glomerulonephritis, characterized by the presence of predominant IgA deposits in the mesangium. Deposition of pathogenic IgA in kidney tissue is a fundamental initiating process that has not been fully studied. Here, we employed optical imaging to directly visualize kidney deposition of IgA with optimized spatial and temporal resolution in BALB/c nude mice. Real-time fluorescence imaging revealed that IgA isolated from patients with IgAN preferentially accumulated in the kidneys, compared with IgA purified from healthy individuals. There was no difference in the distribution of either IgA preparation by the liver. Photoacoustic computed tomography dynamically demonstrated and quantified the enhanced retention of pathological IgA in the kidney cortex. Photoacoustic microscopy tracked IgA deposition in the glomeruli with a resolution down to three microns in a mouse model. Notably, longitudinal fluorescent imaging revealed that galactose-deficient IgA (Gd-IgA), which was elevated in the circulation of patients with IgAN, persisted in the kidney for longer than two weeks, and stable deposition of Gd-IgA induced kidney impairment, including albuminuria and mesangial proliferation. Thus, our study highlights that the aberrant kidney depositional kinetics of Gd-IgA is involved in the pathogenesis of IgAN. Hence, cross-scale optical imaging has potential applications in assessing immune-mediated kidney diseases and uncovering underlying mechanisms of disease.

Increased proportion of follicular helper T cells is associated with B cell activation and disease severity in IgA nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis, characterized by glomerular deposition of IgA immune complexes, mainly produced by B cells under the regulation of CD4+T cells. However, the alterations of specific CD4+T cell subsets and the mechanism of B cells activation in IgAN remain unclear. Therefore, we aimed to investigate the landscape characteristics and role of CD4+T cells in the progression of IgAN. We identified that the proportion of Th2, Th17 and Tfh (follicular helper T) cells in patients with IgAN was significantly higher than that of healthy controls (P < 0.05). Single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) showed that Th cells and B cells in patients with IgAN were more activated. Correspondingly, multiplex immunohistochemistry staining of renal biopsy showed increased infiltration of CD4+T and B cells in the kidneys of patients with IgAN. The degree of infiltration was positively correlated with the degree of renal damage. Interestingly, the proportion of Tfh cells in peripheral blood was positively correlated with the severity of proteinuria. Moreover, the proximity position of Tfh cells and B cells suggested that cell-cell interactions between Tfh and B cells were happening in situ. Intercellular communication analysis also showed enhanced interaction between Tfh cells and B cells in IgAN. Our findings suggested that Tfh cells of patients possibly contributed to the progression of IgAN by activating B cells via cell-cell interactions and TNFSF14-TNFRSF14 may be an underlying signaling pathway.

PyMVPD: A Toolbox for Multivariate Pattern Dependence.

Cognitive tasks engage multiple brain regions. Studying how these regions interact is key to understand the neural bases of cognition. Standard approaches to model the interactions between brain regions rely on univariate statistical dependence. However, newly developed methods can capture multivariate dependence. Multivariate pattern dependence (MVPD) is a powerful and flexible approach that trains and tests multivariate models of the interactions between brain regions using independent data. In this article, we introduce PyMVPD: an open source toolbox for multivariate pattern dependence. The toolbox includes linear regression models and artificial neural network models of the interactions between regions. It is designed to be easily customizable. We demonstrate example applications of PyMVPD using well-studied seed regions such as the fusiform face area (FFA) and the parahippocampal place area (PPA). Next, we compare the performance of different model architectures. Overall, artificial neural networks outperform linear regression. Importantly, the best performing architecture is region-dependent: MVPD subdivides cortex in distinct, contiguous regions whose interaction with FFA and PPA is best captured by different models.

Controlling for Spurious Nonlinear Dependence in Connectivity Analyses.

Recent analysis methods can capture nonlinear interactions between brain regions. However, noise sources might induce spurious nonlinear relationships between the responses in different regions. Previous research has demonstrated that traditional denoising techniques effectively remove noise-induced linear relationships between brain areas, but it is unknown whether these techniques can remove spurious nonlinear relationships. To address this question, we analyzed fMRI responses while participants watched the film Forrest Gump. We tested whether nonlinear Multivariate Pattern Dependence Networks (MVPN) outperform linear MVPN in non-denoised data, and whether this difference is reduced after CompCor denoising. Whereas nonlinear MVPN outperformed linear MVPN in the non-denoised data, denoising removed these nonlinear interactions. We replicated our results using different neural network architectures as the bases of MVPN, different activation functions (ReLU and sigmoid), different dimensionality reduction techniques for CompCor (PCA and ICA), and multiple datasets, demonstrating that CompCor's ability to remove nonlinear interactions is robust across these analysis choices and across different groups of participants. Finally, we asked whether information contributing to the removal of nonlinear interactions is localized to specific anatomical regions of no interest or to specific principal components. We denoised the data 8 separate times by regressing out 5 principal components extracted from combined white matter (WM) and cerebrospinal fluid (CSF), each of the 5 components separately, 5 components extracted from WM only, and 5 components extracted solely from CSF. In all cases, denoising was sufficient to remove the observed nonlinear interactions.

[Advance on pharmacokinetics study of traditional Chinese medicine injections in recent ten years].

Traditional Chinese medicine(TCM) injections boast a definite efficacy and have been widely used in clinic. However, the problems in medication safety have been attracted increasing attention. Pharmacokinetics is of significance to guiding TCM injection administration regimen design and improving safety and effectiveness in clinical use. In recent years, with the improvement of ideas, technology and methods of TCM studies, the pharmacokinetic studies of TCM injections have been broadly performed, with a notable progress. This paper reviewed the advance in pharmacokinetics studies of TCM injections in recent ten years, which mainly focused on pre-clinical concentration-time course, distribution, metabolism and excretion in vivo based on analysis techniques, pharmacokinetic interactions of constitutes, impact of pathological state, pharmacokinetic interactions between TCM injection and chemical drugs, and clinical pharmacokinetics studies of TCM injections, in the expectation of providing reference for studies on quality control, product development and rational clinical use of TCM injections.