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Skilled reading requires the convergent brain network between spoken language and reading. Here, we examined the developmental changes in this convergent network between beginning and skilled readers. We used fMRI data from 41 adults (aged from 20 to 21 years) and 21 children (aged from 9 to 12 years) who performed a Chinese word sound matching task in speech and print. Three complementary analytic approaches, including print-speech conjunction analysis, brain-behavioral analysis, and functional connectivity analysis were performed to reveal the link between print and speech neural systems as well as the developmental changes in this link. We found that (1) adults showed broader convergence than children; (2) coactivation in anterior dorsal regions (i.e., inferior frontal gyrus and insula) predominated in children, while coactivation in the ventral posterior region (i.e., middle temporal gyrus) predominated in adults, which aligns with the dual-stream model of reading; and (3) print-speech convergence regions showed task-specific functional connectivity patterns and there was an increased visual-modal specialization in the functional connectivity patterns with reading development. Our study provides important evidence for developmentally increased coactivation in ventral posterior regions and increased task specialization in print-speech convergence regions, which is crucial for successful reading.

Objective To understand the psychological experience of patients with thromboembolism during pregnancy and after childbirth. Methods A total of 100 patients with thromboembolism during pregnancy or after delivery were selected as the research subjects. All patients completed the Symptom Check List-90 (SCL-90) on the first day of admission and before discharge. Ten patients were randomly selected for a semi-structured qualitative interview to understand their psychological experience of and reaction to thromboembolism. Results The factor scores of somatization, anxiety, depression, paranoid ideation and interpersonal sensibility decreased significantly after hospitalization management compared with those before hospitalization management(P＜0. 01). Qualitative findings were distilled into two major themes: low disease knowledge and awareness among patients with thromboembolism during pregnancy and after childbirth; increased psychological burden as excessive fear of disease and concerns about fetus and newborns. Conclusion Efforts such as risk assessment, risk factors analysis and health education should be made to enhance the non-hospitalized self-prevention and management in women during pregnancy and after childbirth. Early implementation of targeted interventions should also be mentioned to strengthen psychological care for pregnant women, in order to reduce the blindness and passivity of behavior. (目的 了解孕产期血栓栓塞症患者的真实心理体验。方法 选取医院收治的孕产期血栓栓塞症患者100例为研究对象, 所有患者在入院第一天及出院前填写症状自评量表(SCL-90), 了解住院管理前后患者的心理状态。采用质性研究方法, 选取10名孕产妇进行半结构式访谈, 了解患血栓栓塞症后的真实心理体验。结果 住院管理后, SCL-90量表中躯体化、焦虑、抑郁、偏执、人际关系敏感性维度评分均较住院管理前降低, 差异有统计学的意义(P＜0. 01)。质性访谈结果显示, 孕产期血栓栓塞症患者对疾病知识缺乏认知; 患者因对疾病的过度恐惧及对胎儿/婴儿产生影响的担忧而导致心理负担增加。结论 应做好孕产期血栓栓塞症风险筛查, 在探讨危险因素的同时, 加大科普宣传和健康宣教力度, 帮助孕产妇提升自我预防及管理能力。入院后提前实施针对性干预措施, 加强患者心理护理, 能够减少孕产妇行为的盲目性和被动性。)

Ti‐13Nb‐13Zr (TNZ), a representative of β‐type titanium alloys, has garnered significant interest in biomedical implant materials recently because of its high strength, and closer elastic modulus to human bone. However, TNZ alloy does not have antibacterial properties and has the potential to cause implant‐related infection, even implantation failure. Herein, TNZ alloy is alloyed by Cu element and the surface is modified by anodic oxidation (AO) to enhance the biocompatibility and antimicrobial qualities. The corrosion resistance, antimicrobial properties, and cytotoxicity of the TNZ‐3Cu alloy before and after anodization are studied by X‐ray diffraction, X‐ray photoelectron spectroscopy, scanning electron microscopy, electrochemical test, mechanical property test, and cell test. The experimental results show that the primary constituents of the TNZ‐3Cu alloy are α″ martensite and β phase after solid solution treatment. The elastic modulus of TNZ‐3Cu alloy is (65 ± 1.33) GPa, 9 GPa lower than that of TNZ alloy. The AO treatment significantly improves the hydrophilicity and antibacterial properties as well as the corrosion resistance by the formation of a dense oxides composites coating. The cell test results show that the coating improves the initial adhesion of cells by the high hydrophilic surface and promotes the proliferation of cells by the release of copper ions. [ABSTRACT FROM AUTHOR]

Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor involved in innate immunity, but its role in adaptive immunity, specifically in the context of CD8+ T-cell antitumour immunity, remains unclear. Here, we demonstrate that RIG-I is upregulated in tumour-infiltrating CD8+ T cells, where it functions as an intracellular checkpoint to negatively regulate CD8+ T-cell function and limit antitumour immunity. Mechanistically, the upregulation of RIG-I in CD8+ T cells is induced by activated T cells, and directly inhibits the AKT/glycolysis signalling pathway. In addition, knocking out RIG-I enhances the efficacy of adoptively transferred T cells against solid tumours, and inhibiting RIG-I enhances the response to PD-1 blockade. Overall, our study identifies RIG-I as an intracellular checkpoint and a potential target for alleviating inhibitory constraints on T cells in cancer immunotherapy, either alone or in combination with an immune checkpoint inhibitor. Synopsis: RIG-I, an innate immune RNA sensor, plays a crucial role in anti-infection and antitumour effects. This study revealed another role of RIG-I as an intracellular immune checkpoint that negatively regulates the antitumour function of CD8+ T cells in multiple tumour models. RIG-I was upregulated in TILs, especially in terminally exhausted CD8+ T cells. RIG-I knockout in CD8+ T cells significantly enhanced antitumour activity in various tumour models. RIG-I negatively regulates the antitumour function of CD8+ T cells through the TCR/AKT/glycolysis signalling pathway. RIG-I knockout in CD8+ T cells in combination with PD-1 antibodies show significant efficacy in PD-1-insensitive tumours. RIG-I, an innate immune RNA sensor, plays a crucial role in anti-infection and antitumour effects. This study revealed another role of RIG-I as an intracellular immune checkpoint that negatively regulates the antitumour function of CD8+ T cells in multiple tumour models. [ABSTRACT FROM AUTHOR]

BackgroundUlcerative colitis is listed as one of the modern refractory diseases by the World Health Organization. At present, Western medicine still has many shortcomings in its treatment, and studies have shown that fecal bacterial transplantation (FMT) has a certain effect on it, but the mechanism is not clear.ObjectiveFMT was used to treat mouse ulcerative colitis model to verify the efficacy and possible mechanism of FMT.MethodsFrom December 2019 to April 2020, 60 mice were divided into normal control group (Control group) , ulcerative colitis model group (Model group) , ulcerative colitis model + fecal bacteria transplantation treatment group (Model+FMT group) and ulcerative colitis model + 5-aminosalicylic acid (5-ASA) treatment group (Model+5-ASA group) by random number table method, each of 15 mice. Control group did not make any intervention; Model group prepared mouse ulcerative colitis model; after successful modeling, the Model+FMT group was given 0.2 ml of fecal bacteria solution per enema; after successful modeling, the Model+5-ASA group was given 0.019 5 g/ml 5-ASA enema. The ultrastructural changes of intestinal tissue through transmission electron microscope, flow cytometric detection of blood helper T cell (Th) -17, Th-1, Th-2, Treg cell content changes, and enzyme-linked immunosorbent assay (ELISA) were observed to detect serum interferon γ (IFN-γ) , interleukin (IL) -2, IL-17, IL-4, IL-10, transforming growth factor β (TGF-β) level changes.ResultsIntestinal tissue transmission electron microscopy ultrastructure showed that the Model group was successfully modeled; the microvilli in the Model+FMT group and Model+5-ASA group were denser, with normal morphology, more goblet cells, slight swelling of mitochondria, and insignificant rough endoplasmic reticulum lesions. The Th17 cell content of the Model+FMT group was higher than that of the Control group and lower than that of the Model group; the Th17 cell content of the Model+5-ASA group was lower than that of Control group, Model group and Model+FMT group. The Th1 cell content of Model+FMT group and Model+5-ASA group were lower than those of Control group and Model group, respectively; Th2 cell content of Model+FMT group was lower than that of Control group and higher than that of Model group, and Th2 cell content of Model+5-ASA group was lower than that of Control group and higher than that of Model group and Model +FMT group. Treg cell content in Model+FMT group and Model+5-ASA group were lower than that of Control group and higher than that of Model group (P

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease with uncertain genetic predisposition in most sporadic cases. The spatial architecture of cell types and gene expression are the basis of cell–cell interactions, biological function and disease pathology, but are not well investigated in the human motor cortex, a key ALS-relevant brain region. Recent studies indicated single nucleus transcriptomic features of motor neuron vulnerability in ALS motor cortex. However, the brain regional vulnerability of ALS-associated genes and the genetic link between region-specific genes and ALS risk remain largely unclear. Here, we developed an entropy-weighted differential gene expression matrix-based tool (SpatialE) to identify the spatial enrichment of gene sets in spatial transcriptomics. We benchmarked SpatialE against another enrichment tool (multimodal intersection analysis) using spatial transcriptomics data from both human and mouse brain tissues. To investigate regional vulnerability, we analysed three human motor cortex and two dorsolateral prefrontal cortex tissues for spatial enrichment of ALS-associated genes. We also used Cell2location to estimate the abundance of cell types in ALS-related cortex layers. To dissect the link of regionally expressed genes and ALS risk, we performed burden analyses of rare loss-of-function variants detected by whole-genome sequencing in ALS patients and controls, then analysed differential gene expression in the TargetALS RNA-sequencing dataset. SpatialE showed more accurate and specific spatial enrichment of regional cell type markers than multimodal intersection analysis in both mouse brain and human dorsolateral prefrontal cortex. Spatial transcriptomic analyses of human motor cortex showed heterogeneous cell types and spatial gene expression profiles. We found that 260 manually curated ALS-associated genes are significantly enriched in layer 5 of the motor cortex, with abundant expression of upper motor neurons and layer 5 excitatory neurons. Burden analyses of rare loss-of-function variants in Layer 5-associated genes nominated NOMO1 as a novel ALS-associated gene in a combined sample set of 6814 ALS patients and 3324 controls (P = 0.029). Gene expression analyses in CNS tissues revealed downregulation of NOMO1 in ALS, which is consistent with a loss-of-function disease mechanism. In conclusion, our integrated spatial transcriptomics and genomic analyses identified regional brain vulnerability in ALS and the association of a layer 5 gene (NOMO1) with ALS risk. [ABSTRACT FROM AUTHOR]