Increasing evidence indicates that developmental dyslexia (DD) is a "disconnection syndrome", and new probes of connectome were applied to investigate the "disconnection" in DD. However, there is a lack of brain connectome studies of Chinese dyslexics, who may have a different neural impairment pattern due to the logographic nature of Chinese. The aim of this study was to investigate the topological organization characteristics of the DD brain using a structural network based analysis on the volumetric covariance, which is a method with the advantage of reflecting brain developmental changes. Twenty-five children diagnosed with DD and twenty-five typically developing controls were included. The structural networks based on the pair-wise correlation of gray matter volume from 90 brain regions were constructed for the two groups and compared. Compared to controls, the structural network of dyslexic children exhibited significantly increased local efficiency combined with a tendency of decreased global efficiency and prolonged characteristic path length, thus reflecting a more locally specialized topological organization. Two brain areas showed significantly altered local regional network properties: the left precentral gyrus with increased bi, and the right Heschl's gyrus with decreased bi and ki. Moreover, a series of hub regions (especially the right fronto-temporal regions) identified in the network of typically developing children were not presented in the brain of DD. To our knowledge, this is the first whole-brain structural network study on Chinese dyslexics. This study provides evidence of brain topological organization changes in Chinese children with DD, and thus may help shed light on its neurobiological basis.

In this study, the influence of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) on the prognosis of giant cell tumor (GCT) of the extremities were investigated.

Training can induce significant changes in brain functioning and behavioral performance. One consequence of training is changing the pattern of brain activation. Abacus training is of interest because abacus experts gain the ability to handle digits with unusual speed and accuracy. However, the neural correlates of numerical memory in abacus-trained children remain unknown. In the current study, we aimed to detect a training effect of abacus-based mental calculations on numerical working memory in children. We measured brain functional magnetic resonance imaging (fMRI) activation patterns in 17 abacus-trained children and 17 control children as they performed two numerical working memory tasks (digits and beads). Functional MRI results revealed higher activation in abacus-trained children than in the controls in the right posterior superior parietal lobule/superior occipital gyrus (PSPL/SOG) and the right supplementary motor area (SMA) in both tasks. When these regions were used as seeds in a functional connectivity analysis of the resting brain, the abacus-trained children showed significantly enhanced integration between the right SMA and the right inferior frontal gyrus (IFG). The IFG is considered to be the key region for the control of attention. These findings demonstrate that extensive engagement of the fronto-parietal network occurs during numerical memory tasks in the abacus-trained group. Furthermore, abacus training may increase the functional integration of visuospatial-attention circuitry, which and thus enhances high-level cognitive process.

Severe fatal human adenoviral (HAdV) pneumonia is associated with significant mortality and no effective drug is available for clinical therapy. We evaluated the association and safety of high titer neutralizing antibodies (NAbs) plasma in pediatric patients with severe fatal HAdV pneumonia.

Accumulating evidence indicates a positive effect of abacus-based mental calculation (AMC) training on various cognitive functions including short-term memory (STM). Our previous work has shown AMC training-induced activation changes in the frontal-parietal network (FPN) using task fMRI. However, whether AMC training-induced functional plasticity in the same brain network can be detected at resting state remains unknown. The current study aimed to address this question using resting state functional connectivity in a longitudinal AMC training experiment engaging a training group (18 subjects, age = 21.439 ± 0.565) and a control group (18 subjects, age = 21.113 ± 1.140). Our results revealed that the average functional connectivity strength within the FPN showing task activation changes was significantly enhanced after training in the AMC group, whereas it remained stable in the control group. Further analysis indicated that such connectivity increase in the AMC group was primarily driven by the enhanced coupling of bilateral superior parietal lobules (SPL). In addition, a significant and positive correlation between letter forward memory span and SPL connectivity was found at post-training session in the AMC group. While the weakest quartile of SPL connections ranking by pre-training connectivity strength showed the largest effect of enhancement after training, it was the strongest quartile of SPL connectivity that correlated the most with memory span at post-training session. These findings suggest that AMC training may enhance bilateral SPL functional connectivity, through which AMC training might exert a transfer effect to improve short-term memory capacity.

Traditional Chinese medicine (TCM) databases play a vital role in bridging the gap between TCM and modern medicine, as well as in promoting the popularity of TCM. Elucidating the bioactive ingredients of Chinese medicinal materials is key to TCM modernization and new drug discovery. However, one drawback of current TCM databases is the lack of quantitative data on the constituents of Chinese medicinal materials. Herein, we present ccTCM, a web-based platform designed to provide a component and compound-content-based resource on TCM and analysis services for medical experts. In terms of design features, ccTCM combines resource distribution, similarity analysis, and molecular-mechanism analysis to accelerate the discovery of bioactive ingredients in TCM. ccTCM contains 273 Chinese medicinal materials commonly used in clinical settings, covering 29 functional classifications. By searching and comparing, we finally adopted 2043 studies, from which we collected the compounds contained in each TCM with content greater than 0.001 %, and a total of 1449 were extracted. Subsequently, we collected 40,767 compound-target pairs by integrating multiple databases. Taken together, ccTCM is a versatile platform that can be used by TCM scientists to perform scientific and clinical TCM studies based on quantified ingredients of Chinese medicinal materials. ccTCM is freely accessible at http://www.cctcm.org.cn.

This study examined whether long-term abacus-based mental calculation (AMC) training improved numerical processing efficiency and at what stage of information processing the effect appeard. Thirty-three children participated in the study and were randomly assigned to two groups at primary school entry, matched for age, gender and IQ. All children went through the same curriculum except that the abacus group received a 2-h/per week AMC training, while the control group did traditional numerical practice for a similar amount of time. After a 2-year training, they were tested with a numerical Stroop task. Electroencephalographic (EEG) and event related potential (ERP) recording techniques were used to monitor the temporal dynamics during the task. Children were required to determine the numerical magnitude (NC) (NC task) or the physical size (PC task) of two numbers presented simultaneously. In the NC task, the AMC group showed faster response times but similar accuracy compared to the control group. In the PC task, the two groups exhibited the same speed and accuracy. The saliency of numerical information relative to physical information was greater in AMC group. With regards to ERP results, the AMC group displayed congruity effects both in the earlier (N1) and later (N2 and LPC (late positive component) time domain, while the control group only displayed congruity effects for LPC. In the left parietal region, LPC amplitudes were larger for the AMC than the control group. Individual differences for LPC amplitudes over left parietal area showed a positive correlation with RTs in the NC task in both congruent and neutral conditions. After controlling for the N2 amplitude, this correlation also became significant in the incongruent condition. Our results suggest that AMC training can strengthen the relationship between symbolic representation and numerical magnitude so that numerical information processing becomes quicker and automatic in AMC children.

Arithmetic skill is of critical importance for academic achievement, professional success and everyday life, and childhood is the key period to acquire this skill. Neuroimaging studies have identified that left parietal regions are a key neural substrate for representing arithmetic skill. Although the relationship between functional brain activity in left parietal regions and arithmetic skill has been studied in detail, it remains unclear about the relationship between arithmetic achievement and structural properties in left inferior parietal area in schoolchildren. The current study employed a combination of voxel-based morphometry (VBM) for high-resolution T1-weighted images and fiber tracking on diffusion tensor imaging (DTI) to examine the relationship between structural properties in the inferior parietal area and arithmetic achievement in 10-year-old schoolchildren. VBM of the T1-weighted images revealed that individual differences in arithmetic scores were significantly and positively correlated with the gray matter (GM) volume in the left intraparietal sulcus (IPS). Fiber tracking analysis revealed that the forceps major, left superior longitudinal fasciculus (SLF), bilateral inferior longitudinal fasciculus (ILF) and inferior fronto-occipital fasciculus (IFOF) were the primary pathways connecting the left IPS with other brain areas. Furthermore, the regression analysis of the probabilistic pathways revealed a significant and positive correlation between the fractional anisotropy (FA) values in the left SLF, ILF and bilateral IFOF and arithmetic scores. The brain structure-behavior correlation analyses indicated that the GM volumes in the left IPS and the FA values in the tract pathways connecting left IPS were both related to children's arithmetic achievement. The present findings provide evidence that individual structural differences in the left IPS are associated with arithmetic scores in schoolchildren.

This study examined the resting state neural networks for visual Chinese word processing in Chinese children and adults. Both the functional connectivity (FC) and amplitude of low frequency fluctuation (ALFF) approaches were used to analyze the fMRI data collected when Chinese participants were not engaged in any specific explicit tasks. We correlated time series extracted from the visual word form area (VWFA) with those in other regions in the brain. We also performed ALFF analysis in the resting state FC networks. The FC results revealed that, regarding the functionally connected brain regions, there exist similar intrinsically organized resting state networks for visual Chinese word processing in adults and children, suggesting that such networks may already be functional after 3-4 years of informal exposure to reading plus 3-4 years formal schooling. The ALFF results revealed that children appear to recruit more neural resources than adults in generally reading-irrelevant brain regions. Differences between child and adult ALFF results suggest that children's intrinsic word processing network during the resting state, though similar in functional connectivity, is still undergoing development. Further exposure to visual words and experience with reading are needed for children to develop a mature intrinsic network for word processing. The developmental course of the intrinsically organized word processing network may parallel that of the explicit word processing network.

The present study aimed to develop nomograms estimating survival for patients with high-grade osteosarcoma.

Nucleic acids from bacteria or viruses induce potent immune responses in infected cells1-4. The detection of pathogen-derived nucleic acids is a central strategy by which the host senses infection and initiates protective immune responses5,6. Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA sensor7,8. It catalyses the synthesis of cyclic GMP-AMP (cGAMP)9-12, which stimulates the induction of type I interferons through the STING-TBK1-IRF-3 signalling axis13-15. STING oligomerizes after binding of cGAMP, leading to the recruitment and activation of the TBK1 kinase8,16. The IRF-3 transcription factor is then recruited to the signalling complex and activated by TBK18,17-20. Phosphorylated IRF-3 translocates to the nucleus and initiates the expression of type I interferons21. However, the precise mechanisms that govern activation of STING by cGAMP and subsequent activation of TBK1 by STING remain unclear. Here we show that a conserved PLPLRT/SD motif within the C-terminal tail of STING mediates the recruitment and activation of TBK1. Crystal structures of TBK1 bound to STING reveal that the PLPLRT/SD motif binds to the dimer interface of TBK1. Cell-based studies confirm that the direct interaction between TBK1 and STING is essential for induction of IFNβ after cGAMP stimulation. Moreover, we show that full-length STING oligomerizes after it binds cGAMP, and highlight this as an essential step in the activation of STING-mediated signalling. These findings provide a structural basis for the development of STING agonists and antagonists for the treatment of cancer and autoimmune disorders.

Articular cartilage injuries are common orthopedic conditions that severely affect the quality of life of patients. Tissue engineering can facilitate cartilage repair and the key points involve scaffolding and seed cell selection. Pre-experiments found a range of microstructures of bioceramic scaffolds suitable for chondrocyte adhesion and proliferation, and maintaining chondrocyte phenotype. Three-dimensional cultures of bone marrow mesenchymal stem cell (BMSC) scaffolds were implanted into mice. According to the shape of the bioceramic scaffolds and the implantation time in vivo, RNA sequencing was performed on the removed scaffolds to explore the molecular mechanism. The in vitro bone plate culture can induce differentiation of chondrocytes, making culture different to that produced in vitro. Implantation of scaffolds in vivo increases the expression of bone-related genes. The ceramic rod-like material was found to be superior to the disc shape, and the bone repair effect was more marked with longer implantation times. Gene Ontology analysis revealed that 'cell chemotaxis', 'negative regulation of ossification' and 'bone development' pathways were involved in recovery. It was further confirmed that BMSCs were suitable as seed cells for cartilage tissue engineering, and that the β-tricalcium phosphate scaffold maybe ideal as cartilage tissue engineering scaffold material. The present research provided new insights into the molecular mechanism of cartilage repair by BMSCs and bioceramic scaffolds. Bioinformatics analysis revealed that AMMECR1L-like protein, tumor necrosis factor-induced protein 2, inhibitor of nuclear factor-B kinase subunit and protein kinase C type and 'negative regulation of ossification' and 'bone development' pathways may be involved in osteoblast maturation and bone regeneration.

Ginseng can help regulate brain excitability, promote learning and memory, and resist cerebral ischemia in the central nervous system. Ginsenosides are the major effective compounds of Ginseng, but their protein targets in the brain have not been determined.

20(S)-protopanaxadiol (PPD), a ginsenoside metabolite, has prominent benefits for the central nervous system, especially in improving learning and memory. However, its transcriptional targets in brain tissue remain unknown.

Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease associated with high disability, and femoral neck fracture (FNF) is one of the most common reasons for traumatic ONFH. This study was designed to reveal the mechanisms underlying ONFH. Using fastx_toolkit and prinseq-lite tools, quality control was conducted for the sequencing data. The differentially expressed genes (DEGs, including both mRNAs and lncRNAs) between ONFH and FNF samples were identified using the edgeR package in R, and were then subjected to enrichment analysis using the BioCloud platform. Subsequently, protein-protein interaction (PPI) networks were constructed using Cytoscape software. After the target genes of DE-lncRNAs were predicted based on Spearman's rank correlation coefficient, lncRNA-gene coexpression network was visualized using the Cytoscape software. Furthermore, functional enrichment analysis was carried out for the target genes using the clusterprofiler package in R. Additionally, the key genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2965 DEGs were identified from the ONFH samples, including 602 DE-lncRNAs (such as downregulated FAM201A). In the PPI networks, eight upregulated genes (including FGF2, IGF1, SOX9, and COL2A1) and 11 downregulated genes were among the top 20 genes according to all of the scores, such as degree centrality, closeness centrality, and betweenness centrality scores. Functional enrichment analysis showed that IGF1, SOX9, and COL2A1 were significantly enriched during skeletal system development. Moreover, qRT-PCR experiments detected the upregulation of FGF2 and downregulation of FAM201A in ONFH samples. FGF2 and FAM201A were correlated with the development of ONFH. Besides, IGF1, SOX9, and COL2A1 might also affect the pathogenesis of ONFH.

In this study, a fingerprint-activity relationship between chemical fingerprints and hepatoprotective activity was established to evaluate the quality of salt-treated Apocyni Veneti Folium (AVF). Characteristic fingerprints of AVF samples exposed to different concentrations of salt were generated by ultrafast liquid chromatography tandem triple time-of-flight mass/mass spectrometry (UFLC-Triple TOF-MS/MS), and a similarity analysis was performed based on common characteristic peaks by hierarchical clustering analysis (HCA). Then, the hepatoprotective activity of AVF against CCl4-induced acute liver damage in mice was investigated by assessing biochemical markers and histopathology, which showed that a high dose of AVF exposed to low levels of salt stress produced a marked amelioration of hepatic damage compared with the other salt-treated AVF. Finally, fingerprint-activity relationship modeling, which was capable of discovering the bioactive markers used in the quality evaluation, was investigated by the chemical fingerprints and the hepatoprotective activities utilizing multivariate statistical analysis, gray correlation analysis (GCA) and bivariate correlation analysis (BCA). The results showed that the accumulation of polyphenols, such as flavonoids and phenolic acids, in AVF subjected to low levels of salt stress could result in the effective scavenging of free radicals. Therefore, the present study may provide a powerful strategy to holistically evaluate the quality of salt-treated AVF in combination with chemical fingerprint and bioactivity evaluation.

Ginseng effectively reduces fatigue in both animal models and clinical trials. However, the mechanism of action is not completely understood, and its molecular targets remain largely unknown.

Detection of viruses by innate immune sensors induces protective antiviral immunity. The viral DNA sensor cyclic GMP-AMP synthase (cGAS) is necessary for detection of HIV by human dendritic cells and macrophages. However, synthesis of HIV DNA during infection is not sufficient for immune activation. The capsid protein, which associates with viral DNA, has a pivotal role in enabling cGAS-mediated immune activation. We now find that NONO is an essential sensor of the HIV capsid in the nucleus. NONO protein directly binds capsid with higher affinity for weakly pathogenic HIV-2 than highly pathogenic HIV-1. Upon infection, NONO is essential for cGAS activation by HIV and cGAS association with HIV DNA in the nucleus. NONO recognizes a conserved region in HIV capsid with limited tolerance for escape mutations. Detection of nuclear viral capsid by NONO to promote DNA sensing by cGAS reveals an innate strategy to achieve distinction of viruses from self in the nucleus.

Training induces cognitive and neural plasticity, and understanding of the neural mechanisms of training-induced brain plasticity has significant implications for improving children's academic achievement. Previous studies have indicated that training in abacus-based mental calculation (AMC) improves arithmetical capacities and results in brain plasticity within visuospatial brain regions. However, previous studies have reported alterations within distributed brain regions. Thus, it remains unclear whether and how AMC training influences the functional integration and separation between and/or within networks. The current study aimed to address these questions using graph theory, engaging 162 children, 90 of whom were given long-term AMC training. The AMC group exhibited greater local efficiency and intra-module connections within the visual network and less local efficiency and intra-module connections in the cingulo-opercular network (CON). Interestingly, in the AMC group, negative correlations were found between local efficiency and intra-module connections across the two networks. Furthermore, both network characteristics of the CON were negatively correlated with math ability in the AMC group. No such correlations were found in the control group. The current study delineated the enhanced neural mechanisms of visuospatial-related brain regions at an intermediate level and highlighted the intrinsic association between different brain ensembles in neural plasticity, thus furthering the understanding of the effects of AMC training on brain network reconfiguration.

Evidence supports the notion that the fusiform gyrus (FG), as an integral part of the ventral occipitotemporal junction, is involved widely in cognitive processes as perceiving faces, objects, places or words, and this region also might represent the visual form of an abacus in the abacus-based mental calculation process. The current study uses a combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis to test whether long-term abacus training could induce structural changes in the left FG and in the white matter (WM) tracts distribution connecting with this region in school children. We found that, abacus-trained children exhibited significant smaller gray matter (GM) volume than controls in the left FG. And the connectivity mapping identified left forceps major as a key pathway connecting left FG with other brain areas in the trained group, but not in the controls. Furthermore, mean fractional anisotropy (FA) values within left forceps major were significantly increased in the trained group. Interestingly, a significant negative correlation was found in the trained group between the GM volume in left FG and the mean FA value in left forceps major, suggesting an inverse effect of the reported GM and WM structural changes. In the control group, a positive correlation between left FG GM volume and tract FA was found as well. This analysis visualized the group level differences in GM volume, FA and fiber tract between the abacus-trained children and the controls, and provided the first evidence that GM volume change in the left FG is intimately linked with the micro-structural properties of the left forceps major tracts. The present results demonstrate the structural changes in the left FG from the intracortical GM to the subcortical WM regions and provide insights into the neural mechanism of structural plasticity induced by abacus training.