Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of Porcine RIG-I Like Receptors Revealed the Positive Regulation of RIG-I and MDA5 by LGP2

The RLRs play critical roles in sensing and fighting viral infections especially RNA virus infections. Despite the extensive studies on RLRs in humans and mice, there is a lack of systemic investigation of livestock animal RLRs. In this study, we characterized the porcine RLR members RIG-I, MDA5 and LGP2. Compared with their human counterparts, porcine RIG-I and MDA5 exhibited similar signaling activity to distinct dsRNA and viruses, via similar and cooperative recognitions. Porcine LGP2, without signaling activity, was found to positively regulate porcine RIG-I and MDA5 in transfected porcine alveolar macrophages (PAMs), gene knockout PAMs and PK-15 cells. Mechanistically, LGP2 interacts with RIG-I and MDA5 upon cell activation, and promotes the binding of dsRNA ligand by MDA5 as well as RIG-I. Accordingly, porcine LGP2 exerted broad antiviral functions. Intriguingly, we found that porcine LGP2 mutants with defects in ATPase and/or dsRNA binding present constitutive activity which are likely through RIG-I and MDA5. Our work provided significant insights into porcine innate immunity, species specificity and immune biology.
Replacing the Notion of Spacetime Distance by the Notion of Correlation

Spacetime is conventionally viewed as a stage on which actors, in the form of massive and massless matter, move. In this study, we explore what may lie beyond this picture. The starting point is the observation that quantum field fluctuations are the more strongly correlated the shorter their spacetime distance. The notion of spacetime distance can, therefore, be replaced by the notion of correlation strength. This suggests a new picture in which the abstract 2-point and multi-point correlations are the primary structure, a picture which is essentially information-theoretic. In the low energy regime, the secondary notions of spacetime and of matter would then emerge as approximate representations of the abstract correlators, namely, in the form of Feynman rules on curved spacetime.
Regulatory Mechanisms of the RNA Modification m6A and Significance in Brain Function in Health and Disease

RNA modifications have emerged as an additional layer of regulatory complexity governing the function of almost all species of RNA. N6-methyladenosine (m6A), the addition of methyl groups to adenine residues, is the most abundant and well understood RNA modification. The current review discusses the regulatory mechanisms governing m6A, how this influences neuronal development and function and how aberrant m6A signaling may contribute to neurological disease. M6A is known to regulate the stability of mRNA, the processing of microRNAs and function/processing of tRNAs among other roles. The development of antibodies against m6A has facilitated the application of next generation sequencing to profile methylated RNAs in both health and disease contexts, revealing the extent of this transcriptomic modification. The mechanisms by which m6A is deposited, processed, and potentially removed are increasingly understood. Writer enzymes include METTL3 and METTL14 while YTHDC1 and YTHDF1 are key reader proteins, which recognize and bind the m6A mark. Finally, FTO and ALKBH5 have been identified as potential erasers of m6A, although there in vivo activity and the dynamic nature of this modification requires further study. M6A is enriched in the brain and has emerged as a key regulator of neuronal activity and function in processes including neurodevelopment, learning and memory, synaptic plasticity, and the stress response. Changes to m6A have recently been linked with Schizophrenia and Alzheimer disease. Elucidating the functional consequences of m6A changes in these and other brain diseases may lead to novel insight into disease pathomechanisms, molecular biomarkers and novel therapeutic targets.
Significant Association Between XRCC1 Expression and Its rs25487 Polymorphism and Radiotherapy-Related Cancer Prognosis

Background/Aims XRCC1 (X-ray repair cross-complementing protein 1) expression and its single nucleotide polymorphism XRCC1 rs25487 (G>A) may be related to radiotherapy-related cancer prognosis or radiation-induced side effects. However, this association is controversial. We performed a bioinformatic analysis and a meta-analysis to obtain comprehensive results. Methods TCGA data sets and eligible publications published before November 31, 2020 were retrieved by searching the PubMed, Web of Science and CNKI (China National Knowledge Infrastructure) databases. ORs (odds ratios) and HRs (hazard ratios) with their corresponding 95% CIs (confidence intervals) were calculated to evaluate associations. For XRCC1 single nucleotide polymorphisms, we employed three types of comparisons: GA vs GG, AA vs GG and GA+AA vs GG. Results Sixty nine articles with 10232 patients and 17 TCGA data sets with 2705 patients were included in the analysis. We observed that high XRCC1 expression was associated with an increased risk of minor treatment response and poor overall survival, XRCC1 rs25487 was associated with reduced risk of minor treatment response in esophageal cancer and an increased risk of high-grade side effects in head and neck cancer. Conclusion The results suggest that XRCC1 expression and rs25487 polymorphism are prognostic factors for patients receiving radiotherapy-related treatment. Considering the insufficient treatment parameters provided and the various sample sizes in most of the studies, we suggest that genetic association studies related to radiation-based treatment should include more cancer types with sufficient statistical power and more detailed clinical parameters.
Dopamine Neurons That Cotransmit Glutamate, From Synapses to Circuits to Behavior

Discovered just over 20 years ago, dopamine neurons have the ability to cotransmit both dopamine and glutamate. Yet, the functional roles of dopamine neuron glutamate cotransmission and their implications for therapeutic use are just emerging. This review article encompasses the current body of evidence investigating the functions of dopamine neurons of the ventral midbrain that cotransmit glutamate. Since its discovery in dopamine neuron cultures, further work in vivo confirmed dopamine neuron glutamate cotransmission across species. From there, growing interest has led to research related to neural functioning including roles in synaptic signaling, development, and behavior. Functional connectome mapping reveals robust connections in multiple forebrain regions to various cell types, most notably to cholinergic interneurons in both the medial shell of the nucleus accumbens and the lateral dorsal striatum. Glutamate markers in dopamine neurons reach peak levels during embryonic development and increase in response to various toxins, suggesting dopamine neuron glutamate cotransmission may serve neuroprotective roles. Findings from behavioral analyses reveal prominent roles for dopamine neuron glutamate cotransmission in responses to psychostimulants, in positive valence and cognitive systems and for subtle roles in negative valence systems. Insight into dopamine neuron glutamate cotransmission informs the pathophysiology of neuropsychiatric disorders such as addiction, schizophrenia and Parkinson Disease, with therapeutic implications.
Expression and Prognostic Value of ARID5A and its Correlation With Tumor-Infiltrating Immune Cells in Glioma

AT-rich interaction domain 5A (ARID5A) is a member of the ARID family with a function that has been linked to autoimmune as well as inflammatory diseases. Some ARID family members are involved in the initiation and progression of human cancers. However, the function of ARID5A in glioma remains unknown. In this study, ARID5A expression levels were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database. Subsequently, the relationship between ARID5A expression and the clinical characteristics of glioma patients was evaluated using the Chinese Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) database. The prognostic value of ARID5A in glioma was estimated by Kaplan-Meier analysis and the receiver operating characteristic (ROC) curve analysis. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were performed for functional prediction. The Tumor Immune Estimation Resource (TIMER) database was used to analyze the relationship between ARID5A and immune cell infiltration in glioma. Our results demonstrate that the expression of ARID5A was upregulated in glioma compared with that in nontumor brain tissues. High expression of ARID5A is associated with poor prognosis in glioma. We found that the expression of ARID5A was significantly upregulated with an increase in tumor malignancy. GO analysis revealed that co-expression genes of ARID5A are significantly involved in some important functions in glioma, and GSEA showed that multiple cancer-associated and immune-associated signaling pathways are enriched in the high ARID5A expression group. TIMER database indicated that ARID5A is correlated with tumor-infiltrating immune cells in glioma. Collectively, these findings indicate that ARID5A may be a potential prognostic biomarker and is correlated with immune infiltration in glioma.
Sport Events for Sport Participation: A Scoping Review

Research on sport participation impacts from sport events has been sporadic. This scoping review assesses the current state of literature that addresses impacts, legacies, and leveraging of sport events for sport participation outcomes and the gaps in terms of study context and research designs. Two systematic approaches of article identification were performed: a traditional database search and a systematic manual search. Studies on sport participation outcomes from events mainly focused on mega sport events and adult populations, with the majority employing cross-sectional data and quantitative methods. The use theoretical of frameworks is limited and inconsistent. There is a need for longitudinal investigations, as well as more focus on youth populations, participant events, and smaller-sized events to advance the research agenda for sport participation outcomes from sport events.
Tryptophan Catabolites in Bipolar Disorder: A Meta-Analysis

Objective Tryptophan catabolites (TRYCATs) are implicated in the pathophysiology of mood disorders by mediating immune-inflammation and neurodegenerative processes. We performed a meta-analysis of TRYCAT levels in bipolar disorder (BD) patients compared to healthy controls. Methods A systematic literature search in seven electronic databases (PubMed, Embase, Web of Science, Cochrane, Emcare, PsycINFO, Academic Search Premier) was conducted on TRYCAT levels in cerebrospinal fluid or peripheral blood according to the PRISMA statement. A minimum of three studies per TRYCAT was required for inclusion. Standardized mean differences (SMD) were computed using random effect models. Subgroup analyses were performed for BD patients in a different mood state (depressed, manic). The methodological quality of the studies was rated using the modified Newcastle-Ottawa Quality assessment Scale. Results Twenty-one eligible studies were identified. Peripheral levels of tryptophan (SMD = -0.44; p < 0.001), kynurenine (SMD = - 0.3; p = 0.001) and kynurenic acid (SMD = -.45; p = < 0.001) were lower in BD patients versus healthy controls. In the only three eligible studies investigating TRP in cerebrospinal fluid, tryptophan was not significantly different between BD and healthy controls. The methodological quality of the studies was moderate. Subgroup analyses revealed no significant difference in TRP and KYN values between manic and depressed BD patients, but these results were based on a limited number of studies. Conclusion The TRYCAT pathway appears to be downregulated in BD patients. There is a need for more and high-quality studies of peripheral and central TRYCAT levels, preferably using longitudinal designs.
Intraoperative B-Mode Ultrasound Guided Surgery and the Extent of Glioblastoma Resection: A Randomized Controlled Trial

Background Intraoperative MRI and 5-aminolaevulinic acid guided surgery are useful to maximize the extent of glioblastoma resection. Intraoperative ultrasound is used as a time-and cost-effective alternative, but its value has never been assessed in a trial. The goal of this randomized controlled trial was to assess the value of intraoperative B-mode ultrasound guided surgery on the extent of glioblastoma resection. Materials and Methods In this randomized controlled trial, patients of 18 years or older with a newly diagnosed presumed glioblastoma, deemed totally resectable, presenting at the Erasmus MC (Rotterdam, The Netherlands) were enrolled and randomized (1:1) into intraoperative B-mode ultrasound guided surgery or resection under standard neuronavigation. The primary outcome of this study was complete contrast-enhancing tumor resection, assessed quantitatively by a blinded neuroradiologist on pre- and post-operative MRI scans. This trial was registered with ClinicalTrials.gov (NCT03531333). Results We enrolled 50 patients between November 1, 2016 and October 30, 2019. Analysis was done in 23 of 25 (92%) patients in the intraoperative B-mode ultrasound group and 24 of 25 (96%) patients in the standard surgery group. Eight (35%) of 23 patients in the intraoperative B-mode ultrasound group and two (8%) of 24 patients in the standard surgery group underwent complete resection (p=0.036). Baseline characteristics, neurological outcome, functional performance, quality of life, complication rates, overall survival and progression-free survival did not differ between treatment groups (p>0.05). Conclusions Intraoperative B-mode ultrasound enables complete resection more often than standard surgery without harming patients and can be considered to maximize the extent of glioblastoma resection during surgery.
Tell Me Who You Vote for, and I'll Tell You Who You Are? The Associations of Political Orientation With Personality and Prosocial Behavior and the Plausibility of Evolutionary Approaches

Blatantly observable in the U.S. currently, the political chasm grows, representing a prototype of political polarization in most if not all western democratic political systems. Differential political psychology strives to trace back increasingly polarized political convictions to differences on the individual level. Recent evolutionary informed approaches suggest that interindividual differences in political orientation reflect differences in group-mindedness and cooperativeness. Contrarily, the existence of meaningful associations between political orientation, personality traits, and interpersonal behavior has been questioned critically. Here, we shortly review evidence showing that these relationships do exist, which supports the assumption that political orientation is deeply rooted in the human condition. Potential reasons for the premature rejection of these relationships and directions for future research are outlined and implications for refinements and extensions of evolutionary informed approaches are derived.
The Expression of Chemokines Is Downregulated in a Pre-Clinical Model of TTR V30M Amyloidosis

Inflammation is a hallmark of several neurodegenerative disorders including hereditary amyloidogenic transthyretin amyloidosis (ATTRv). ATTRv is an autosomal dominant neurodegenerative disorder with extracellular deposition of mutant transthyretin (TTR) aggregates and fibrils, particularly in nerves and ganglia of the peripheral nervous system. Nerve biopsies from ATTRv patients show increased cytokine production, but interestingly no immune inflammatory cellular infiltrate is observed around TTR aggregates. Here we show that as compared to Wild Type (WT) animals, the expression of several chemokines is highly downregulated in the peripheral nervous system of a mouse model of the disease. Interestingly, we found that stimulation of mouse Schwann cells (SCs) with WT TTR results in the secretion of several chemokines, a process that is mediated by toll-like receptor 4 (TLR4). In contrast, the secretion of all tested chemokines is compromised upon stimulation of SCs with mutant TTR (V30M), suggesting that V30M TTR fails to activate TLR4 signaling. Altogether, our data shed light into a previously unappreciated mechanism linking TTR activation of SCs and possibly underlying the lack of inflammatory response observed in the peripheral nervous system of ATTRv patients.
How Parenting Styles Link Career Decision-Making Difficulties in Chinese College Students? The Mediating Effects of Core Self-Evaluation and Career Calling

The purpose of this study was to explore the relationship between parenting styles and career decision-making difficulties in college students, and uncovered the mediating roles of core self-evaluation and career calling. A total of 1,127 undergraduates were recruited to complete the questionnaires about parenting styles, core self-evaluation, career calling, and career decision-making difficulties. The results showed that: (1) Positive and negative parenting styles could positively predict career decision-making difficulties in college students. (2) Core self-evaluation and career calling mediated the relationship between parenting styles and career decision-making difficulties. Sequential dual mediators only found in which positive paternal and maternal parenting styles predict career decision-making difficulties through core self-evaluation and career calling. (3) Further analysis revealed gender difference in the relationship between parenting styles and career decision-making difficulties. The relation between paternal positive parenting style and career decision-making difficulties was significant in male students, but absent in female students; the relation between maternal positive parenting and career decision-making difficulties and the relation between paternal negative parenting and career calling were significant in female students, but absent in male students; and the relation between career calling and career decision-making difficulties was greater in male than in female. The current study expanded and deepened those existing understandings about the relationship between parenting styles and adolescents’ career decisions, so as to further reveal its internal mechanism and provide more reasonable suggestions and targeted guidance for career counseling.
Facile Synthesis of Pd@PtM (M = Rh, Ni, Pd, Cu) Multimetallic Nanorings as Efficient Catalysts for Ethanol Oxidation Reaction

Pt-based multimetallic nanorings with a hollow structure are attractive as advanced catalysts due to their fantastic structure feature. However, the general method for the synthesis of such unique nanostructures is still lack. Here we report the synthesis of Pd@PtM (M = Rh, Ni, Pd, Cu) multimetallic nanorings by selective epitaxial growth of Pt alloyed shells on the periphery of Pd nanoplates in combination with oxidative etching of partial Pd in the interior. In situ generation of CO and benzoic acid arising from interfacial catalytic reactions between Pd nanoplates and benzaldehyde are critical to achieve high-quality Pt-based multimetallic nanorings. Specifically, the in-situ generated CO promotes the formation of Pt alloyed shells and their epitaxial growth on Pd nanoplates. In addition, the as-formed benzoic acid and residual oxygen are responsible for selective oxidative etching of partial Pd in the interior. When evaluated as electrocatalysts, the Pd@PtRh nanorings exhibit remarkably enhanced activity and stability for ethanol oxidation reaction (EOR) compared to the Pd@PtRh nanoplates and commercial Pt/C due to their hollow nanostructures.
Co-expression Network Revealed Roles of RNA m6A Methylation in Human β-Cell of Type 2 Diabetes Mellitus

RNA m6A methylation plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). RNA modifications and RNA-modifying regulators have recently emerged as critical factors involved in β-cell function and insulin resistance, including “writers,” “erasers,” and “readers. ” However, their key roles in regulating gene expression in T2DM remain unclear. The construction of co-expression network could provide a cue to resolve this complex regulatory pathway. We collected the transcriptome datasets of β-cell in diabetic patients, calculated the partial correlation coefficient, excluded the influence from control variables of diabetes related genes, and identified the genes significantly co-expressed with m6A regulators. A total of 985 genes co-expressed with m6A regulators (Co-m6AR) were identified, which were enriched in metabolic process, MAPK and EGFR signaling pathways. Some of them have been confirmed to play a pivotal role in T2DM, including CCNL2, CSAD, COX5A, GAB2, and MIRLET7I, etc. Further, we analyzed the m6A modification characteristics of Co-m6AR in β-cell and identified 228 Co-m6AR containing m6A methylation sites, involving in several key signaling pathways regulating T2DM. We finally screened out 13 eQTL-SNPs localized in Co-m6ARs, and 4 have been reported strongly associated with diabetes, including GAB2, LMNB2, XAB2, and RBM39. This co-expression analysis provides important information to reveal the potential regulatory mechanism of RNA m6A methylation in T2DM.
Tau Pathology Profile Across a Parietal-Hippocampal Brain Network Is Associated With Spatial Reorientation Learning and Memory Performance in the 3xTg-AD Mouse

In early Alzheimer's disease (AD) spatial navigation is one of the first impairments to emerge; however, the precise cause of this impairment is unclear. Previously, we showed that, in a mouse model of tau and amyloid beta (Aβ) aggregation, getting lost represents, at least in part, a failure to use distal cues to get oriented in space and that impaired parietal-hippocampal network level plasticity during sleep may underlie this spatial disorientation. However, the relationship between tau and amyloid beta aggregation in this brain network and impaired spatial orientation has not been assessed. Therefore, we used several approaches, including canonical correlation analysis and independent components analysis tools, to examine the relationship between pathology profile across the parietal-hippocampal brain network and spatial reorientation learning and memory performance. We found that consistent with the exclusive impairment in 3xTg-AD 6-month female mice, only 6-month female mice had an ICA identified pattern of tau pathology across the parietal-hippocampal network that were positively correlated with behavior. Specifically, a higher density of pTau positive cells predicted worse spatial learning and memory. Surprisingly, despite a lack of impairment relative to controls, 3-month female, as well as 6- and 12- month male mice all had patterns of tau pathology across the parietal-hippocampal brain network that are predictive of spatial learning and memory performance. However, the direction of the effect was opposite, a negative correlation, meaning that a higher density of pTau positive cells predicted better performance. Finally, there were not significant group or region differences in M78 density at any of the ages examined and ICA analyses were not able to identify any patterns of 6E10 staining across brain regions that were significant predictors of behavioral performance. Thus, the pattern of pTau staining across the parietal-hippocampal network is a strong predictor of spatial learning and memory performance, even for mice with low levels of tau accumulation and intact spatial re-orientation learning and memory. This suggests that AD may cause spatial disorientation as a result of early tau accumulation in the parietal-hippocampal network.