Frontoparietal and salience network synchronizations during nonsymbolic magnitude processing predict brain age and mathematical performance in youth.

The development and refinement of functional brain circuits crucial to human cognition is a continuous process that spans from childhood to adulthood. Research increasingly focuses on mapping these evolving configurations, with the aim to identify markers for functional impairments and atypical development. Among human cognitive systems, nonsymbolic magnitude representations serve as a foundational building block for future success in mathematical learning and achievement for individuals. Using task-based frontoparietal (FPN) and salience network (SN) features during nonsymbolic magnitude processing alongside machine learning algorithms, we developed a framework to construct brain age prediction models for participants aged 7-30. Our study revealed differential developmental profiles in the synchronization within and between FPN and SN networks. Specifically, we observed a linear increase in FPN connectivity, concomitant with a decline in SN connectivity across the age span. A nonlinear U-shaped trajectory in the connectivity between the FPN and SN was discerned, revealing reduced FPN-SN synchronization among adolescents compared to both pediatric and adult cohorts. Leveraging the Gradient Boosting machine learning algorithm and nested fivefold stratified cross-validation with independent training datasets, we demonstrated that functional connectivity measures of the FPN and SN nodes predict chronological age, with a correlation coefficient of .727 and a mean absolute error of 2.944 between actual and predicted ages. Notably, connectivity within the FPN emerged as the most contributing feature for age prediction. Critically, a more matured brain age estimate is associated with better arithmetic performance. Our findings shed light on the intricate developmental changes occurring in the neural networks supporting magnitude representations. We emphasize brain age estimation as a potent tool for understanding cognitive development and its relationship to mathematical abilities across the critical developmental period of youth. PRACTITIONER POINTS: This study investigated the prolonged changes in the brain's architecture across childhood, adolescence, and adulthood, with a focus on task-state frontoparietal and salience networks. Distinct developmental pathways were identified: frontoparietal synchronization strengthens consistently throughout development, while salience network connectivity diminishes with age. Furthermore, adolescents show a unique dip in connectivity between these networks. Leveraging advanced machine learning methods, we accurately predicted individuals' ages based on these brain circuits, with a more mature estimated brain age correlating with better math skills.

The visuo-sensorimotor substrate of co-speech gesture processing.

Co-speech gestures are integral to human communication and exhibit diverse forms, each serving a distinct communication function. However, existing literature has focused on individual gesture types, leaving a gap in understanding the comparative neural processing of these diverse forms. To address this, our study investigated the neural processing of two types of iconic gestures: those representing attributes or event knowledge of entity concepts, beat gestures enacting rhythmic manual movements without semantic information, and self-adaptors. During functional magnetic resonance imaging, systematic randomization and attentive observation of video stimuli revealed a general neural substrate for co-speech gesture processing primarily in the bilateral middle temporal and inferior parietal cortices, characterizing visuospatial attention, semantic integration of cross-modal information, and multisensory processing of manual and audiovisual inputs. Specific types of gestures and grooming movements elicited distinct neural responses. Greater activity in the right supramarginal and inferior frontal regions was specific to self-adaptors, and is relevant to the spatiomotor and integrative processing of speech and gestures. The semantic and sensorimotor regions were least active for beat gestures. The processing of attribute gestures was most pronounced in the left posterior middle temporal gyrus upon access to knowledge of entity concepts. This fMRI study illuminated the neural underpinnings of gesture-speech integration and highlighted the differential processing pathways for various co-speech gestures.

Interval timing relative to response inhibition in the differential reinforcement of low-rate responding in normally developing young adults.

With recent proposal suggesting the multifaceted nature of impulsivity, researchers have been intrigued by the question of whether the impulsive behaviour measured in the traditionally psychological paradigms is unitary. One such paradigm, the differential reinforcement of low-rate responding (DRL), has been used to assess response inhibition, but its underlying mechanism has still been debated. In present research, we examined and differentiated the effects of both response inhibition and interval timing on a multisession DRL-10 s (DRL-10 s) in a large sample of normally developing young adults, as well as with three other measures including the stop-signal reaction task (SSRT), time production task-10 s (TPT-10 s), and the Barrett impulsivity scale-11 (BIS-11). The results showed that behavioural changes existed in DRL. As the task sessions progressed, there was an increase in both reinforcement probability and peak time, but a decrease in burst responses. Most importantly, both principal component analysis and generalized multilevel modeling yielded consistent results that as the task progressed, there was an increasing involvement of the TPT in the late sessions of DRL. However, none of the effect of SSRT was found. In sum, the differential degrees of involvement of the timing process, relative to response inhibition, were observed in DRL.

Evaluation of math anxiety and its remediation through a digital training program in mathematics for first and second graders.

INTRODUCTION: Math anxiety severely impacts individuals' learning and future success. However, limited is understood about the profile in East Asian cultures where students genuinely show high-level math anxiety, despite that they outperform their Western counterparts. Here, we investigate the relation between math anxiety and math achievement in children as young as first and second graders in Taiwan. Further, we evaluate whether intensive exposure to digital game-based learning in mathematics could ameliorate math anxiety. METHODS: The study first evaluated a group of 159 first and second graders' math anxiety and its correlation with math performance. Subsequently, a quasi-experimental design was adopted: 77 of the children continued and participated in multi-component digital game training targeting enumeration, speeded calculation, and working memory. Post-assessment was administered afterward for further evaluation of training-associated effects. RESULTS: Results confirmed that math anxiety was negatively associated with school math achievement, which assessed numerical knowledge and arithmetic calculation. Furthermore, children's math anxiety was remarkably reduced via digital training in mathematics after 6-week intensive remediation. Crucially, this math anxiety relief was more prominent in those with high-level math anxiety. Although the children who underwent the training showed training-induced math achievement and working memory enhancement, this cognitive improvement appeared to be independent of the math anxiety relief. CONCLUSION: Our findings demonstrate that students can show highly negative emotions and perceptions toward learning even in high-achieving countries. Auspiciously, the feeling of distress toward learning has the feasibility to be relieved from short-term intensive training. Our study suggests a new approach of early treatments to emotional disturbance that can lead to permanent consequences in individuals.

Targeting Indoleamine 2,3-Dioxygenase 1: Fighting Cancers via Dormancy Regulation.

The connection between indoleamine 2,3-dioxygenase 1 (IDO1) and tumour dormancy - a quiescent state of tumour cells which has been consistently linked to metastasis and cancer recurrence - is rarely discussed despite the pivotal role of IDO1 in cancer development and progression. Whilst the underlying mechanisms of IDO1-mediated dormancy are elusive, we summarize the IDO1 pathways which potentially contribute to dormancy in this review. Critically, distinct IDO1 activities are involved in dormancy initiation and maintenance; factors outside the well-studied IDO1/kynurenine/aryl hydrocarbon receptor axis, including the mammalian target of rapamycin and general control nonderepressible 2, appear to be implicated in dormancy. We also discuss various strategies for cancer treatment via regulating IDO1-dependent dormancy and suggest the application of nanotechnology to deliver effective treatment.

Operation-Specific Lexical Consistency Effect in Fronto-Insular-Parietal Network During Word Problem Solving.

The practice of mathematical word problem is ubiquitous and thought to impact academic achievement. However, the underlying neural mechanisms are still poorly understood. In this study, we investigate how lexical consistency of word problem description is modulated in adults' brain responses during word problem solution. Using functional magnetic resonance imaging methods, we examined compare word problems that included relational statements, such as "A dumpling costs 9 dollars. A wonton is 2 dollars less than a dumpling. How much does a wonton cost?" and manipulated lexical consistency (consistent: the relational term consistent with the operation to be performed, e.g., more-addition/inconsistent: e.g., less-addition) and problem operation (addition/subtraction). We found a consistency by operation interaction in the widespread fronto-insular-parietal activations, including the anterior insula, dorsoanterior cingulate cortex, middle frontal gyrus, and intraparietal sulcus, such that inconsistent problems engaged stronger activations than consistent problems for addition, whereas the consistency effect was inverse for subtraction. Critically, these results were more salient in the less successful problem solvers than their more successful peers. Our study is the first to demonstrate that lexical consistency effects on arithmetic neural networks are modulated during reading word problem that required distinct arithmetic operations. More broadly, our study has strong potentials to add linkage between neuroscience and education by remediating deficits and enhance instruction design in the school curriculum.

Uncovering mechanisms of greengage wine fermentation against acidic stress via genomic, transcriptomic, and metabolic analyses of Saccharomyces cerevisiae.

Acid stress is one of the most common adverse conditions during fermentation of fruit wines, and the acid tolerance of yeasts is, therefore, critical for fruit wine production. However, the biological mechanism underlying the acquired tolerance of yeasts against acid stress is poorly understood. We have previously obtained an evolved Saccharomyces cerevisiae strain ET008-c54 with increased tolerance against acid stress, and potentially, it serves as a promising yeast strain for greengage wine fermentation. In the current study, we further revealed the alterations responsible for the adaptation of ET008-c54 to low pH by whole-genome re-sequencing, transcriptomic, and metabolic analyses. Results confirmed the outstanding fermenting performance of ET008-c54 at low pH as compared with the parental ET008. More specifically, the growth rate of ET008-c54 at low pH was increased by 6.24 times and the fermentation time was shortened by 70%. Differences were also observed in the physiology of the strains through ergosterol, H+-ATPase activity, and aroma determinations. By integrating both RNA-seq and whole-genome re-sequencing data, we demonstrated some metabolic pathways in ET008-c54, namely ergosterol synthesis and ferrous iron uptake, in which several acid-responsive genes were involved being upregulated. Also, upregulation of the pathways responsible for aroma compound formation, including fatty acid ethyl ester synthesis and aromatic amino acid biosynthesis, was identified. Thus, the enhanced fermentation ability of ET008-c54 at low pH should be, at least partly, contributed by the altered gene expressions associated with the aforementioned pathways. By elucidating the biological mechanism of yeasts against acid stress, this current study allows better-defined targets for future studies of genetic improvement of wine yeasts and enhancement of the fermentation processes. KEY POINTS: • Metabolic analysis confirmed the excellent fermentation performance of ET008-c54. • Acid tolerance genes for ergosterol synthesis and ferrous iron uptake were upregulated. • Aroma genes for fatty acid ethyl ester and aromatic amino acid synthesis were upregulated.

A multiple-step strategy for screening Saccharomyces cerevisiae strains with improved acid tolerance and aroma profiles.

Acid tolerance and aroma profile are crucial factors for wine production in Saccharomyces cerevisiae. However, most wine yeasts to date fail to endure low-pH environments, therefore resulting in problems such as lengthened fermentation and poor flavor during acidic fruit wine production. In the present study, we established a multiple-step screening strategy, which was composed of atmospheric and room temperature plasma (ARTP), high-throughput screening (HTS), and laboratory adaptive evolution (ALE), to screen yeast strains for potential wine-producing with enhanced performances during low pH conditions. Importantly, we obtained the S. cerevisiae strain from the mutant library, ET008-c54, which displayed exhibited excellent performances in survival rate, fermentation time, aroma profile, and genetic stability. More specifically, the survival rate of ET008-c54 at low pH was increased by 10-fold, the fermentation time of greengage plum wine was shortened by about 70%, and the content of main aroma compounds was significantly increased by 52%. Collectively, we demonstrate the practical application of the screening platform designed for discovering mutant strains in winemaking technology.

Fronto-insular-parietal network engagement underlying arithmetic word problem solving.

Mathematical word problems are ubiquitous and standard for teaching and evaluating generalization of mathematical knowledge for real-world contexts. It is therefore concerning that the neural mechanisms of word problem solving are not well understood, as these insights represent strong potential for improving education and remediating deficits in this domain. Here, we investigate neural response to word problems via functional magnetic resonance imaging (fMRI). Healthy adults performed sentence judgment tasks on word problems that either contained one-step mathematical operations, or nonarithmetic judgments on parallel narratives without any numerical information. Behavioral results suggested that the composite efficiency measurement of combining accuracy and RT did not differ between the two problem types. Arithmetic sentence judgments elicited greater activation in the fronto-insular-parietal network including intraparietal sulcus (IPS), dorsolateral prefrontal cortex (PFC), and anterior insula (AI) than narrative sentence judgment. Narrative sentence judgments, conversely, resulted in greater activation predominantly in the left ventral PFC, angular gyrus and perisylvian cortex compared with reading arithmetic sentences. Moreover, task-dependent functional connectivity analyses showed the AI circuits were more strongly coupled with IPS during arithmetic sentence judgments than nonarithmetic sentences. Finally, activations in the IPS during arithmetic were highly correlated with out-of-scanner performance on a distinct set of problems with the same characteristics. These results show arithmetic word problem performance differences may rely more heavily on fronto-insular-parietal circuits for mathematical model building than narrative text comprehension of similar difficulty. More broadly, our study suggests that quantitative measurements of brain mechanisms can provide pivotal role for uncovering crucial arithmetic skills.

Identification of an Iridium(III)-Based Inhibitor of Tumor Necrosis Factor-α.

The novel iridium(III) complex 1 was verified as a potent inhibitor of the TNF-α-TNFR protein-protein interaction in vitro and in cellulo. The iridium(III) center plays a critical role in organizing the structure of the bioactive metal complex, as the isolated ligands were found to be completely inactive. Both iridium enantiomers inhibited TNF-α-induced NF-κB activity and TNF-α-TNFR binding. 1 represents a promising scaffold for the further development of more potent organometallic TNF-α inhibitors.

Rhodium complexes as therapeutic agents.

The landscape of inorganic medicinal chemistry has been dominated by the investigation of platinum, and to a lesser extent ruthenium, complexes over the past few decades. Recently, complexes based on other metal centers such as rhodium have attracted attention due to their tunable chemical and biological properties as well as distinct mechanisms of action. This perspective highlights recent examples of rhodium complexes that show diverse biological activities against various targets, including enzymes and protein-protein interactions.