Functional network modules overlap and are linked to interindividual connectome differences during human brain development.

The modular structure of functional connectomes in the human brain undergoes substantial reorganization during development. However, previous studies have implicitly assumed that each region participates in one single module, ignoring the potential spatial overlap between modules. How the overlapping functional modules develop and whether this development is related to gray and white matter features remain unknown. Using longitudinal multimodal structural, functional, and diffusion MRI data from 305 children (aged 6 to 14 years), we investigated the maturation of overlapping modules of functional networks and further revealed their structural associations. An edge-centric network model was used to identify the overlapping modules, and the nodal overlap in module affiliations was quantified using the entropy measure. We showed a regionally heterogeneous spatial topography of the overlapping extent of brain nodes in module affiliations in children, with higher entropy (i.e., more module involvement) in the ventral attention, somatomotor, and subcortical regions and lower entropy (i.e., less module involvement) in the visual and default-mode regions. The overlapping modules developed in a linear, spatially dissociable manner, with decreased entropy (i.e., decreased module involvement) in the dorsomedial prefrontal cortex, ventral prefrontal cortex, and putamen and increased entropy (i.e., increased module involvement) in the parietal lobules and lateral prefrontal cortex. The overlapping modular patterns captured individual brain maturity as characterized by chronological age and were predicted by integrating gray matter morphology and white matter microstructural properties. Our findings highlight the maturation of overlapping functional modules and their structural substrates, thereby advancing our understanding of the principles of connectome development.

Red and far-red light improve the antagonistic ability of Trichoderma guizhouense against phytopathogenic fungi by promoting phytochrome-dependent aerial hyphal growth.

Light as a source of information regulates morphological and physiological processes of fungi, including development, primary and secondary metabolism, or the circadian rhythm. Light signaling in fungi depends on photoreceptors and downstream components that amplify the signal to govern the expression of an array of genes. Here, we investigated the effects of red and far-red light in the mycoparasite Trichoderma guizhouense on its mycoparasitic potential. We show that the invasion strategy of T. guizhouense depends on the attacked species and that red and far-red light increased aerial hyphal growth and led to faster overgrowth or invasion of the colonies. Molecular experiments and transcriptome analyses revealed that red and far-red light are sensed by phytochrome FPH1 and further transmitted by the downstream MAPK HOG pathway and the bZIP transcription factor ATF1. Overexpression of the red- and far-red light-induced fluffy gene fluG in the dark resulted in abundant aerial hyphae formation and thereby improvement of its antagonistic ability against phytopathogenic fungi. Hence, light-induced fluG expression is important for the mycoparasitic interaction. The increased aggressiveness of fluG-overexpressing strains was phenocopied by four random mutants obtained after UV mutagenesis. Therefore, aerial hyphae formation appears to be a trait for the antagonistic potential of T. guizhouense.

MyoV: a deep learning-based tool for the automated quantification of muscle fibers.

Accurate approaches for quantifying muscle fibers are essential in biomedical research and meat production. In this study, we address the limitations of existing approaches for hematoxylin and eosin-stained muscle fibers by manually and semiautomatically labeling over 660 000 muscle fibers to create a large dataset. Subsequently, an automated image segmentation and quantification tool named MyoV is designed using mask regions with convolutional neural networks and a residual network and feature pyramid network as the backbone network. This design enables the tool to allow muscle fiber processing with different sizes and ages. MyoV, which achieves impressive detection rates of 0.93-0.96 and precision levels of 0.91-0.97, exhibits a superior performance in quantification, surpassing both manual methods and commonly employed algorithms and software, particularly for whole slide images (WSIs). Moreover, MyoV is proven as a powerful and suitable tool for various species with different muscle development, including mice, which are a crucial model for muscle disease diagnosis, and agricultural animals, which are a significant meat source for humans. Finally, we integrate this tool into visualization software with functions, such as segmentation, area determination and automatic labeling, allowing seamless processing for over 400 000 muscle fibers within a WSI, eliminating the model adjustment and providing researchers with an easy-to-use visual interface to browse functional options and realize muscle fiber quantification from WSIs.

Decoding the temporal structures and interactions of multiple face dimensions using optically pumped magnetometer magnetoencephalography (OPM-MEG).

Humans possess a remarkable ability to rapidly access diverse information from others' faces with just a brief glance, which is crucial for intricate social interactions. While previous studies using event-related potentials/fields have explored various face dimensions during this process, the interplay between these dimensions remains unclear. Here, by applying multivariate decoding analysis to neural signals recorded with optically pumped magnetometer magnetoencephalography (OPM-MEG), we systematically investigated the temporal interactions between invariant and variable aspects of face stimuli, including race, gender, age and expression. First, our analysis revealed unique temporal structures for each face dimension with high test-retest reliability. Notably, expression and race exhibited a dominant and stably maintained temporal structure according to temporal generalization analysis. Further exploration into the mutual interactions among face dimensions uncovered age effects on gender and race, as well as expression effects on race, during the early stage (around 200-300 ms post face presentation). Additionally, we observed a relatively late effect of race on gender representation, peaking around 350 ms after stimulus onset. Taken together, our findings provide novel insights into the neural dynamics underlying the multi-dimensional aspects of face perception and illuminate the promising future of utilizing OPM-MEG for exploring higher-level human cognition.Significance statement In everyday social activities, people can quickly interpret a wide range of information from others' faces. Although converging evidence has shed light upon the neural substrates underpinning the perception of invariant and variable aspects of faces, such as race, gender, age and expression, it is still not fully understood how the information of one face dimension alters the perception of another. In this study, we utilized multivariate decoding analysis on neural activity captured through OPM-MEG during face perception. Our approach enabled a comprehensive exploration of the temporal interactions among different face dimensions, providing an improved understanding of the temporally structured neural dynamics that support the multi-dimensional face perception in the human brain.

Molecular mechanisms underlying low temperature inhibition of grain filling in maize (Zea mays L.): coordination of growth and cold responses.

Low temperature (LT) greatly restricts grain filling in maize (Zea mays L.), but the relevant molecular mechanisms are not fully understood. To better understand the effect of LT on grain development, 17 hybrids were subjected to LT stress in field trials over 3 years, and two hybrids of them with contrasting LT responses were exposed to 30/20°C and 20/10°C for 7 days during grain filling in a greenhouse. At LT, thousand-kernel weight declined, especially in LT-sensitive hybrid FM985, while grain-filling rate was on average about 48% higher in LT-tolerant hybrid DK159 than FM985. LT reduced starch synthesis in kernel mainly by suppression of transcript levels and enzyme activities for sucrose synthase and hexokinase. Brassinolide (BR) was abundant in DK159 kernel, and genes involved in BR and cytokinin signals were inducible by stress. LT downregulated the genes in light-harvesting complex and photosystem I/II subunits, accompanied by reduced photosynthetic rate and Fv/Fm in ear leaf. The LT-tolerant hybrid could maintain a high soluble sugar content and fast interconversion between sucrose and hexose in the stem internode and cob, improving assimilate allocation to kernel at LT stress and paving the way for simultaneous growth and LT stress responses.

Complexity of fungal polyketide biosynthesis and function.

Where does one draw the line between primary and secondary metabolism? The answer depends on the perspective. Microbial secondary metabolites (SMs) were at first believed not to be very important for the producers because they are dispensable for growth under laboratory conditions. However, such compounds become important in natural niches of the organisms, and some are of prime importance for humanity. Polyketides are an important group of SMs with aflatoxin as a well-known and well-characterized example. In Aspergillus spp., all 34 afl genes encoding the enzymes for aflatoxin biosynthesis are located in close vicinity on chromosome III in a so-called gene cluster. This led to the assumption that most genes required for polyketide biosynthesis are organized in gene clusters. Recent research, however, revealed an enormous complexity of the biosynthesis of different polyketides, ranging from individual polyketide synthases to a gene cluster producing several compounds, or to several clusters with additional genes scattered in the genome for the production of one compound. Research of the last decade furthermore revealed a huge potential for SM biosynthesis hidden in fungal genomes, and methods were developed to wake up such sleeping genes. The analysis of organismic interactions starts to reveal some of the ecological functions of polyketides for the producing fungi.

Comprehensive analysis of the m6A demethylase FTO in endothelial dysfunction by MeRIP sequencing.

N6-methyladenosine (m6A) is the most general post-transcriptional modification of eukaryotic mRNAs and long-stranded non-coding RNAs. In this process, It has been shown that FTO associates with the m6A mRNA demethylase and plays a role in diabetic vascular endothelial dysfunction. In the present study, we detected FTO protein expression in HUVECs by Western blot and found that FTO was highly expressed in all disease groups relative to the control group. To explore the mechanism of FTO in T2DM vasculopathy, we performed an analysis by methylated RNA immunoprecipitation sequencing (MeRIP-seq) to elucidate the role of aberrant m6A modification and mRNA expression in endothelial dysfunction. The results showed 202 overlapping genes with varying m6A modifications and varied mRNA expression, and GO and KEGG enrichment analysis revealed that these genes were predominantly enriched in pathways associated with T2DM complications and endothelial dysfunction. By an integrated analysis of MeRIP-seq and RNA-seq results, the IGV plots showed elevated kurtosis of downstream candidate gene modifications, which may be downstream targets for FTO to exercise biological functions. HOXA9 and PLAU mRNA expression levels were significantly down after FTO inhibition. In the current work, we set up a typological profile of the m6A genes among HUVECs as well as uncovered a hidden relationship between RNA methylation modifications for T2DM vasculopathy-associated genes. Taken together, this study indicates that endothelial functional impairment is present in T2DM patients and may be related to aberrant expression of FTO.

Theta Signal Transfer from Parietal to Prefrontal Cortex Ignites Conscious Awareness of Implicit Knowledge during Sequence Learning.

Unconscious acquisition of sequence structure from experienced events can lead to explicit awareness of the pattern through extended practice. Although the implicit-to-explicit transition has been extensively studied in humans using the serial reaction time (SRT) task, the subtle neural activity supporting this transition remains unclear. Here, we investigated whether frequency-specific neural signal transfer contributes to this transition. A total of 208 participants (107 females) learned a sequence pattern through a multisession SRT task, allowing us to observe the transitions. Session-by-session measures of participants' awareness for sequence knowledge were conducted during the SRT task to identify the session when the transition occurred. By analyzing time course RT data using switchpoint modeling, we identified an increase in learning benefit specifically at the transition session. Electroencephalogram (EEG)/magnetoencephalogram (MEG) recordings revealed increased theta power in parietal (precuneus) regions one session before the transition (pretransition) and a prefrontal (superior frontal gyrus; SFG) one at the transition session. Phase transfer entropy (PTE) analysis confirmed that directional theta transfer from precuneus → SFG occurred at the pretransition session and its strength positively predicted learning improvement at the subsequent transition session. Furthermore, repetitive transcranial magnetic stimulation (TMS) modulated precuneus theta power and altered transfer strength from precuneus to SFG, resulting in changes in both transition rate and learning benefit at that specific point of transition. Our brain-stimulation evidence supports a role for parietal → prefrontal theta signal transfer in igniting conscious awareness of implicitly acquired knowledge.SIGNIFICANCE STATEMENT There exists a pervasive phenomenon wherein individuals unconsciously acquire sequence patterns from their environment, gradually becoming aware of the underlying regularities through repeated practice. While previous studies have established the robustness of this implicit-to-explicit transition in humans, the refined neural mechanisms facilitating conscious access to implicit knowledge remain poorly understood. Here, we demonstrate that prefrontal activity, known to be crucial for conscious awareness, is triggered by neural signal transfer originating from the posterior brain region, specifically the precuneus. By employing brain stimulation techniques, we establish a causal link between neural signal transfer and the occurrence of awareness. Our findings unveil a mechanism by which implicit knowledge becomes consciously accessible in human cognition.

Abscisic acid collaborates with lignin and flavonoid to improve pre-silking drought tolerance by tuning stem elongation and ear development in maize (Zea mays L.).

Drought is a major abiotic stress reducing maize (Zea mays) yield worldwide especially before and during silking. The mechanism underlying drought tolerance in maize and the roles of different organs have not been elucidated. Hence, we conducted field trials under pre-silking drought conditions using two maize genotypes: FM985 (drought-tolerant) and ZD958 (drought-sensitive). The two genotypes did not differ in plant height, grain number, and yield under control conditions. However, the grain number per ear and the yield of FM985 were 38.1 and 35.1% higher and plants were 17.6% shorter than ZD958 under drought conditions. More 13 C photosynthates were transported to the ear in FM985 than in ZD958, which increased floret fertility and grain number. The number of differentially expressed genes was much higher in stem than in other organs. Stem-ear interactions are key determinants of drought tolerance, in which expression of genes related to abscisic acid, lignin, and flavonoid biosynthesis and carbon metabolism in the stem was induced by drought, which inhibited stem elongation and promoted assimilate allocation to the ear in FM985. In comparison with ZD958, the activities of trehalose 6-phosphate phosphatase and sucrose non-fermentation-associated kinase 1 were higher in the stem and lower in the kernel of FM985, which facilitated kernel formation. These results reveal that, beyond the ear response, stem elongation is involved in the whole process of drought tolerance before silking. Abscisic acid together with trehalose 6-phosphate, lignin, and flavonoid suppresses stem elongation and allocates assimilates into the ear, providing a novel and systematic regulatory pathway for drought tolerance in maize.

HvGST plays a key role in anthocyanin accumulation in colored barley.

Blue aleurone of barley is caused by the accumulation of delphinidin-based derivatives. Although these compounds are ideal nutrients for human health, they are undesirable contaminants in malt brewing. Therefore, the ability to add and remove this trait easily would facilitate breeding barley for different purposes. Here we identified a glutathione S-transferase gene (HvGST) that was responsible for the blue aleurone trait in Tibetan qingke barley by performing a genome-wide association study and RNA-sequencing analysis. Gene variation and expression analysis indicated that HvGST also participates in the transport and accumulation of anthocyanin in purple barley. Haplotype and the geographic distribution analyses of HvGST alleles revealed two independent natural variants responsible for the emergence of white aleurone: a 203-bp deletion causing premature termination of translation in qingke barley and two key single nucleotide polymorphisms in the promoter resulting in low transcription in Western barley. This study contributes to a better understanding of mechanisms of colored barley formation, and provides a comprehensive reference for marker-assisted barley breeding.

The dorsomedial prefrontal cortex promotes self-control by inhibiting the egocentric perspective.

The dorsomedial prefrontal cortex (dmPFC) plays a crucial role in social cognitive functions, including perspective-taking. Although perspective-taking has been linked to self-control, the mechanism by which the dmPFC might facilitate self-control remains unclear. Using the multimodal neuroimaging dataset from the Human Connectome Project (Study 1, N =978 adults), we established a reliable association between the dmPFC and self-control, as measured by discounting rate-the tendency to prefer smaller, immediate rewards over larger, delayed ones. Experiments (Study 2, N = 36 adults) involving high-definition transcranial direct current stimulation showed that anodal stimulation of the dmPFC reduces the discounting of delayed rewards and decreases the congruency effect in egocentric but not allocentric perspective in the visual perspective-taking tasks. These findings suggest that the dmPFC promotes self-control by inhibiting the egocentric perspective, offering new insights into the neural underpinnings of self-control and perspective-taking, and opening new avenues for interventions targeting disorders characterized by impaired self-regulation.

Higher emotional synchronization is modulated by relationship quality in romantic relationships and not in close friendships.

Emotions are fundamental to social interaction and deeply intertwined with interpersonal dynamics, especially in romantic relationships. Although the neural basis of interaction processes in romance has been widely explored, the underlying emotions and the connection between relationship quality and neural synchronization remain less understood. Our study employed EEG hyperscanning during a non-interactive video-watching paradigm to compare the emotional coordination between romantic couples and close friends. Couples showed significantly greater behavioral and prefrontal alpha synchronization than friends. Notably, couples with low relationship quality required heightened neural synchronization to maintain robust behavioral synchronization. Further support vector machine analysis underscores the crucial role of prefrontal activity in differentiating couples from friends. In summary, our research addresses gaps concerning how intrinsic emotions linked to relationship quality influence neural and behavioral synchronization by investigating a natural non-interactive context, thereby advancing our understanding of the neural mechanisms underlying emotional coordination in romantic relationships.

Wireless optically pumped magnetometer MEG.

The current magnetoencephalography (MEG) systems, which rely on cables for control and signal transmission, do not fully realize the potential of wearable optically pumped magnetometers (OPM). This study presents a significant advancement in wireless OPM-MEG by reducing magnetization in the electronics and developing a tailored wireless communication protocol. Our protocol effectively eliminates electromagnetic interference, particularly in the critical frequency bands of MEG signals, and accurately synchronizes the acquisition and stimulation channels with the host computer's clock. We have successfully achieved single-channel wireless OPM-MEG measurement and demonstrated its reliability by replicating three well-established experiments: The alpha rhythm, auditory evoked field, and steady-state visual evoked field in the human brain. Our prototype wireless OPM-MEG system not only streamlines the measurement process but also represents a major step forward in the development of wearable OPM-MEG applications in both neuroscience and clinical research.

Deciphering the Kinetics of Spontaneous Generation of H2O2 in Individual Water Microdroplets.

Spontaneous generation of H2O2 in sub-10 µm-sized water microdroplets has received increasing interest since its first discovery in 2019. On the other hand, due to the short lifetime of these microdroplets (rapid evaporation) and lack of suitable tools to real-time monitor the generation of H2O2 in individual microdroplets, such a seemingly thermodynamically unfavorable process has also raised vigorous debates on the origin of H2O2 and the underlying mechanism. Herein, we prepared water microdroplets with a long lifetime (>1 h) by virtue of microwell confinement and dynamically monitored the spontaneous generation of H2O2 in individual microdroplets via time-lapsed fluorescence imaging. It was unveiled that H2O2 was continuously generated in the as-prepared water microdroplets and an apparent equilibrium concentration of ∼3 µM of H2O2 in the presence of a H2O2-consuming reaction can be obtained. Through engineering the geometry of these microdroplets, we further revealed that the generation rates of H2O2 in individual microdroplets were positively proportional to their surface-to-volume ratios. This also allowed us to extract a maximal H2O2 generation rate of 7.7 nmol m-2 min-1 in the presence of a H2O2-consuming reaction and derive the corresponding probability of spontaneous conversion of interfacial H2O into H2O2 for the first time, that is, ∼1 of 65,000 water molecules in 1 s. These findings delivered strong evidence that the spontaneous generation of H2O2 indeed occurs at the surface of microdroplets and provided us with an important starting point to further enhance the yield of H2O2 in water microdroplets for future applications.

Age-related decline in melatonin contributes to enhanced osteoclastogenesis via disruption of redox homeostasis.

BACKGROUND: Increased oxidative stress contributes to enhanced osteoclastogenesis and age-related bone loss. Melatonin (MT) is an endogenous antioxidant and declines with aging. However, it was unclear whether the decline of MT was involved in the enhanced osteoclastogenesis during the aging process. METHODS: The plasma level of MT, oxidative stress status, bone mass, the number of bone marrow-derived monocytes (BMMs) and its osteoclastogenesis were analyzed in young (3-month old) and old (18-month old) mice (n = 6 per group). In vitro, BMMs isolated from aged mice were treated with or without MT, followed by detecting the change of osteoclastogenesis and intracellular reactive oxygen species (ROS) level. Furthermore, old mice were treated with MT for 2 months to investigate the therapeutic effect. RESULTS: The plasma level of MT was markedly lower in aged mice compared with young mice. Age-related decline in MT was accompanied by enhanced oxidative stress, osteoclastogenic potential and bone loss. MT intervention significantly suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, decreased intracellular ROS and enhanced antioxidant capacity of BMMs from aged mice. MT supplementation significantly attenuated oxidative stress, osteoclastogenesis, bone loss and deterioration of bone microstructure in aged mice. CONCLUSIONS: These results suggest that age-related decline of MT enhanced osteoclastogenesis via disruption of redox homeostasis. MT may serve as a key regulator in osteoclastogenesis and bone homeostasis, thereby highlighting its potential as a preventive agent for age-related bone loss.

Optically Imaging In Situ Effects of Electrochemical Cycling on Single Nanoparticle Electrocatalysis.

Single-nanoparticle studies often need one or a series of nanoparticle populations that are designed with differences in a nominally particular structural parameter to clarify the structure-activity relationship (SAR). However, the heterogeneity of various properties within any population would make it rather difficult to approach an ideal one-parameter control. In situ modification ensures the same nanoparticle to be investigated and also avoids complicating effects from the otherwise often needed ex situ operations. Herein, we apply electrochemical cycling to single platinum nanoparticles and optically examine their SAR. An electrocatalytic fluorescent microscopic method is established to evaluate the apparent catalytic activity of a number of single nanoparticles toward the oxygen reduction reaction. Meanwhile, dark-field microscopy with the substrate electrode under a cyclic potential control is found to be able to assess the electrochemically active surface area (ECSA) of single nanoparticles via induced chloride redox electrochemistry. Consequently, nanoparticles with drastically increased catalytic activity are discovered to have larger ECSAs upon potential regulation, and interestingly, there are also a few particles with decreased activity, as opposed to the overall trend, that all develop a smaller ECSA in the process. The deactivated nanoparticles against the overall enhancement effects of potential cycling are revealed for the first time. As such, the SAR of single nanoparticles when subjected to an in situ structural control is optically demonstrated.

Brain-age prediction: Systematic evaluation of site effects, and sample age range and size.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

The neural and genetic underpinnings of different developmental trajectories of Attention-Deficit/Hyperactivity Symptoms in children and adolescents.

BACKGROUND: The trajectory of attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents, encompassing descending, stable, and ascending patterns, delineates their ADHD status as remission, persistence or late onset. However, the neural and genetic underpinnings governing the trajectory of ADHD remain inadequately elucidated. METHODS: In this study, we employed neuroimaging techniques, behavioral assessments, and genetic analyses on a cohort of 487 children aged 6-15 from the Children School Functions and Brain Development project at baseline and two follow-up tests for 1 year each (interval 1: 1.14 ± 0.32 years; interval 2: 1.14 ± 0.30 years). We applied a Latent class mixed model (LCMM) to identify the developmental trajectory of ADHD symptoms in children and adolescents, while investigating the neural correlates through gray matter volume (GMV) analysis and exploring the genetic underpinnings using polygenic risk scores (PRS). RESULTS: This study identified three distinct trajectories (ascending-high, stable-low, and descending-medium) of ADHD symptoms from childhood through adolescence. Utilizing the linear mixed-effects (LME) model, we discovered that attention hub regions served as the neural basis for these three developmental trajectories. These regions encompassed the left anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), responsible for inhibitory control; the right inferior parietal lobule (IPL), which facilitated conscious focus on exogenous stimuli; and the bilateral middle frontal gyrus/precentral gyrus (MFG/PCG), accountable for regulating both dorsal and ventral attention networks while playing a crucial role in flexible modulation of endogenous and extrinsic attention. Furthermore, our findings revealed that individuals in the ascending-high group exhibited the highest PRS for ADHD, followed by those in the descending-medium group, with individuals in the stable-low group displaying the lowest PRS. Notably, both ascending-high and descending-medium groups had significantly higher PRS compared to the stable-low group. CONCLUSIONS: The developmental trajectory of ADHD symptoms in the general population throughout childhood and adolescence can be reliably classified into ascending-high, stable-low, and descending-medium groups. The bilateral MFG/PCG, left ACC/mPFC, and right IPL may serve as crucial brain regions involved in attention processing, potentially determining these trajectories. Furthermore, the ascending-high pattern of ADHD symptoms exhibited the highest PRS for ADHD.

Fibrotic Matrix Induces Mesenchymal Transformation of Epithelial Cells in Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.

Comparative single-cell RNA sequencing analysis of immune response to inactivated vaccine and natural SARS-CoV-2 infection.

Uncovering the immune response to an inactivated SARS-CoV-2 vaccine (In-Vac) and natural infection is crucial for comprehending COVID-19 immunology. Here we conducted an integrated analysis of single-cell RNA sequencing (scRNA-seq) data from serial peripheral blood mononuclear cell (PBMC) samples derived from 12 individuals receiving In-Vac compared with those from COVID-19 patients. Our study reveals that In-Vac induces subtle immunological changes in PBMC, including cell proportions and transcriptomes, compared with profound changes for natural infection. In-Vac modestly upregulates IFN-α but downregulates NF-κB pathways, while natural infection triggers hyperactive IFN-α and NF-κB pathways. Both In-Vac and natural infection alter T/B cell receptor repertoires, but COVID-19 has more significant change in preferential VJ gene, indicating a vigorous immune response. Our study reveals distinct patterns of cellular communications, including a selective activation of IL-15RA/IL-15 receptor pathway after In-Vac boost, suggesting its potential role in enhancing In-Vac-induced immunity. Collectively, our study illuminates multifaceted immune responses to In-Vac and natural infection, providing insights for optimizing SARS-CoV-2 vaccine efficacy.