Search bioRxiv⌕ Search

Biology subjects

Gong, G.

Publications and source records attributed to Gong, G..

15 recordsLinked to original sources

Pediatric brain charts reveal ADHD biotypes with distinct developmental, molecular, and therapeutic profiles

Attention-deficit/hyperactivity disorder (ADHD) exhibits profound clinical heterogeneity; however, its underlying neurobiological substrates remain unclear. Here, leveraging large - scale structural magnetic resonance imaging data from 12,663 typically developing children and 1,699 children with ADHD across Chinese and United States cohorts, we construct population specific pediatric brain charts via hierarchical Bayesian normative modeling to quantify individual deviations in cortical morphology. Data-driven clustering identifies two robust, cross - ethnically replicable ADHD biotypes: an infra - normal biotype characterized by widespread cortical thinning and a supra - normal biotype marked by cortical thickening. Multivariate analyses reveal distinct brain-behavior architectures: cortical deviations correlate preferentially with symptom severity in the infra-normal biotype but with both symptom severity and cognitive performance in the supranormal biotype. Clinically, the infra-normal biotype demonstrates a superior response to methylphenidate over atomoxetine, whereas the supra-normal biotype responds comparably to both. Transcriptomic analyses identify biotype-specific molecular signatures converging with ADHD genome-wide association study (GWAS) risk loci but exhibiting distinct expression patterns in the brain. These findings classify ADHD heterogeneity into neurobiologically distinct, clinically informed biotypes, providing a mechanistic framework for precision psychiatry in pediatric ADHD.

neuroscience↗

Adaptive Laboratory Evolution (ALE) enables carbon-negative mixotrophic fermentation and enhanced chain elongation in Clostridium sp. JS66

Improving carbon recovery during sugar fermentation remains a major challenge because a substantial fraction of substrate carbon is lost as CO2 during central metabolism. To overcome this limitation, Clostridium sp. JS66 (JS66), an acetogen producing hexanoic acid from glucose, was subjected to adaptive laboratory evolution under CO2/H2 conditions to enhance H2-assisted CO2 reassimilation during glucose fermentation. The evolved strain, ALECO2, exhibited CO2 consumption without a lag phase under autotrophic conditions and reached a 9.5-fold higher CO2 uptake rate than JS66. Under fed-batch conditions, glucose-only fermentation yielded a carbon molar yield (Cmetabolite/Csugar, CM/CS) of 0.60, whereas H2 supplementation increased CM/CS to 0.91 and redirected carbon flux toward C6 products (hexanoic acid and hexanol), which accounted for 49% of total C_output. With additional CO2 supplementation, ALECO2 further assimilated externally supplied CO2, increasing the CM/CS to 1.10 and demonstrating carbon-negative fermentation. Assimilation of externally supplied CO2 further redirected carbon flux toward chain elongation, producing 7.14 g/L hexanoic acid and increasing the C6 carbon fraction to 57% of total C_output. Constraint-based flux analysis supported increased acetyl-CoA formation through the Wood-Ljungdahl pathway and enhanced flux toward reverse {beta}-oxidation under H2- and CO2/H2-supplemented conditions. Genome analysis identified mutations including genes encoding a putative HytB homolog and a LysR-type transcriptional regulator. These results establish ALECO2 as a promising evolved anaerobic non-photosynthetic (ANP) mixotrophy platform that links CO2 reassimilation and external CO2 assimilation with chain elongation, enabling carbon-neutral and carbon-negative production of value-added C6 products from glucose.

bioengineering↗

Structural brain networks shape individual-level progression of brain atrophy after stroke

Stroke starts as a focal vascular lesion, but its structural consequences often extend beyond the lesion site, resulting in distributed brain atrophy whose organizing principles remain unclear. Here, using longitudinal MRI data from two stroke cohorts spanning the hyperacute to chronic stages, we tested whether and how post-stroke grey matter volume (GMV) change over time is constrained by large-scale brain networks across individuals. Coordinated deformation modelling showed that longitudinal GMV atrophy patterns were more strongly shaped by structural than by functional connectivity, with structural constraints already detectable in the acute phase. Network diffusion modelling further showed that atrophy patterns at 3 and 12 months were consistent with lesion-initiated propagation on the structural connectome, whereas model performance was weak in the early acute stage. The model-derived propagation stage did not increase monotonically with chronological time, indicating that it reflects the degree to which observed atrophy conforms to a network-consistent diffusion-like pattern rather than elapsed biological time. Inter-individual variation in propagation stage was associated with lesion size and with the topological and molecular properties of lesioned regions. Finally, lesion information combined with network diffusion modelling supported individualized prediction of later GMV atrophy patterns. These findings provide a network-based account of secondary degeneration after stroke and may inform individualized characterization of post-stroke structural reorganization.

neuroscience↗

Arousal modulates functional connectivity through structured and hemispherically asymmetric community architecture during wakefulness

Arousal fluctuates continuously during wakefulness, yet how these moment-to-moment variations shape large-scale functional connectivity (FC) remains unclear. Here, we combined 7T fMRI with concurrent pupillometry to quantify, for every functional connection, how time-varying FC covaries with spontaneous arousal in the awake human brain. Rather than exerting a uniform influence across the connectome, arousal organized FC into a low-dimensional set of seven connectivity communities, each defined by characteristic network compositions. These communities exhibited systematic hemispheric asymmetries, specifically identifying a "left-hemisphere centripetal architecture" where the left hemisphere serves as a structural sink for the asymmetric convergence of arousal-modulated signals. Importantly, hemispheric asymmetry did not arise from global shifts in connectivity strength, but instead reflected structured spatial heterogeneity embedded within community architecture. This modular and asymmetric organization was highly preserved during naturalistic movie watching, indicating that arousal-related modulation of FC reflects intrinsic principles that generalize across awake cognitive contexts. Together, these findings demonstrate that moment-to-moment arousal fluctuations shape large-scale FC through structured, hemispherically asymmetric network organization during wakefulness.

neuroscience↗

A multivariate pattern metric of individualized hemispheric functional asymmetry

Functional asymmetry is a fundamental feature of human brain organization, yet existing measures of functional connectivity asymmetry rely mainly on univariate indices that miss distributed pattern structure. We introduce the Pattern Dissimilarity of Hemispheric Functional Connectivity (PDHC), a multivariate metric that quantifies the pattern-level distance between each individuals left- and right-hemisphere connectivity architecture. In over one thousand adults, PDHC showed high test-retest reliability, cross-atlas robustness, and strong individual specificity. Network analyses indicated that hemispheric similarity is anchored in conserved sensorimotor and subcortical systems, whereas higher-order networks drive divergence. Developmental data from infancy through early adulthood revealed a characteristic trajectory: dissimilarity declines sharply early in life and increases modestly thereafter. Twin and Turner syndrome samples further demonstrated moderate heritability and sensitivity to X-chromosome dosage. PDHC thus provides a reliable and individualized metric of hemispheric functional architecture, offering a scalable tool for probing lateralization across development, genetics, cognition, and clinical conditions.

neuroscience↗

Population-level super-pangenome reveals genome evolution and empowers precision breeding in watermelon

Pangenomes are increasingly critical for harnessing crop genetic diversity, yet their resolution and utility are often limited by insufficient sampling of high-quality genome assemblies. Here, we report a population-level watermelon super-pangenome constructed from 138 reference-grade assemblies, including 135 newly generated near-gapless genomes representing all seven watermelon species. The super-pangenome captures approximately one million structural variants (SVs), enabling accurate variant genotyping across ~900 watermelon accessions and substantially expanding variant discovery both across and within species. Broader sampling within the pangenome provides insights into genome evolution among watermelon species and sheds light on the origin of cultivated watermelon. SV-inclusive genome-wide association studies enhance trait mapping resolution and identify a copy number variation upstream of ClFCI1 that regulates flesh color intensity in a dosage-dependent manner. Leveraging this comprehensive variation map, we developed high-accuracy genomic prediction models for 18 agronomic traits. Together, our findings and genomic resources establish a foundational framework for dissecting complex traits and accelerating precision breeding in watermelon, while offering a valuable model for SV-resolved pangenomics in crop species.

plant biology↗

Functional divergence between the two cerebral hemispheres contributes to human fluid intelligence

Hemispheric lateralization is linked to potential cognitive advantages. It is considered a driving force behind the generation of human intelligence. However, establishing quantitative links between the degree of lateralization and intelligence in humans remains elusive. In this study, we propose a framework that utilizes the functional aligned multidimensional representation space derived from hemispheric functional gradients to compute between-hemisphere distances within this space. Applying this framework to a large cohort (N=777 from the Human Connectome Project), we identified high functional divergence across the two hemispheres within the frontoparietal control network. We found that both global divergence between the cerebral hemispheres and regional divergence within the multiple demand network were positively associated with fluid composite score and partially mediated the influence of brain size on individual differences in fluid intelligence. Together, these findings illuminate the profound significance of brain lateralization as a fundamental organizational principle of the human brain, providing direct evidence that hemispheric lateralization supports human fluid intelligence.

neuroscience↗

Gap-free X and Y chromosomes of Salix arbutifolia reveal an evolutionary change from male to female heterogamety in willows, without a change in the sex-determining region

In the Vetrix clade of Salix, a genus of woody flowering plants, sex determination involves chromosome 15, but an XY system has changed to a ZW system. We used genome sequencing (with chromosome conformation capture (Hi-C) and PacBio HiFi high-fidelity reads) to study the evolutionary history of the sex-linked regions before and after the transition. We assembled chromosome level gap-free X and Y chromosomes of Salix arbutifolia, and distinguished the haplotypes in the 15X- and 15Y-linked regions. This revealed "micro-heteromorphism" differentiating the haplotypes of the Y- and X-linked regions, including insertions, deletions and duplications. Unusually, the X-linked region is considerably larger than the corresponding Y region, and we show that this primarily reflects extensive accumulation of repetitive sequences and gene duplications. The phylogenies of single-copy orthogroups within the sex-linked regions of S. arbutifolia (X and Y) and S. purpurea (Z and W) indicate that they possess a common ancestral sex-linked region that is physically small and located in a repeat-rich region near the chromosome 15 centromere. During the change in heterogamety, the W-linked region was derived from the X-linked one and the Z from the Y. The W may subsequently have evolved a region in which recombination became suppressed. We also detected accumulation of genes with opposite sex-biases in the sex-linked regions.

plant biology↗

Functional connectome through the human life span

The lifespan growth of the functional connectome remains unknown. Here, we assemble task-free functional and structural magnetic resonance imaging data from 33,250 individuals aged 32 postmenstrual weeks to 80 years from 132 global sites. We report critical inflection points in the nonlinear growth curves of the global mean and variance of the connectome, peaking in the late fourth and late third decades of life, respectively. After constructing a fine-grained, lifespan-wide suite of system-level brain atlases, we show distinct maturation timelines for functional segregation within different systems. Lifespan growth of regional connectivity is organized along a primary-to-association cortical axis. These connectome-based normative models reveal substantial individual heterogeneities in functional brain networks in patients with autism spectrum disorder, major depressive disorder, and Alzheimers disease. These findings elucidate the lifespan evolution of the functional connectome and can serve as a normative reference for quantifying individual variation in development, aging, and neuropsychiatric disorders.

neuroscience↗

Longitudinal structural change of gray matter before and after hemispherotomy

BackgroundHemispherotomy is an effective surgery developed to treat refractory epilepsy caused by diffuse unihemispheric pathologies. Post-surgery neuroplastic mechanisms supporting behavioral recovery after left and right hemispherotomy as well as their difference remain largely unclear. MethodsIn a large cohort of 57 pediatric patients who underwent hemispherotomy, voxel-wise GMV in unaffected regions (contralesional cerebrum and bilateral cerebellum) and behavioral abilities were assessed before and after surgery. Using linear mixed models, we evaluated changes in GMV and behavioral scores, and how GMV changes correlated with improvements in behavioral scores. In addition, three machine learning regression algorithms were applied to assess whether preoperative GMV can predict postoperative behavior. ResultsIn the two patient groups (29 left hemispherotomy patients, age of surgery mean {+/-} standard deviation = 3.5 {+/-} 2.5; 28 right hemispherotomy patients, age of surgery 4.6 {+/-} 2.5), widespread increases in the postoperative GMV in the contralateral cerebrum and ipsilateral cerebellum but decreases in the postoperative GMV in the contralateral cerebellum were consistently observed. Importantly, the decrease in GMV in the contralateral cerebellum was significantly correlated with improvement in behavioral scores in right but not left hemispherotomy patients. Moreover, the preoperative GMV around the most longitudinally changed locations significantly predicted postoperative behavioral scores in left but not right hemispherotomy patients. ConclusionsOur findings indicate an important role for the contralateral cerebellum in the recovery after right hemispherotomy, and postoperative behavioral scores can be predicted with preoperative GMV features. What is already known on this topicThe contralesional cerebrum plays a key role in the recovery after hemispherotomy. What this study addsDespite suffering from gray matter atrophy, GMV decrease in contralesional cerebellum is associated with improvement in behavioral score in patients after hemispherotomy. How this study might affect research, practice or policyThese results provide novel insight into the prominence of the contralateral cerebellum in the recovery after hemispherotomy and highlight the clinical role of presurgery GMV in the prediction of postsurgery behavior.

neuroscience↗

Development of Functional Connectome Gradients during Childhood and Adolescence

Connectome mapping studies have documented a principal primary-to-transmodal gradient in the adult brain network, capturing a functional spectrum which ranges from perception and action to abstract cognition. However, how this gradient pattern develops and whether its development is linked to cognitive growth, topological reorganization, and gene expression profiles remain largely unknown. Using longitudinal resting-state functional magnetic resonance imaging data from 305 children (ages 6-14), we describe substantial changes in the primary-to-transmodal gradient between childhood and adolescence, including emergence as the principal gradient, expansion of global topography, and focal tuning in primary and default-mode regions. These gradient changes are mediated by developmental changes in network integration and segregation, and are associated with abstract processing functions such as working memory and expression levels of calcium ion regulated exocytosis, synaptic transmission, and axon and synapse part related genes. Our findings have implications for understanding connectome maturation principles in normal development and developmental disorders. TeaserOur study reported the maturation of the core connectome gradient and its association with cognitions and genes expression.

neuroscience↗

Callosal fiber length scales with brain size according to functional lateralization, evolution, and development

Brain size significantly impacts the organization of white matter fibers. Fiber length scaling - the degree to which fiber length varies according to brain size - was overlooked. We investigated how fiber lengths within the corpus callosum, the most prominent white matter tract, vary according to brain size. The results showed substantial variation in length scaling among callosal fibers, replicated in two large healthy cohorts ([~]2000 individuals). The underscaled callosal fibers mainly connected the precentral gyrus and parietal cortices, whereas the overscaled callosal fibers mainly connected the prefrontal cortices. The variation in such length scaling was biologically meaningful: larger scaling corresponded to larger neurite density index but smaller fractional anisotropy values; cortical regions connected by the callosal fibers with larger scaling were more lateralized functionally as well as phylogenetically and ontogenetically more recent than their counterparts. These findings highlight an interaction between interhemispheric communication and organizational and adaptive principles underlying brain development and evolution. Significance StatementBrain size varies across evolution, development, and individuals. Relative to small brains, the neural fiber length in large brains is inevitably increased, but the degree of such increase may differ between fiber tracts. Such a difference, if it exists, is valuable for understanding adaptive neural principles in large versus small brains during evolution and development. The present study showed a substantial difference in the length increase between the callosal fibers that connect the two hemispheres, replicated in two large healthy cohorts. Altogether, our study demonstrates that reorganization of interhemispheric fibers length according to brain size is intrinsically related to fiber composition, functional lateralization, cortical myelin content, evolutionary and developmental expansion.

neuroscience↗

Divergent Connectional Asymmetries of the Inferior Parietal Lobule Shape Hemispheric Specialization in Humans, Chimpanzees, and Macaque Monkeys

The inferior parietal lobule (IPL) is one of the most expanded cortical regions in humans relative to other primates. It is also among the most structurally and functionally asymmetric regions in the human cerebral cortex. Whether the structural and connectional asymmetries of IPL subdivisions differ across primate species and how this relates to functional asymmetries remain unclear. We identified IPL subregions that exhibited positive allometric in both hemispheres, scaling across rhesus macaque monkeys, chimpanzees, and humans. The patterns of IPL subregions asymmetry were similar in chimpanzees and humans, but no IPL asymmetries were evident in macaques. Among the comparative sample of primates, humans showed the most widespread asymmetric connections in the frontal, parietal, and temporal cortices, constituting leftward asymmetric networks that may provide an anatomical basis for language and tool use. Unique human asymmetric connectivity between the IPL and primary motor cortex might be related to handedness. These findings suggest that structural and connectional asymmetries may underlie hemispheric specialization of the human brain.

neuroscience↗

Improving multi-site autism classification based on site-dependence minimisation and second-order functional connectivity

Autism spectrum disorder (ASD) has no objective diagnosis method despite having a high prevalence. Machine learning has been widely used to develop classification models for ASD using neuroimaging data. Recently, studies have shifted towards using large multi-site neuroimaging datasets to boost the clinical applicability and statistical power of results. However, the classification performance is hindered by the heterogeneous nature of agglomerative datasets. In this paper, we propose new methods for multi-site autism classification using the Autism Brain Imaging Data Exchange (ABIDE) dataset. We firstly propose a new second-order measure of functional connectivity (FC) named as Tangent Pearson embedding to extract better features for classification. Then we assess the statistical dependence between acquisition sites and FC features, and apply a domain adaptation approach to minimise the site dependence of FC features to improve classification. Our analysis shows that 1) statistical dependence between site and FC features is statistically significant at the 5% level, and 2) extracting second-order features from neuroimaging data and minimising their site dependence can improve over state-of-the-art classification results on the ABIDE dataset, achieving a classification accuracy of 73%.

neuroscience↗

Karyotype stability and unbiased fractionation in the paleo-allotetraploid Cucurbita genomes

The Cucurbita genus contains several economically important species in the Cucurbitaceae family. Interspecific hybrids between C. maxima and C. moschata are widely used as rootstocks for other cucurbit crops. We report high-quality genome sequences of C. maxima and C. moschata and provide evidence supporting an allotetraploidization event in Cucurbita. We are able to partition the genome into two homoeologous subgenomes based on different genetic distances to melon, cucumber and watermelon in the Benincaseae tribe. We estimate that the two diploid progenitors successively diverged from Benincaseae around 31 and 26 million years ago (Mya), and the allotetraploidization happened earlier than 3 Mya, when C. maxima and C. moschata diverged. The subgenomes have largely maintained the chromosome structures of their diploid progenitors. Such long-term karyotype stability after polyploidization is uncommon in plant polyploids. The two subgenomes have retained similar numbers of genes, and neither subgenome is globally dominant in gene expression. Allele-specific expression analysis in the C. maxima x C. moschata interspecific F1 hybrid and the two parents indicates the predominance of trans-regulatory effects underlying expression divergence of the parents, and detects transgressive gene expression changes in the hybrid correlated with heterosis in important agronomic traits. Our study provides insights into plant genome evolution and valuable resources for genetic improvement of cucurbit crops.

genomics↗