Biology subjects

Cui, Z.

Publications and source records attributed to Cui, Z..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Small Extracellular Vesicles from Human Bone Marrow Mesenchymal Stromal Cells enhance migration and regulate gene expression of reparative mechanisms in human dermal fibroblasts

Studies have showed that mesenchymal stromal cells (MSCs) could secrete a variety of bioactive particles, including small extracellular vesicles (sEVs), a type of membrane bound vesicle produced by cells, that might be a key intermediate to the beneficial paracrine effects of MSC therapy. In this study, we harvested the conditioned medium (CM) from both human bone marrow mesenchymal stromal cells (hBM-MSCs) and normal human dermal fibroblasts (NHDFs), fractionated CM of each into the sEV fraction and non-small extracellular vesicle (NsEV) fraction and compared their functions on NHDF-based migration and proliferation assays, as crucial processes in wound healing, coupled with transcriptomic analysis through mRNA sequencing to assess the regulation on gene expression of the recipient NHDFs by secretome exposure. Our findings show that both sEV and NsEV as well as CM from hBM-MSCs showed an overall promotive effect on migration behaviour of NHDFs, but MSC-sEV seems to be more potent for NHDF migration among different MSC secretome fractions and is also superior in effect to the corresponding sEVs produced by the recipient NHDFs (HDF-sEV). Gene ontology analysis revealed enrichment of pathways related to migration, corroborating in vitro results; changes in genes within the regulation of proliferation pathway were also significant. Our study provides referential significance for the choice of cellular secretome fractions to be used in wound healing studies and trials. The secretome fractionation and functional comparison strategy using cell-based model and comparative transcriptomics analysis would be a useful tool for comprehensive functional evaluation of cellular secretome.

cell biology↗

bioRxiv2024

Structural connectivity matures along a sensorimotor-association connectional axis in youth

Childhood and adolescence are marked by protracted developmental remodeling of cortico-cortical structural connectivity. However, the spatiotemporal variability of white matter connectivity development across the human connectome and its relevance to cognition and psychopathology remains unclear. Using diffusion MRI data from three independent developmental cohorts spanning youth, we identified a robust divergence in structural connectivity maturation along a predefined sensorimotor-association (S-A) connectional axis during youth (http://connectcharts.cibr.ac.cn). This developmental continuum ranged from early childhood increases in sensorimotor-sensorimotor connectivity strength to late adolescent increases in association-association connectivity strength, with the transition occurring around age 15. The S-A connectional axis also captured spatial variations in the associations between structural connectivity and both higher-order cognition and general psychopathology. Moreover, group-level developmental trajectories of structural connectivity differed by cognitive and psychopathological levels, with psychopathological effects predominantly observed in association connections. These findings delineate a spatiotemporal continuum of structural connectivity development during youth, providing a normative reference for quantifying developmental variability in psychiatric disorders.

neuroscience↗

bioRxiv2024

Unveiling the Core Functional Networks of Cognition: An Ontology-Guided Machine Learning Approach

Deciphering the functional architecture that underpins diverse cognitive functions is fundamental quest in neuroscience. In this study, we employed an innovative machine learning framework that integrated cognitive ontology with functional connectivity analysis to identify brain networks essential for cognition. We identified a core assembly of functional connectomes, primarily located within the association cortex, which showed superior predictive performance compared to two conventional methods widely employed in previous research across various cognitive domains. Our approach achieved a mean prediction accuracy of 0.13 across 16 cognitive tasks, including working memory, reading comprehension, and sustained attention, outperforming the traditional methods accuracy of 0.08. In contrast, our method showed limited predictive power for sensory, motor, and emotional functions, with a mean prediction accuracy of 0.03 across 9 relevant tasks, slightly lower than the traditional methods accuracy of 0.04. These cognitive connectomes were further characterized by distinctive patterns of resting-state functional connectivity, structural connectivity via white matter tracts, and gene expression, highlighting their neurogenetic underpinnings. Our findings reveal a domain-general functional network fingerprint that pivotal to cognition, offering a novel computational approach to explore the neural foundations of cognitive abilities.

neuroscience↗

bioRxiv2024

Normative growth modeling of brain morphology reveals neuroanatomical heterogeneity and biological subtypes in children with ADHD

BackgroundNeuroimaging studies suggest substantial individual heterogeneity in brain phenotypes in attention-deficit/hyperactivity disorder (ADHD). However, how these individual-level brain phenotypes contribute to the identification of ADHD biotypes and whether these biotypes have different treatment outcomes and neurobiological underpinnings remain largely unknown. MethodsWe collected multisite, high-quality structural magnetic resonance imaging data from 1,006 children aged 6-14 years, including 351 children with ADHD and 655 typically developing children. Normative growth models of cortical thickness were established for 219 regions in the typically developing children. Individual-level deviations from these normal references were quantified and clustered to identify ADHD biotypes. We validated the replicability and generalizability of the ADHD biotypes using two independent datasets and evaluated the associations of the biotypes with symptomatic, cognitive, and gene expression profiles, as well as follow-up treatment outcomes. FindingsNo more than 10% of children with ADHD had extreme deviations in cortical thickness in a single region, suggesting high heterogeneity among individuals with ADHD. On the basis of the brain deviation maps, we discovered two robust ADHD biotypes, an infra-normal subtype with cortical thinning associated with ADHD symptoms and a supranormal subtype with cortical thickening associated with cognition. Patients with the infra-normal subtype responded better to methylphenidate than to atomoxetine, although both subtypes showed treatment efficacy. Brain deviations in the infra-normal subtype were explained by the expression levels of genes enriched in presynaptic and axonal development and polygenic risk of ADHD. InterpretationWe identified anatomically distinct, clinically valuable, and biologically informed ADHD subtypes, providing insight into the neurobiological basis of clinical heterogeneity and facilitating a personalized medication strategy for ADHD patients. Panel: Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSubstantial individual heterogeneity in brain phenotypes in attention-deficit/hyperactivity disorder (ADHD) motivates the need to discover homogeneous biotypes. We searched PubMed for research articles on ADHD biotypes using brain MRI published before December 1, 2023, using the search terms ((attention deficit hyperactivity disorder [Title/Abstract]) OR (ADHD [Title/Abstract])) AND ((subtypes [Title/Abstract]) OR (subgroups [Title/Abstract]) OR (subtyping [Title/Abstract])) AND ((MRI [Title/Abstract]) OR (neuroimaging [Title/Abstract]) OR (brain [Title/Abstract])) without language restrictions. Of the eight included studies, two identified ADHD biotypes using structural morphology, four used functional activity, and two used multimodal features. However, none of these studies considered the developmental effect of the brain phenotypes, examined treatment response, or investigated the genetic correlates of the biotypes. Added value of this studyThis study is the first to use individualized brain measures extracted from normative models to investigate ADHD biotypes in a large sample of more than 1,000 children. We identified two reproducible ADHD biotypes, characterized by distinct symptomatic, cognitive, and gene expression profiles, as well as differential treatment responses. This study advances our understanding of the neurobiological basis underlying the clinical heterogeneity of ADHD and highlights the critical need to discover ADHD biotypes using an unbiased and individualized approach. Implications of all the available evidenceThis study revealed remarkable neuroanatomical heterogeneity in ADHD patients and identified anatomically distinct, clinically valuable, and biologically informed ADHD biotypes. Our findings have potential value for the investigation of data-driven biotypes to evaluate treatment efficacy and facilitate personalized treatment. We also highlight the need for future studies to move beyond the understanding of ADHD solely based on the "average patient" perspective.

neuroscience↗

bioRxiv2023

Phylogeny-metabolism dual-directed single-cell genomics for dissecting and mining ecosystem function

Although microbiome-wide association studies (MWAS) have uncovered many marker organisms for an ecosystem trait, mechanisms of most microbiota-mediated processes remain elusive, due to challenges in validating the markers in situ metabolic activities and tracing such activities to individual genomes. Here we introduced a phylogeny-metabolism dual-directed single-cell genomics approach called Fluorescence-In-Situ-Hybridization-guided Single-Cell Raman-activated Sorting and Sequencing (FISH-scRACS-Seq). It directly localizes individual cells from target taxon via a FISH probe for marker organism, profiles their in situ metabolic functions via single-cell Raman spectra, sorts cells of target taxonomy and target metabolism, and produces indexed, high-coverage and precisely-one-cell genomes. From cyclohexane-contaminated seawater, cells representing the MWAS-derived marker taxon of {gamma}-Proteobacteria and that are actively degrading cyclohexane in situ were directly identified via FISH and Raman respectively, then sorted and sequenced for one-cell full genomes. In such a Pseudoalteromonas fuliginea cell, we discovered a three-component cytochrome P450 system that can convert cyclohexane to cyclohexanol in vitro, representing a previously unknown group of cyclohexane-degrading enzymes and organisms. By culture-independently unveiling enzymes, pathways, genomes and their in situ functions specifically for those single-cells with ecological relevance, FISH-scRACS-Seq is a rational and generally applicable approach for dissecting and mining microbiota functions. TeaserFISH-scRACS-Seq is a new strategy to dissect microbiota functional mechanism at single-cell resolution.

microbiology↗

bioRxiv2023

Group-common and individual-specific effects of structure-function coupling in human brain networks with graph neural networks

The human cerebral cortex is organized into functionally segregated but synchronized regions bridged by the structural connectivity of white matter pathways. While structure-function coupling has been implicated in cognitive development and neuropsychiatric disorders, it remains unclear to what extent the structure-function coupling reflects a group-common characteristic or varies across individuals, at both the global and regional brain levels. By leveraging two independent, high-quality datasets, we found that the graph neural network accurately predicted unseen individuals functional connectivity from structural connectivity, reflecting a strong structure-function coupling. This coupling was primarily driven by network topology and was substantially stronger than that of the correlation approaches. Moreover, we observed that structure-function coupling was dominated by group-common effects, with subtle yet significant individual-specific effects. The regional group and individual effects of coupling were hierarchically organized across the cortex along a sensorimotor-association axis, with lower group and higher individual effects in association cortices. These findings emphasize the importance of considering both group and individual effects in understanding cortical structure-function coupling, suggesting insights into interpreting individual differences of the coupling and informing connectivity-guided therapeutics.

neuroscience↗

bioRxiv2023

LightRoseTTA: High-efficient and Accurate Protein Structure Prediction Using an Ultra-Lightweight Deep Graph Model

Accurately predicting protein structure, from amino acid sequences to three-dimensional structures, is of great significance in biological research. To tackle this issue, a representative deep big model, RoseTTAFold, has been proposed with promising success. Here, we report an ultra-lightweight deep graph network, named LightRoseTTA, to achieve accurate and high-efficient prediction for proteins. Notably, three highlights are possessed by our LightRoseTTA: (i) high-accurate structure prediction for proteins, being competitive with RoseTTAFold on multiple popular datasets including CASP14 and CAMEO; (ii) high-efficient training and inference with an ultra-lightweight model, costing only one week on one single general NVIDIA 3090 GPU for model-training (vs 30 days on 8 high-speed NVIDIA V100 GPUs for RoseTTAFold) and containing only 1.4M parameters (vs 130M in RoseTTAFold); (iii) low dependency on multi-sequence alignments (MSA, widely-used homologous information), achieving the best performance on three MSA-insufficient datasets: Orphan, De novo, and Orphan25. Besides, our LightRoseTTA is transferable from general proteins to antibody data, as verified in our experiments. We visualize some case studies to demonstrate the high-quality prediction, and provide some insights on how the structure predictions facilitate the understanding of biological functions. We further make a discussion on the time and resource costs of LightRoseTTA and RoseTTAFold, and demonstrate the feasibility of lightweight models for protein structure prediction, which may be crucial in the resource-limited research for universities and academy institutions. We release our code and model to speed biological research.

bioinformatics↗

bioRxiv2023

Feasibility of intranasal delivery of thin-film freeze-dried monoclonal antibodies

Monoclonal antibodies (mAbs) administered intranasally as dry powders can be potentially applied for the treatment or pre-exposure prevention of viral infections in the upper respiratory tract. However, a method to transform the mAbs from liquid to dry powders suitable for intranasal administration and a device that can spray the dry powders to the desired region of the nasal cavity are needed to fully realize the potentials of the mAbs. Herein, we report that thin-film freeze-drying can be applied to prepare aerosolizable mAb dry powders and that the dry powders can be sprayed into the posterior nasal cavity using Aptar Pharmas Unidose (UDS) Powder Nasal Spray System. AUG-3387, a human-derived mAb that neutralizes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was used in the present study. First, we prepared AUG-3387 thin-film freeze-dried powders (i.e., TFF AUG-3387 powders) from liquid formulations containing different levels of mAbs. The TFF AUG-3387 powder with the highest solid content (i.e., TFF AUG-3387C powder) was then chosen for further characterization, including the evaluation of the plume geometry, spray pattern, and particle size distribution after the powder was sprayed using the UDS Powder device. Finally, the deposition patterns of the TFF AUG-3387C powder sprayed using the UDS Powder device were studied using 3D-printed nasal replica casts based on an adult model and a child model. It is concluded that it is feasible to intranasally deliver mAbs as dry powders by transforming the mAbs into dry powders using thin-film freeze-drying and then spray the powder using the UDS Powder device.

pharmacology and toxicology↗

bioRxiv2023

Cell-autonomous targeting of arabinogalactan by host immune factors inhibits mycobacterial growth

Deeper understanding of the crosstalk between host cells and Mycobacterium tuberculosis (Mtb) provides crucial guidelines for the rational design of novel intervention strategies against tuberculosis (TB). Mycobacteria possess a unique complex cell wall with arabinogalactan (AG) as critical component. AG has been identified as a virulence factor of Mtb which is recognized by host galectin-9. Here we demonstrate that galectin-9 directly inhibited mycobacterial growth through AG-binding property of carbohydrate-recognition domain 2. Furthermore, IgG antibodies with AG specificity were detected in serum of TB patients. Based on the interaction between galectin-9 and AG, we developed monoclonal antibody (mAb) screening assay and identified AG-specific mAbs which profoundly inhibit Mtb growth. Mechanistically, proteomic profiling and morphological characterizations revealed that AG-specific mAbs regulate AG biosynthesis, thereby inducing cell wall swelling. Thus, direct AG-binding by galectin-9 or antibodies contributes to protection against TB. Our findings pave the way for the rational design of novel immunotherapeutic strategies for TB control.

immunology↗

bioRxiv2023

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↗

bioRxiv2023

The brain's topographical organization shapes dynamic interaction patterns to support flexible behavior

Understanding how human cognition flexibly supports distinct forms of behavior is a key goal of neuroscience. Adaptive behavior relies on context-specific rules that vary across situations, as well as on stable knowledge gained from experience. However, the mechanisms that allow these influences to be appropriately balanced remain elusive. Here, we show that this cognitive flexibility is partly supported by the topographical organization of the cortex. The frontoparietal control network (FPCN) is located between regions implicated in top-down attention and memory-guided cognition. We hypothesized that the FPCN is topographically divided into discrete systems that support these distinct forms of behavior. These FPCN subsystems exhibit multiple anatomical and functional similarities to their neighboring systems (the dorsal attention network and default mode network respectively). This topographic architecture is also mirrored in the functional patterns that emerge in different situations: the FPCN subnetworks act as a unified system when long-term memory can support behavior, but they segregate into discrete units when working memory, rather than long term memory, is necessary for behavioral control. In this way, the topographic organization of brain function provides crucial insights into how the human cortex supports flexible behavior.

neuroscience↗

bioRxiv2023

A general exposome factor explains individual differences in functional brain network topography and cognition in youth

Our minds and brains are highly unique. Despite the long-recognized importance of the environment in shaping individual differences in cognitive neurodevelopment, only with the combination of deep phenotyping approaches and the availability of large-scale datasets have we been able to more comprehensively characterize the many inter-connected features of an individuals environment and experience ("exposome"). Moreover, despite clear evidence that brain organization is highly individualized, most neuroimaging studies still rely on group atlases to define functional networks, smearing away inter-individual variation in the spatial layout of functional networks across the cortex ("functional topography"). Here, we leverage the largest longitudinal study of brain and behavior development in the United States to investigate how an individuals exposome may contribute to functional brain network organization leading to differences in cognitive functioning. To do so, we apply three previously-validated data driven computational models to characterize an individuals multidimensional exposome, define individual-specific maps of functional brain networks, and measure cognitive functioning across broad domains. In pre-registered analyses replicated across matched discovery (n=5,139, 48.5% female) and replication (n=5,137, 47.1% female) samples, we find that a childs exposome is associated with multiple domains of cognitive functioning both at baseline assessment and two years later - over and above associations with baseline cognition. Cross-validated ridge regression models reveal that the exposome is reflected in childrens unique patterns of functional topography. Finally, we uncover both shared and unique contributions of the exposome and functional topography to cognitive abilities, finding that models trained on a single variable capturing a childs exposome can more accurately and parsimoniously predict future cognitive performance than models trained on a wealth of personalized neuroimaging data. This study advances our understanding of how childhood environments contribute to unique patterns of functional brain organization and variability in cognitive abilities.

neuroscience↗

bioRxiv2023

Pontiella agarivorans sp. nov., a novel marine anaerobic bacterium capable of degrading macroalgal polysaccharides and fixing nitrogen

Marine macroalgae produce abundant and diverse polysaccharides which contribute substantially to the organic matter exported to the deep ocean. Microbial degradation of these polysaccharides plays an important role in the turnover of macroalgal biomass. Various members of the Planctomycetes-Verrucomicrobia-Chlamydia (PVC) superphylum are degraders of recalcitrant polysaccharides in widespread anoxic environments. In this study, we isolated a novel anaerobic bacterial strain NLcol2T from microbial mats on the surface of marine sediments offshore Santa Barbara, California, USA. Based on 16S rRNA gene and phylogenomic analyses, strain NLcol2T represents a novel species within the Pontiella genus in the Kiritimaitellaeota phylum (within the PVC superphylum). Strain NLcol2T is able to utilize various monosaccharides, disaccharides, and macroalgal polysaccharides such as agar and iota-carrageenan. A near-complete genome also revealed an extensive metabolic capacity for anaerobic degradation of sulfated polysaccharides, as evidenced by 202 carbohydrate-active enzymes (CAZymes) and 165 sulfatases. Additionally, its ability of nitrogen fixation was confirmed by nitrogenase activity detected during growth on nitrogen-free medium, and the presence of nitrogenases (nifDKH) encoded in the genome. Based on the physiological and genomic analyses, this strain represents a group of bacteria that may play an important role in the degradation of macroalgal polysaccharides and with relevance to the biogeochemical cycling of carbon, sulfur, and nitrogen in marine environments. Strain NLcol2T (= DSM 113125T = MCCC 1K08672) is proposed to be the type strain of a novel species in Pontiella genus, and the name Pontiella agarivorans sp. nov. is proposed.

microbiology↗

bioRxiv2023

Impact of inter-species interactions between flower microbiota commensals and a floral pathogen on disease incidence and pathogen activity

Flowers are colonized by a diverse community of microorganisms that alter plant health and interact with floral pathogens. Erwinia amylovora is a flower-inhabiting bacterium and a pathogen that infects different plant species, including Malus x domestica (apple). Previously, we showed that the co-inoculation of two bacterial strains, Pseudomonas and Pantoea natural inhabitants of apple flowers, reduced disease incidence caused by this floral pathogen. Here, we decipher the ecological interactions between these two flower-associated bacteria and E. amylovora in field experimentation and in vitro co-cultures. The two flower microbiota strains did not competitively exclude E. amylovora from the stigma habitat, as both commensal bacteria and the pathogen co-existed on the apple flowers, proscribing microbial antibiosis or niche exclusion as predominant mechanisms of host protection. Inspection of the total and the active microbiota populations on flowers revealed that strain co-inoculations altered microbiota activity. Using synthetic stigma exudation medium, tripartite co-culture of the bacterial strains strongly acidified the growth milieu and led to a substantial alteration of gene expression in both the pathogen and the two microbiota members. Our study emphasizes the critical role of emergent properties mediated by inter-species interactions within the plant holobiont and their impact on plant health and pathogen behavior. ImportanceFire blight, caused by Erwinia amylovora, is one of the most important plant diseases of pome fruits. Plant-associated microbiota can influence plant disease occurrence through inter-species interactions. Previous studies have shown that plant microbiota commensals could suppress disease mainly by antagonizing of the pathogen growth, however, whether plant-associated microbiota could alter pathogen activity and behavior have not been well studied. Here, we show that the co-inoculation of two bacterial strains that naturally colonize the apple flowers reduce disease pressure. We further demonstrate that the interactions between these two microbiota commensals and the floral pathogen lead to a strong alteration of the pH and to the emergence of new gene expression patterns that may alter the pathogen behavior. Our findings emphasize the critical role of emergent properties mediated by inter-species interactions between plant microbiota and plant pathogens and their impact on plant health.

microbiology↗

bioRxiv2023

Standardizing and applying a mating-based whole-genome simulation approach reveals caution in using chromosome-level PCA and kinship estimates

This paper presents a new and efficient method for simulating pseudo-genotype data using the standardized protocol of SLiM, which offers a flexible alternative to traditional methods that rely on large genetic datasets. These datasets can be time-consuming to obtain, especially when institutional review board (IRB) review is involved, making simulation an attractive alternative. While HapGen v2 is the most popular genotype simulator, we found that SLiM has the potential for more customizable simulation to meet multiple needs. To validate our new method, we compared its performance among parallel simulations varying multiple parameters. Our results showed that SLiM is capable of simulating samples up to 333 times the input size, with a low rate of simulated samples that are 2nd or closer relatives (REV), making it a promising alternative to HapGen. We also applied our whole-genome simulation approach to sensitivity analyses of chromosome-level principal component analysis (PCA) and kinship estimation. Our findings revealed important insights into the sensitivity of PCA and kinship estimation, highlighting the unequal distribution of population structure across chromosomes and ancestries. Furthermore, our study provides experimental support for avoiding chromosome-level quality control statistics. Overall, our standardized protocol of SLiM offers a flexible new way to produce pseudo-genotype data, and our findings provide valuable insights that can advance research in the field. By demonstrating the potential of SLiM for more customizable simulations and highlighting the importance of considering the distribution of population structure across chromosomes and ancestries, our research has significant implications for the study of genetics and genomics. Author SummaryIn this publication, we introduce a novel approach to genotype simulation using a mating-based strategy in SLiM. Our approach mimics mitosis computationally and stands out as the only one available as of December 2022 that can maintain cross-chromosome associations during whole-genome level simulation, with no competitors in sight. Additionally, our approach is applicable to regional or chromosomal genotype simulation. When compared to the current gold-standard chromosome-level simulator, HapGen, our approach exhibits superior performance when generating large sample sizes (>13,000). We provide an application example that uses whole-genome simulation to underscore the importance of whole-genome quality control (QC) statistics, such as principal component analysis (PCA) and kinship estimates, compared to the chromosome-level ones. Results of the application indicate instability and bias in the chromosome-level QC statistics. Overall, our approach represents a valuable tool for genetics research that can assist in the evaluation and validation of genetic analyses, and people should avoid chromosome-level QC statistics.

bioinformatics↗

bioRxiv2023

Connectional Hierarchy in Human Brain Revealed by Individual Variability of Functional Network Edges

The human cerebral cortex exhibits intricate interareal functional synchronization at the macroscale, with substantial individual variability in these functional connections. However, the spatial organization of functional connectivity (FC) variability across the human connectome edges and its significance in cognitive development remain unclear. Here, we identified a connectional axis in the edge-level FC variability. The variability declined continuously along this axis from within-network to between-network connections, and from the edges linking association networks to those linking the sensorimotor and association networks. This connectional axis of functional variability is associated with spatial pattern of structural connectivity variability. Moreover, the connectional variability axis evolves in youth with an increasing flatter axis slope. We also observed that the slope of connectional variability axis was positively related to the performance in the higher-order cognition. Together, our results reveal a connectional axis in functional variability that is linked with structural connectome variability, refines during development, and is relevant to cognition. Significance StatementUnderstanding the spatial organization of inter-individual variability in functional connectivity across the human connectome can offer insights into which connections are most susceptible to insults and interventions. We identify a stable axis on functional connectome along which connectivity variability continuously varies, aligning with structural connectivity variability. We find that the pattern of this axis evolves during development, marked by a decrease in functional connectivity variability among association connections. Moreover, the variability axis is associated with individual differences in higher-order cognitions, driven by increased variability in higher-order association connections linked to enhanced cognitive performance. These findings highlight the importance of connectivity-specific plasticity in understanding both typical and atypical cognitive development across diverse populations.

neuroscience↗

bioRxiv2023

MicroRNA-195-3p as a potential regulator of hypoxic injury in HUVECs

Coronary heart disease is the most common heart disease and is the leading cause of cardiovascular death worldwide. Revascularization methods are considered effective against coronary heart disease However, the mechanism of molecular revascularization remains largely unknown. Endothelial cells are the primary cells that initiate angiogenesis and arteriogenesis and require a hypoxic environment for induction. In this study, we aimed to determine the expression and role of microRNA-195-3p in hypoxia-treated HUVEs(human umbilical vein endothelial cells). Herein, we induced hypoxia in human umbilical vein endothelial cells using the "Anaerobic tank method." Hypoxia injured human umbilical vein endothelial cells showed upregulation of microRNA-195-3p; decreased cell proliferation, migration, and autophagy; and increased apoptosis. Furthermore, the microRNA-195-3p inhibitor partially reversed the effects of hypoxia-induced injury of human umbilical vein endothelial cells. Therapeutic intervention using microRNA-195-3p inhibitor could maintain endothelial cell function under hypoxic conditions, improve cell activity, and be considered a new treatment strategy for coronary heart diseases.

cell biology↗

bioRxiv2022

Feasibility of intranasal delivery of thin-film freeze-dried, mucoadhesive AS01B-adjuvanted vaccine powders

Intranasal vaccination by directly applying a vaccine dry powder is appealing. However, a method that can be used to transform a vaccine from a liquid to a dry powder and a device that can be used to administer the powder to the desired region(s) of the nasal cavity are critical for a successful intranasal vaccination. In the present study, using a model vaccine that contains the liposomal AS01B as an adjuvant and ovalbumin (OVA) as a model antigen, it was shown that thin-film freeze-drying can be applied to convert the liquid vaccine containing sucrose at a sucrose to lipid ratio of 15:1 (w/w), in the presence or absence of carboxymethyl cellulose sodium salt (CMC) as a mucoadhesive agent, into dry powders. Ultimately, the thin-film freeze-dried AS01B/OVA vaccine powder containing 1.9% w/w of CMC (i.e., TFF AS01B/OVA/CMC1.9% powder) was selected for additional evaluation because the TFF AS01B/OVA/CMC1.9% powder was mucoadhesive and maintained the integrity of the antigen and the physical properties of the vaccine. Compared to the TFF AS01B/OVA powder that did not contain CMC, the TFF AS01B/OVA/CMC1.9% powder had a lower moisture content and a higher glass transition temperature and was more porous. In addition, the TFF AS01B/OVA/CMC1.9% thin films were relatively thicker than the TFF AS01B/OVA thin films without CMC. When sprayed with the Unit Dose System Powder (UDSP) nasal device, the TFF AS01B/OVA powder and the TFF AS01B/OVA/CMC1.9% powder generated similar particle size distribution curves, spray patterns, and plume geometries. Importantly, after the TFF AS01B/OVA/CMC1.9% powder was sprayed with the UDSP nasal device, the integrity of the OVA antigen and the AS01B liposomal adjuvant did not change. Finally, a Taguchi L8 orthogonal array was applied to identify the optimal parameters for using the UDSP device to deliver the TFF AS01B/OVA/CMC1.9% vaccine powder to the middle and lower turbinate and the nasopharynx regions in both adult and child nasal casts. Results from this study showed that it is feasible to apply the TFF technology to transform a nasal vaccine candidate from liquid to a dry powder and then use the UDSP nasal device to deliver the TFF vaccine powder to the desired regions in the nasal cavity for intranasal vaccination.

pharmacology and toxicology↗