Drug repurposing to tackle parainfluenza 3 based on multi-similarities and network proximity analysis.

Given that there is currently no clinically approved drug or vaccine for parainfluenza 3 (PIV3), we applied a drug repurposing method based on disease similarity and chemical similarity to screen 2,585 clinically approved chemical drugs using PIV3 potential drugs BCX-2798 and zanamivir as our controls. Twelve candidate drugs were obtained after being screened with good disease similarity and chemical similarity (S > 0.50, T > 0.56). When docking them with the PIV3 target protein, hemagglutinin-neuraminidase (HN), only oseltamivir was docked with a better score than BCX-2798, which indicates that oseltamivir has an inhibitory effect on PIV3. After the distance ( Z d c ) between the drug target of 14 drugs and the PIV3 disease target was measured by the network proximity method based on the PIV3 disease module, it was found that the Z d c values of amikacin, oseltamivir, ribavirin, and streptomycin were less than those of the control. Thus, oseltamivir is the best potential drug because it met all the above screening requirements. Additionally, to explore whether oseltamivir binds to HN stably, molecular dynamics simulation of the binding of oseltamivir to HN was carried out, and the results showed that the RMSD value of the complex tended to be stable within 100 ns, and the binding free energy of the complex was low (-10.60 kcal/mol). It was proved that oseltamivir screened by our drug repurposing method had the potential feasibility of treating PIV3.

Evolutionary and Expression Analyses of the bZIP Family in Tea Plants (Camellia sinensis) and Functional Characterization of CsbZIP3/42/6 in Response to Environmental Stresses.

Basic leucine zipper (bZIP) transcription factors play crucial roles in various biological processes and responses to environmental stresses. However, the functions of the bZIP family in tea plants remain largely unexplored. Here, we identified 74 bZIP genes in tea plants (Camellia sinensis) and classified them into 12 phylogenetic groups, supported by analyses of conserved motifs and gene structures. Cis-element analysis provided insights into the potential roles of CsbZIP genes in phytohormone signaling and stress responses. Tissue-specific expression analysis demonstrated differential expression profiles of CsbZIP genes, suggesting their tissue- and stage-specific functions. Additionally, varying expression levels under different abiotic stresses indicated functional divergence of the CsbZIP family during the long-term evolution. Notably, CsbZIP3/42/6 were identified as positive regulators of drought and salt stress responses but negative regulators in response to pathogen infection, and CsbZIP42 could interact with CsbZIP3 and CsbZIP6 in regulating these environmental stresses. This study provides valuable information on potential applications for improving stress tolerance and overall plant health of tea plants.

Modeling nonlinear stress-strain model for sulfate dry-wet cycle erosion of concrete: considerations for the initial compaction stage.

Sulfate dry-wet cycle erosion significantly affects the mechanical properties of concrete. Investigating the uniaxial compressive stress-strain relationship under these conditions is essential for developing accurate constitutive models. This study analyzes the uniaxial stress-strain curves of concrete subjected to dry-wet cycles in 5% and 15% sulfate solutions. The results show that the initial compaction phase in the stress-strain relationship is particularly pronounced under increasing sulfate concentrations and cycle counts. The concrete experiences an extended compaction phase, which accounts for up to 35.71% of the total strain process. This finding challenge traditional constitutive models, which struggle to accurately describe this phase. To address this issue, the study develops a nonlinear stress-strain model for concrete, incorporating the initial damage caused by sulfate dry-wet cycle erosion, based on Weibull statistical damage mechanics principles. The research indicates that the effects of sulfate concentration and cycle count are predominantly reflected in the pronounced nonlinearity of the skeleton strain function's opening size (a) and shape characteristics (b), modeled using a fourth-degree polynomial. The model demonstrates an excellent fit to experimental data with an R2 value of 0.99989, showing that the proposed nonlinear stress-strain relationship effectively captures the uniaxial mechanical behavior of concrete under sulfate dry-wet cycle erosion and provides a robust framework for developing constitutive models in such environments.

Tannic acid etching construction of hollow heterogeneous CoSe2-FeSe2@nitrogen-doped carbon rhombic dodecahedron for high-performance sodium storage.

Metal selenides are very promising anode materials for sodium ion batteries (SIBs) due to their rich redox behaviors, low cost, high theoretical capacity, and environmentally benign. However, the poor cycle performance and rate capability greatly hinder their widespread applications. In this paper, we have proposed a tannic acid etching zeolitic imidazolate framework-67 (ZIF-67)-derived selenide strategy to construct hollow heterogeneous CoSe2-FeSe2@N-doped carbon rhombic dodecahedron (CoSe2-FeSe2@NC) as anode for high-performance SIBs. The special microstructural characteristics with hollow rhombic dodecahedron can reduce the Na+/electron migration path and alleviate the volume variations during cycling. The NC can improve conductivity and reduce volume effects during cycling. What's more, the built-in electric fields (BIEF) at the CoSe2-FeSe2 heterointerfaces can modulate the electronic structure and accelerate the kinetics of ionic diffusion, resulting in the improvement electrochemical properties. When applied as anodes for SIBs, the CoSe2-FeSe2@NC can deliver a remarkable electrochemical performance in terms of sodium storage capacity (648.5 mAh g-1 at 0.2 A/g), initial coulombic efficiency (82.0 %), cycle performance (92.6 % capacity retention after 100 cycles), and rate capability of 450.6 mAh g-1 after 1000 cycles at a high rate of 1 A/g. The kinetic analysis indicates that the discharging-charging process of CoSe2-FeSe2@NC is ascribed to both capacitive behavior and controlled diffusion.

Macroscale connectome topographical structure reveals the biomechanisms of brain dysfunction in Alzheimer's disease.

The intricate spatial configurations of brain networks offer essential insights into understanding the specific patterns of brain abnormalities and the underlying biological mechanisms associated with Alzheimer's disease (AD), normal aging, and other neurodegenerative disorders. This study investigated alterations in the topographical structure of the brain related to aging and neurodegenerative diseases by analyzing brain gradients derived from structural MRI data across multiple cohorts (n = 7323). The analysis identified distinct gradient patterns in AD, aging, and other neurodegenerative conditions. Gene enrichment analysis indicated that inorganic ion transmembrane transport was the most significant term in normal aging, while chemical synaptic transmission is a common enrichment term across various neurodegenerative diseases. Moreover, the findings show that each disorder exhibits unique dysfunctional neurophysiological characteristics. These insights are pivotal for elucidating the distinct biological mechanisms underlying AD, thereby enhancing our understanding of its unique clinical phenotypes in contrast to normal aging and other neurodegenerative disorders.

Asymmetric one-carbon ring expansion of diverse N-heterocycles via copper-catalyzed diyne cyclization.

One-carbon ring expansion reaction of N-heterocycles has gained particular attention in the past decade because this method allows for the conversion of readily available N-heterocycles into potentially useful complex ring-expanded N-heterocycles, which are inaccessible by traditional methods. However, the catalytic asymmetric variant of this reaction has been rarely reported to date. Herein, we disclose an enantioselective one-carbon ring expansion reaction through chiral copper-catalyzed diyne cyclization, leading to the practical, atom-economic and divergent assembly of an array of valuable chiral N-heterocycles bearing a quaternary stereocenter in generally good to excellent yields with excellent enantioselectivities (up to >99% ee). This protocol represents the first example of asymmetric one-carbon ring expansion reaction of N-heterocycles based on alkynes.

Unified Noise-aware Network for Low-count PET Denoising with Varying Count Levels.

As PET imaging is accompanied by substantial radiation exposure and cancer risk, reducing radiation dose in PET scans is an important topic. However, low-count PET scans often suffer from high image noise, which can negatively impact image quality and diagnostic performance. Recent advances in deep learning have shown great potential for recovering underlying signal from noisy counterparts. However, neural networks trained on a specific noise level cannot be easily generalized to other noise levels due to different noise amplitude and variances. To obtain optimal denoised results, we may need to train multiple networks using data with different noise levels. But this approach may be infeasible in reality due to limited data availability. Denoising dynamic PET images presents additional challenge due to tracer decay and continuously changing noise levels across dynamic frames. To address these issues, we propose a Unified Noise-aware Network (UNN) that combines multiple sub-networks with varying denoising power to generate optimal denoised results regardless of the input noise levels. Evaluated using large-scale data from two medical centers with different vendors, presented results showed that the UNN can consistently produce promising denoised results regardless of input noise levels, and demonstrate superior performance over networks trained on single noise level data, especially for extremely low-count data.

Trophoblast cell-derived extracellular vesicles regulate the polarization of decidual macrophages by carrying miR-141-3p in the pathogenesis of preeclampsia.

Dysregulation of macrophage polarization can prevent the invasion of trophoblast cells and further limit spiral artery remodeling in preeclampsia (PE). However, its mechanism is obscure. HTR8-/Svneo cells were cultured under normoxic or hypoxic conditions and extracellular vesicles (EVs) in the culture supernatants were extracted. Next, the cells were incubated with those EVs to investigate their effects on trophoblasts. A co-culture system consisting of HTR8-/Svneo cells and macrophages was used to reveal how the trophoblast-derived EVs affected the macrophage subtype. Finally, a PE mouse model and miR-141-3p knockout mice were used to verify the function of miR-141-3p in PE. Hypoxia induced abnormal increases in the levels of miR-141-3p in HTR8-/Svneo cells and EVs. EVs from hypoxia-treated HTR8-/Svneo cells could downregulate PTEN, a potential target of miR-141-3p, and inhibit trophoblast mitophagy and invasion. However, HTR8-/Svneo cells transfected with an miR-141-3p inhibitor could attenuate the influence of EVs. In an HTR8-/Svneo cell plus macrophage co-culture system, hypoxia-pretreated cells promoted the transformation of macrophages into the M1-phenotye, and HTR8-/Svneo invasion was inhibited by the macrophages. MiR-141 from EVs could target and downregulate dual specificity phosphatase 1 (DUSP1) expression in macrophages, induce formation of the M1 macrophage phenotype in THP-1 cells, downregulate DUSP1 expression, and upregulate TAB2/TAK1 signaling. These results were also demonstrated in normal pregnant mice and PE pregnant mice. A hypoxic environment could upregulate miR-141 expression in the EVs of HTR8-/Svneo cells, and THP-1-derived macrophages could uptake EVs releasing miR-141 to downregulate DUSP1 expression and induce the formation of M1 macrophages, which can lead to the development of PE.

Genomic insights into Aspergillus tamarii TPD11: enhancing polyphyllin production and uncovering potential therapeutic applications.

BACKGROUND: The excavation and utilization of endophytic fungi from medicinal plants is highly important for the development of new drugs. The endophytic fungus Aspergillus tamarii TPD11, which was isolated and obtained by the authors in the previous stage, can produce a variety of polyphyllins with important potential applications in hemostasis, inflammation and antitumor activities; however, the genomic information of TPD11 is still unknown. RESULTS: In this study, we sequenced and assembled the whole genome of the endophytic fungus A. tamarii TPD11, resolved the genome evolutionary relationships of 24 Aspergillus strains, and phylogenetic analysis of the genomes of 16 strains revealed the evolutionary differences between Aspergillus and Penicillium and the mechanisms of genome expansion and contraction. CAZy annotation analysis revealed that TPD11 obtains nutrients mainly by ingesting starch from the host plant. TPD11 has a biosynthesis-related gene cluster for the synthesis of squalestatin S1, and the silencing of this biosynthesis-related gene cluster might increase the content of polyphyllin. Annotation of 11 UDP-glycosyltransferase genes helps to further reveal the biosynthetic pathway of polyphyllin. In addition, secondary metabolism gene cluster and CAZy analyses confirmed the potential probiotic, insecticidal and antimicrobial activities of TPD11 on host plants. CONCLUSIONS: This study reveals the intrinsic mechanism by which endophytic fungi increase the content of polyphyllin, which provides a basis for the synthetic synthesis of the natural product polyphyllin.

Detection and analysis of complex structural variation in human genomes across populations and in brains of donors with psychiatric disorders.

Complex structural variations (cxSVs) are often overlooked in genome analyses due to detection challenges. We developed ARC-SV, a probabilistic and machine-learning-based method that enables accurate detection and reconstruction of cxSVs from standard datasets. By applying ARC-SV across 4,262 genomes representing all continental populations, we identified cxSVs as a significant source of natural human genetic variation. Rare cxSVs have a propensity to occur in neural genes and loci that underwent rapid human-specific evolution, including those regulating corticogenesis. By performing single-nucleus multiomics in postmortem brains, we discovered cxSVs associated with differential gene expression and chromatin accessibility across various brain regions and cell types. Additionally, cxSVs detected in brains of psychiatric cases are enriched for linkage with psychiatric GWAS risk alleles detected in the same brains. Furthermore, our analysis revealed significantly decreased brain-region- and cell-type-specific expression of cxSV genes, specifically for psychiatric cases, implicating cxSVs in the molecular etiology of major neuropsychiatric disorders.

LH-stimulated periodic lincRNA HEOE regulates follicular dynamics and influences estrous cycle and fertility via miR-16-ZMAT3 and PGF2α in pigs.

Disruption of the estrous cycle affects fertility and reproductive health. Follicular dynamics are key to the regularity of the estrous cycle. We identified a novel lincRNA, HEOE, showing significant upregulation in the ovaries during the estrus phase across various pig breeds. Functional analysis revealed that HEOE is responsive to luteinizing hormone (LH) stimulation, modulating transcriptional suppression and alternative splicing in ovarian granulosa cells (GCs). This leads to increased GC apoptosis and inhibition of proliferation. Mechanistically, HEOE inhibits miR-16 maturation in the nucleus, and sequesters miR-16 in the cytoplasm, thereby collectively reducing miR-16's inhibition on ZMAT3, enhancing the expression of ZMAT3, a key factor in the p53 pathway and alternative splicing, thereby regulating follicular development. This effect was validated in both mice and pig follicles. Persistent overexpression or suppression of HEOE throughout the estrous cycle impairs cycle regularity and reduces litter size. These outcomes are associated with HEOE reduced follicular PGF2α levels and modulation of the cAMP signaling pathway. Our data, combined with public databases, indicate that the high expression of HEOE during the estrus phase is crucial for maintaining the estrous cycle. HEOE is a potential therapeutic target for regulating fertility and ensuring estrous cycle regularity in pigs.

Major depressive disorder, neuroticism, suicidal behaviors, and depression severity are associated with cytokine networks and their intricate interactions with metabolic syndrome.

OBJECTIVES: To identify alterations in the immune profiles in outpatients with major depression (MDD), and its associations with key features, such as suicidal ideation, neuroticism, cognitive symptoms, and the depression phenome while accounting for metabolic syndrome (MetS). METHODS: In this case-control study, we assayed 48 serum cytokines, chemokines, and growth factors in 67 healthy controls and 66 MDD outpatients. Around 50 % of the outpatient MDD and control participants had a diagnosis of MetS. RESULTS: Ten differentially expressed proteins (DEPs) were upregulated in outpatient MDD (i.e., CXCL12, tumor necrosis factor [TNF]ß, platelet-derived growth factor [PDGF], CCL11, interleukins [IL]9, IL4, CCL5, CCL2, CCL4, IL1 receptor antagonist [IL1RN]), indicating an immune and defense response. Six DEPs were downregulated (vascular endothelial growth factor A [VEGFA], IL12, CCL3, colony stimulating factor [CSF]1, IL1B, nerve growth factor [NGF]), indicating lowered neurogenesis and neuron death regulation. Significant interactions between outpatient MDD and MetS caused a) substantial increases in IL4, IL17, TNF, TNFB, CCL2, CCL5, PDGF, IL1RN; and b) downregulation of VEGFA and FGF. A large part of the variance in neuroticism (26 %), suicidal behaviors (23 %), and the MDD phenome (31 %) was predicted by immunological data and interactions between MetS and CCL5, TNFB or VEGFA. CONCLUSION: Outpatient MDD is characterized by a cytokine profile with neurotoxic potential which partly explains neuroticism, suicidal behaviors, and the phenome's severity. Lowered IL-10 and activated cytokine profiles with neurotoxic potential are characteristics of outpatient MDD and other depression phenotypes, including severe first-episode inpatient MDD. The presence of MetS in outpatient MDD considerably activates immune profiles with neurotoxic potential. Consequently, immune studies in MDD should always be performed in subjects with and without MetS.

Quantifying the Ecological Performance of Migratory Bird Conservation: Evidence from Poyang Lake Wetlands in China.

Protected areas are essential for the conservation of biodiversity. However, the rapid expansion of urbanization and the intensification of human activities have significantly disrupted environmental integrity, leading to a continuous deterioration in both the quantity and quality of large ecological patches. This has further diminished the connectivity among ecological patches, leading to significant consequences for regional biodiversity conservation. Taking Poyang Lake as a case study, which serves as a crucial wintering habitat for migratory birds along the East Asia-Australasia flyway, this research employs ArcMap technology. It considers various factors including land use type, slope, and elevation to evaluate habitat quality and degradation through the application of the InVEST model. Additionally, the study utilizes the minimum cumulative resistance (MCR) model alongside circuit theory to delineate ecological corridors within the area and to establish a comprehensive ecological network system. The research results in this paper are as follows. (i) During the period from 2000 to 2020, there was an overall decline in habitat quality within the study area, indicating a clear trend of habitat degradation. However, it is worth noting that there was an increase in habitat quality in certain local areas within the protected area. (ii) The ecological resistance values in the core area of the migratory bird reserve in Poyang Lake are generally low. However, the ecological resistance values of the habitats have shown a consistent increase from 2000 to 2020. Additionally, there has been a significant decrease in the density of ecological corridors during this time period. (iii) Over the period from 2000 to 2020, both the number and connectivity of ecological corridors decreased and their integrity and functionality degraded. Consequently, this weakened role of the ecological network has had implications for maintaining regional biodiversity and ecosystem service functions. The findings indicate two conclusions. (i) Ecological connectivity is essential for the conservation of migratory bird habitats. Strengthening control measures aimed at expanding ecological corridors can effectively safeguard flagship and umbrella species, thereby promoting biodiversity conservation. (ii) The establishment of ecological corridors can help reconcile conflicts between conservation efforts and development objectives. This reconciliation carries significant theoretical implications for fostering a harmonious coexistence between humans and birds in Poyang Lake's migratory bird sanctuary.

Valuable Data "Gain" and "Loss": The Quantitative Impact of Information Choice on Consumers' Decision to Buy Selenium-Rich Agricultural Products.

Biotechnology assumes a paramount role in addressing micronutrient deficiencies. The promotion thereof and the augmentation of public awareness are indispensable for implementation. The advancement of big data presents challenges due to the plethora of information and the constrained processing capacity, thereby inducing difficulties in consumer decision-making. The study is obliged to intensify information dissemination to empower consumers to apprehend the value of selenium-enriched products as an integral constituent of positive nutrition guidance. The study undertook an experiment related to nutrition information acquisition, in which participants provided relevant interferences. The study utilized the structural equation model (SEM) and fuzzy set qualitative comparative analysis (fsQCA) to analyze the data. The study arrived at three research conclusions. Firstly, the furnishing of valuable information constitutes a significant factor in motivating consumers to purchase selenium-rich agricultural products. Secondly, the communication of brand information holds crucial significance in shaping the perception of product advantages and plays a salient role in the promotion and construction of selenium-rich agricultural products. Finally, the dissemination of health information can be incorporated into the process of promoting selenium-rich agricultural products. This conforms to the urgent necessity to address hidden hunger and establish a value identity.

CMAGN: circRNA-miRNA association prediction based on graph attention auto-encoder and network consistency projection.

BACKGROUND: As noncoding RNAs, circular RNAs (circRNAs) can act as microRNA (miRNA) sponges due to their abundant miRNA binding sites, allowing them to regulate gene expression and influence disease development. Accurately identifying circRNA-miRNA associations (CMAs) is helpful to understand complex disease mechanisms. Given that biological experiments are time consuming and labor intensive, alternative computational methods to predict CMAs are urgently needed. RESULTS: This study proposes a novel computational model named CMAGN, which incorporates several advanced computational methods, for predicting CMAs. First, similarity networks for circRNAs and miRNAs are constructed according to their sequences. Graph attention autoencoder is then applied to these networks to generate the first representations of circRNAs and miRNAs. The second representations of circRNAs and miRNAs are obtained from the CMA network via node2vec. The similarity networks of circRNAs and miRNAs are reconstructed on the basis of these new representations. Finally, network consistency projection is applied to the reconstructed similarity networks and the CMA network to generate a recommendation matrix. CONCLUSION: Five-fold cross-validation of CMAGN reveals that the area under ROC and PR curves exceed 0.96 on two widely used CMA datasets, outperforming several existing models. Additional tests elaborate the reasonability of the architecture of CMAGN and uncover its strengths and weaknesses.

ß-Carboline-3-carboxamide Antimalarials: Structure-Activity Relationship, ADME-Tox Studies, and Resistance Profiling.

The development of parasite resistance to both artemisinin derivatives and their partner drugs jeopardizes the effectiveness of the artemisinin combination therapy. Thus, the discovery of new antimalarial drugs, with new mechanisms of action, is urgently needed. We recently disclosed that ß-carboline 1a was orally efficacious in Plasmodium berghei-infected mice and that it showed low cross-resistance between susceptible Plasmodium falciparum and four different drug-resistant strains. In this report, we describe the synthesis and in vitro antimalarial evaluation of 91 new derivatives of 1a. The asexual blood stage growth inhibition data show a clear preference for a 3,4-dihalogenated, 3,5-dihalogenated, 3,4,5-trichloro-, or 4-trifluoromethyphenyl ring at the C1-position. The most potent compound, 3,4,5-trichlorophenyl-substituted 42a, is twice as potent as 1a. Six potent analogues were assessed for their drug-like properties, and four of these were subjected to in vitro barcoded cross-resistance profiling. Compounds 1a, 1m, 42a, and 42m showed no cross-resistance to 32 resistance mutations on the Dd2 genetic background and 10 resistance mutations on the 3D7 genetic background. These data suggest that compounds in this scaffold possess a novel mechanism of antimalarial action.

Effectiveness of an HIV peer support precision matching platform: a randomized controlled trial protocol.

BACKGROUND: Peer support is a promising and significant way for people living with HIV (PLWH) to improve their health outcomes. Matching PLWH with HIV peer volunteers can effectively stimulate and mobilize the function of peer support in health management. We develop the online platform Aspark, which features a precision matching function for PLWH and volunteers. This protocol provides a comprehensive overview of the randomized controlled trial design based on Aspark. METHOD: A parallel randomized controlled trial using block randomization will be conducted at the Beijing YouAn Home of Loving Care. The intervention group (n = 70) will have access to all 12 features of Aspark, including precise volunteer matching, health management tools, drug interaction queries, and medication reminders. The control group (n = 70) will have access to two features of informational support on Aspark. The outcomes of both groups will be evaluated at baseline and at 3, 6, 9, and 12 months after platform registration. The primary outcome is perceived social support. The secondary outcomes include mental symptoms, quality of life, self-efficacy, medication adherence, and health behaviors. Linear mixed models or generalized linear mixed models will be applied to test the intervention effects. DISCUSSION: The Aspark trial is a randomized controlled trial designed to examine the influence of a mobile health (mHealth) application that integrates peer support and precision matching to strengthen social support for PLWH in China. This trial has the potential to significantly enhance social support for PLWH while also optimizing the delivery of peer support services and fully mobilizing the role of peer support in the overall health management of PLWH. TRIAL REGISTRATION: Clinical registration number: ChiCTR2300077454.

The dynamic immune response of the liver and spleen in leopard coral grouper (Plectropomus leopardus) to Vibrio harveyi infection based on transcriptome analysis.

Leopard coral grouper (Plectropomus leopardus) is one of the most important cultured fish in the Pacific and Indian oceans. Vibrio harveyi is a serious pathogen causing serious skin ulceration and high mortality in P. leopardus. To gain more insight into the tissue-specific and dynamic immune regulation process of P. leopardus in response to V. harveyi infection, RNA sequencing (RNA-seq) was used to examine the transcriptome profiles in the spleen and liver at 0, 6, 12, 24, 48, and 72 h post-infection. The upregulated differentially expressed genes (DEGs) were predominantly involved in the immune response in the spleen and liver at the early infection stage (6-12 h), and downregulated DEGs were mainly involved in metabolic processes in the liver at the early and middle infection stage (6-48 h). Moreover, an overview of the immune response of P. leopardus against V. harveyi was exhibited including innate and adaptive immune-related pathways. Afterwards, the results of WGCNA analysis in the spleen indicated that TAP2, IRF1, SOCS1, and CFLAR were the hub genes closely involved in immune regulation in the gene co-expression network. This study provides a global picture of V. harveyi-induced gene expression profiles of P. leopardus at the transcriptome level and uncovers a set of key immune pathways and genes closely linked to V. harveyi infection, which will lay a foundation for further study the immune regulation of bacterial diseases in P. leopardus.

Macroscale Gradient Dysfunction in Alzheimer's Disease: Patterns With Cognition Terms and Gene Expression Profiles.

Macroscale functional gradient techniques provide a continuous coordinate system that extends from unimodal regions to transmodal higher-order networks. However, the alterations of these functional gradients in AD and their correlations with cognitive terms and gene expression profiles remain to be established. In the present study, we directly studied the functional gradients with functional MRI data from seven scanners. We adopted data-driven meta-analytic techniques to unveil AD-associated changes in the functional gradients. The principal primary-to-transmodal gradient was suppressed in AD. Compared to NCs, AD patients exhibited global connectome gradient alterations, including reduced gradient range and gradient variation, increased gradient scores in the somatomotor, ventral attention, and frontoparietal regions, and decreased in the default mode network. More importantly, the Gene Ontology terms of biological processes were significantly enriched in the potassium ion transport and protein-containing complex remodeling. Our compelling evidence provides a new perspective in understanding the connectome alterations in AD.