Structural and functional remodeling of neural networks in ß-amyloid driven hippocampal hyperactivity.

Early detection of Alzheimer's disease (AD) is essential for improving the patients outcomes and advancing our understanding of disease, allowing for timely intervention and treatment. However, accurate biomarkers are still lacking. Recent evidence indicates that hippocampal hyperexcitability precedes the diagnosis of AD decades ago, can predict cognitive decline. Thus, could hippocampal hyperactivity be a robust biomarker for early-AD, and what drives hippocampal hyperactivity in early-AD? these critical questions remain to be answered. Increasing clinical and experimental studies suggest that early hippocampal activation is closely associated with longitudinal ß-amyloid (Aß) accumulation, Aß aggregates, in turn, enhances hippocampal activity. Therefore, in this narrative review, we discuss the role of Aß-induced altered intrinsic neuronal properties as well as structural and functional remodeling of glutamatergic, GABAergic, cholinergic, noradrenergic, serotonergic circuits in hippocampal hyperactivity. In addition, we analyze the available therapies and trials that can potentially be used clinically to attenuate hippocampal hyperexcitability in AD. Overall, the present review sheds lights on the mechanism behind Aß-induced hippocampal hyperactivity, and highlights that hippocampal hyperactivity could be a robust biomarker and therapeutic target in prodromal AD.

3D Printing-Induced Hierarchically Aligned Nanocomposites With Exceptional Multidirectional Strain Sensing Performance.

High-performance sensors capable of detecting multidirectional strains are indispensable to understand the complex motions involved in flexible electronics. Conventional isotropic strain sensors can only measure uniaxial deformations or single stimuli, hindering their practical application fields. The answer to such challenge resides in the construction of engineered anisotropic sensing structures. Herein, a hierarchically aligned carbon nanofiber (CNF)/polydimethylsiloxane nanocomposite strain sensor is developed by one-step 3D printing. The precisely controlled printing path and shear flow bring about highly aligned nanocomposite filaments at macroscale and orientated CNF network within each filament at microscale. The periodically orientated nanocomposite filaments along with the inner aligned CNF network successfully control the strain distribution and the appearance of microcracks, giving rise to anisotropic structural response to external deformations. The synergetic effect of the multiscale structural design leads to distinguishable gauge factors of 164 and 0.5 for applied loadings along and transverse to the alignment direction, leading to an exceptional selectivity of 3.77. The real-world applications of the hierarchically aligned sensors in multiaxial movement detector and posture-correction device are further demonstrated. The above findings propose new ideas for manufacturing nanocomposites with engineered anisotropic structure and properties, verifying promising applications in emerging wearable electronics and soft robotics.

Exploring flavonoid intake and all-cause mortality in diverse health conditions: Insights from NHANES 2007-2010 and 2017-2018.

OBJECTIVES: Flavonoids exhibit antioxidative, anti-inflammatory, and anticancer properties, yet the relationship between flavonoid intake and all-cause mortality in the obese population remains unclear. METHODS: This study included NHANES participants from 2007 to 2010 and 2017 to 2018. Cox regression analysis evaluated the impact of total flavonoid intake on all-cause mortality among participants with varying comorbidity profiles. Subgroup analysis was conducted by separately analyzing the six sub-classes of total flavonoids (anthocyanidins, flavan-3-ols, flavanones, flavones, flavonols, and isoflavones). Sensitivity analysis was used to investigate the impact of total flavonoid intake on all-cause mortality among patients with different comorbidities. RESULTS: During a median follow-up period of 9.92 years (interquartile range (IQR), 5.54-14.29 years), a total of 639 participants died. COX regression analysis revealed a positive impact of flavonoid intake on all-cause mortality among participants with chronic kidney disease, with greater benefits observed in obese participants [hazard ratio (HR): 0.22, 95% CI: 0.11-0.44). In metabolically healthy obese participants (HR: 0.15, 95% CI: 0.07-0.35), obese individuals with diabetes (HR: 0.51, 95% CI: 0.29-0.88), and obese individuals with comorbid cardiovascular disease (HR: 0.37, 95% CI: 0.17-0.83), flavonoid intake was associated with a reduced risk of all-cause mortality. Restricted cubic spline (RCS) analysis indicated a non-linear relationship in obese participants, with optimal intake levels ranging from 319.4978 to 448.6907 mg/day, varying based on different comorbidity profiles. Subgroup analysis revealed varying effects of total flavonoid components in different health conditions, with hazard ratios ranging from 0.06 for higher levels of flavonol to 0.59 for higher levels of anthocyanidins in the Cox model. Sensitivity analyses further indicated that individuals with obesity and comorbid diabetes or CKD see the greatest benefit from flavonoid intake. CONCLUSIONS: The consumption of flavonoids may be associated with a decreased risk of all-cause mortality. Consumption of flavonoids is particularly beneficial for individuals with obesity and comorbidities.

Differences in the effects of contrast agents on kidney injury and inflammatory response between diabetic and non-diabetic patients and their clinical significance.

With the increasing incidence of coronary heart disease (CHD), contrast-associated nephropathy (CAN) caused by contrast agents required in coronary angiography has gradually become a clinical concern that needs to be solved urgently. At present, CAN has become one of the most common causes of hospital-acquired acute kidney injury, which seriously affects the prognosis and health of patients. How to effectively identify high-risk CAN patients and prevent the occurrence of CAN has become a hotspot of clinical research. In this study, we attempted to evaluate the effect of contrast agents on renal injury in diabetes mellitus (DM) and non-DM patients by observing some indexes of early renal injury and inflammatory factors, so as to provide a more comprehensive reference for early identification of CAN in the future. The results showed that compared with non-DM patients, contrast agents caused more obvious renal damage in DM patients and more significantly activated inflammatory responses, increasing the risk of CAN. Cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), C-reactive protein (CRP), and neutrophil-lymphocyte ratio (NLR) all showed excellent predictive effects for the occurrence of CAN after coronary angiography in both DM and non-DM patients.

Complete mitochondrial genomes of Dactylogyrus crucifer and Dactylogyrus zandti reveal distinct patterns of codon usage within Dactylogyrus.

Monogeneans of the genus Dactylogyrus Diesing, 1850, the largest genus in the family Dactylogyridae, mostly parasitize the gills of cyprinoid hosts; however, only 3 Dactylogyrus' mitochondrial genomes (mitogenomes) are studied so far. The aim of this research is to extend our understanding of the mitogenomes of Dactylogyrus. We sequenced the mitogenomes of D. crucifer and D. zandti isolated from Rutilus rutilus and Abramis brama orientalis in northwest China, and then we compared these mitogenomes with other monogeneans. We used Illumina NovaSeq to sequence the entire mitochondrial genomes of D. crucifer and D. zandti and characterized the mitogenomes to understand the gene structure, gene identity, the secondary structures of the 22 tRNA genes, and relative synonymous codon usage. We used the analytic Bayesian Information and Maximum Likelihood methods to determine their associated phylogenetic trees. The mitogenomes of D. crucifer and D. zandti were 14,403 and 18,584 bp, respectively. Organization and positioning of these genes were in accordance with Dactylogyrus lamellatus and Dactylogyrus tuba. The nucleotide composition of Dactylogyridae was different from other families of Monogenea, and the A+T count of genus Dactylogyrus (54 - 58.4 %) was lower than other genus species of the family Dactylogyridea (63.9 - 78.4 %) in protein-coding genes. Dactylogyrus members displayed a codon usage bias. The relative synonymous codon used by Dactylogyrus was not conserved and was lower than other monogeneans. The codon use patterns of closely-related species isolated from closely-related hosts were identical. Phylogenetic analyses using mitogenomic dataset produced Dactylogyrus isolated from host subfamily Leuciscinae formed a sister-group. Our results contributed significantly to an increased database of mitogenomes, more than 50 %, for Dactylogyrus that may help future studies of mitochondrial genes and codon uses for the analysis of monogenean phylogenetics.

Unraveling the role of ubiquitin-conjugating enzyme 5 (UBC5) in disease pathogenesis: A comprehensive review.

While certain members of ubiquitin-coupled enzymes (E2s) have garnered attention as potential therapeutic targets across diverse diseases, research progress on Ubiquitin-Conjugating Enzyme 5 (UBC5)-a pivotal member of the E2s family involved in crucial cellular processes such as apoptosis, DNA repair, and signal transduction-has been relatively sluggish. Previous findings suggest that UBC5 plays a vital role in the ubiquitination of various target proteins implicated in diseases and homeostasis, particularly in various cancer types. This review comprehensively introduces the structure and biological functions of UBC5, with a specific focus on its contributions to the onset and advancement of diverse diseases. It suggests that targeting UBC5 holds promise as a therapeutic approach for disease therapy. Recent discoveries highlighting the high homology between UBC5, UBC1, and UBC4 have provided insight into the mechanism of UBC5 in protein degradation and the regulation of cellular functions. As our comprehension of the structural distinctions among UBC5 and its homologues, namely UBC1 and UBC4, advances, our understanding of UBC5's functional significance also expands.

Physical effects of 3D microenvironments on confined cell behaviors.

Cell migration is a fundamental and functional cellular process, influenced by complex microenvironment consisting of different cells and extracellular matrix (ECM). Recent research has highlighted that, besides biochemical cues from the microenvironment, physical cues can also greatly alter cellular behavior. However, due to the complexity of the microenvironment, little is known about how the physical interactions between migrating cells and surrounding microenvironment instruct cell movement. Here, we explore various examples of 3D microenvironment reconstruction models in vitro and describe how the physical interplay between migrating cells and the neighboring microenvironment controls cell behavior. Understanding this mechanical cooperation will provide key insights into organ development, regeneration, and tumor metastasis.

Pyramid Textured Photonic Films with High-Refractive Index Fillers for Efficient Radiative Cooling.

Sub-ambient cooling technologies relying on passive radiation have garnered escalating research attention owing to the challenges posed by global warming and substantial energy consumption inherent in active cooling systems. However, achieving highly efficient radiative cooling devices capable of effective heat dissipation remains a challenge. Herein, by synergic optimization of the micro-pyramid surface structures and 2D hexagonal boron nitride nanoplates (h-BNNs) scattering fillers, pyramid textured photonic films with remarkable solar reflectivity of 98.5% and a mid-infrared (MIR) emittance of 97.2% are presented. The h-BNNs scattering filler with high thermal conductivity contributed to the enhanced through-plane thermal conductivity up to 0.496 W m-1 K-1 and the in-plane thermal conductivity of 3.175 W m-1 K-1. The photonic films exhibit an optimized effective radiative cooling power of 201.2 W m-2 at 40 °C under a solar irradiance of 900 W m-2 and a daily sub-ambient cooling effect up to 11 °C. Even with simultaneous internal heat generation by a 10 W ceramic heater and external solar irradiance of 500 W m-2, a sub-ambient cooling of 5 °C can be realized. The synergic matching strategy of high thermal conductivity scattering fillers and microstructured photonic surfaces holds promise for scalable sub-ambient radiative cooling technologies.

Integrated Transcriptomics and Proteomics Identified CMPK1 as a Potential Biomarker for Type 2 Diabetes Mellitus.

Aim/Introduction: Type 2 diabetes mellitus (T2DM) is one of the most frequent and widespread disease in the world.Obesity is the most significant predictor of T2DM, but the exact mechanism how obesity promotes T2DM remains unknown. Finding specific biomarkers to assist in diagnosing and treating patients with obese and T2DM is critical. Materials and Methods: We collected liver tissues from obesity patients with and without T2DM for proteomic sequencing and immunohistochemistry assay. Analysis Gene Ontology(GO) enrichment, Kyoto Encyclopedia of Genes and Genomes(KEGG), and protein interaction network (PPI) were performed on the parameters and data derived from the Tandem Mass Tags(TMT)-based proteomics analysis of liver tissues. Transcriptome data were downloaded from the Gene Expression Omnibus(GEO)website and genes that are deferentially expressed in both transcriptome and proteome were selected. Results: We identified 140 deferentially expressed proteins from proteomic sequencing. Six biomarkers were deferentially expressed in both proteome and transcriptome with consistent changes in direction. The protein-protein interaction (PPI) analysis suggested CMPK1, the expression with greatest difference, was the core protein among the six biomarkers. Immunohistochemistry validated CMPK1 was upregulated significantly in the liver tissues of T2DM patients. The correlation analysis revealed that the expression of CMPK1 was significantly associated with key molecules in T2DM-related pathways at both protein and transcriptome levels. Conclusion and Novelty: Our study showed CMPK1 was upregulated in the liver of T2DM patients and provides a possible new target for screening and diagnosing T2DM in patients with obese and a novel theoretical basis for the pathophysiological mechanism of obesity-related metabolic diseases.

Alpine grassland community productivity and diversity differences influence significantly plant sexual reproduction strategies.

Whether and how community structure variation affects plant sexual reproduction is crucial for understanding species' local adaptation and plant community assembly, but remains unrevealed. In Qinghai-Tibetan grassland communities that differed in aboveground biomass (AGB) and species diversity, we found significant influence of AGB on both species' reproductive biomass allocation (RBA) and flowering and fruiting time, but of species diversity only on species' reproductive time. In high-AGB or high-diversity communities, smaller and earlier flowering species generally advanced their reproductive phenology and increased their reproductive allocation for maximizing their reproductive success, whereas larger and later flowering species delayed their reproductive phenology and decreased their reproductive allocation for maximizing their vegetative growth and resource competition. This change in reproductive allocation with the variation in community structures was more pronounced in nonclonal as compared to clonal plant species. Thus, we evidence an important influence of community structure on plant sexual reproduction strategies, and the pattern of the influence depends largely on species biological attributes.

Determination of 16 ultraviolet-absorbing compounds in marine invertebrates by using LC-USI-MS/MS coupled with QuEChERS.

In this study, we examined multiple endocrine-disrupting ultraviolet-absorbing compounds (UVACs) in marine invertebrates used in personal care products and packaging. Modified QuEChERS and liquid chromatography UniSpray ionization tandem mass spectrometry were used to identify 16 UVACs in marine invertebrates. Matrix-matched calibration curves revealed high linearity (r ≥ 0.9929), with limits of detection and quantification of 0.006-1.000 and 0.020-3.000 ng/g w.w., respectively. In oysters, intraday and interday analyses revealed acceptable accuracy (93%-120%) and precision (≤18%), except for benzophenone (BP) and ethylhexyl 4-(dimethylamino) benzoate. Analysis of 100 marine invertebrate samples revealed detection frequencies of 100%, 98%, 89%, 64%, and 100% for BP, 4-hydroxybenzophenone, 4-methylbenzophenone, 4-methylbenzylidene camphor, and benzophenone-3 (BP-3), respectively. BP and BP-3 were detected at concentrations of 4.40-27.39 and < 0.020-0.560 ng/g w.w., respectively, indicating their widespread presence. Overall, our proposed method successfully detected UVACs in marine invertebrates, raising concerns regarding their potential environmental and health effects.

Combined UPLC-QqQ-MS/MS and AP-MALDI Mass Spectrometry Imaging Method for Phospholipidomics in Obese Mouse Kidneys: Alleviation by Feeding Sea Cucumber Phospholipids.

Sea cucumber phospholipids have ameliorative effects on various diseases related to lipid metabolism. However, it is unclear whether it can ameliorate obesity-associated glomerulopathy (ORG) induced by a high-fat diet (HFD). The present study applied UPLC-QqQ-MS/MS and atmospheric pressure matrix-assisted laser desorption ionization mass spectrometry imaging (AP-MALDI MSI) to investigate the effects of sea cucumber phospholipids, including plasmalogen PlsEtn and plasmanylcholine PakCho, on phospholipid profiles in the HFD-induced ORG mouse kidney. Quantitative analysis of 135 phospholipids revealed that PlsEtn and PakCho significantly modulated phospholipid levels. Notably, PlsEtn modulated kidney overall phospholipids better than PakCho. Imaging the "space-content" of 9 phospholipids indicated that HFD significantly increased phospholipid content within the renal cortex. Furthermore, PlsEtn and PakCho significantly decreased the expression of transport-related proteins CD36, while elevating the expression of fatty acid ß-oxidation-related protein PPAR-α in the renal cortex. In conclusion, sea cucumber phospholipids reduced renal lipid accumulation, ameliorated renal damage, effectively regulated the content and distribution of renal phospholipids, and improved phospholipid homeostasis, exerting an anti-OGR effect.

Flow-induced fabrication of ZnO nanostructures in pillar-arrayed microchannels.

The emergence of microfluidic devices integrated with nanostructures enables highly efficient, flexible and controllable biosensing, among which zinc oxide (ZnO) nanostructure-based fluorescence detection has been demonstrated to be a promising methodology due to its high electrical point and unique fluorescence enhancement properties. The optimization of microfluidic synthesis of ZnO nanostructures for biosensing on chip has been in demand due to its low cost and high efficiency, but still the flow-induced growth of ZnO nanostructures is not extensively studied. Here, we report a simple and versatile strategy that could manipulate the local flow field by creating periodically arranged micropillars within a straight microchannel. We have explored the effects of perfusion speed and flow direction of seed solution, localized flow variation of growth solution and growth time on the morphology of nanostructures. This provided a comprehensive understanding which governs nanostructure fabrication controlled by flow. The results demonstrated that localized flow in microfluidic devices was essential for the initiation and growth of zinc oxide crystals, enabling precise control over their properties and morphology. Furthermore, a model protein was used to demonstrate the intrinsic fluorescence enhancement of ZnO nanostructures as an example to reveal the morphology-related enhancement properties.

Corrigendum: Gut microbiome alterations during gastric cancer: evidence assessment of case-control studies.

[This corrects the article DOI: 10.3389/fmicb.2024.1406526.].

Risk Factors of Sarcopenia in COPD Patients: A Meta-Analysis.

Objective: Sarcopenia is a common complication of COPD associated with an age-related reduction in skeletal muscle mass associated with decreased muscle strength and / or reduced mobility. The incidence of sarcopenia in patients with COPD is twice that of non-COPD patients and is associated with poor prognosis, this study aimed to investigate the influencing factors of sarcopenia in COPD patients. Methods: Selected studies from PubMed, Embase, Web of Science, Cochrane Library, Wanfang, Wanfang, CNKI, CBM, and Wanfang databases as of November 12023. Patients aged 18 were selected; data were then independently extracted by two reviewers using a standard data collection form. Results: In total, 17 articles reporting on 5408 patients were included. Age (OR = 1.083; 95% CI, 1.024-1.145), ALB (OR = 0.752; 95% CI, 0.724-0.780), BMI(OR = 0.701; 95% CI, 0.586-0.838), smoking (OR = 1.859; 95% CI, 1.037-3.334), diabetes (OR = 1.361; 95% CI, 1.095-1.692), qi deficiency (OR = 9.883; 95% CI, 2.052, 47.593), GOLD C (OR =2.232; 95% CI, 1.866, 2.670) and GOLD D (OR = 2.195; 95% CI, 1.826-2.637) were factors affecting muscle loss in COPD patients. Conclusion: Sarcopenia is more prevalent in patients with COPD. Age, body mass index, smoking, diabetes mellitus, qi deficiency, ALB, and GOLD grade were the contributing factors for sarcopenia in patients with chronic obstructive pulmonary disease. In the future, medical staff should not only pay attention to the early screening of sarcopenia in high-risk groups, but also provide relevant prevention information.

Identification of metabolites reproducibly associated with Parkinson's Disease via meta-analysis and computational modelling.

Many studies have reported metabolomic analysis of different bio-specimens from Parkinson's disease (PD) patients. However, inconsistencies in reported metabolite concentration changes make it difficult to draw conclusions as to the role of metabolism in the occurrence or development of Parkinson's disease. We reviewed the literature on metabolomic analysis of PD patients. From 74 studies that passed quality control metrics, 928 metabolites were identified with significant changes in PD patients, but only 190 were replicated with the same changes in more than one study. Of these metabolites, 60 exclusively increased, such as 3-methoxytyrosine and glycine, 54 exclusively decreased, such as pantothenic acid and caffeine, and 76 inconsistently changed in concentration in PD versus control subjects, such as ornithine and tyrosine. A genome-scale metabolic model of PD and corresponding metabolic map linking most of the replicated metabolites enabled a better understanding of the dysfunctional pathways of PD and the prediction of additional potential metabolic markers from pathways with consistent metabolite changes to target in future studies.

Comprehensive Lipidomic Analysis of Three Edible Microalgae Species Based on RPLC-Q-TOF-MS/MS.

Microalgae, integral to marine ecosystems for their rich nutrient content, notably lipids and proteins, were investigated by using reversed-phase liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RPLC-Q-TOF-MS/MS). This study focused on lipid composition in three commonly used microalgae species (Spirulina platensis, Chlorella vulgaris, and Schizochytrium limacinum) for functional food applications. The analysis unveiled more than 700 lipid molecular species, including glycolipids (GLs), phospholipids (PLs), sphingolipids (SLs), glycerolipids, and betaine lipids (BLs). GLs (19.9-64.8%) and glycerolipids (24.1-70.4%) comprised the primary lipid. Some novel lipid content, such as acylated monogalactosyldiacylglycerols (acMGDG) and acylated digalactosyldiacylglycerols (acDGDG), ranged from 0.62 to 9.68%. The analysis revealed substantial GLs, PLs, and glycerolipid variations across microalgae species. Notably, S. platensis and C. vulgaris displayed a predominance of fatty acid (FA) 18:2 and FA 18:3 in GLs, while S. limacinum exhibited a prevalence of FA 16:0, collectively constituting over 60% of the FAs of GLs. In terms of PLs and glycerolipids, S. platensis and C. vulgaris displayed elevated levels of arachidonic acid (AA) and eicosapentaenoic acid (EPA), whereas S. limacinum exhibited a significant presence of docosahexaenoic acid (DHA). Principal component analysis (PCA) revealed MGDG (16:0/18:1), DG (16:0/22:5), Cer (d18:1/20:0), and LPC (16:1) as promising lipid markers for discriminating between these microalgae samples. This study contributes to a comprehensive understanding of lipid profiles in three microalgae species, emphasizing their distinct biochemical characteristics and potentially informing us of their high-value utilization in the food industry.

Effect of cytochrome c release on the mitochondrial-dependent apoptosis and quality deterioration of black rockfish (Sebastes schlegelii) postmortem storage.

Apoptosis was associated with decreased sensory quality attributes of fish during postmortem storage. Based on cytochrome c (cyt-c) release plays a crucial role in apoptosis, the study aims to investigate the factors regulating cyt-c release and whether cyt-c acts as an endogenous pro-oxidant to trigger lipid oxidation. Within 12 h postmortem, dramatic changes in the intramuscular environment (glycogen from 1.57 mg/g to 0.65 mg/g; ATP reduced by 92.91%; pH value reaching the lowest (pH = 7.14)) and the mitochondrial environment (accumulation of mitochondrial ROS and Ca2+ levels) are induced mitochondrial swelling and opening of the MPTP (increased 34.35% and 31.91%), leading to the release of cyt-c from the mitochondria into the cytoplasm and the activation of caspase-3. This leads to lipid oxidation and degradation of myofibrillar proteins, accelerating quality deterioration in color and texture. The results suggest that cyt-c is involved in lipid oxidation during postmortem through the apoptotic mitochondrial pathway.

PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.

Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.

Dynamics of endothelial cells migration in nature-mimicking blood vessels.

Endothelial cells (ECs) migration is a crucial early step in vascular repair and tissue neovascularization. While extensive research has elucidated the biochemical drivers of endothelial motility, the impact of biophysical cues, including vessel geometry and topography, remains unclear. Herein, we present a novel approach to reconstruct 3D self-assembly blood vessels-on-a-chip that accurately replicates real vessel geometry and topography, surpassing conventional 2D flat tube formation models. This vessels-on-a-chip system enables real-time monitoring of vasculogenesis and ECs migration at high spatiotemporal resolution. Our findings reveal that ECs exhibit increased migration speed and directionality in response to narrower vessel geometries, transitioning from a rounded to a polarized morphology. These observations underscore the critical influence of vessel size in regulating ECs migration and morphology. Overall, our study highlights the importance of biophysical factors in shaping ECs behavior, emphasizing the need to consider such factors in future studies of endothelial function and vessel biology.