Biology subjects

yang, x.

Publications and source records attributed to yang, x..

10 recordsLinked to original sources

bioRxiv2026

Transferable IncX3-blaNDM-15 in an uncommon ST580 Klebsiella pneumoniae recovered during paediatric intensive-care surveillance

Objective: Carbapenem-resistant Klebsiella pneumoniae harboring blaNDM poses a serious threat to public health; however, blaNDM-15 remains poorly characterized outside the dominant epidemic lineages. Methods: We characterized K. pneumoniae strain ETFK6090, isolated from a perianal surveillance swab of an 11-month-old immunocompromised child in a paediatric intensive care unit. Investigations included antimicrobial susceptibility testing, broth conjugation, S1 nuclease PFGE with Southern blotting, complete genome sequencing, and comparative genomic analysis against 465 curated blaNDM-positive K. pneumoniae genomes from 37 countries. Results: ETFK6090 belonged to ST580 and exhibited resistance to carbapenems, ceftazidime-avibactam, broad-spectrum cephalosporins, fluoroquinolones, gentamicin, chloramphenicol and trimethoprim-sulfamethoxazole; amikacin and fosfomycin retained low MICs. The complete genome comprised one chromosome and five plasmids, blaNDM-15 was localized on a 46,161-bp IncX3 plasmid, confirmed by Southern blotting. Conjugation into Escherichia coli EC600 transferred carbapenem and cephalosporin resistance, confirming in vitro mobility. The blaNDM-15 genetic environment retained a conserved blaNDM module, with IS-mediated rearrangements at the downstream boundary. In the global comparison, blaNDM-1 and blaNDM-5 predominated, the ST580-blaNDM-15 combination was exceedingly rare, and ETFK6090 constituted a distinct branch apart from major epidemic lineages. Conclusions: A transferable IncX3-blaNDM-15 plasmid can emerge in an uncommon ST580 background, underscoring the necessity to extend genomic surveillance of carbapenem-resistant K. pneumoniae beyond dominant epidemic clones, particularly in high-risk paediatric and intensive-care settings.

microbiology↗

bioRxiv2026

Dissociation of Diffusion and Perfusion Responses After Intracerebral Hemorrhage

Background and PurposeIntracerebral hemorrhage (ICH) triggers complex secondary injury processes that extend beyond hematoma formation. While structural and diffusion MRI are widely used to characterize tissue injury, the spatiotemporal evolution of cerebral perfusion after ICH, particularly in small-animal models, remains poorly defined. Here, we performed a longitudinal multiparametric MRI study to delineate the relationship between microstructural injury and cerebral perfusion following experimental ICH. MethodsA collagenase-induced mouse model of ICH was studied longitudinally from baseline to 21 days post-stroke. Hematoma volume, tissue microstructure, and cerebral blood perfusion (CBP) were quantified using T2*-weighted MRI, diffusion-weighted imaging, and pseudo-continuous arterial spin labeling (pCASL) MRI, respectively. Apparent diffusion coefficient (ADC) and CBP were quantified in multiple brain regions from both ipsilateral and contralateral hemispheres and analyzed using linear mixed-effects models. ResultsHematoma volume peaked acutely and gradually attenuated over time. ADC exhibited an early reduction largely confined to the striatum, followed by progressive recovery, consistent with localized cytotoxic edema and subsequent attenuation. In contrast, CBP showed a marked bilateral hypoperfusion during the acute phase, followed by a delayed perfusion increase that was spatially restricted to the ipsilateral striatum. Notably, significant contralateral perfusion alterations were observed despite minimal contralateral diffusion changes, indicating a dissociation between microstructural injury and vascular regulation. ConclusionsMicrostructural and perfusion responses after ICH follow distinct spatiotemporal trajectories. Whereas diffusion abnormalities are largely localized to the hemorrhagic core, perfusion disturbances extend bilaterally beyond the lesion site. These findings challenge the common assumption of contralateral physiological stability after focal hemorrhage and highlight the value of quantitative perfusion MRI for capturing systemic cerebrovascular responses that are not reflected by diffusion or anatomical measures alone.

physiology↗

bioRxiv2025

Vascular Microbleeds Without Brain Atrophy: A Microvascular Signature of Mid-Stage 5xFAD Pathology

Cerebral microbleeds are increasingly recognized as a downstream manifestation of vascular injury in Alzheimers disease (AD), arising secondary to cerebral amyloid angiopathy (CAA). Here, we examined the pathological specificity of microbleeds by comparing an amyloidosis mouse model (5xFAD) with a small-vessel disease (SVD) model characterized by vascular smooth-muscle cell loss. In vivo multimodal MRI, including gradient-echo, spin-echo, and diffusion-weighted imaging, was complemented by ex vivo high-resolution anatomical scans for validation. Both in vivo and ex vivo gradient-echo MRI consistently revealed hippocampal microbleeds in the 5xFAD model without macroscopic atrophy or ventricular enlargement, whereas no microbleeds or blood-brain barrier disruption were detected in the SVD model. Diffusion-weighted MRI further showed region-specific alterations in apparent diffusion coefficient within the midbrain of 5xFAD mice, but not in other regions or in the SVD cohort. These findings indicate that microbleeds are a pathology-specific marker of amyloid-related vascular injury. The imaging evidence underscores the potential of microbleeds as a disease-specific biomarker for detecting amyloid-driven vascular fragility and refining diagnostic and therapeutic strategies for AD.

neuroscience↗

bioRxiv2025

Vascular smooth muscle cell loss, but not neuroinflammation, drives cerebrovascular reactivity impairment in Alzheimer disease

INTRODUCTIONCerebrovascular reactivity (CVR) impairment is a key feature of Alzheimers disease (AD), but its mechanistic basis remains unclear. This study examined whether vascular smooth muscle cell (VSMC) loss, rather than amyloidosis or neuroinflammation, underlies CVR deficits. METHODSNon-contrast MRI, including phase-contrast and pseudo-continuous arterial spin labeling, was performed in mouse models of amyloidosis (5xFAD), VSMC degeneration (CADASIL), and lipopolysaccharide-induced neuroinflammation. Characterization of vascular, amyloid-{beta}, and inflammatory markers were performed for pathological assessment. RESULTSCVR impairment emerged only when VSMC loss was present in CADASIL mice and at older ages in 5xFAD mice (9-12 months). Amyloid-{beta} deposition occurred earlier than VSMC loss or CVR decline. Neuroinflammation primarily altered baseline cerebral blood flow without affecting CVR or VSMC integrity. DISCUSSIONThese findings identify VSMC degeneration as an important driver of CVR impairment independent of cerebral amyloid angiopathy or inflammation, highlighting vascular integrity as a potential therapeutic target in AD. HighlightsO_LICerebrovascular reactivity (CVR) impairment occurred in 5xFAD mice only when vascular smooth muscle cell (VSMC) loss was present C_LIO_LI5xFAD mice exhibited prominent parenchymal but minimal vascular amyloid-{beta} deposition C_LIO_LIVSMC developmental deficiency resulted in CVR impairment in a small-vessel disease (SVD) model C_LIO_LINeuroinflammation primarily altered baseline cerebral blood flow (CBF) without affecting CVR C_LI

bioengineering↗

bioRxiv2025

Genetic association between posterior parietal cortex and intelligence

The identification of intelligence-associated loci raises questions for functional association of brain regions and for different intelligence concepts of either a general capability or discrete abilities. By generating single-nucleus transcriptomic atlas of mouse posterior parietal cortex (PPC), which is implicated in quantification behavior, we find that human intelligence-associated gene homologs are significantly enriched in certain specific neurons within the PPC. We also find 73% of the human intelligence gene homologs are highly enriched in PPC. In addition to PPC, several regions at different locations, not cortex next to PPC, are also significantly associated with intelligence genes. The separate locations of these cortex regions and their regional-specific expressed intelligence genes raise the possibility for discrete intelligence capabilities. Animal behavior analysis reveals that mutations for two top intelligence-associated genes with specific expression in either PPC or entorhinal cortex (ENT) affect quantification or learning and memory, respectively. Finally, five patients with PPC resection in the left hemisphere also display quantification defects, but not other cognitive abilities. Together, our studies provide the first genetic and functional evidence for the involvement of PPC in intelligence. Our data also support the model of multiple intelligence over a general capability for intelligence.

genetics↗

bioRxiv2024

Improving the accuracy of cerebral blood flow measurement by phase contrast MRI

Cerebral blood flow (CBF) is a critical hemodynamic marker for natural aging and pathological conditions. It can be assessed non-invasively by the phase-contrast (PC) magnetic resonance imaging (MRI) technique. Although the technical principle of PC MRI is straightforward, related experimental settings, e.g., spatial resolution, partial volume effect, slice positioning angle, and signal-to-noise ratio (SNR), require deliberate considerations to ensure measurement accuracy. In this study, we performed simulations to systematically investigate the dependence of measurement accuracy of PC MRI on the spatial resolution, extent of partial volume effect, slice imperfection angle, and SNR. It has been found that at least 6 voxels along the vessel diameter are required to ensure accurate CBF measurements. Partial volume effect acts to underestimate CBF measurements. The tolerance against slice imperfection angle is [≤]15 degree for the commonly seen artery in mice under isoflurane anesthesia. A normalized SNR of 25.47 dB is required to ensure the accuracy of CBF measurement. Our study will promote the utilization of CBF as a pathophysiological marker for future studies by delineating the factors affecting measurement accuracy in PC MRI.

physiology↗

bioRxiv2024

Artificial Intelligence-Enabled AlphaFold II Pipeline Guides Functional Fluorescence Labeling of Tubulin Across Species

Dynamic properties are essential for microtubule (MT) physiology. Current techniques for in vivo imaging of MTs present intrinsic limitations in elucidating the isotype-specific nuances of tubulins, which contribute to their versatile functions. Harnessing the power of AlphaFold II pipeline, we engineered a strategy for the minimally invasive fluorescence labeling of endogenous tubulin isotypes or those harboring missense mutations. We demonstrated that a specifically designed 16-amino acid linker, coupled with sfGFP11 from the split-sfGFP system and integration into the H1-S2 loop of tubulin, facilitated tubulin labeling without compromising MT dynamics, embryonic development, or ciliogenesis in C. elegans. Extending this technique to human cells and murine oocytes, we visualized MTs with the minimal background fluorescence and a pathogenic tubulin isoform with fidelity. The utility of our approach across biological contexts and species set an additional paradigm for studying tubulin dynamics and functional specificity, with implications for understanding tubulin-related diseases known as tubulinopathies.

cell biology↗

bioRxiv2023

Neural stem cells protect the integrity of blood-brain barrier via the p38, JNK and ERK1/2 pathways following intracerebral hemorrhage in rats

Neural stem cells (NSCs) have displayed great potential in ameliorating brain damage following intracerebral hemorrhage (ICH) via proliferation, differentiation, and immunomodulation. However, it remains unclear whether NSCs can improve microvascular function, e.g., blood-brain barrier (BBB) integrity, after ICH. In this study, we investigate the potential therapeutic benefit of NSCs on BBB integrity as well as the underlying mechanism. Adult male Sprague-Dawley rats were randomly divided into sham, ICH+PBS, and ICH+NSCs groups for comparisons. ICH was induced by intrastriatal injection of bacterial collagenase. An aliquot of NSCs or PBS was injected via the tail vein 2 h after ICH induction. The following multiparametric measurements were compared: brain edema, hematoma volume, behavior, BBB permeability, and mitogen-activated protein kinase (MAPK) signaling pathway activity. We found that NSCs treatment attenuates BBB permeability, reduces brain edema, and promotes brain function recovery after ICH by inhibiting ERK1/2, p38, and JNK signaling pathway activation. These findings provide novel insight for future therapies aiming to prevent BBB dysfunction and improve functional recovery in ICH patients.

neuroscience↗

bioRxiv2022

Embracing fine-root system complexity to improve the predictive understanding of ecosystem functioning

Projecting the functioning of the biosphere requires a holistic consideration of whole-ecosystem processes. Although improving leaf and canopy processes has been the focus of ecosystem model development since the 1970s, the arbitrary homogenization of fine-root systems into a single pool is at odds with observations. This discrepancy has increased in the last two decades as accelerated conceptual and empirical advances have revealed functional differentiation and cooperation conferred by the hierarchical structure of fine-root orders and associations with mycorrhizal fungi in fine-root systems. To close this model-data gap, we propose a 3-pool structure comprising Transport and Absorptive fine roots with Mycorrhizal fungi (TAM) to model vertically resolved fine-root systems across organizational and spatial-temporal scales. A comparison of TAM to the single fine-root structure in a state-of-the-art Earth System Model using the big-leaf approach demonstrates robust impacts on carbon cycling in temperate forests, lending further quantitative support to the empirical and theoretical basis for TAM. Strong support in both theory and practice therefore suggests a move beyond the useful but incorrect paradigm of single-pool homogenization, echoing a broad trend of embracing ecological complexities in terrestrial ecosystem modelling. Although challenges lay ahead towards realizing TAM in ecologically realistic demography models simulating emergent functioning from pattern and diversity, adoption of TAM by both modelers and empiricists holds promise to build a better predictive understanding of ecosystem functioning in the context of global change.

ecology↗

bioRxiv2020

Controlled-release urea combined with potassium chloride improved the soil fertility and growth of Italian ryegrass

A field experiment with a split-plot design was conducted to study the effect of nitrogen fertilizer type combined with different potassium fertilizer rates on the soil fertility and growth of Italian ryegrass. The main plots were assigned to controlled-release urea (CRU) and common urea, while low, moderate and high potassium chloride (KCl) rates (150, 300 and 450 kg ha-1, respectively) were assigned to the subplots. The results showed compared with the common urea, the CRU significantly increased the SPAD value, plant height, leaf area, and photosynthetic index. Moreover, the dry and fresh yields of the CRU increased by 10.9-25.3% and 11.8-17.7%, respectively. At the same time, compared with the KCl150 and KCl450 treatments, the KCl300 treatment resulted in better plant growth. Overall, the CRUxKCl300 maximized the soil inorganic nitrogen and different soil potassium forms. The root length, volume, surface area, average diameter, tips and branches were also improved, and there was a significant NxK interaction effect on the tips. Our analysis corroborated the CRU combined with 300 kg ha-1 KCl fertilization enhances crop growth by improving leaf photosynthesis, soil fertility, and yield and should be recommended as the best fertilizer ratio for Italian ryegrass production.

plant biology↗