Biology subjects

zhu, y.

Publications and source records attributed to zhu, y..

4 recordsLinked to original sources

bioRxiv2026

Disease stage-sensitive MFSD2A-caveolae axis insigates hippocampal blood-brain barrier disruption in Alzheimer's disease

Blood-brain barrier (BBB) malfunction contributes to pathophysiology of Alzheimer's disease (AD), yet the mechanisms that confer hippocampal endotheliocytes vulnerability remain unclear. Here we identify loss of endothelial major facilitator superfamily domain-containing protein 2A (MFSD2A), a suppressor of caveolae-mediated transcytosis, as an early and hippocampus-specific feature of AD-associated vascular impairment. In post-mortem human AD brains, reduction in hippocampal MFSD2A was accompanied with increased levels of caveolin-1 and perivascular albumin extravasation. Analysis of human single-nucleus transcriptomic data further demonstrated that vascular expression of MFSD2A declined during transition from mild cognitive impairment to established AD. In APP/PS1 mice, MFSD2A loss occurred early in hippocampal microvessels and coincided with disproportionately high hippocampal BBB leakage and reductions in GLUT1 and claudin-5, despite broader amyloid deposition throughout other brain regions. Restoration of endothelial MFSD2A using an AAV-BR1-based vascular vector during early stage of amyloid pathology, reduced albumin extravasation and preserved GLUT1 and claudin-5. Early intervention also reduced amyloid plaque burden and plaque-associated neuritic dystrophy, whereas this treatment during established amyloid pathology, although modifying selected endothelial markers, failed to reverse BBB leakage, amyloid pathology, or cognitive impairment. Sustained MFSD2A restoration from the early disease stage provided the greatest protection, preserving hippocampal BBB integrity, reducing amyloid and neuritic pathology, improving long-term potentiation and ameliorating spatial learning and memory deficits. These findings define endothelial MFSD2A loss as a disease stage-sensitive mechanism of hippocampal BBB vulnerability and highlight the MFSD2A-caveolae axis as a therapeutic target for early-stage AD.

neuroscience↗

bioRxiv2026

β-Catenin Drives Apical-Basal Polarization to facilitate TE lineage commitment In Vitro and In Vivo

Embryo polarization is critical for the first cell fate segregation. While mechanisms underlying its initiation have been described, the intrinsic signaling pathways that regulate this process remain poorly understood. Here, we show that mouse embryonic stem cells, when aggregated under defined conditions, recapitulate the first lineage segregation to generate trophectoderm (TE)-like cell populations and undergo self-organized morphogenesis into blastocyst-like structures. In the blastoid-forming medium, we identify CHIR99021 is essential for the generation of blastoids from both ESCs and totipotent-like cells. CHIR99021 promotes cell polarization and TE differentiation by activating the WNT/{beta}-catenin pathway and upregulating associated genes. Consistent with this, genetic ablation of {beta}-catenin abolished the cell polarization and disrupted blastoid formation from ESCs, a defect that was restored by {beta}-catenin overexpression. Moreover, {beta}-catenin depletion compromised cell polarization in natural embryos. Collectively, this study establishes the Wnt/{beta}-catenin as a critical regulator initiating polarization in vitro and in mouse early embryo development.

developmental biology↗

bioRxiv2025

Bioactive 3D-bioprinted scaffolds with endothelial progenitor cells and Zn2+-enhanced SFMA/HisMA/nHAP for healing of infected bone defect

Infected bone defects remain one of the greatest challenges in orthopedics, as bacterial contamination and insufficient vascularization severely compromise regeneration. Here, we report the development of a multifunctional 3D-bioprinted scaffold composed of zinc ion (Zn{superscript 2}{square}) functionalized silk fibroin methacryloyl (SFMA), histidine methacryloyl (HisMA), and nano-hydroxyapatite (nHAP), further loaded with endothelial progenitor cells (EPCs) to promote simultaneous antibacterial, angiogenic, and osteogenic responses. The photocrosslinkable SFMA/HisMA bio-ink reinforced with nHAP provided mechanical stability, controlled swelling and degradation, while Zn{superscript 2}{square} coordination endowed strong antibacterial activity against E. coli and S. aureus. EPCs adhered and proliferated on the scaffolds, and in co-culture with bone marrow stromal cells (BMSCs) markedly enhanced osteogenic differentiation, as evidenced by increased expression of OCN, RUNX2, COL1, and OPN. Proteomic profiling further revealed that EPC-loaded scaffolds modulated osteoblast protein expression patterns consistent with both immunoregulation and active extracellular matrix reconstruction to promote tissue regeneration. In a murine femoral infected defect model, EPC-loaded scaffolds suppressed pro-inflammatory cytokines (IL-6, TNF-), stimulated angiogenesis, and supported robust new bone formation, leading to accelerated defect repair confirmed by {micro}CT and histological analyses. Together, these findings demonstrate that the EPC-loaded Zn{superscript 2}{square} functionalized SFMA/HisMA/nHAP scaffold integrates antibacterial defence with vascular and osteogenic stimulation, offering a promising translational strategy for the treatment of complex infected bone defects. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/676384v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1a75a57org.highwire.dtl.DTLVardef@1c32b6org.highwire.dtl.DTLVardef@1456159org.highwire.dtl.DTLVardef@1fa5321_HPS_FORMAT_FIGEXP M_FIG C_FIG Schematic illustration of materials synthesis and application. Silk fibroin was modified with glycidyl methacrylate (GMA) to obtain silk fibroin methacryloyl (SFMA), while histidine was functionalized with acryloyl chloride to generate histidine methacryloyl (HisMA). SFMA and HisMA were then combined and coordinated with Zn{superscript 2}{square} ions and incorporated with nHAP to form the full-component bioactive scaffold (SFMA/HisMA/nHAP/Zn{superscript 2}{square}). The resulting material can be 3D-printed and loaded with endothelial progenitor cells (EPCs) to yield a multifunctional scaffold with antibacterial activity, pro-osteogenic and pro-angiogenic properties, favorable physicochemical characteristics, and excellent biocompatibility, making it a promising candidate for the treatment of infected bone defects.

bioengineering↗

bioRxiv2018

Convolutional Sparse Coded Dynamic Brain Functional Connectivity

Functional brain network has been widely studied in many previous work for brain disorder diagnosis and brain network analysis. However, most previous work focus on static dynamic brain network research. Lots of recent work reveals that the brain shows dynamic activity even in resting state. Such dynamic brain functional connectivity reveals discriminative patterns for identifying many brain disorders. Current sliding window based dynamic brain connectivity framework are not easy to be applied to real clinical applications due to many issues: First, how to set up the optimal sliding window size and how to determine the threshold for the brain connectivity patterns. Secondly, how to represent the high dimensional dynamic brain connectivity pattern in a low dimensional representations for diagnosis purpose. Last, how to deal with the different length dynamic brain network patterns especially when the raw data are of different length. In order to address all those above issues, we proposed a new framework, which employs multiple scale sliding windows and automatically learns a sparse and low ran dynamic brain functional connectivity patterns from raw fMRI data. Furthermore, we are able to measure different length dynamic brain functional connectivity patterns in an equal space by learning a sparse coded convolutional filters. We have evaluated our method with state of the art dynamic brain network methods and the results demonstrated the strong potential of our methods for brain disorder diagnosis in real clinical applications.

bioinformatics↗