Biology subjects

Qiao, T.

Publications and source records attributed to Qiao, T..

4 recordsLinked to original sources

bioRxiv2025

Nanoplastics Penetration Across the Blood-Brain Barrier

Microplastics and nanoplastics (MNPs), originating from plastic degradation, have arisen to be a threat to ecology and human health. Alarmingly, the penetration of MNPs across the highly selective blood-brain barrier (BBB) poses an emerging and urgent risk, yet its molecular mechanism remains unexplored. In this work, using long-time-scale (over 27 s) all-atom explicit solvent steered molecular dynamics, we examine the free energy of the passive permeation of four polymer nanoparticles: polyethylene, polypropylene, polystyrene, and polyethylene terephthalate. Polyethylene and polypropylene nanoparticles exhibited a remarkable preference for entering the BBB, attributed to their high hydrophobicity. Our study reveals that polymers can enter the BBB as polymerized nanoplastics and exit as dispersed polymer chains as the nanoparticles dissolve within the BBB. Further, the crystalline structure of polyethylene nanoparticles is found to adopt varying orientations. Our work advances the knowledge about the mechanism of nanoplastic penetration across the BBB, which could aid in the rational design of therapeutics for nanoplastic penetration inhibitors. TOC Graphics O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/675462v1_ufig1.gif" ALT="Figure 1"> View larger version (71K): org.highwire.dtl.DTLVardef@1b20796org.highwire.dtl.DTLVardef@1102985org.highwire.dtl.DTLVardef@15fc22org.highwire.dtl.DTLVardef@15c2260_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2024

Silaffins-Driven Genetic Engineering of Diatom Cell Walls: Insight into Biosilica Morphology and Nanomaterial Design

Diatoms synthesize silica cell walls (frustules) with genetically encoded morphologies, ranging from nanopatterns to micropatterns, that far exceed current synthetic chemistry. Silaffins, a family of phosphoproteins undergoing complex post-translational modifications, have been isolated from frustules and shown to facilitate and regulate biosilica formation in vitro with long-chain polyamines. However, their particular role in frustule morphogenesis and functionality remains unclear. In this study, functions of two representative silaffins, TpSil1 and TpSil3, were investigated in the model organism Thalassiosira pseudonana using gene overexpression and CRISPR/Cas9-mediated knockout approaches. Due to high sequence homology, TpSil2 was concurrently disrupted in TpSil1 knockout strains, while the homozygous knockout of TpSil3 proved to be lethal. Quantitative morphological analysis revealed distinct yet complementary roles: TpSil3 governs both microscale overall size and mesoscale features, including macropore (fultoportula) density and mesopore (cribrum pore) pattern, whereas TpSil1/2 exclusively contribute to macropore morphogenesis and mesopore density. Overexpression of silaffins increased silica deposition, while knockouts exhibited reduced silicification but enhanced cell growth and photosynthetic efficiency. Furthermore, these genetic modifications significantly influenced the physicochemical and optical properties of bulk frustules, potentially enhancing the hemostatic, catalytic and photonic performances, thereby positioning them as versatile candidates for a wide range of biotechnological and industrial applications. Collectively, our findings elucidate the distinct roles of TpSil1/2 and TpSil3 in diatom physiology and frustule morphology, highlighting a promising pathway for engineering nanostructured silica materials with tailored properties through synthetic biology.

synthetic biology↗

bioRxiv2022

Aging-related iron deposit prevents the benefits of HRT from late postmenopausal atherosclerosis

Postmenopausal atherosclerosis has been attributed to estrogen deficiency. The beneficial effect of hormone replacement therapy (HRT), however, is lost in late postmenopausal women with atherogenesis. We asked whether aging-related iron accumulation affects estrogen receptor (ER) expression explaining HRT inefficacy. A negative correlation between aging-related systemic iron deposition and ER expression in postmenopausal AS patients was established. In an ovariectomized ApoE-/- mouse model, estradiol treatment had contrasting effects on ER expression in early versus late postmenopausal mice. ER expression was inhibited by iron treatment in cell culture and iron-overloaded mice. Combined treatment with estradiol and iron further decreased ER expression, mediated by iron-regulated E3 ligase Mdm2. In line with these observations, cellular cholesterol efflux was reduced and endothelial homeostasis was disrupted and, consequently, atherosclerosis was aggravated. Accordingly, systemic iron chelation attenuated estradiol-triggered progressive atherosclerosis in late postmenopausal mice. Thus, iron and estradiol together downregulate ER through Mdm2-mediated proteolysis, explaining failures of HRT in late postmenopausal subjects with aging-related iron accumulation. HRT is recommended immediately after menopause along with appropriate iron chelation to protect from atherosclerosis.

cell biology↗

bioRxiv2021

Low-level overexpression of wild type TDP-43 causes late-onset, progressive neurodegeneration and paralysis in mice

Modestly increased expression of transactive response DNA binding protein (TDP-43) gene have been reported in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neuromuscular diseases. However, whether this modest elevation triggers neurodegeneration is not known. Although high levels of TDP-43 overexpression have been modeled in mice and shown to cause early death, models with low-level overexpression that mimic the human condition have not been established. In this study, transgenic mice overexpressing wild type TDP-43 at less than 60% above the endogenous CNS levels were constructed, and their phenotypes analyzed by a variety of techniques, including biochemical, molecular, histological, behavioral techniques and electromyography. The TDP-43 transgene was expressed in neurons, astrocytes, and oligodendrocytes in the cortex and predominantly in astrocytes and oligodendrocytes in the spinal cord. The mice developed a reproducible progressive weakness ending in paralysis in mid-life. Detailed analysis showed [~]30% loss of large pyramidal neurons in the layer V motor cortex; in the spinal cord, severe demyelination was accompanied by oligodendrocyte injury, protein aggregation, astrogliosis and microgliosis, and elevation of neuroinflammation. Surprisingly, there was no loss of lower motor neurons in the lumbar spinal cord despite the complete paralysis of the hindlimbs. However, denervation was detected at the neuromuscular junction. These results demonstrate that low-level TDP-43 overexpression can cause diverse aspects of ALS, including late-onset and progressive motor dysfunction, neuroinflammation, and neurodegeneration. Our findings suggest that persistent modest elevations in TDP-43 expression can lead to ALS and other neurological disorders involving TDP-43 proteinopathy. Because of the predictable and progressive clinical paralytic phenotype, this transgenic mouse model will be useful in preclinical trial of therapeutics targeting neurological disorders associated with elevated levels of TDP-43.

genetics↗