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1.
J Cell Mol Med ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32168434

RESUMO

The non-POU domain-containing octamer-binding protein NONO/p54nrb , which belongs to the Drosophila behaviour/human splicing (DBHS) family, is a multifunctional nuclear protein rarely functioning alone. Emerging solid evidences showed that NONO engages in almost every step of gene regulation, including but not limited to mRNA splicing, DNA unwinding, transcriptional regulation, nuclear retention of defective RNA and DNA repair. NONO is involved in many biological processes including cell proliferation, apoptosis, migration and DNA damage repair. Dysregulation of NONO has been found in many types of cancer. In this review, we summarize the current and fast-growing knowledge about the regulation of NONO, its biological function and implications in tumorigenesis and cancer progression. Overall, significant findings about the roles of NONO have been made, which might make NONO to be a new biomarker or/and a possible therapeutic target for cancers.

2.
Biomed Environ Sci ; 33(2): 114-122, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32131958

RESUMO

Objective: To compare the pathogenicity of isolates of sequence type 7 (ST-7) Neisseria meningitidis( N. meningitidis) belonging to four different serogroups (A, B, C, and X). Methods: Four ST-7 N. meningitidis isolates serogrouped as A, B, C, and X and characterized by different capsule structures, were examined for their adhesion and invasion properties, and their ability to induce cytokine release and apoptosis in the host cell (the A549 cell line). Results: Among the four ST-7 N. meningitidis isolates, the serogroup A isolate possessed the strongest adhesion and invasion ability. This isolate also induced the release of the highest levels of the pro-inflammatory mediators interleukin-6, interleukin-1ß, and interferon, and the highest apoptosis rate in the host cells. However, there was no significant difference in interleukin-8 and tumor necrosis factor-α secretion between the four isolates. Based on the findings, the serogroup X N. meningitidis isolate had the weakest pathogenicity, whereas there was almost no difference in the pathogenicity of the isolates from serogroups B and C. Conclusions: The differences in the capsular structure of the four isolates of ST-7 N. meningitidis affected their pathogenic capacities. The findings also imply that the hyperinvasive ST-7 N. meningitidis lineage may include hypoinvasive isolates.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 233: 118169, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32143169

RESUMO

A highly sensitive detection system for sulfur dioxide (SO2) and nitric oxide (NO) was developed via deep ultraviolet differential optical absorption spectroscopy (DUV-DOAS). The wavelength range of 200-230 nm was used which was rarely used before as result of severe cross sensitivity to SO2 and NO, in this work, this problem was overcame. A system detection limit (DL) of 60 ppb for SO2 has been reached which was among the best ones. Meanwhile, a novel method based on spectrum superposition theory was proposed to decompose the differential optical density (DOD) of NO from that of gas mixture in cross sensitive band. The advantage of this method is that the most sensitive absorption peak of NO was used, which cannot be used by conventional methods due to the cross sensitive to SO2. A system DL of 7 ppb for NO has been achieved which is among the best ones reported before. Furthermore, the effect of gas temperature and humidity on concentration retrieval has also been studied, gas temperature and humidity compensation models have also been proposed. The experimental results show that the compensation models succeed in compensating the deviation caused by gas temperature and humidity. The environmental adaptability of the system has been enhanced. This work achieves the aim of monitoring ultra-low concentration of SO2 and NO in a complex environment simultaneously.

4.
Molecules ; 25(6)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204524

RESUMO

Five 8,17-epoxybriaranes, including three new compounds-briarenols I-K (1-3), along with two known analogues, briaexcavatolide P (4) and briaexcavatin P (5), were isolated from the octocoral Briareum excavatum. The structures of briaranes 1-3 were elucidated by spectroscopic methods, including 1D and 2D NMR studies and (+)-HRESIMS. Briarane 4 exerted inhibition effects on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) release from RAW 264.7.

5.
Water Res ; 175: 115673, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32171097

RESUMO

Due to the increase of emerging contaminants in water, how to use new treatment technology to make up for the defects of traditional wastewater treatment method has become one of the research hotspots at present. Intimate coupling of photocatalysis and biodegradation (ICPB) as a novel wastewater treatment method, which combines the advantages of biological treatment and photocatalytic reactions, has shown a great potential as a low-cost, environmental friendly and sustainable treatment technology. The system mainly consists of photocatalytic materials, porous carriers and biofilm. The key principle of ICPB is to transform bio-recalcitrant pollutants into biodegradable products by photocatalysis on the surface of porous carriers. The biodegradable products were mineralized simultaneously through the biofilm inside the carriers. Because of the protection of the carriers, the microorganism can remain active even under the UV-light, the mechanical force of water flow or the attack of free radicals. ICPB breaks the traditional concept that photocatalytic reaction and biodegradation must be separated in different reactors, improves the purification capacity of sewage and saves the cost. This review summarizes the recent advances of ICPB photocatalysts, carriers and biofilm being applied, and focuses on the mechanisms and reactor configurations which is particularly novel. Furthermore, the possible ongoing researches on ICPB are also put forward. This review will provide a valuable insight into the design and application of ICPB in environment and energy field.

6.
ACS Nano ; 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32167276

RESUMO

The "Zeeman effect" offers unique opportunities for magnetic manipulation of the spin degree of freedom (DOF). Recently, valley Zeeman splitting, referring to the lifting of valley degeneracy, has been demonstrated in two-dimensional transition metal dichalcogenides (TMDs) at liquid helium temperature. However, to realize the practical applications of valley pseudospins, the valley DOF must be controllable by a magnetic field at room temperature, which remains a significant challenge. Magnetic doping in TMDs can enhance the Zeeman splitting; however, to achieve this experimentally is not easy. Here, we report unambiguous magnetic manipulation of valley Zeeman splitting at 300 K (geff = -6.4) and 10 K (geff = -11) in a CVD-grown Fe-doped MoS2 monolayer; the effective Landé geff factor can be tuned to -20.7 by increasing the Fe dopant concentration, which represents an approximately 5-fold enhancement as compared to undoped MoS2. Our measurements and calculations reveal that the enhanced splitting and geff factors are due to the Heisenberg exchange interaction of the localized magnetic moments (Fe 3d electrons) with MoS2 through the d-orbital hybridization.

7.
Mol Med Rep ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186762

RESUMO

MicroRNAs (miRNAs/miRs) are non-coding RNAs that regulate protein synthesis by targeting mRNAs for translational repression or degradation. Previous studies have reported that aberrant expression of miR­744 may be involved in human osteosarcoma; however, the underlying mechanisms remain elusive. In the present study, the expression levels of miR­744 and its downstream signals were determined by reverse transcription­quantitative PCR and western blotting. Cell proliferation was assessed using the bromodeoxyuridine assay, and the target of miR­744 was investigated using a dual­luciferase activity assay. The present study identified a significant upregulation of miR­744 in osteosarcoma tissues compared with adjacent non­tumor tissues. Furthermore, it was demonstrated that ectopic overexpression of miR­744 induced by a miR­744 precursor significantly enhanced proliferation of the osteosarcoma cell line MG63, whereas opposite results were observed following suppression of miR­744 with its inhibitor. Moreover, as a unique anti­oncogene, PTEN was identified as a direct target of miR­744. It was confirmed that miR­744 downregulated PTEN expression in MG63 cells by targeting the PTEN 3'untranslated region, and that the downstream AKT signal was also regulated by miR­744. Collectively, the present results suggested that miR­744 promoted proliferation of human osteosarcoma cells by directly regulating the PTEN/AKT signaling pathway.

8.
J Neurosci ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32198185

RESUMO

Revealing the organization and function of neural circuits is greatly facilitated by viral tools that spread transsynaptically. Adeno-associated virus (AAV) exhibits anterograde transneuronal transport, however the synaptic specificity of this spread and its broad application within a diverse set of circuits remains to be explored. Here, using anatomical, functional, and molecular approaches, we provide evidence for the preferential transport of AAV1 to post-synaptically connected neurons and reveal its spread is strongly dependent on synaptic transmitter release. In addition to glutamatergic pathways, AAV1 also spreads through GABAergic synapses to both excitatory and inhibitory cell-types. We observed little or no transport, however, through neuromodulatory projections (e.g. serotonergic, cholinergic, and noradrenergic). In addition, we found that AAV1 can be transported through long-distance descending projections from various brain regions to effectively transduce spinal cord neurons. Combined with newly designed intersectional and sparse labeling strategies, AAV1 can be applied within a wide variety of pathways to categorize neurons according to their input sources, morphology, and molecular identities. These properties make AAV1 a promising anterograde transsynaptic tool for establishing a comprehensive cell-atlas of the brain, however, its capacity for retrograde transport currently limits its use to unidirectional circuits.SIGNIFICANCE STATEMENT: The discovery of anterograde transneuronal spread of AAV1 generates great promise for its application as a unique tool for manipulating input-defined cell populations and mapping their outputs. However, several outstanding questions remain for anterograde transsynaptic approaches in the field: 1) whether AAV1 spreads exclusively or specifically to synaptically connected neurons; 2) how broad its application could be in various types of neural circuits in the brain. This study provides several lines of evidence in terms of anatomy, functional innervation, and underlying mechanisms, to strongly support that AAV1 anterograde transneuronal spread is highly synapse specific. In addition, several potentially important applications of transsynaptic AAV1 in probing neural circuits are described.

9.
Elife ; 92020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32142411

RESUMO

Lateral posterior nucleus (LP) of thalamus, the rodent homologue of primate pulvinar, projects extensively to sensory cortices. However, its functional role in sensory cortical processing remains largely unclear. Here, bidirectional activity modulations of LP or its projection to the primary auditory cortex (A1) in awake mice reveal that LP improves auditory processing in A1 supragranular-layer neurons by sharpening their receptive fields and frequency tuning, as well as increasing the signal-to-noise ratio (SNR). This is achieved through a subtractive-suppression mechanism, mediated largely by LP-to-A1 axons preferentially innervating specific inhibitory neurons in layer 1 and superficial layers. LP is strongly activated by specific sensory signals relayed from the superior colliculus (SC), contributing to the maintenance and enhancement of A1 processing in the presence of auditory background noise and threatening visual looming stimuli respectively. Thus, a multisensory bottom-up SC-pulvinar-A1 pathway plays a role in contextual and cross-modality modulation of auditory cortical processing.

10.
J Am Chem Soc ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32164406

RESUMO

Here we describe an asymmetric [3,3]-sigmatropic rearrangement of aryl iodanes that enables the enantioselective α-arylation of chiral 2-oxazolines, thereby producing valuable chiral α-aryl carbonyl compounds. The success of this protocol hinges on the selective assembly of aryl iodanes with 2-oxazolines and the smooth deprotonation of the in situ-generated iodonium-imine species. The nearly neutral and mild conditions of the reaction allow it to tolerate a wide variety of functional groups. Moreover, the remaining iodine atom in the products not only provides a versatile platform for further elaboration of such molecules but also supplies the asymmetric hypervalent iodine chemistry with a new class of chiral scaffolds.

11.
Microb Biotechnol ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32212318

RESUMO

Vibrio alginolyticus threatens both humans and marine animals, but hosts respond to V. alginolyticus infection is not fully understood. Here, functional metabolomics was adopted to investigate the metabolic differences between the dying and surviving zebrafish upon V. alginolyticus infection. Tryptophan was identified as the most crucial metabolite, whose abundance was decreased in the dying group but increased in the survival group as compared to control group without infection. Concurrently, the dying zebrafish displayed excessive immune response and produced higher level of reactive oxygen species (ROS). Interestingly, exogenous tryptophan reverted dying rate through metabolome re-programming, thereby enhancing the survival from V. alginolyticus infection. It is preceded by the following mechanism: tryptophan fluxed into the glycolysis and tricarboxylic acid cycle (TCA cycle), promoted adenosine triphosphate (ATP) production and further increased the generation of NADPH. Meanwhile, tryptophan decreased NADPH oxidation. These together ameliorate ROS, key molecules in excessive immune response. This is further supported by the event that the inhibition of pyruvate metabolism and TCA cycle by inhibitors decreased D. reiro survival. Thus, our data indicate that tryptophan is a key metabolite for the host to fight against V. alginolyticus infection, representing an alternative strategy to treat bacterial infection in an antibiotic-independent way.

12.
Mol Med Rep ; 21(3): 1572-1580, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32016474

RESUMO

Chlamydia trachomatis (C. trachomatis) is the leading cause of bacterial sexually transmitted diseases and infectious diseases that cause blindness. The pathophysiology of chlamydial infections is poorly understood, but secreted proteins have emerged as key virulence factors. C. trachomatis glycogen synthase (GlgA) is a chlamydial secretory protein, which localizes in the lumen of chlamydial inclusion bodies and the cytosol of host cells. In order to improve understanding of the roles of GlgA in chlamydial pathogenesis, four proteins that interact with GlgA, Homo sapiens CXXC finger protein 1, prohibitin (PHB), gelsolin­like actin­capping protein and apolipoprotein A­I binding protein were identified using yeast two­hybrid assays. The functions of these proteins are complex, and preliminary results suggested that PHB interacts with GlgA. However, further studies are required to determine the specific interactions of these proteins with GlgA. The findings of the present study may provide a direction and foundation for future studies focusing on the mechanism of GlgA in C. trachomatis infection.

13.
J Am Chem Soc ; 142(10): 4663-4670, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32033517

RESUMO

Gigantic coordination molecules assembled from a large number of metal ions and organic ligands are structurally and functionally challenging to characterize. Here we show that a heterometallic cluster [Ni36Gd102(OH)132(mmt)18(dmpa)18(H2dmpa)24(CH3COO)84(SO4)18(NO3)18(H2O)30]·Br6(NO3)6·(H2O)x·(CH3OH)y, (1, x ≈ 130, y ≈ 60), shaped like a "Star of David", can be synthesized using a "mixed-ligand" and "sulfate-template" strategy. In terms of metal nuclearity number, 1 is the second largest 3d-4f cluster to date. In the solid state, 1 is porous after removing the lattice guests. The N2 adsoption experiment reveals that the BET and Langmuir surface areas are 299.8 and 412.0 cm2 g-1, respectively. CO2 adsorption at 298 K gives the amount of 45 cm3 g-1 for 1. More importantly, 1 is soluble in common organic solvents and exhibits high solution stability revealed by high resolution MALDI-TOF mass spectroscopy, small-angle X-ray scattering (SAXS), and low-dose transmission electron microscopy. The solubility and the potential open metal sites owing to the labile coordinating components prompted us to investigate the photocatalytic properties of 1, which displays high selectivity and efficiency for reduction of CO2 to CO with turnover number and turnover frequency of 29700 and 1.2 s-1, respectively. These values are higher than most catalysts working under the same conditions, presumably due to the strong Ni-CO2 binding effect. In addition, the large percentage of Gd(III) in 1 leads to a large magnetic entropy change (41.3 J·kg-1·K-1) at 2.0 K for ΔH = 7 T.

14.
Cell Death Dis ; 11(2): 79, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015330

RESUMO

Erythropoietin (EPO) is an evolutionarily conserved hormone well documented for its erythropoietic role via binding the homodimeric EPO receptor (EPOR)2. In past decades, evidence has proved that EPO acts far beyond erythropoiesis. By binding the tissue-protective receptor (TPR), EPO suppresses proinflammatory cytokines, protects cells from apoptosis and promotes wound healing. Very recently, new data revealed that TPR is widely expressed on a variety of immune cells, and EPO could directly modulate their activation, differentiation and function. Notably, nonerythropoietic EPO derivatives, which mimic the structure of helix B within EPO, specifically bind TPR and show great potency in tissue protection and immune regulation. These small peptides prevent the cardiovascular side effects of EPO and are promising as clinical drugs. This review briefly introduces the receptors and tissue-protective effects of EPO and its derivatives and highlights their immunomodulatory functions and application prospects.

15.
Nano Lett ; 20(3): 2129-2136, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32078769

RESUMO

Valley pseudospin in two-dimensional (2D) transition-metal dichalcogenides (TMDs) allows optical control of spin-valley polarization and intervalley quantum coherence. Defect states in TMDs give rise to new exciton features and theoretically exhibit spin-valley polarization; however, experimental achievement of this phenomenon remains challenges. Here, we report unambiguous valley pseudospin of defect-bound localized excitons in CVD-grown monolayer MoS2; enhanced valley Zeeman splitting with an effective g-factor of -6.2 is observed. Our results reveal that all five d-orbitals and the increased effective electron mass contribute to the band shift of defect states, demonstrating a new physics of the magnetic responses of defect-bound localized excitons, strikingly different from that of A excitons. Our work paves the way for the manipulation of the spin-valley degrees of freedom through defects toward valleytronic devices.

16.
Life Sci ; 248: 117444, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32084433

RESUMO

AIMS: Nonhuman primates have been used to investigate pathogenic mechanisms and evaluate immune responses following Chlamydia trachomatis inoculation. This study aimed to systemically profile antibody responses to C. trachomatis infection in nonhuman primates. MATERIALS AND METHODS: Sera were obtained from 4 pig-tailed and 8 long-tailed macaques which were intravaginally or ocularly infected with live C. trachomatis organisms, and analyzed by C. trachomatis proteome array of antigens. KEY FINDINGS: The sera from 12 macaques recognized total 172 C. trachomatis antigens. While 84 antigens were recognized by pig-tailed macaques intravaginally infected with serovar D strain, 125 antigens were recognized by long-tailed macaques ocularly infected with serovar A, and 37 antigens were recognized by both. Ocular inoculation with virulent A2497 strain induced antibodies to more antigens. Among the antigens uniquely recognized by A2497 strain infected macaques, outer membrane complex B antigen (OmcB) induced robust antibody response. Although macaques infected by less virulent A/HAR-13 strain failed to develop antibodies to OmcB, reinfection by A2497 strain induced high levels of antibodies to OmcB. SIGNIFICANCE: Proteome array has revealed a correlation of chlamydial infection invasiveness with chlamydial antigen immunogenicity, and identified antibody responses to OmcB potentially as biomarkers for invasive infection with C. trachomatis.


Assuntos
Anticorpos Antibacterianos/biossíntese , Antígenos de Bactérias/sangue , Infecções por Chlamydia/imunologia , Chlamydia trachomatis/imunologia , Infecções do Sistema Genital/imunologia , Tracoma/imunologia , Animais , Anticorpos Antibacterianos/classificação , Antígenos de Bactérias/classificação , Proteínas da Membrana Bacteriana Externa/sangue , Infecções por Chlamydia/sangue , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/patogenicidade , Olho/imunologia , Olho/microbiologia , Feminino , Soros Imunes/química , Macaca fascicularis , Macaca nemestrina , Masculino , Análise Serial de Proteínas , Proteoma/química , Proteoma/imunologia , Infecções do Sistema Genital/sangue , Infecções do Sistema Genital/microbiologia , Tracoma/sangue , Tracoma/microbiologia , Vagina/imunologia , Vagina/microbiologia
17.
Biomed Pharmacother ; 125: 110029, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32106378

RESUMO

Faciogenital Dysplasia 1 (FGD1) has been involved in a variety of biological processes, including cytoskeleton restructuring, cell morphology, cell cycle progression, and cell polarity. Abnormal expression of FGD1 was also identified in several types of cancers, indicating its critical role in the development of cancers. However, little is known about the role of FGD1 in hepatocellular carcinoma (HCC). In this study, the expression of FGD1 in HCC was mined with the RNA sequencing data from the cancer genome atlas. By over-expressing or knocking down of FGD1, the effects of FGD1 on the malignant behavior of HCC were evaluated both in vitro and in vivo. We find that FGD1 is up-regulated in HCC and correlated with the development and prognosis of HCC. By over-expressing or knocking down of FGD1, the effects of FGD1 on the malignant behavior of HCC were evaluated both in vitro and in vivo. Knockdown of FGD1 remarkably inhibits the malignant behaviors and causes morphological disorder of pseudopodia, autophagy inhibition and mitochondrial dyfunction in HCC cells. Further investigation shows that Cdc42, a Rho GTPase, plays a role in these processes. Overexpression of FGD1 significantly promotes the oncogenic properties of HCC cells. Collectively, these findings reveal that FGD1 exhibits oncogenic properties in HCC through regulating cell morphology, autophagy and mitochondrial function, suggesting that FGD1 may serve as a potential therapeutic target for HCC.

18.
Proc Natl Acad Sci U S A ; 117(10): 5463-5471, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32079726

RESUMO

Chronic pain is a major clinical problem of which the mechanisms are incompletely understood. Here, we describe the concept that PI16, a protein of unknown function mainly produced by fibroblasts, controls neuropathic pain. The spared nerve injury (SNI) model of neuropathic pain increases PI16 protein levels in fibroblasts in dorsal root ganglia (DRG) meninges and in the epi/perineurium of the sciatic nerve. We did not detect PI16 expression in neurons or glia in spinal cord, DRG, and nerve. Mice deficient in PI16 are protected against neuropathic pain. In vitro, PI16 promotes transendothelial leukocyte migration. In vivo, Pi16 -/- mice show reduced endothelial barrier permeability, lower leukocyte infiltration and reduced activation of the endothelial barrier regulator MLCK, and reduced phosphorylation of its substrate MLC2 in response to SNI. In summary, our findings support a model in which PI16 promotes neuropathic pain by mediating a cross-talk between fibroblasts and the endothelial barrier leading to barrier opening, cellular influx, and increased pain. Its key role in neuropathic pain and its limited cellular and tissue distribution makes PI16 an attractive target for pain management.

19.
Nanoscale ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016276

RESUMO

The well-known Stöber method has been widely used to synthesize nonporous silica nanospheres (NPs), however, in the absence of surfactant templates, the synthesis of mesoporous silica nanospheres (MSNs) has not been achieved. Herein, in the absence of organic surfactant templates, by a simple premixing of three components tetraethoxysilane-water-ethanol (TEOS-H2O-EtOH) with a precise molar ratio, the parent silica nanoparticles with a low condensation degree and controlled particle size can be readily obtained. Subsequently, via a simple two-step post-treatment, the obtained MSNs exhibited a high surface area (ca. 500 m2 g-1), accessible mesopores (3.0 nm), and a large pore volume (0.87 mL g-1), similar to those of MCM-41 and SBA-15 silicas. The unique self-templating role of the 'pre-Ouzo' effect of ternary surfactant-free TEOS-H2O-EtOH systems was proposed to understand the formation of mesoporosity.

20.
Sci Rep ; 10(1): 2320, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32047170

RESUMO

Mortality of glioblastoma multiforme (GBM) has not improved over the last two decades despite medical breakthroughs in the treatment of other types of cancers. Nanoparticles hold tremendous promise to overcome the pharmacokinetic challenges and off-target adverse effects. However, an inhibitory effect of nanoparticles by themselves on metastasis has not been explored. In this study, we developed transferrin-conjugated porous silicon nanoparticles (Tf@pSiNP) and studied their effect on inhibiting GBM migration by means of a microfluidic-based migration chip. This platform, designed to mimic the tight extracellular migration tracts in brain parenchyma, allowed high-content time-resolved imaging of cell migration. Tf@pSiNP were colloidally stable, biocompatible, and their uptake into GBM cells was enhanced by receptor-mediated internalisation. The migration of Tf@pSiNP-exposed cells across the confined microchannels was suppressed, but unconfined migration was unaffected. The pSiNP-induced destabilisation of focal adhesions at the leading front may partially explain the migration inhibition. More corroborating evidence suggests that pSiNP uptake reduced the plasticity of GBM cells in reducing cell volume, an effect that proved crucial in facilitating migration across the tight confined tracts. We believe that the inhibitory effect of Tf@pSiNP on cell migration, together with the drug-delivery capability of pSiNP, could potentially offer a disruptive strategy to treat GBM.

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