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29Si silica nanoparticles (SiO2 NPs) are promising magnetic resonance imaging (MRI) probes that possess advantageous properties for in vivo applications, including suitable biocompatibility, tailorable properties, and high water dispersibility. Dynamic nuclear polarization (DNP) is used to enhance 29Si MR signals via enhanced nuclear spin alignment; to date, there has been limited success employing DNP for SiO2 NPs due to the lack of endogenous electronic defects that are required for the process. To create opportunities for SiO2-based 29Si MRI probes, we synthesized variously featured SiO2 NPs with selective 29Si isotope enrichment on homogeneous and core@shell structures (shell thickness: 10 nm, core size: 40 nm), and identified the critical factors for optimal DNP signal enhancement as well as the effective hyperpolarization depth when using an exogenous radical. Based on the synthetic design, this critical factor is the proportion of 29Si in the shell layer regardless of core enrichment. Furthermore, the effective depth of hyperpolarization is less than 10 nm between the surface and core, which demonstrates an approximately 40% elongated diffusion length for the shell-enriched NPs compared to the natural abundance NPs. This improved regulation of surface properties facilitates the development of isotopically enriched SiO2 NPs as hyperpolarized contrast agents for in vivo MRI.
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Nanopartículas , Dióxido de Silicio , Dióxido de Silicio/química , Nanopartículas/química , Medios de Contraste/química , Imagen por Resonancia Magnética , Espectroscopía de Resonancia MagnéticaRESUMEN
This study demonstrated the potential of 50 nm PEGylated Si NPs for high-resolution in vivo29Si MR imaging, emphasizing their biocompatibility and water dispersibility. The acquisition of in vivo Si MR images using the lowest reported dose after subcutaneous and intraperitoneal administration opens new avenues for future 29Si MR studies.
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The nitrogen-vacancy (NV) centers in diamond have the ability to sense alternating-current (AC) magnetic fields with high spatial resolution. However, the frequency range of AC sensing protocols based on dynamical decoupling (DD) sequences has not been thoroughly explored experimentally. In this work, we aimed to determine the sensitivity of the ac magnetic field as a function of frequency using the sequential readout method. The upper limit at high frequency is clearly determined by Rabi frequency, in line with the expected effect of finite DD-pulse width. In contrast, the lower frequency limit is primarily governed by the duration of optical repolarization rather than the decoherence time (T2) of NV spins. This becomes particularly crucial when the repetition (dwell) time of the sequential readout is fixed to maintain the acquisition bandwidth. The equation we provide successfully describes the tendency in the frequency dependence. In addition, at the near-optimal frequency of 1 MHz, we reached a maximum sensitivity of 229 pT/Hz by employing the XY4-(4) DD sequence.
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The embedding of radicals at different locations within core@shell silica nanoparticles contributes to enhanced polarization capability and can be self-polarized without adding external radicals. With grafting the radical source homogenously inside of the nanoparticles, a significant 29Si hyperpolarization signal enhancement of 49.4 was obtained.
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Nanopartículas , Dióxido de Silicio , Dióxido de Silicio/química , Espectroscopía de Resonancia Magnética/métodos , Imagen por Resonancia Magnética/métodos , Nanopartículas/químicaRESUMEN
Majority of dynamic nuclear polarization (DNP) experiments have been requiring helium cryogenics and strong magnetic fields for a high degree of nuclear polarization. In this work, we instead demonstrate an optical hyperpolarization of naturally abundant 13C nuclei in a diamond crystal at a low magnetic field and the room temperature. It exploits continuous laser irradiation for polarizing electronic spins of nitrogen vacancy centers and microwave irradiation for transferring the electronic polarization to 13C nuclear spins. We have studied the dependence of 13C polarization on laser and microwave powers. For the first time, a triplet structure corresponding to the 14N hyperfine splitting has been observed in the 13C polarization spectrum. By simultaneously exciting three microwave frequencies at the peaks of the triplet, we have achieved 13C bulk polarization of 0.113 %, leading to an enhancement of 90,000 over the thermal polarization at 17.6 mT. We believe that the multi-tone irradiation can be extended to further enhance the 13C polarization at a low magnetic field.
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Postmenopausal osteoporosis is one of the most prominent diseases in postmenopausal women and it is increasing in prevalence with the aging population. Furthermore, osteoporosis and osteoporotic vertebral compression fractures (OVCFs) are related to mortality and decreased quality of life. Therefore, searching for biomarkers that are able to identify postmenopausal women who are at high risk of developing OVCFs is an effective strategy for improving the quality of life of patients and alleviating social and economic burdens. In this study, we investigated methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) gene polymorphisms in postmenopausal women with OVCF. We recruited 301 postmenopausal women and performed genotyping for the presence of MTHFR 2572C>A, 4869C>G and TS 1100C>T, 1170A>G. Genotyping was analyzed using the polymerization chain reaction restriction fragment length polymorphism assay. MTHFR 2572C>A and TS 1100C>T were associated with the prevalence of osteoporosis (MTHFR 2572CC versus CA+AA: odd ratio [OR] adjusted age, hypertention [HTN], and diabetes mellitus [DM] = 0.49, p = 0.012) and the occurrence of OVCFs (MTHFR 2572CC versus CA+AA: OR adjusted age, HTN, and DM = 0.38, p = 0.013; TS 1100CC versus CT+TT: OR adjusted age, HTN, and DM = 0.46, p = 0.02). Our novel finding is the identification of MTHFR and TS genetic variants that decrease susceptibility to OVCFs. Our findings suggest that polymorphisms in the MTHFR and TS genes are associated with susceptibility to osteoporosis and OVCFs in postmenopausal women.
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Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Osteoporosis Posmenopáusica/genética , Fracturas Osteoporóticas/genética , Polimorfismo de Nucleótido Simple , Fracturas de la Columna Vertebral/genética , Timidilato Sintasa/genética , Regiones no Traducidas 3' , Anciano , Estudios de Casos y Controles , Femenino , Fracturas por Compresión/genética , Humanos , Persona de Mediana EdadRESUMEN
The Maillard reaction products are known to be effective in chemoprevention. Here, we focused on the anti-cancer effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal on in vitro and in vivo colon cancer. We analysed the anti-cancer activity of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal on colon cancer cells by using cell cycle and apoptosis analysis. To elucidate it's mechanism, NF-κB DNA binding activity, docking model as well as pull-down assay. Further, a xenograft model of colon cancer was studied to test the in vivo effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal. (E)-2,4-Bis(p-hydroxyphenyl)-2-butenal inhibited colon cancer cells (SW620 and HCT116) growth followed by induction of apoptosis in a concentration-dependent manner via down-regulation of NF-κB activity. In docking model as well as pull-down assay, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal directly binds to three amino acid residues of IKKß, thereby inhibited IKKß activity in addition to induction of death receptor 6 (DR6) as well as their target apoptotic genes. Finally, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal suppressed anchorage-independent cancer cell growth, and tumor growth in xenograft model accompanied with apoptosis through inhibition of IKKß/NF-κB activity, and overexpression of DR6. These results suggest that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal inhibits colon cancer cell growth through inhibition of IKKß/NF-κB activity and induction of DR6 expression.
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Aldehídos/administración & dosificación , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , FN-kappa B/metabolismo , Fenoles/administración & dosificación , Receptores del Factor de Necrosis Tumoral/metabolismo , Aldehídos/química , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/fisiopatología , Regulación hacia Abajo/efectos de los fármacos , Humanos , Quinasa I-kappa B/química , Quinasa I-kappa B/genética , Quinasa I-kappa B/metabolismo , Masculino , Ratones Endogámicos BALB C , Simulación del Acoplamiento Molecular , FN-kappa B/genética , Fenoles/química , Estructura Terciaria de Proteína , Receptores del Factor de Necrosis Tumoral/genéticaRESUMEN
We demonstrate that the use of negative feedback extends the detection bandwidth of an atomic magnetometer in a spin-exchange relaxation free (SERF) regime. A flat-frequency response from zero to 190 Hz was achieved, which is nearly a three-fold enhancement while maintaining sensitivity, 3 fT/Hz1/2 at 100 Hz. With the extension of the bandwidth, the linear correlation between measured signals and a magne-tocardiographic field synthesized for comparison was increased from 0.21 to 0.74. This result supports the feasibility of measuring weak biomagnetic signals containing multiple frequency components using a SERF atomic magnetometer under negative feedback.
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Quantum adiabatic passages can be greatly accelerated by a suitable control field, called a counter-diabatic field, which varies during the scan through resonance. Here, we implement this technique on the electron spin of a single nitrogen-vacancy center in diamond. We demonstrate two versions of this scheme. The first follows closely the procedure originally proposed by Demirplak and Rice [J. Phys. Chem. A 107, 9937 (2003)]. In the second scheme, we use a control field whose amplitude is constant but whose phase varies with time. This version, which we call the rapid-scan approach, allows an even faster passage through resonance and therefore makes it applicable also for systems with shorter decoherence times.
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Low-field nuclear magnetic resonance (NMR) spectroscopy, conducted at or below a few millitesla, provides only limited spectral information due to its inability to resolve chemical shifts. Thus, chemical analysis based on this technique remains challenging. One potential solution to overcome this limitation is the use of isotopically labeled molecules. However, such compounds, particularly their use in two-dimensional (2D) NMR techniques, have rarely been studied. This study presents the results of both experimental and simulated correlation spectroscopy (COSY) on 1-13C-ethanol at 34.38 µT. The strong heteronuclear coupling in this molecule breaks the magnetic equivalence, causing all J-couplings, including homonuclear coupling, to split the 1H spectrum. The obtained COSY spectrum clearly shows the spectral details. Furthermore, we observed that homonuclear coupling between 1H spins generated cross-peaks only when the associated 1H spins were coupled to identical 13C spin states. Our findings demonstrate that a low-field 2D spectrum, even with a moderate spectral line width, can reveal the J-coupling networks of isotopically labeled molecules.
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Fluorescent nanodiamonds (FNDs) are versatile nanomaterials with promising properties. However, efficient functionalization of FNDs for biomedical applications remains challenging. In this study, we demonstrate mesoporous polydopamine (mPDA) encapsulation of FNDs. The mPDA shell is generated by sequential formation of micelles via self-assembly of Pluronic F127 (F127) with 1,3,5-trimethyl benzene (TMB) and composite micelles via oxidation and self-polymerization of dopamine hydrochloride (DA). The surface of the mPDA shell can be readily functionalized with thiol-terminated methoxy polyethylene glycol (mPEG-SH), hyperbranched polyglycerol (HPG), and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). The PEGylated FND@mPDA particles are efficiently taken up by, and employed as a fluorescent imaging probe for, HeLa cells. HPG-functionalized FND@mPDA is conjugated with an amino-terminated oligonucleotide to detect microRNA via hybridization. Finally, the increased surface area of the mPDA shell permits efficient loading of doxorubicin hydrochloride. Further modification with TPGS increases drug delivery efficiency, resulting in high toxicity to cancer cells.
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Nanodiamantes , Humanos , Micelas , Células HeLa , Colorantes FluorescentesRESUMEN
Diverse strategies have been developed to visualize latent fingerprints (LFPs) that are undetectable by the naked eye. Among them, fluorescence-based approaches have emerged as an attractive method for enabling high-resolution LFP imaging. However, the use of fluorescent probes for LFP detection remains challenging due to cumbersome processing, low selectivity, and high background interference. Here, we demonstrate highly efficient, sensitive, and background-free LFP detection with dual-color emission arising from manganese (Mn)-doped lead halide perovskite (CsPb(Cl1-yBry)3) nanocrystals (NCs). The resulting bright, fluorescent, solid-state nanopowder (NP) permits the visualization of LFP ridge structures and the resolution of level 1-3 LFP features. The dual-color emission of the Mn-doped perovskite NP provides a simple, robust, and effective route to overcome background interference, thereby increasing the resolution and sensitivity of the LFP detection. The combination of the high quantum efficiency and dual emission of Mn-doped perovskite NP offers great potential for forensic science.
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Magnetoencephalography (MEG) is a functional neuroimaging technique that noninvasively detects the brain magnetic field from neuronal activations. Conventional MEG measures brain signals using superconducting quantum interference devices (SQUIDs). SQUID-MEG requires a cryogenic environment involving a bulky non-magnetic Dewar flask and the consumption of liquid helium, which restricts the variability of the sensor array and the gap between the cortical sources and sensors. Recently, miniature optically pumped magnetometers (OPMs) have been developed and commercialized. OPMs do not require cryogenic cooling and can be placed within millimeters from the scalp. In the present study, we arranged six OPM sensors on the temporal area to detect auditory-related brain responses in a two-layer magnetically shielded room. We presented the auditory stimuli of 1 kHz pure-tone bursts with 200 ms duration and obtained the M50 and M100 components of auditory-evoked fields. We delivered the periodic stimuli with a 40 Hz repetition rate and observed the gamma-band power changes and inter-trial phase coherence of auditory steady-state responses at 40 Hz. We found that the OPM sensors have a performance comparable to that of conventional SQUID-MEG sensors, and our results suggest the feasibility of using OPM sensors for functional neuroimaging and brain-computer interface applications.
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Helio , Magnetoencefalografía , Magnetoencefalografía/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Neuroimagen , Neuroimagen FuncionalRESUMEN
Endocrine therapies, which inhibit estrogen receptor signaling, are the most common and effective treatments for estrogen receptoralpha-positive breast cancer. However, the utility of these agents is limited by the frequent development of resistance, and the precise mechanisms underlying endocrine therapy resistance remain incompletely understood. Here, we demonstrate that peptidyl-prolyl isomerase Pin1 is an important determinant of resistance to tamoxifen and show that Pin1 increases E2F-4- and Egr-1-driven expression of LC-3 as a result of an increased interaction with and phosphorylation of MEK1/2. In human tamoxifen-resistant breast cancer, our results show a significant correlation between Pin1 overexpression and high levels of LC-3. Promoter activity as well as expression levels of Pin1 were drastically higher in tamoxifen-resistant MCF7 cells than control MCF7 cells, as were levels of LC-3 mRNA and protein, an autophagy marker. Pin1(-/-) mouse embryonic fibroblasts showed lower 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MEK1/2 phosphorylation than Pin1(+/+) mouse embryonic fibroblasts. Silencing of Pin1 expression inhibited TPA-induced MEK1/2 phosphorylation in MCF7 cells. Moreover, PD98059, a specific inhibitor of MEK1/2, and juglone, a potent Pin1 inhibitor, significantly suppressed the TPA-induced expression of E2F-4 as well as Egr-1 transcription factors, which control LC-3 gene expression. Importantly, 4-hydroxy tamoxifen, when used in combination with silencing of Pin1 or LC-3, increased cleaved poly(ADP-ribose) polymerase and DNA fragmentation to inhibit cologenic growth of MCF7 cells. We therefore link the Pin1-MEK pathway and LC-3-mediated tamoxifen resistance and show the therapeutic potential of Pin1 in the treatment of tamoxifen-resistant breast cancer.
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Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Proteínas Asociadas a Microtúbulos/metabolismo , Isomerasa de Peptidilprolil/metabolismo , Tamoxifeno/farmacología , Animales , Antineoplásicos/farmacología , Neoplasias de la Mama/enzimología , Línea Celular Tumoral , Inhibidores Enzimáticos/farmacología , Femenino , Flavonoides/farmacología , Humanos , Ratones , Peptidilprolil Isomerasa de Interacción con NIMA , Naftoquinonas/farmacologíaRESUMEN
Silicon particles have garnered attention as promising biomedical probes for hyperpolarized 29Si magnetic resonance imaging and spectroscopy. However, due to the limited levels of hyperpolarization for nanosized silicon particles, microscale silicon particles have primarily been the focus of dynamic nuclear polarization (DNP) applications, including in vivo magnetic resonance imaging (MRI). To address these current challenges, we developed a facile synthetic method for partially 29Si-enriched porous silicon nanoparticles (NPs) (160 nm) and examined their usability in hyperpolarized 29Si MRI agents with enhanced signals in spectroscopy and imaging. Hyperpolarization characteristics, such as the build-up constant, the depolarization time (T1), and the overall enhancement of the 29Si-enriched silicon NPs (10 and 15%), were thoroughly investigated and compared with those of a naturally abundant NP (4.7%). During optimal DNP conditions, the 15% enriched silicon NPs showed more than 16-fold higher enhancementsâfar beyond the enrichment ratioâthan the naturally abundant sample, further improving the signal-to-noise ratio in in vivo 29Si MRI. The 29Si-enriched porous silicon NPs used in this work are potentially capable to serve as drug-delivery vehicles in addition to hyperpolarized 29Si in vivo, further enabling their potential future applicability as a theragnostic platform.
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Materiales Biomiméticos/química , Medios de Contraste/química , Imagen por Resonancia Magnética , Nanopartículas/química , Miembro Fantasma/diagnóstico por imagen , Silicio/química , Animales , Materiales Biomiméticos/administración & dosificación , Materiales Biomiméticos/síntesis química , Medios de Contraste/administración & dosificación , Medios de Contraste/síntesis química , Isótopos , Masculino , Ensayo de Materiales , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/administración & dosificación , Tamaño de la Partícula , Porosidad , Silicio/administración & dosificaciónRESUMEN
The development of atomic magnetometers has led to nuclear magnetic resonance (NMR) in zero and ultralow magnetic fields without using cryogenic sensors. However, in-situ detection, meaning that a sample locates in the detection space beside a vapor cell, has been conducted only with parahydrogen-induced polarization. Other hyperpolarization techniques remain unexplored yet. In this work, we demonstrate that Overhauser dynamic nuclear polarization allows in-situ NMR detection with an atomic magnetometer at less than 1⯵T. The 1H NMR signal of a nitroxide radical solution was observed at 13.83â¯Hz, which corresponds to 325â¯nT. Signal-to-noise ratio was 32 after sixteen averages. On the Larmor precession of 1H spins, a decaying oscillation was superimposed. We attribute it to a transient 87Rb spin precession in response to a non-adiabatic field variation. This work shows a new capability of zero- and ultralow-field NMR.
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Magnetic resonance imaging in ultra-low fields is often limited by mediocre signal-to-noise ratio hindering a higher resolution. Overhauser dynamic nuclear polarisation (O-DNP) using nitroxide radicals has been an efficient solution for enhancing the thermal nuclear polarisation. However, the concurrence of positive and negative polarisation enhancements arises in ultra-low fields resulting in a significantly reduced net enhancement, making O-DNP far less attractive. Here, we address this issue by applying circularly polarised RF. O-DNP with circularly polarised RF renders a considerably improved enhancement factor of around 150,000 at 1.2⯵T. A birdcage coil was adopted into an ultra-low field MRI system to generate the circularly polarised RF field homogeneously over a large volume. We acquired an MR image of a nitroxide radical solution with an average in-plane resolution of 1â¯mm. De-noising through compressive sensing further improved the image quality.
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The signal amplification by reversible exchange (SABRE) technique is a very promising method for increasing magnetic resonance (MR) signals. SABRE can play a particularly large role in studies with a low or ultralow magnetic field because they suffer from a low signal-to-noise ratio. In this work, we conducted real-time superconducting quantum interference device (SQUID)-based nuclear magnetic resonance (NMR)/magnetic resonance imaging (MRI) studies in a microtesla-range magnetic field using the SABRE technique after designing a bubble-separated phantom. A maximum enhancement of 2658 for 1H was obtained for pyridine in the SABRE-NMR experiment. A clear SABRE-enhanced MR image of the bubble-separated phantom, in which the para-hydrogen gas was bubbling at only the margin, was successfully obtained at 34.3 µT. The results show that SABRE can be successfully incorporated into an ultralow-field MRI system, which enables new SQUID-based MRI applications. SABRE can shorten the MRI operation time by more than 6 orders of magnitude and establish a firm basis for future low-field MRI applications.
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We investigated the physical properties of Cr ions in half-metallic CrO(2) using 53Cr nuclear magnetic resonance (NMR). The 53Cr NMR spectra showed two peaks with a similar intensity instead of the single peak anticipated from a uniform single valence Cr(+4). Both Cr peaks exhibited a strong anisotropy in the hyperfine field and similar values in the enhancement factor and T2 relaxation time. These results suggest the coexistence of two different Cr ions (provisionally, Cr(+4 +/- 1/3)) by a self-doping effect, which is a likely origin of the metallic ferromagnetism in CrO(2).
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A 15-year-old man presented with stupor following a motorcycle traffic accident. The patient was diagnosed with a traumatic left carotid cavernous fistula (CCF) with pseudoaneurysm of the left internal carotid artery. Brain magnetic resonance imaging (MRI) showed transiently restricted diffusion in the left centrum semiovale white matter and lower temporo-occipital area extending to the splenium of the corpus callosum, with high signal intensity on diffusion-weighted imaging. On the 35th day of admission, the patient had complete neurological recovery and a follow-up brain MRI revealed complete resolution of the lesions in the left centrum semiovale and splenium of the corpus callosum. These clinical and radiological features are highly suggestive of complete reversal of diffusion restriction after successful embolization of traumatic CCF.