Increased Cerebral Level of P2X7R in a Tauopathy Mouse Model by PET Using [18F]GSK1482160.

Neuroinflammation plays an important role in Alzheimer's disease and primary tauopathies. The aim of the current study was to map [18F]GSK1482160 for imaging of purinergic P2X7R in Alzheimer's disease and primary tauopathy mouse models. Small animal PET was performed using [18F]GSK1482160 in widely used mouse models of Alzheimer's disease (APP/PS1, 5×FAD, and 3×Tg), 4-repeat tauopathy (rTg4510) mice, and age-matched wild-type mice. Increased uptake of [18F]GSK1482160 was observed in the brains of 7-month-old rTg4510 mice compared to wild-type mice and compared to 3-month-old rTg4510 mice. A positive correlation between hippocampal tau [18F]APN-1607 and [18F]GSK1482160 uptake was found in rTg4510 mice. No significant differences in the uptake of [18F]GSK1482160 was observed for APP/PS1 mice, 5×FAD mice, or 3×Tg mice. Immunofluorescence staining further indicated the distribution of P2X7Rs in the brains of 7-month-old rTg4510 mice with accumulation of tau inclusion. These findings provide in vivo imaging evidence for an increased level of P2X7R in the brains of tauopathy mice.

Synthesis and Evaluation of [64Cu]Cu-NOTA-HFn for PET Imaging of Transferrin Receptor 1 Expression in Nasopharyngeal Carcinoma.

As recurrent and metastatic nasopharyngeal carcinoma (NPC) is the most common cause of death among patients with NPC, there is an urgent clinical need for the development of precision diagnosis to guide personalized treatment. Recent emerging evidence substantiates the increased expression of transferrin receptor 1 (also known as cluster of differentiation 71, CD71) within tumor tissues and the inherent targeting capability of natural heavy-chain ferritin (HFn) toward CD71. This study aimed to synthesize and assess a radiotracer ([64Cu]Cu-NOTA-HFn) designed to target CD71 for positron emission tomography (PET) imaging in an NPC tumor-bearing mouse model. The entire radiolabeling process of [64Cu]Cu-NOTA-HFn was completed within 15 min with high yield (>98.5%) and high molar activity (72.96 ± 21.33 GBq/µmol). The in vitro solubility and stability experiments indicated that [64Cu]Cu-NOTA-HFn had a high water solubility (log P = -2.42 ± 0.52, n = 6) and good stability in phosphate-buffered saline (PBS) for up to 48 h. The cell saturation binding assay indicated that [64Cu]Cu-NOTA-HFn had a nanomolar affinity (Kd = 10.9 ± 6.1 nM) for CD71-overexpressing C666-1 cells. To test the target engagement in vivo, prolonged-time PET imaging was performed at 1, 6, 12, 24, and 36 h postinjection (p.i.) of [64Cu]Cu-NOTA-HFn to C666-1 NPC tumor-bearing mice. The C666-1 tumors could be visualized by [64Cu]Cu-NOTA-HFn and blocked by nonradiolabeled HFn. PET imaging quantitative analysis demonstrated that the uptake of [64Cu]Cu-NOTA-HFn in C666-1 tumors peaked at 6 h p.i. and the best radioactive tumor-to-muscle ratio was 10.53 ± 3.11 (n = 3). Ex vivo biodistribution assay at 6 h p.i. showed that the tumor uptakes were 1.43 ± 0.23%ID/g in the nonblock group and 0.92 ± 0.2%ID/g in the block group (n = 3, p < 0.05). Immunohistochemistry and immunofluorescence staining confirmed positive expression of CD71 and the uptake of HFn in C666-1 tumor tissues. In conclusion, our experiments demonstrated that [64Cu]Cu-NOTA-HFn possesses a very high target engagement for CD71-positive NPC tumors and provided a fundamental basis for further clinical translation.

Orbitronics: light-induced orbital currents in Ni studied by terahertz emission experiments.

Orbitronics is based on the use of orbital currents as information carriers. Orbital currents can be generated from the conversion of charge or spin currents, and inversely, they could be converted back to charge or spin currents. Here we demonstrate that orbital currents can also be generated by femtosecond light pulses on Ni. In multilayers associating Ni with oxides and nonmagnetic metals such as Cu, we detect the orbital currents by their conversion into charge currents and the resulting terahertz emission. We show that the orbital currents extraordinarily predominate the light-induced spin currents in Ni-based systems, whereas only spin currents can be detected with CoFeB-based systems. In addition, the analysis of the time delays of the terahertz pulses leads to relevant information on the velocity and propagation length of orbital carriers. Our finding of light-induced orbital currents and our observation of their conversion into charge currents opens new avenues in orbitronics, including the development of orbitronic terahertz devices.

An integrated ultra-high vacuum cluster for atomic-scale deposition, interface regulation, and characterization of spintronic multilayers.

The study of interface spin effects in spintronic multilayer films requires distinguishing the effects generated by different interfaces. However, testing in atmospheric conditions requires a capping layer to protect the films, which introduces new interfaces and limits the study of interface spin-dependent effects. To address this challenge, we have developed an integrated ultra-high vacuum cluster system that includes magnetron sputtering equipment, ion irradiation equipment, and time-resolved magneto-optical Kerr effect (TR-MOKE) equipment. Our sputtering system integrates 12 cathodes in a single chamber, allowing the co-sputtering of four targets. The ultimate vacuum can reach 1 × 10-10 mbar, and the deposition resolution of 0.1 nm can be achieved. Ion irradiation equipment can ionize to produce He+, and by screening and accelerating the implantation of He+ into multilayer films, ion scanning is realized, and up to 30 keV energy can be applied to the films. The TR-MOKE equipment can detect ultra-fast magnetic dynamics processes in vacuum conditions, and its external magnetic field can be rotated 360°. Our vacuum cluster system connects the three subsystems, allowing in situ film deposition, regulation, and characterization. By accurately detecting the effects of different layers, the system can distinguish the interface effects of multilayers. Experimental results demonstrate that the three subsystems can work independently or coordinate to observe the interface effects of multilayers.

Activated Microglia in the Early Stage of a Rat Model of Parkinson's Disease: Revealed by PET-MRI Imaging by [18F]DPA-714 Targeting TSPO.

In the past decades, translocator protein (TSPO) has been considered as an in vivo biomarker to measure the presence of neuroinflammatory reactions. In this study, expression of TSPO was quantified via [18F]DPA-714 positron emission tomography-magnetic resonance imaging (PET-MRI) to investigate the effects of microglial activation associated with motor behavioral impairments in the 6-hydroxydopamine (6-OHDA)-treated rodent model of Parkinson's disease (PD). [18F]FDG PET-MRI (for non-specific inflammation), [18F]D6-FP-(+)-DTBZ PET-MRI (for damaged dopaminergic (DA) neurons), post-PET immunofluorescence, and Pearson's correlation analyses were also performed. The time course of striatal [18F]DPA-714 binding ratio was elevated in 6-OHDA-treated rats during 1-3 weeks post-treatments, with peak TSPO binding in the 1st week. No difference between the bilateral striatum in [18F]FDG PET imaging were found. Moreover, an obvious correlation between [18F]DPA-714 SUVRR/L and rotation numbers was found (r = 0.434, *p = 0.049). No correlation between [18F]FDG SUVRR/L and rotation behavior was found. [18F]DPA-714 appeared to be a potential PET tracer for imaging the microglia-mediated neuroinflammation in the early stage of PD.

Generation of Tunable Terahertz Waves from Tailored Versatile Spintronic Meta-Antenna Arrays.

Broadband spintronic terahertz (THz) radiation can be efficiently generated by spin-to-charge current conversion in a ferromagnetic/nonmagnetic heterostructure. There had been many studies on realizing the enhancement or the modulation of spintronic terahertz waves. However, reported devices so far focus on implementing certain specific modulation methods, either related to the spintronic stacks or related to the metamaterial structures. In this study, a set of femtosecond laser-driven versatile spintronic terahertz devices are proposed by integrating meta-antenna structures with W/CoFeB/Pt nanolayer stacks. These monolithic integrated devices exhibit spintronic terahertz wave emission, spectral modulation, and polarization manipulation simultaneously. The terahertz pulses are generated within the ferromagnetic heterostructure interfaces and transmitted along the metallic structures, leading to the modulation of the spintronic terahertz waves. Results have shown that the center-frequency shift is up to 140 GHz and the value of ellipticity can reach 0.6, demonstrating a set of integrated and efficient spintronic terahertz devices to modulate the emitted wave. In addition, compared with the slotline antenna, the maximum peak value of the bandpass band is enhanced up to 1.63 times by carefully designing the metamaterial structure. The spintronic meta-antenna array proposed here paves an integrated way for the manipulation of spintronic terahertz optoelectronic devices.

Flexible Control of Broadband Polarization in a Spintronic Terahertz Emitter Integrated with Liquid Crystal and Metasurface.

Flexible polarization control of the terahertz wave in the wide bandwidth is crucial for numerous applications, such as terahertz communication, material characterization, imaging, and biosensing diagnosis. However, this promise is impeded by the operating bandwidth of circular polarization states, control modes, and the efficiency of the regulation. Here, we report a spintronic terahertz emitter integrated with phase complementary elements, consisting of a liquid crystal and metasurface, to achieve broadband polarization control with high flexibility. This strategy allows the broadband conversion between linear, elliptical, and circular polarization by changing the rotation angle to modulate the space-variant Pancharatnam-Berry phase. The device is characterized with a terahertz time-domain spectroscopy system, demonstrating that the ellipticity of the circular polarization state could keep greater than 0.9 in 0.60-0.99 THz. In the case of an external electro-magnetic field, further polarization modulation experiments are carried out to provide multiple conversion approaches for multi-azimuth. We first propose a method of full broadband polarization state control of the terahertz emitter based on Pancharatnam-Berry phase modulation and an external electro-magnetic field. We believe that such integrated devices with broadband working bandwidth and multiple control modes will make valuable contributions to the development and multi-scene applications of ultrafast terahertz technologies.

Generation of tailored terahertz waves from monolithic integrated metamaterials onto spintronic terahertz emitters.

Recently emerging spintronic terahertz (THz) emitters, featuring many appreciable merits such as low-cost, high efficiency, ultrabroadband, and ease of integration, offer multifaceted capabilities not only in understanding the fundamental ultrafast magnetism physics but also for exploring multifarious practical applications. Integration of various flexible and tunable functions at the source such as polarization manipulation, amplitude tailoring, phase modulation, and radiation beam steering with the spintronic THz emitters and their derivatives can yield more compact and elegant devices. Here, we demonstrate a monolithic metamaterial integrated onto a W/CoFeB/Pt THz nanoemitter for a purpose-designed functionality of the electromagnetically induced transparency analog. Through elaborate engineering the asymmetry degree and geometric parameters of the metamaterial structure, we successfully verified the feasibility of monolithic modulations for the radiated THz waves. The integrated device was eventually compared with a set of stand-alone metamaterial positioning scenarios, and the negligible frequency difference between two of the positioning schemes further manifests almost an ideal realization of the proposed monolithic integrated metamaterial device with a spintronic THz emitter. We believe that such adaptable and scalable devices may make valuable contributions to the designable spintronic THz devices with pre-shaping THz waves and enable chip-scale spintronic THz optics, sensing, and imaging.

Near-field Terahertz Sensing of HeLa Cells and Pseudomonas Based on Monolithic Integrated Metamaterials with a Spintronic Terahertz Emitter.

Label-free biosensors operating within the terahertz (THz) spectra have helped to unlock a myriad of potential THz applications, ranging from biomaterial detection to point-of-care diagnostics. However, the THz wave diffraction limit and the lack of emitter-integrated THz biosensors hinder the proliferation of high-resolution near-field label-free THz biosensing. Here, a monolithic THz emission biosensor (TEB) is achieved for the first time by integrating asymmetric double-split ring resonator metamaterials with a ferromagnetic heterojunction spintronic THz emitter. This device exhibits an electromagnetically induced transparency window with a resonance frequency of 1.02 THz and a spintronic THz radiation source with a bandwidth of 900 GHz, which are integrated on a fused silica substrate monolithically for the first time. It was observed that the resonance frequency experienced a red-shift behavior with increasing concentration of HeLa cells and Pseudomonas because of the strong interaction between the spintronic THz radiation and the biological samples on the metamaterials. The spatial frequency red-shift resolution is ∼0.01 THz with a Pseudomonas concentration increase from ∼0.5 × 104 to ∼1 × 104/mL. The monolithic THz biosensor is also sensitive to the sample concentration distribution with a 15.68 sensitivity under a spatial resolution of 500 µm, which is determined by the infrared pump light diffraction limit. This TEB shows great potential for high-resolution near-field biosensing applications of trace biological samples.

Molecular characterization and expression profiles of insulin-like growth factors in yellowtail kingfish (Seriola lalandi) during embryonic development.

In this study, to understand the role of the insulin-like growth factor (IGF) system in the regulation of early development in yellowtail kingfish (YTK, Seriola lalandi), an economically important marine fish species with a high potential for aquaculture, we first cloned the full-length cDNAs for igf1 and igf2 from the liver. YTK igf1 cDNA was 1946 base pairs (bp) in length with an open reading frame (ORF) of 558 bp encoding preproIGF1 of 185 amino acids (aa). The preproIGF1 consisted of 44 aa for the signal peptide, 68 aa for the mature peptide comprising B, C, A, and D domains, and 73 aa for the E domain. YTK igf2 cDNA had an ORF of 648 bp that encoded a total of 215 aa spanning the signal peptide (47 aa), the mature peptide (70 aa), and the E domain (98 aa). At the protein level, both YTK IGF1 and IGF2 exhibited high sequence identities with their corresponding fish counterparts, respectively. Subsequently, quantitative RT-PCR analysis indicated that the highest level of igf1 mRNA expression was recorded in the gonad and liver, while the igf2 mRNA expression was most abundant in the gill and liver. In addition, both igf1 and igf2 were detected in all stages of embryonic development and exhibited different gene expression patterns, supporting that IGF1 and IGF2 could be functional and play important roles during YTK embryogenesis. Overall, this initial study of IGF1 and IGF2 provides an insight into the endocrine mechanism involved in the early development of yellowtail kingfish.

MR imaging of intracranial solitary fibrous tumor: a retrospective study of 7 cases.

OBJECTIVE: To investigate the MR imaging diagnostic features of intracranial solitary fibrous tumors (ISFTs). MATERIALS AND METHODS: Seven patients (mean age of 52.9 years; M:F=3:4) with histopathologically proven ISFTs were identified at our institute. Clinical presentations and pathological features were reviewed. MR Imaging findings including signal intensity, gadopentetate dimeglumine enhanced pattern, and diffusion-weighted imaging (DWI) characterization of the tumors were retrospectively evaluated. RESULTS: Six tumors showed a multi-lobular contour. Five tumors showed heterogeneous signal intensity, and two tumors showed homogeneous signal intensity on T1WI. Low signal intensity linear, curved or interlacing lines were observed within the tumors in all seven cases. Seven tumors demonstrated moderate or strong enhancement, six showed heterogeneous enhancement, and one homogenous enhancement. All tumors showed heterogeneous signal intensity on DWI.A ring-like high signal intensity band distributed around within the tumor was noted in six cases on DWI. CONCLUSION: Diagnostic evidence for ISFT on MR image includes heterogeneous signal intensity, intense enhancement of T2 signal intensity, low signal intensity lines within the tumor, heterogeneous signal intensity on DWI and a ring-like band around the tumor on DWI.