Development of an FAP-Targeted PET Probe Based on a Novel Quinolinium Molecular Scaffold.

Fibroblast activation protein (FAP) has recently gained significant attention as a promising tumor biomarker for both diagnosis and therapeutic applications. A series of radiopharmaceuticals based on fibroblast activation protein inhibitors (FAPIs) have been developed and translated into the clinic. Though some of them such as radiolabeled FAPI-04 probes have achieved favorable in vivo imaging performance, further improvement is still highly desired for obtaining radiopharmaceuticals with a high theranostics potential. In this study, we innovatively designed an FAPI ligand SMIC-3002 by changing the core quinoline motif of FAPI-04 to the quinolinium scaffold. The engineered molecule was further radiolabeled with 68Ga to generate a positron emission tomography (PET) probe, [68Ga]Ga-SMIC-3002, which was then evaluated in vitro and in vivo. [68Ga]Ga-SMIC-3002 demonstrated high in vitro stability, nanomolar affinity for FAP (8 nM for protein, 23 nM for U87MG cells), and specific uptake in FAP-expressing tumors, with a tumor/muscle ratio of 19.1 and a tumor uptake of 1.48 ± 0.03 ID/g% at 0.5 h in U87MG tumor-bearing mice. In summary, the quinolinium scaffold can be successfully used for the development of the FAP-targeted tracer. [68Ga]Ga-SMIC-3002 not only shows high potential for clinical translation but also offers insights into designing a new generation of FAPI tracers.

Nature Products Chlorophyll Derivatives for NIR-II Fluorescence Bioimaging and Plant-Imaging.

The second near-infrared window (NIR-II, 1000-1700 nm) fluorescence imaging has attracted significant attention in research fields because of its unique advantages compared with conventional optical windows (400-900 nm). A variety of NIR-II fluorophores have been actively studied because they serve as a key component of fluorescence imaging. Among them, organic small molecule NIR-II fluorophores display outstanding imaging performance and many advantages, but types of small molecule NIR-II fluorophores with high biocompatibility are still quite limited. Novel molecular scaffolds based NIR-II dyes are highly desired. Herein, we hypothesized that chlorophyll is a new promising molecular platform for discovery NIR-II fluorophores. Thus, seven derivatives of derivatives were selected to characterize their optical properties. Interestingly, six chlorophyll derivatives displayed NIR-II fluorescence imaging capability. This characteristic allowed the successful NIR-II imaging of green leaves of various plants. Furthermore, most of these fluorophores showed capacity to monitor viscosity change because of their sensitive for viscosity. For demonstration of its biomedical applications, these probes were successfully used for NIR-II fluorescence-guided surgical resection of lymph nodes. In summary, chlorophylls are novel valuable tool molecules for NIR-II fluorescence imaging and have potential to expand their applications in biomedical field and plant science.

Protein-peptide binding residue prediction based on protein language models and cross-attention mechanism.

Accurate identifications of protein-peptide binding residues are essential for protein-peptide interactions and advancing drug discovery. To address this problem, extensive research efforts have been made to design more discriminative feature representations. However, extracting these explicit features usually depend on third-party tools, resulting in low computational efficacy and suffering from low predictive performance. In this study, we design an end-to-end deep learning-based method, E2EPep, for protein-peptide binding residue prediction using protein sequence only. E2EPep first employs and fine-tunes two state-of-the-art pre-trained protein language models that can extract two different high-latent feature representations from protein sequences relevant for protein structures and functions. A novel feature fusion module is then designed in E2EPep to fuse and optimize the above two feature representations of binding residues. In addition, we have also design E2EPep+, which integrates E2EPep and PepBCL models, to improve the prediction performance. Experimental results on two independent testing data sets demonstrate that E2EPep and E2EPep + could achieve the average AUC values of 0.846 and 0.842 while achieving an average Matthew's correlation coefficient value that is significantly higher than that of existing most of sequence-based methods and comparable to that of the state-of-the-art structure-based predictors. Detailed data analysis shows that the primary strength of E2EPep lies in the effectiveness of feature representation using cross-attention mechanism to fuse the embeddings generated by two fine-tuned protein language models. The standalone package of E2EPep and E2EPep + can be obtained at https://github.com/ckx259/E2EPep.git for academic use only.

Thermo-optic reconfigurable three-mode (de)multiplexer based on an asymmetrical horizontal directional coupler.

In this paper, we propose a thermo-optic reconfigurable three-mode (de)multiplexer based on an asymmetrical horizontal three-waveguide directional coupler that includes two identical single-mode waveguides and a three-mode waveguide. Over the whole wavelength range of 1540-1560 nm, and for the TE (TM) polarization, our typical fabricated device with polymer material shows coupling efficiencies as high as 94% (93%) and 93% (92%) for the mode conversions of L P 01-L P 11a and L P 01-L P 11b , with the heating powers of 53.57 mW and 71.19 mW, respectively. Our proposed device can be employed in the fields of reconfigurable mode-division multiplexing systems.

Efficient and polarization insensitive edge coupler based on cascaded vertical waveguide tapers.

We propose an efficient and polarization-insensitive edge coupler (EC) constructed principally with two cascaded vertical waveguide tapers. The proposed edge coupler only requires ordinary 365 nm (i-line) ultraviolet source for lithography process. We experimentally demonstrate the proposed EC on two kinds of photonic integrated circuit (PIC) platforms: silicon nitride (Si3N4) and lithium niobate thin film. Both achieve polarization-insensitive fiber chip coupling efficiency of >70% in the C-band. Our proposed EC have the advantages of efficient, cost-saving, and easy to implement and could serve as an effective solution to facilitate low-loss chip-fiber coupling.

Electro-optic tunable optical filter based on long-period waveguide grating in lithium niobate on insulator with absorption ribbons.

We propose an electro-optic tunable optical filter based on sidewall long period waveguide grating (LPWG) in lithium niobate on insolator (LNOI). The operation of our proposed filter is based on the mode coupling, filtering, and absorption achieved, respectively, with two corrugated sidewall LPWGs, a tapered waveguide, and two metal ribbons. Our typical fabricated devices achieved a 16.32-dB rejection band and an EO tuning efficiency of ∼0.344 nm/V. Our proposed LPWG and filter are compact and could be integrated with other LNOI waveguide devices to realize more sophisticated functions for on-chip optical signal processing.

Fully Integrated Line Array Angular Displacement Sensing Chip.

The angular displacement sensor is a digital angular displacement measurement device that integrates optics, mechanics, and electronics. It has important applications in communication, servo control, aerospace, and other fields. Although conventional angular displacement sensors can achieve extremely high measurement accuracy and resolution, they cannot be integrated because complex signal processing circuitry is required at the photoelectric receiver, which limits their suitability for robotics and automotive applications. The design of a fully integrated line array angular displacement-sensing chip is presented for the first time using a combination of pseudo-random and incremental code channel designs. Based on the charge redistribution principle, a fully differential 12-bit, 1 MSPS sampling rate successive approximation analog-to-digital converter (SAR ADC) is designed for quantization and subdivision of the incremental code channel output signal. The design is verified with a 0.35 µm CMOS process and the area of the overall system is 3.5 × 1.8 mm2. The fully integrated design of the detector array and readout circuit is realized for the angular displacement sensing.

Fuel Characteristics and Removal of AAEMs in Hydrochars Derived from Sewage Sludge and Corn Straw.

Co-hydrothermal carbonization (Co-HTC) of sewage sludge (SS) and corn straw (CS) for fuel preparation is a waste treatment method that reduces the pre-treatment cost of solid waste and biomass fuel. Based on the response surface methodology (RSM), a test was designed to prepare SS and CS hydrochars using a hydrothermal high-pressure reactor. The test examined the higher heating value (HHV) and the concentrations of alkali metals and alkaline earth metals (AAEMs) and Cl. The HHV of SS-hydrochar decreased with an increase in reaction temperature, but that of CS-hydrochar increased. The yield of CS-hydrochar was at 26.74−61.26%, substantially lower than that of SS-hydrochar. Co-hydrochar has the advantages of HHV and an acceptable yield. The HHV of co-hydrochar was 9215.51−12,083.2 kJ/kg, representing an increase of 12.6−47.6% over single component hydrochar, while the yield of co-hydrochar was 41.46−72.81%. In addition, the stabilities of AAEM and Cl in the co-hydrochar were Mg > Ca > K > Na > Cl. SS and CS had a synergistic effect on dechlorination efficiency (DE), which had a negative effect on the removal efficiency (RE) of Ca and Na. The optimal hydrocharization conditions were a temperature of approximately 246.14 °C, a residence time of approximately 90 min, and a mixing ratio of SS−CS of approximately 57.18%. The results offer a way to utilize SS and CS by Co-HTC and convert them into low-chlorine and low-alkali fuel, thus pushing the improvement of this promising waste-to-energy technology.

Thin-film lithium-niobate modulator with a combined passive bias and thermo-optic bias.

It is essential to bias a thin-film lithium-niobate Mach-Zehnder electro-optic (EO) modulator at the desired operation condition to ensure optimal performance of the modulator. While thermo-optic (TO) control can solve the problem of bias drift, it consumes significant electric power. In this paper, we propose a technique to largely reduce bias power consumption by combining passive bias and TO bias. In our design, waveguide sections with different widths are introduced in the two arms of the MZ modulator to produce a desired phase difference of π/2 rad (the desired operation condition), and local heating with electrode heaters placed on the waveguides is employed to provide compensation for any phase drift caused by fabrication errors and other effects. As the TO control only serves to compensate for small errors, the electric power required is low and the response is fast. To demonstrate our technique experimentally, we fabricate several modulators of the same design on the same chip. Our experimental modulators can operate up to ∼40 GHz with a half-wave voltage of ∼2.0 V over a wide optical bandwidth, and the performances are insensitive to ambient temperature variations. The TO bias powers required range from 1 mW to 15 mW, and the thermal rise and fall times are 47 µs and 14 µs, respectively. Our technique can facilitate the development of practical high-speed EO modulators on the lithium-niobate-on-insulator platform.

A Background-Free SERS Strategy for Sensitive Detection of Hydrogen Peroxide.

The accurate and sensitive detection of biomolecules by surface-enhanced Raman spectroscopy (SERS) is possible, but remains challenging due to the interference from biomolecules in complex samples. Herein, a new SERS sensor is developed for background-free detection of hydrogen peroxide (H2O2) with an ultralow detection limit (1 × 10-10 mol/L), using a Raman-silent strategy. The Au microparticles (Au-RSMPs) resembling rose-stones are devised as SERS substrates with a high enhancement effect, and 4-mercaptophenylboronic acid (4-MPBA) is selected as an H2O2-responsive Raman reporter. Upon the reaction with H2O2, the phenylboronic group of 4-MPBA was converted to a phenol group, which subsequently reacted with 4-diazonium-phenylalkyne (4-DP), an alkyne-carrying molecule via the azo reaction. The formed product exhibits an intense and sharp SERS signal in the Raman-silent region, avoiding interference of impurities and biomolecules. As a proof-of-concept demonstration, we show that this SERS sensor possesses significant merits towards the determination of H2O2 in terms of broad linear range, low limit of detection, and high selectivity, showing promise for the quantitative analysis of H2O2 in complicated biological samples.

Nutritional Composition, Efficacy, and Processing of Vigna angularis (Adzuki Bean) for the Human Diet: An Overview.

Adzuki beans are grown in several countries around the world and are widely popular in Asia, where they are often prepared in various food forms. Adzuki beans are rich in starch, and their proteins contain a balanced variety of amino acids with high lysine content, making up for the lack of protein content of cereals in the daily diet. Therefore, the research on adzuki beans and the development of their products have broad prospects for development. The starch, protein, fat, polysaccharide, and polyphenol contents and compositions of adzuki beans vary greatly among different varieties. The processing characteristic components of adzuki beans, such as starch, isolated protein, and heated flavor, are reported with a view to further promote the processing and development of adzuki bean foods. In addition to favorable edibility, the human health benefits of adzuki beans include antioxidant, antibacterial, and anti-inflammatory properties. Furtherly, adzuki beans and extracts have positive effects on the prevention and treatment of diseases, including diabetes, diabetes-induced kidney disease or kidney damage, obesity, and high-fat-induced cognitive decline. This also makes a case for the dual use of adzuki beans for food and medicine and contributes to the promotion of adzuki beans as a healthy, edible legume.

Salt-Stabilized Silylzinc Pivalates for Nickel-Catalyzed Carbosilylation of Alkenes.

We herein report the preparation of solid and salt-stabilized silylzinc pivalates from the corresponding silyllithium reagents via transmetalation with Zn(OPiv)2 . These resulting organosilylzinc pivalates show enhanced air and moisture stability and unique reactivity in the silylative difunctionalization of alkenes. Thus, a practical chelation-assisted nickel-catalyzed regioselective alkyl and benzylsilylation of alkenes has been developed, which provides an easy method to access alkyl silanes with broad substrate scope and wide functional group compatibility. Kinetic experiments highlight that the OPiv-coordination is crucial to improve the reactivity of silylzinc pivalates. Furthermore, late-stage functionalizations of druglike molecules and versatile modifications of the products illustrate the synthetical utility of this protocol.

Electro-optic reconfigurable two-mode (de)multiplexer on thin-film lithium niobate.

We propose and demonstrate a compact electro-optic reconfigurable two-mode (de)multiplexer using the configuration of cascaded Mach-Zehnder interferometers formed on thin-film X-cut lithium niobate on silica. Our fabricated device, which is 9.5-mm long, can spatially switch between the two transverse-electric modes with an efficiency higher than 98% from 1530-1560 nm and beyond at an applied voltage of 6.5 V. The switching speed is faster than 30 ns. Our proposed mode switch could find applications in fiber-based and on-chip mode-division-multiplexing systems.

Planar light-wave circuit-based switchable LP11a-LP11b mode rotator.

A simple planar light-wave circuit-based switchable LP11a-LP11b mode rotator for reconfigurable mode division multiplexing is proposed, which consists of a polymer waveguide and an electrode heater located on the waveguide. Because of the asymmetric refractive index distribution in the horizontal and vertical directions, induced by the thermo-optic effect, mode rotation between the LP11a and LP11b modes can be achieved when the heater is ON but there can be no mode rotation when the heater is OFF. Numerical simulations show that our well-designed mode rotator with optical polymer materials, which has a length of 2750 µm, can achieve a mode conversion efficiency (MCE) larger than 84% over the entire C+L band (1530-1610 nm) and a maximum MCE of 96% at 1550 nm. The switching electric power is 161.5 mW. The calculated temperature within the waveguide core is from 186°C (close to the heater) to 86°C (away from the heater).

Exosomes derived from umbilical cord mesenchymal stem cells alleviate viral myocarditis through activating AMPK/mTOR-mediated autophagy flux pathway.

Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-exosomes) have been implicated as a novel therapeutic approach for tissue injury repair and regeneration, but the effects of hucMSC-exosomes on coxsackievirus B3 (CVB3)-induced myocarditis remain unknown. The object of the present study is to investigate whether hucMSC-exosomes have therapeutic effects on CVB3-induced myocarditis (VMC). HucMSC-exosomes were identified using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot. The purified hucMSC-exosomes tagged with PKH26 were tail intravenously injected into VMC model mice in vivo and used to administrate CVB3-infected human cardiomyocytes (HCMs) in vitro, respectively. The effects of hucMSC-exosomes on myocardial pathology injury, proinflammatory cytokines and cardiac function were evaluated through haematoxylin and eosin (H&E) staining, quantitative polymerase chain reaction (qPCR) and Doppler echocardiography. The anti-apoptosis role and potential mechanism of hucMSC-exosomes were explored using TUNEL staining, flow cytometry, immunohistochemistry, Ad-mRFP-GFP-LC3 transduction and Western blot. In vivo results showed that hucMSC-exosomes (50 µg iv) significantly alleviated myocardium injury, shrank the production of proinflammatory cytokines and improved cardiac function. Moreover, in vitro data showed that hucMSC-exosomes (50 µg/mL) inhibited the apoptosis of CVB3-infected HCM through increasing pAMPK/AMPK ratio and up-regulating autophagy proteins LC3II/I, BECLIN-1 and anti-apoptosis protein BCL-2 as well as decreasing pmTOR/mTOR ratio, promoting the degradation of autophagy flux protein P62 and down-regulating apoptosis protein BAX. In conclusion, hucMSC-exosomes could alleviate CVB3-induced myocarditis via activating AMPK/mTOR-mediated autophagy flux pathway to attenuate cardiomyocyte apoptosis, which will be benefit for MSC-exosome therapy of myocarditis in the future.

Electro-optic mode-selective switch based on cascaded three-dimensional lithium-niobate waveguide directional couplers.

We propose an electro-optic mode-selective switch based on cascaded three-dimensional lithium-niobate waveguide directional couplers fabricated with a single-step annealed proton-exchange process. To compensate for discrepancies due to uncertainties in the fabrication process, we develop a post-tuning technique to improve the performance of the coupler by means of depositing a layer of titanium oxide (TiO2) onto one of the waveguides of the coupler. By integrating two cascaded dissimilar directional couplers, we experimentally demonstrate switchable (de)multiplexing of the LP01, LP11a, and LP11b modes, where the LP11a mode can be switched at an efficiency over 75% from 1530 nm to 1612 nm with an applied voltage varying between -9 V and +30 V, and the LP11b mode can be switched at an efficiency higher than 90% from 1534 nm to 1577 nm with an applied voltage varying between -21 V to 0 V. The switching times are 230-300 ns. Our proposed waveguide platform could be employed to develop advanced switches for applications in areas where high-speed switching of spatial modes is required, such as reconfigurable mode-division-multiplexing communication.

Thin-film lithium niobate electro-optic modulator on a D-shaped fiber.

We propose a low-insertion-loss electro-optic modulator formed with LNOI bonded on a D-shaped SMF. The proposed modulator employs high-performance Mach-Zehnder interferometer (MZI) formed with ridge LNOI waveguides and driven by travelling-wave electrodes. The light from the fiber core is coupled into a thin strip LNOI waveguide and then launched into the MZI via a ridge LNOI waveguide with tapered slab height and vice versa. Such all-fiber configuration exempts the need of the butt-coupling with an SMF. The calculated results show that our proposed modulator is capable of achieving a low insertion loss of less than 1.5 dB, an EO modulation efficiency (Vπ·L) of 2.05 V·cm, and a 3-dB modulation bandwidth of larger than 80 GHz. Our all-fiber LNOI modulator is feasible in practice and opens a new door to realize high-speed fiber devices by the integration of an optical fiber and thin film LN.

Graphene electrodes for electric poling of electro-optic polymer films.

We propose electric poling of electro-optic (EO) polymer films with graphene electrodes. The use of graphene electrodes can waive the use of buffer layers and minimize the poling voltage. To demonstrate the idea, we prepared EO polymer thin-film waveguides for poling with traditional Au/ITO electrodes and graphene electrodes, where the EO polymer is a guest-host system formed by doping 15 wt% of dipolar polyene chromophore AJLZ53 into the random copolymer P(S-co-MMA). Our experiments confirm that the use of graphene electrodes can significantly reduce the poling voltage. For a 3.8-µm-thick EO polymer film, we achieve high EO coefficients of 82 pm/V at 1541 nm and 110 pm/V at 1300 nm with a poling voltage of 420 V. In addition, the use of graphene electrodes allows more flexible waveguide designs and can potentially simplify the fabrication of devices based on EO polymer.

An enhanced adaptive non-local means algorithm for Rician noise reduction in magnetic resonance brain images.

BACKGROUND: The Rician noise formed in magnetic resonance (MR) imaging greatly reduced the accuracy and reliability of subsequent analysis, and most of the existing denoising methods are suitable for Gaussian noise rather than Rician noise. Aiming to solve this problem, we proposed fuzzy c-means and adaptive non-local means (FANLM), which combined the adaptive non-local means (NLM) with fuzzy c-means (FCM), as a novel method to reduce noise in the study. METHOD: The algorithm chose the optimal size of search window automatically based on the noise variance which was estimated by the improved estimator of the median absolute deviation (MAD) for Rician noise. Meanwhile, it solved the problem that the traditional NLM algorithm had to use a fixed size of search window. Considering the distribution characteristics for each pixel, we designed three types of search window sizes as large, medium and small instead of using a fixed size. In addition, the combination with the FCM algorithm helped to achieve better denoising effect since the improved the FCM algorithm divided the membership degrees of images and introduced the morphological reconstruction to preserve the image details. RESULTS: The experimental results showed that the proposed algorithm (FANLM) can effectively remove the noise. Moreover, it had the highest peak signal-noise ratio (PSNR) and structural similarity (SSIM), compared with other three methods: non-local means (NLM), linear minimum mean square error (LMMSE) and undecimated wavelet transform (UWT). Using the FANLM method, the image details can be well preserved with the noise being mostly removed. CONCLUSION: Compared with the traditional denoising methods, the experimental results showed that the proposed approach effectively suppressed the noise and the edge details were well retained. However, the FANLM method took an average of 13 s throughout the experiment, and its computational cost was not the shortest. Addressing these can be part of our future research.

Structure-property analysis of julolidine-based nonlinear optical chromophores for the optimization of microscopic and macroscopic nonlinearity.

Four NLO chromophores with different acceptors and modified julolidine donors were facilely synthesized to tune their intramolecular charge-transfer energy gaps for the investigation of the structure-property relationships. The photophysical properties of the UV-Vis absorption spectra, fluorescence spectra and solvatochromism were measured and analyzed to understand the effect of electron-donating strength and electron-withdrawing strength on intramolecular charge-transfer. Density functional theory calculations were carried out to investigate the electron density of the frontier orbitals, energy gap, molecular microscopic dipole moment and hyperpolarizability. The change tendency of the microscopic hyperpolarizability in different dielectric environments in association with the solvatochromism in absorption was analyzed. Meanwhile, the macroscopic electro-optic performance in relation to molecular structure variation and microscopic properties was further analyzed, revealing that chromophores with a larger solvatochromism exhibited higher microscopic hyperpolarizability and macroscopic electro-optic coefficients. Our investigation of the structure-property relationship gave a reliable insight into molecular design for high performance nonlinear optical chromophores.