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Idiopathic pulmonary fibrosis (IPF) is a serious interstitial lung disease. However, the definitive diagnosis of IPF is impeded by the limited capabilities of current diagnostic methods, which may fail to capture the optimal timing for treatment. The main goal of this study is to determine the feasibility of a nitroreductase (NTR) responsive probe, 18F-NCRP, for early detection and deterioration monitoring of IPF. 18F-NCRP was obtained with high radiochemical purity (>95 %). BLM-injured mice were established by intratracheal instillation with bleomycin (BLM) and characterized through histological analysis. Longitudinal PET/CT imaging, biodistribution study and in vitro autoradiography were performed. The correlations between the uptake of 18F-NCRP and mean lung density (tested by CT), as well as histopathological characteristics were analyzed. In PET imaging study, 18F-NCRP exhibited promising efficacy in monitoring the progression of IPF, which was earlier than CT. The ratio of uptake in BLM-injured lung to control lung increased from 1.4-fold on D15 to 2.2-fold on D22. Biodistribution data showed a significant lung uptake of 18F-NCRP in BLM-injured mice. There was a strong positive correlation between the 18F-NCRP uptake in the BLM-injured lungs and the histopathological characteristics. Given that, 18F-NCRP PET imaging of NTR, a promising biomarker for investigating the underlying pathogenic mechanism of IPF, is attainable as well as desirable, which might lay the foundation for establishing an NTR-targeted imaging evaluation system of IPF.

Abstract Background Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranostics. Herein, we propose a proof-of-concept strategy aiming to address the profound differences in the specific requirements of the diagnosis and treatment of radiotheranostics. Results To validate the concept, we designed an s-tetrazine (Tz) conjugated prostate-specific membrane antigen (PSMA) ligand (DOTA-PSMA-Tz) for 68Ga or 177Lu radiolabeling and tumor radiotheranostics, a trans-cyclooctene (TCO) modified Pd@Au nanoplates (Pd@Au-PEG-TCO) for signal amplification, respectively. We then demonstrated this radiotheranostic strategy in the tumor-bearing mice with the following three-step procedures: (1) i.v. injection of the [68Ga]Ga-PSMA-Tz for diagnosis; (2) i.v. injection of the signal amplification module Pd@Au-PEG-TCO; (3) i.v. injection of the [177Lu]Lu-PSMA-Tz for therapy. Firstly, this strategy was demonstrated in 22Rv1 tumor-bearing mice via positron emission tomography (PET) imaging with [68Ga]Ga-PSMA-Tz. We observed significantly higher tumor uptake (11.5 ± 0.8%ID/g) with the injection of Pd@Au-PEG-TCO than with the injection [68Ga]Ga-PSMA-Tz alone (5.5 ± 0.9%ID/g). Furthermore, we validated this strategy through biodistribution studies of [177Lu]Lu-PSMA-Tz, with the injection of the signal amplification module, approximately five-fold higher tumor uptake of [177Lu]Lu-PSMA-Tz (24.33 ± 2.53% ID/g) was obtained when compared to [177Lu]Lu-PSMA-Tz alone (5.19 ± 0.26%ID/g) at 48 h post-injection. Conclusion In summary, the proposed strategy has the potential to expand the toolbox of pretargeted radiotherapy in the field of theranostics. Graphical Abstract

Abstract Background Triple-negative breast cancer (TNBC) is one of the most lethal malignant tumors among women, characterized by high invasiveness, high heterogeneity, and lack of specific therapeutic targets such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Trophoblast cell-surface antigen-2 (TROP-2) is a transmembrane glycoprotein over-expressed in 80% of TNBC patients and is associated with the occurrence, progress, and poor prognosis of TNBC. The TROP-2 targeted immunoPET imaging allows non-invasive quantification of the TROP-2 expression levels of tumors, which could help to screen beneficiaries most likely to respond to SG and predict the response. This study aimed to develop a 89Zr/177Lu-radiolabeled anti-TROP-2 antibody (NY003) for immunoPET and SPECT imaging, as well as radioimmunotherapy (RIT) in TROP-2 (+)TNBC tumor-bearing model. Based on the camelid antibody, we developed a TROP-2 targeted recombinant antibody NY003. NY003 was conjugated with DFO and DTPA for 89Zr and 177Lu radiolabelling, respectively. The theranostic potential of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003 was evaluated through immunoPET, SPECT imaging, and RIT studies in the subcutaneous TROP-2 positive TNBC xenograft mice model. Results The high binding affinity of NY003 to TROP-2 was verified through ELISA. The radiochemical purity of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003 exceeded 95% and remained stable within 144h p.i. in vitro. ImmunoPET and SPECT imaging showed the specific accumulation of [89Zr]Zr-DFO-NY003/[177Lu]Lu-DTPA-NY003 in MDA-MB-231 tumors and gradually increased with the time tested, significantly higher than that in control groups (P

Rayleigh lidar equipped on airborne floating platforms has received increasing attention in recent years due to the demand for exploring the middle atmosphere. However, the inevitable attitude fluctuation of the platform affects the measurement accuracy of the photon profile, which greatly affects temperature retrieval. Here, an extensive theoretical analysis model of geometrical transformations between the actual altitude and detection distance under attitude fluctuations was constructed by taking pitch, roll, and observation angles into consideration. Based on this model and measured attitude angles, the influence of platform fluctuation on lidar measurement was analyzed by calculating the deviations between temperature retrieval results and the NRLMSISE-00 model at different observation angles, which demonstrated that the altitude displacement from the variation of pitch angle is a crucial factor in causing temperature retrieval error, especially at large observation angles. Then, an attitude compensation method was designed to eliminate the impact of fluctuations, incorporating the merits of good robustness. Under the observation angle of 45° and average pitch angle of around 4°, the maximum temperature deviation after attitude compensation was reduced from 21.29 K to 0.366 K, a reduction of around two orders of magnitude, indicating that the method can significantly improve the measurement accuracy of Rayleigh lidar.

With the development of PD-1/PD-L1 immune checkpoint inhibitor therapy, the ability to monitor PD-L1 expression in the tumor microenvironment is important for guiding therapy. This study was performed to develop a novel radiotracer with optimal pharmacokinetic properties to reflect PD-L1 expression in vivo via single-photon emission computed tomography (SPECT) imaging. [99mTc]Tc-HYNIC-WL12-tricine/M (M = TPPTS, PDA, ISONIC, 4-PSA) complexes with high radiochemical purity (>97%) and suitable molar activity (from 100.5 GBq/μmol to 300 GBq/μmol) were prepared through a kit preparation process. All 99mTc-labeled HYNIC-WL12 radiotracers displayed good in vitro stability for 4 h. The affinity and specificity of the four radiotracers for PD-L1 were demonstrated both in vitro and in vivo. The results of biodistribution studies displayed that the pharmacokinetics of the 99mTc-HYNIC-conjugated radiotracers were significantly influenced by the coligands of the radiotracers. Among them, [99mTc]Tc-HYNIC-WL12-tricine/ISONIC exhibited the optimal pharmacokinetic properties (t1/2α = 8.55 min, t1/2β = 54.05 min), including the fastest clearance in nontarget tissues, highest tumor-to-background contrast (e.g., tumor-to-muscle ratio, tumor-to-blood ratio: 40.42 ± 1.59, 14.72 ± 2.77 at 4 h p.i., respectively), and the lowest estimated radiation absorbed dose, highlighting its potential as a clinical SPECT imaging probe for tumor PD-L1 detection.

Abstract Background Sarcopenia is highly prevalent in elderly individuals and has a significant adverse effect on their physical health and quality of life, but the mechanisms remain unclear. Studies have indicated that transcription factors (TFs) and the immune microenvironment play a vital role in skeletal muscle atrophy. Methods RNA-seq data of 40 muscle samples were downloaded from the GEO database. Then, differentially expressed genes (DEGs), TFs(DETFs), pathways(DEPs), and the expression of immune gene sets were identified with limma, edgeR, GO, KEGG, ORA, GSVA, and ssGSEA. Furthermore, the results above were integrated into coexpression analysis by Pearson correlation analysis (PCA). Significant coexpression patterns were used to construct the immune-related transcriptional regulatory network by Cytoscape and potential medicine targeting the network was screened by Connectivity Map. Finally, the regulatory mechanisms and RNA expression of DEGs and DETFs were identified by multiple online databases and RT‒qPCR. Results We screened 808 DEGs (log2 fold change (FC) > 1 or 0.7 or 1 or 0.4 or

A high-power dual-wavelength laser based on coaxial end-pumping scheme with composite Nd:YAG and Nd:YAP crystals was demonstrated. A theoretical model was built to analyze the thermal lens and accurately calculate the thermal focal length of laser gain medium pumped by a divergent beam. The experiment was carried out with a plane-convex cavity and a V-shape cavity for high-power output. The Q-switched laser produced 9.1 W pulsed dual-wavelength output (4.7 W at 1064 nm and 4.4 W at 1079 nm) at 25-kHz pulse repetition rate with synchronized pulse duration of 35 ns, corresponding to the optical-to-optical efficiency of 30.3%. The continuous-wave (CW) output power reached 15.5 W at laser diode (LD) pump power of 40 W, corresponding to a slope efficiency of 40.9% and an optical-to-optical conversion efficiency of 38.9%. The powers at two wavelengths were almost equivalent and the fluctuations were both less than 2.3%. To our best knowledge, it was the highest output power for stable CW dual-wavelength lasers based on diode-end-pumped configuration.

Riboflavin receptor 3 (RFVT3) is a key protein in energetic metabolism reprogramming and is overexpressed in multiple cancers involved in malignant proliferation, angiogenesis, chemotherapy resistance, and immunosuppression. To enable non-invasive real-time quantification of RFVT3 in tumors, we sought to develop a suitable PET probe that would allow specific and selective RFVT3 imaging in vivo. A novel radiofluorinated riboflavin probe (18F-RFTA) based on riboflavin was synthesized and characterized in terms of radiochemical purity, hydrophilicity, binding affinity, and stability. Positron emission tomography (PET) imaging of 18F-RFTA was performed in U87MG tumor-bearing mice. Immunohistochemistry staining was carried out to determine the expression of RFVT3 in U87MG tumors. 18F-RFTA was characterized by high radiochemical purity and RFVT3 binding affinity, and remarkable stability in vitro and in vivo. Small-animal PET imaging with 18F-RFTA revealed significantly higher uptake in RFVT3-expressing U87MG tumors than in muscle. In conclusion, we have developed the first radiofluorinated riboflavin-based PET probe that is suitable for imaging RFVT3-positive tumors. The new target/probe system can be leveraged for extensive use in the diagnosis and treatment of RFVT3 overexpressing diseases, such as oncologic, cardiovascular, and neurodegenerative diseases.

Lidar is important active remote sensing equipment in the field of atmospheric environment detection. However, the detection range of lidar is severely limited by the dynamic range of photodetectors. To solve this problem, atmospheric lidars are often equipped with two or more channels to receive signals from different altitude ranges, where gluing the multi-channel echo signals becomes a key issue for accurate data inversion. In this paper, a multi-channel signal gluing algorithm based on the Improved Gray Wolf Optimizer (IGWO) and Neighborhood Rough Set (NRS), named IGWO-RSD, is proposed. The fitness function F is formed by three objective functions: correlation coefficient R, regression stability coefficient S and mean fit deviation D. All three objective functions are obtained from the data itself and do not rely on prior information. The weights of the objective functions R, S and D are pre-trained by NRS, and IGWO is used to optimize the fitness function F. With ground-based aerosol lidar data, all-day signal gluing experiments are performed, where IGWO-RSD demonstrates obvious advantages in stability, accuracy and applicability in lidar signal processing compared with NRSWNSGA-II.

Measurement uncertainty is an extremely important parameter for characterizing the quality of measurement results. In order to measure the reliability of atmospheric temperature detection, the uncertainty needs to be evaluated. In this paper, based on the measurement models originating from the Chanin-Hauchecorne (CH) method, the atmospheric temperature uncertainty was evaluated using the Guide to the Expression of Uncertainty in Measurement (GUM) and the Monte Carlo Method (MCM) by considering the ancillary temperature uncertainty and the detection noise as the major uncertainty sources. For the first time, the GUM atmospheric temperature uncertainty framework was comprehensively and quantitatively validated by MCM following the instructions of JCGM 101: 2008 GUM Supplement 1. The results show that the GUM method is reliable when discarding the data in the range of 10–15 km below the reference altitude. Compared with MCM, the GUM method is recommended to evaluate the atmospheric temperature uncertainty of Rayleigh lidar detection in terms of operability, reliability, and calculation efficiency.

A novel scheme to realize widely tunable optical parametric oscillator (OPO) based on an x-cut KTP crystal is demonstrated. The tuning range from 1572.5 nm to 1697 nm was enabled by a 1:1 imaging optical system with a variable deflection mirror to couple the 1064-nm laser pulses into the OPO cavity in the noncollinear phase-matching (PM) configuration. Benefitting from varying the pump direction rather than the cavity axis, the OPO cavity was unaffected so that the stability of the output signal energy and beam direction could be maintained, which greatly facilitates subsequent applications. The change of pump threshold, output energy, linewidth and temporal pulse shapes during wavelength tuning were also discussed.

A passively Q-switched dual-wavelength laser with tunable power ratio and pulse interval is demonstrated based on the coaxial diode end-pumping configuration by varying the pump wavelength. A theoretical model was built by a set of time-domain rate equations illustrating the dynamic process of both the pulse generation of two wavelengths from a shared pump source and a saturable absorber. The simulation showed that both the power ratio and the time interval between the pulses at two resonant wavelengths in the Q-switched mode could be tuned by balancing the gains in two laser crystals by varying the pump wavelength, realized by controlling the working temperature of the pump laser diode. The experiment was performed with Nd:YAG/Nd:YAP composite laser crystals and a Cr4+:YAG slice working as the saturable absorber for pulse generation. The continuous-wave and Q-switched total output power reached 5.62 W and 2.12 W, corresponding to overall optical-optical conversion efficiencies of 37.5% and 14.1%, respectively. The manipulation of power ratio and pulse interval between 1064 nm and 1080 nm agreed well with the simulation results.

Flies carry pathogens that endanger the health of humans and animals. The color and shape of the fly species are very similar, which is difficult to recognize. This paper proposes a fly species recognition method based on improved RetinaNet and convolutional block attention module (CBAM). Firstly, the proposed method used ResNeXt101 as a feature extraction network, and the improved CBAM called Stochastic-CBAM was added. Then, we built a multi-scale feature pyramid through an improved feature pyramid network (FPN) and integrated multi-level feature information. Finally, the small full convolutional network (FCN) was used as the classification subnet and the bounding box regression subnet. The Kullback-Leibler (KL) loss replaced smooth L1 loss as a bounding box regression loss function for learning bounding box regression and positioning uncertainty at the same time. We experimentally compared the proposed method with other the state-of-the-art methods on the established dataset. Experimental results showed that the mean Average Precision (mAP) of this method reached 90.38%, which was better than the state-of-the-art methods. The average time to recognize a single image was 0.131s. This method has a good detection effect on the fly species recognition.

Gut microbiota dysbiosis correlates with many diseases, but such correlations derive mostly from relationships between one or a few bacteria and a particular disease. Since microbiota resemble complex forest ecosystems more closely than individual patches of trees, the overall landscape (spatial and temporal distribution) of gut bacteria may also affect/reflect disease development.

The synthesis of 18F-labeled positron emission tomography (PET) tracers is difficult and typically requires anhydrous conditions. Here, the authors developed organophosphine precursors that allow for quick, high-yield synthesis of 18F-labeled probes in either organic solvents or aqueous media.

Lidar is an active remote sensing technology that has many advantages, but the echo lidar signal is extremely susceptible to noise and complex atmospheric environment, which affects the effective detection range and retrieval accuracy. In this paper, a wavelet transform (WT) and locally weighted scatterplot smoothing (LOWESS) based on ensemble empirical mode decomposition (EEMD) for Rayleigh lidar signal denoising was proposed. The WT method was used to remove the noise in the signal with a signal-to-noise ratio (SNR) higher than 16 dB. The EEMD method was applied to decompose the remaining signal into a series of intrinsic modal functions (IMFs), and then detrended fluctuation analysis (DFA) was conducted to determine the threshold for distinguishing whether noise or signal was the main component of the IMFs. Moreover, the LOWESS method was adopted to remove the noise in the IMFs component containing the signal, and thus, finely extract the signal. The simulation results showed that the denoising effect of the proposed WT-EEMD-LOWESS method was superior to EEMD-WT, EEMD-SVD and VMD-WOA. Finally, the use of WT-EEMD-LOWESS on the measured lidar signal led to significant improvement in retrieval accuracy. The maximum error of density and temperature retrievals was decreased from 1.36% and 125.79 K to 1.1% and 13.84 K, respectively.

In order to achieve collinear phase-matched nonlinear optical frequency conversion in cubic crystals, a novel method to induce and modulate the birefringence based on the linear electro-optic effect was studied. Taking terahertz generation with ZnTe and CdTe crystals of the 4¯3m point group as an example, an external electric field provided the freedom to realize perfect phase matching (PM) in a wide bandwidth up to 2 THz for difference frequency generation, with monochromatic optical waves at around 800 nm and 1010 nm, respectively. Theoretical simulations showed that such a method helps to extend the terahertz frequency, enhance the conversion efficiency, and alleviate the limitation on the pump wavelength, which is highly favorable for nonlinear optical uses of cubic crystals. Simultaneous wideband terahertz generation pumped by ultrashort laser pulses via optical rectification or difference frequency mixing was also discussed, indicating that an electric field can be used to modulate the PM characteristics without changing the group velocity-matching condition. Tuning the nonlinear interaction by an applied voltage is fast, robust, and convenient compared to other approaches. In addition, the linear electro-optic effect can make the nonlinear crystal a compact and high-speed terahertz amplitude modulator, which has great potential in radar, communication, imaging, etc.

Under complex sea conditions, ship detection from remote sensing images is easily affected by sea clutter, thin clouds, and islands, resulting in unreliable detection results. In this paper, an end-to-end convolution neural network method is introduced that combines a deep convolution neural network with a fully connected conditional random field. Based on the Resnet architecture, the remote sensing image is roughly segmented using a deep convolution neural network as the input. Using the Gaussian pairwise potential method and mean field approximation theorem, a conditional random field is established as the output of the recurrent neural network, thus achieving end-to-end connection. We compared the proposed method with other state-of-the-art methods on the dataset established by Google Earth and NWPU-RESISC45. Experiments show that the target detection accuracy of the proposed method and the ability of capturing fine details of images are improved. The mean intersection over union is 83.2% compared with other models, which indicates obvious advantages. The proposed method is fast enough to meet the needs for ship detection in remote sensing images.

The degradation of caffeic acid under ultrasound treatment in a model system was investigated. The type of solvent and temperature were important factors in determining the outcome of the degradation reactions. Liquid height, ultrasonic intensity and duty cycle only affected degradation rate, but did not change the nature of the degradation. The degradation rate of caffeic acid decreased with increasing temperature. Degradation kinetics of caffeic acid under ultrasound fitted a zero-order reaction from −5 to 25 °C. Caffeic acid underwent decomposition and oligomerization reactions under ultrasound. The degradation products were tentatively identified by FT-IR and HPLC-UV-ESIMS to include the corresponding decarboxylation products and their dimers.

The aim of this study is to develop a copolymer-based single-photon emission computed tomography/magnetic resonance (SPECT/MR) dual-modality imaging agent that can be labeled with both technetium-99m ( 99m Tc) and gadolinium (Gd) and target asialoglycoprotein receptor (ASGPR) via galactose. Monomers of N - p -vinylbenzyl-6-(2-(4-dimethylamino)benzaldehydehydrazono) nicotinate (VNI) for labeling of 99m Tc, 5,8- bis (carboxymethyl)-3-oxo-11-(2-oxo-2-((4-vinylbenzyl)amino)ethyl)-1-(4-vinylphenzyl)-2,5,8,11-tetraazatridecan-13-oic acid (V 2 DTPA) for labeling of Gd, and vinylbenzyl- O -β- d -galactopyranosyl- d -gluconamide (VLA) for targeting ASGPR were synthesized, respectively. Then the copolymer P(VLA-co-VNI-co-V 2 DTPA) ( p VLND 2 ) was synthesized and characterized by gel permeation chromatography, dynamic light scattering, and high-performance liquid chromatography analysis. After labeling with 99m Tc and Gd simultaneously, the radiochemical purity, toxicity, relaxivity (r 1 ), and in vivo SPECT/MR imaging in mice were evaluated. Single-photon emission computed tomography/magnetic resonance imaging and biodistribution results showed that p VLND 2 could target ASGPR well. The significantly improved signal to noise ratio was observed in mice liver during MR imaging. All the results suggest that this novel kind of copolymer has the potential to be further developed as a functional SPECT/MR imaging agent.

The folate receptor (FR) is overexpressed in a wide variety of human tumors. In our study, the multimeric concept was used to synthesize a dimeric folate derivative via a click reaction. The novel folate derivative (HYNIC-D1-FA2) was radiolabeled with 99mTc using tricine and trisodium triphenylphosphine-3,3′,3″-trisulfonate (TPPTS) as coligands (99mTc-HYNIC-D1-FA2) and its in vitro physicochemical properties, ex vivo biodistribution and in vivo micro-SPECT/CT imaging as a potential FR targeted agent were evaluated. It is a hydrophilic compound (log P = −2.52 ± 0.13) with high binding affinity (IC50 = 19.06 nM). Biodistribution in KB tumor-bearing mice showed that 99mTc-HYNIC-D1-FA2 had high uptake in FR overexpressed tumor and kidney at all time-points, and both of them could obviously be inhibited when blocking with free FA in the blocking studies. From the in vivo micro-SPECT/CT imaging results, good tumor uptake of 99mTc-HYNIC-D1-FA2 was observed in KB tumor-bearing mice and it could be blocked obviously. Based on the results, this new radiolabeled dimeric FA tracer might be a promising candidate for FR-targeting imaging with high affinity and selectivity.

In the title compound, C17H20ClFN2O3, the dihedral angle between the pyridazine and benzene rings is 41.37 (10)°. In the crystal, there are no significant intermolecular interactions present. The terminal –CH2F group is disordered over two sets of sites with an occupancy ratio of 0.737 (2):0.263 (2).