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Gypsum-based composites were prepared via a slurry casting process using construction gypsum as the binding material and poplar fibers as reinforcing material. The effects of different fiber content and curing time on the mechanical properties, water resistance, and flame retardancy of these composites were investigated, and the influence mechanism was characterized by infrared spectroscopy, scanning electron microscopy, and X-ray diffractometry. The results showed that the best composite mechanical strength was achieved with 10% poplar fiber- content, and the absolute dry flexural and compressive strengths reached 3.59 and 8.06 MPa, respectively. Compared with pure gypsum, the flexural strength and compressive strength increased by 10% and 19%, respectively. The inclusion of fibers somewhat prevented the migration of free water within the composites and enhanced their water resistance. At 10% fiber content, the composite's 24 h water absorption rate was 34.3%, 8% lower than that of pure gypsum, with a softening coefficient of 0.55. However, fiber content increases the porosity of gypsum-based composites. When heated, this increased porosity accelerates' heat conduction within the matrix, raising the peak and total exothermic rates, thereby weakening the composites' inherently flame-retardant properties. Poplar-fiber-reinforced gypsum-based composites offered superior performance in commercial applications, compared to pure gypsum board, providing a sustainable and green alternative for ceilings, partitions, and other applications, while broadening the prospects for gypsum-based composites in the engineering field. [ABSTRACT FROM AUTHOR]

Reed charcoal/polypropylene (RC/PP) composites were prepared by melt-blending and molding processes. The effects of RC addition (by mass fraction) on its mechanical properties were investigated and the mechanism characterized. The results showed that RC and PP were physically bonded and formed a mechanical interlocking matrix. The water absorption rate of these composites was <1% at 168 h. As the RC mass fraction increased, the tensile modulus, crystallinity, and energy storage modulus of the composites increased and then decreased, with the tensile modulus reaching a maximum of 679.4 MPa. The thermal decomposition rate peak and starting melt temperature increased by 14.8 and 2.5 °C, respectively, compared to pure PP, and the energy storage modulus reached a maximum of 3752.8 MPa at 40 wt% RC. The addition of RC in appropriate amounts improved the rigidity and thermal stability of these composites. [ABSTRACT FROM AUTHOR]

Abstract: A new near-infrared fluorescent compound containing two cyclic RGD motifs, cypate-[c(RGDfK)]2 (1), was synthesized based on a carbocyanine fluorophore bearing two carboxylic acid groups (cypate) for integrin αvβ3-targeting. Compared with its monovalent counterpart cypate-c(RGDfK) (2), 1 exhibited remarkable improvements in integrin αvβ3 binding affinity and tumor uptake in nude mice of A549. The results suggest that cypate-linked divalent ligands can serve as an important molecular platform for exploring receptor-targeted optical imaging and treatment of various diseases. [Copyright &y& Elsevier]

Purpose: Near-infrared fluorescence (NIRF) imaging is an attractive technique for studying diseases at the molecular level in vivo. Glucose transporters are often used as targets for in vivo imaging of tumors. The efficiency of a tumor-seeking fluorescent probe can be enhanced by attaching one or more glucosamine (GlcN) moieties. This study was designed to evaluate the use of previously developed GlcN-linked NIRF probes for in vitro and in vivo optical imaging of cancer. Procedures: Cellular uptake of the probes (1 μM) was investigated in monolayer cultures of luciferase-expressing PC3 (PC3-luc) cells. The prostate tumors were established as subcutaneous xenografts using PC3-luc cells in nude mice. The biodistributions and tumor-targeting specificities of cypate (cyp), cypate- d-(+)-glucosamine (cyp-GlcN), and d-(+)-gluosamine-cypate- d-(+)-gluosamine (cyp-2GlcN) were studied. The tumor, muscle, and major organs were collected for ex vivo optical imaging. Results: The tumor cell uptake of the probe containing two glucosamine residues, cyp-2GlcN, was significantly higher than the uptake of both the probe with one glucosamine residue, cyp-GlcN, and the probe without glucosamine, cyp only. Similarly, in in vivo experiments, cyp-2GlcN demonstrated higher maximum fluorescence intensity and longer residence lifetime in tumors than cyp-GlcN or cyp. The ex vivo biodistribution analysis revealed that tumor uptake of cyp-2GlcN and cyp-GlcN was four- and twofold higher than that of cyp at 24 h post-injection, respectively. Conclusion: Both cyp-GlcN and cyp-2GlcN NIRF probes exhibited good tumor-targeting properties in prostate cancer cell cultures and live mice. The cyp-2GlcN probe showed the highest uptake with good retention characteristics in vivo. The uptake of cyp-2GlcN and cyp-GlcN is likely mediated by glucosamine-recognizing transporters. The uptake mechanism is being explored further for developing cypate-glucosamine-based probes for in vivo imaging. [ABSTRACT FROM AUTHOR]

Abstract: We synthesized disulfide-based cyclic RGD pentapeptides bearing a near-infrared fluorescent dye (cypate), represented by cypate-c(CRGDC) (1) for integrin-targeted optical imaging. These compounds were compared with the traditional lactam-based cyclic RGD counterpart, cypate-c(RGDfK) (2). Molecular modeling suggests that the binding affinity of 2 to integrin αvβ3 is an order of magnitude higher than that of 1. This was confirmed experimentally, which further showed that substitution of Gly with Pro, Val and Tyr in 1 remarkably hampered the αvβ3 binding. Interestingly, cell microscopy with A549 cells showed that 1 exhibited higher cellular staining than 2. These results indicate that factors other than receptor binding affinity to αvβ3 dimeric proteins mediate cellular uptake. Consequently, 1 and its analogs may serve as valuable molecular probes for investigating the selectivity and specificity of integrin targeting by optical imaging. [Copyright &y& Elsevier]

Abstract: Recently, a disulfide-based cyclic RGD peptide called iRGD, that is, c(CRGDKGPDC), has been reported to interact with both integrin and neuropilin-1 receptors for cellular and deep tissue penetration to improve the imaging sensitivity and therapeutic efficacy. In this study, two new near-infrared fluorescent iRGD conjugates, that is, Ac-Cys(IRDye®800CW)-iRGD (1), and its dual labeling analog DOTA-Cys(IRDye®800CW)-iRGD (2) were synthesized via the specific mercapto–maleimide reaction for tumor imaging. Both 1 and 2 showed significant tumor localization in optical imaging of MDA-MB-435 tumor-bearing mice. The potential of such iRGD compounds in tumor-targeted imaging and drug delivery deserves further exploration. [Copyright &y& Elsevier]

Abstract: Objectives: The αvβ3 integrin is a cell adhesion molecule known to be involved in stages of angiogenesis and metastasis. In this study, the chelators CB-TE2A and diamsar were conjugated to cyclic RGDyK and RGDfD and the biological properties of 64Cu-labeled peptides were compared. Methods: CB-TE2A-c(RGDyK) and diamsar-c(RGDfD) were labeled with 64Cu in 0.1 M NH4OAc (pH=8) at 95°C and 25°C, respectively. PET and biodistribution studies were carried out on M21 (αvβ3-positive) and M21L (αv-negative) melanoma-bearing mice. Binding affinity of the Cu-chelator–RGD peptides to αvβ3 integrins was determined by a competitive binding affinity assay. Results: Biological studies showed higher concentration of 64Cu-CB-TE2A-c(RGDyK) in M21 tumor compared to M21L tumor at 1 and 4 h pi. Tumor concentration of 64Cu-CB-TE2A-c(RGDyK) was higher than that of 64Cu-diamsar-c(RGDfD). The difference is not due to differing binding affinities, since similar values were obtained for the agents. Compared to 64Cu-diamsar-c(RGDfD), there is more rapid liver and blood clearance of 64Cu-CB-TE2A-c(RGDyK), resulting in a lower liver and blood concentration at 24 h pi. Both 64Cu-labeled RGD peptides show similar binding affinities to αvβ3. The differences in their biodistribution properties are likely related to different linkers, charges and lipophilicities. The M21 tumor is clearly visualized with 64Cu-CB-TE2A-c(RGDyK) by microPET imaging. Administration of c(RGDyK) as a block significantly reduced the tumor concentration; however, the radioactivity background was also decreased by the blocking dose. Conclusions: Both 64Cu-CB-TE2A-c(RGDyK) and 64Cu-diamsar-c(RGDfD) are potential candidates for imaging tumor angiogenesis. For diamsar-c(RGDfD), a linker may be needed between the Cu-chelator moiety and the RGD peptide to achieve optimal in vivo tumor concentration and clearance from nontarget organs. [Copyright &y& Elsevier]

Biodegradable composites were prepared from polylactic acid (PLA) and bamboo charcoal (BC) by melt blending and hot pressing. The effects of BC addition on the mechanical properties, water absorption, DMA, TGA, DSC, and CONE of BC/PLA composites were investigated. The microscopic morphology of the composites was analyzed by SEM. The results showed that for BC addition of 40 wt%, the mechanical strength, thermal properties, and flame retardant properties of the composites were improved compared with those of PLA, with a 2.24 % increase in flexural strength and a 1535 % increase (500 °C) in TG mass retention rate. The crystallinity increased by 129.66 %, the peak loss factor decreased by 31.15 %, the time required for combustion was delayed by 168 s, the peak heat release rate decreased by 29.40 %, the carbon residue rate detected by cone calorimetry increased by 48.50 %, and the peak mass loss rate decreased by 48.82 %. The addition of BC enhanced the crystallization capacity of PLA, and improved the thermal properties and flame retardant properties of the prepared composites. The results showed that materials prepared with a BC content of 40 wt% exhibited the best overall performance. • Bamboo charcoal/polylactic acid biodegradable composites were prepared by melt blending and hot pressing. • The effects of the amount of added BC on properties of composites and their mechanisms were determined. • BC/PLA composites obtained high water resistance, thermal properties, thermal stability, and flame retardant properties. • The application field of Bamboo charcoal has been expanded. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are involved in tissue remodeling. Accordingly, MMP inhibitors and related radiolabeled analogs are important tools for MMP-targeted imaging and therapy in a number of diseases. Herein, we report design, synthesis, and evaluation of a new Arginine-containing macrocyclic hydroxamate analog, RYM, its hydrazinonicotinamide conjugate, RYM1 and 99mTc-labeled analog 99mTc-RYM1 for molecular imaging. RYM exhibited potent inhibition against a panel of recombinant human (rh) MMPs in vitro. RYM1 was efficiently labeled with 99mTcO4− to give 99mTc-RYM1 in a high radiochemical yield and high radiochemical purity. RYM1 and its decayed labeling product displayed similar inhibition potencies against rhMMP-12. Furthermore, 99mTc-RYM1 exhibited specific binding with lung tissue from lung-specific interleukin-13 transgenic mice, in which MMP activity is increased in conjunction with tissue remodeling and inflammation. The results support further development of such new water-soluble Arginine-containing macrocyclic hydroxamate MMP inhibitors for targeted imaging and therapy. [ABSTRACT FROM AUTHOR]

Purpose: Exploring synaptic density changes during brain growth is crucial to understanding brain development. Previous studies in nonhuman primates report a rapid increase in synapse number between the late gestational period and the early neonatal period, such that synaptic density approaches adult levels by birth. Prenatal synaptic development may have an enduring impact on postnatal brain development, but precisely how synaptic density changes in utero are unknown because current methods to quantify synaptic density are invasive and require post-mortem brain tissue. Methods: We used synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) radioligands [11C]UCB-J and [18F]Syn-VesT-1 to conduct the first assessment of synaptic density in the developing fetal brain in gravid rhesus monkeys. Eight pregnant monkeys were scanned twice during the third trimester at two imaging sites. Fetal post-mortem samples were collected near term in a subset of subjects to quantify SV2A density by Western blot. Results: Image-derived fetal brain SV2A measures increased during the third trimester. SV2A concentrations were greater in subcortical regions than in cortical regions at both gestational ages. Near term, SV2A density was higher in primary motor and visual areas than respective associative regions. Post-mortem quantification of SV2A density was significantly correlated with regional SV2A PET measures. Conclusion: While further study is needed to determine the exact relationship of SV2A and synaptic density, the imaging paradigm developed in the current study allows for the effective in vivo study of SV2A development in the fetal brain. [ABSTRACT FROM AUTHOR]

• Develop a novel pixel-wise calibration method for telecentric structured light systems, offering higher accuracy and distortion-free 3D reconstruction. • Implement a global calibration strategy based on the virtual plane, addressing calibration degeneracy and enhancing robustness. • Introduce an orthographic projection model to essentially eliminate XY fluctuation issues, simplifying the pixel-wise strategy and the 3D reconstruction process. • Design a best stripe selection algorithm for optimizing calibration and improving accuracy in the pixel-wise strategy. • Experimentally demonstrate the calibration framework's versatility for different system setups and its capability to rapidly achieve high precision in experimental results. Micro three-dimensional (3D) imaging technology based on structured light is widely used in industrial applications, as it can obtain high-precision morphology of tiny objects using a camera equipped with a telecentric lens and a distorted pinhole projector. However, the telecentric structured light system suffers from problems caused by stereo-vision degeneracy, and their measurement accuracy is limited due to local distortions in stereo-vision calibration. To overcome these issues, the paper proposed a pixel-wise calibration method based on the virtual plane. In this method, first, the virtual plane is applied to the telecentric structured light system to ensure spatial relationships between the camera and projector, which is achieved easily by the Levenberg-Marquardt-based Perspective-n-Point(PnP) algorithm. Second, a pixel-wise polynomial regression model is introduced for local distortions, which converts phase information into refined 3D coordinates. Third, considering orthogonal stripes have poor sensitivity in one direction, the optimal fringe selection based on a reference plane is used in the calibration process to make the system more sensitive to depth. In addition, the proposed method can be extended to multi-projector systems and allows uncalibrated projectors to be calibrated with unidirectional fringe patterns. The proposed calibration method is flexible and easy to conduct. Experimental results demonstrate that our proposed method can effectively reduce local measurement errors and significantly improve reconstruction speed. [ABSTRACT FROM AUTHOR]

Abstract: The nuclear internalization of biomolecules by Tat peptide provides a mechanism to deliver drugs to cells. However, translocation of molecular imaging probes to the nucleus may induce undesirable mutagenesis. To assess the feasibility of retaining its cell permeating effect without nuclear translocation, Tat-peptide was conjugated with a somatostatin receptor (STR)-avid ligand (Oct) and labeled with fluorescent dyes. The results show that Tat-Oct-5-FAM (fluorescein 5′-carboxylic acid) remained in the cytoplasm of STR-positive AR42J cells. Co-incubation of Tat-Oct-5-FAM with ATP induced nuclear translocation. These data suggest that both dye and Oct-STR endocytosis complex could modulate nuclear internalization of Tat peptides. [Copyright &y& Elsevier]

To identify inhibitors of the intrinsic N-acetylated α-linked acidic dipeptidase (NAALADase) activity of prostate specific membrane antigen (PSMA) that may be useful for targeting imaging agents or chemotherapeutic drugs to disseminated prostate cancer, analogs of the tetrahedral transition state for hydrolysis of the natural substrate, N-acetylaspartylglutamate (NAAG), were synthesized. These compounds were assayed for their ability to inhibit the membrane-associated enzyme isolated from LNCaP prostate cancer cells. Active inhibitors were further assayed for their cytotoxicity and membrane binding. We have identified nine compounds, including fluorescent and iodine-labeled conjugates, which inhibit NAALADase enzyme activity with IC50s at, or below, 120 nM. The binding of these compounds to the cell surface of viable LNCaP prostate tumor cells appears to be specific and saturable, and none of the compounds alter the cell cycle kinetics or induce apoptosis in LNCaP cells, suggesting that they are relatively innocuous and are suitable for targeting imaging agents or cytotoxic drugs to disseminated prostate cancer. [Copyright &y& Elsevier]

Background: Attempts to associate amyloid-β (Aβ) pathogenesis with synaptic loss in Alzheimer's disease (AD) have thus far been limited to small numbers of postmortem studies. Aβ plaque burden is not well-correlated with indices of clinical severity or neurodegeneration—at least in the dementia stage—as deposition of Aβ reaches a ceiling. In this study, we examined in vivo the association between fibrillar Aβ deposition and synaptic density in early AD using positron emission tomography (PET). We hypothesized that global Aβ deposition would be more strongly inversely associated with hippocampal synaptic density in participants with amnestic mild cognitive impairment (aMCI; a stage of continued Aβ accumulation) compared to those with dementia (a stage of relative Aβ plateau). Methods: We measured SV2A binding ([11C]UCB-J) and Aβ deposition ([11C]PiB) in 14 participants with aMCI due to AD and 24 participants with mild AD dementia. Distribution volume ratios (DVR) with a cerebellar reference region were calculated for both tracers to investigate the association between global Aβ deposition and SV2A binding in hippocampus. Exploratory analyses examined correlations between both global and regional Aβ deposition and SV2A binding across a broad range of brain regions using both ROI- and surface-based approaches. Results: We observed a significant inverse association between global Aβ deposition and hippocampal SV2A binding in participants with aMCI (r = − 0.55, P = 0.04), but not mild dementia (r = 0.05, P = 0.82; difference statistically significant by Fisher z = − 1.80, P = 0.04). Exploratory analyses across other ROIs and whole brain analyses demonstrated no broad or consistent associations between global Aβ deposition and regional SV2A binding in either diagnostic group. ROI-based analyses of the association between regional Aβ deposition and SV2A binding also revealed no consistent pattern but suggested a "paradoxical" positive association between local Aβ deposition and SV2A binding in the hippocampus. Conclusions: Our findings lend support to a model in which fibrillar Aβ is still accumulating in the early stages of clinical disease but approaching a relative plateau, a point at which Aβ may uncouple from neurodegenerative processes including synaptic loss. Future research should investigate the relationship between Aβ deposition and synaptic loss in larger cohorts beginning preclinically and followed longitudinally in conjunction with other biomarkers. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6-K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2+ AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo-vasculature. These results show that conjugate 1 might have potential as an in-vivo sst2 targeting photosensitizer conjugate. [ABSTRACT FROM AUTHOR]

Abstract: Fluorescent Cybesin (Cypate-Bombesin Peptide Analogue Conjugate) was synthesized from Indocyanine Green (ICG) and the bombesin receptor ligand as a contrast agent for detecting pancreas tumors. However, the LC–MS analysis indicated that the target compound was only a minor component in the reaction mixture. Since preparative HPLC can hardly separate such a small amount of the target compound directly from the original crude reaction mixture without a considerable adsorptive loss onto the solid support, high-speed counter-current chromatography (HSCCC) was used for purification since the method uses no solid support and promises high sample recovery. A suitable two-phase solvent system composed of hexane/ethyl acetate/methanol/methyl t-butyl ether/acetonitrile/water) at a volume ratio of 1:1:1:4:4:7 was selected based on the partition coefficient of Cybesin (K ≈0.9) determined by LC–MS. The separation was performed in two steps using the same solvent system with lower aqueous mobile phase. From 400mg of the crude reaction mixture the first separation yielded 7.7mg of fractions containing the target compound at 12.8% purity, and in the second run 1mg of Cybesin was obtained at purity of 94.0% with a sample recovery rate of over 95% based on the LC–MS analysis. [ABSTRACT FROM AUTHOR]

Background: Dopaminergic mechanisms that may underlie cannabis' reinforcing effects are not well elucidated in humans. This positron emission tomography (PET) imaging study used the dopamine D2/3 receptor antagonist [11C]raclopride and kinetic modelling testing for transient changes in radiotracer uptake to assess the striatal dopamine response to smoked cannabis in a preliminary sample.Methods: PET emission data were acquired from regular cannabis users (n = 14; 7 M/7 F; 19-32 years old) over 90 min immediately after [11C]raclopride administration (584 ± 95 MBq) as bolus followed by constant infusion (Kbol = 105 min). Participants smoked a cannabis cigarette, using a paced puff protocol, 35 min after scan start. Plasma concentrations of Δ9-THC and metabolites and ratings of subjective "high" were collected during imaging. Striatal dopamine responses were assessed voxelwise with a kinetic model testing for transient reductions in [11C]raclopride binding, linear-parametric neurotransmitter PET (lp-ntPET) (cerebellum as a reference region).Results: Cannabis smoking increased plasma Δ9-THC levels (peak: 0-10 min) and subjective high (peak: 0-30 min). Significant clusters (>16 voxels) modeled by transient reductions in [11C]raclopride binding were identified for all 12 analyzed scans. In total, 26 clusters of significant responses to cannabis were detected, of which 16 were located in the ventral striatum, including at least one ventral striatum cluster in 11 of the 12 analyzed scans.Conclusions: These preliminary data support the sensitivity of [11C]raclopride PET with analysis of transient changes in radiotracer uptake to detect cannabis smoking-induced dopamine responses. This approach shows future promise to further elucidate roles of mesolimbic dopaminergic signaling in chronic cannabis use. ClinicalTrials.gov Identifier: NCT02817698. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase (MMP)-12 plays a key role in the development of aneurysm. Like other members of MMP family, MMP-12 is produced as a proenzyme, mainly by macrophages, and undergoes proteolytic activation to generate an active form. Accordingly, molecular imaging of the MMP-12 active form can inform of the pathogenic process in aneurysm. Here, we developed a novel family of fluorescent probes based on a selective MMP-12 inhibitor, RXP470.1 to target the active form of MMP-12. These probes were stable in complex media and retained the high affinity and selectivity of RXP470.1 for MMP-12. Amongst these, probe 3 containing a zwitterionic fluorophore, ZW800-1, combined a favorable affinity profile toward MMP-12 and faster blood clearance. In vivo binding of probe 3 was observed in murine models of sterile inflammation and carotid aneurysm. Binding specificity was demonstrated using a non-binding homolog. Co-immunostaining localized MMP-12 probe binding to MMP-12 positive areas and F4/80 positive macrophages in aneurysm. In conclusion, the active form of MMP-12 can be detected by optical imaging using RXP470.1-based probes. This is a valuable adjunct for pathophysiology research, drug development, and potentially clinical applications. [ABSTRACT FROM AUTHOR]