Biodistribution, degradability and clearance of 2D materials for their biomedical applications.

Two-dimensional (2D) materials have evolved to be a class of rapidly advancing chemical entities in the biomedical field. Nevertheless, potential side effects and safety concerns severely limit their clinical translation. After administration, 2D materials cross multiple biological barriers and are distributed throughout the body. Only the portion that accumulates at the diseased sites exerts a therapeutic effect, whereas those distributed elsewhere may cause damage to healthy tissues and interference to normal physiological function of various organs. To achieve maximum therapeutic efficacy and minimum adverse effects simultaneously, the delivery of 2D materials must be targeted at diseased sites to reach therapeutic concentrations, and the materials must possess sufficient degradation and clearance rates to avoid long-term toxicity. Therefore, it is essential to understand the biodistribution and destiny of 2D materials in vivo. In this review, first, we provide a comprehensive picture of the strategies that are currently adopted for regulating the in vivo fate of 2D materials, including modulations of their size, surface properties, composition, and external stimuli. Second, we systematically review the biodistribution, degradation, and metabolism of several newly emerged 2D materials. Finally, we also discuss the development opportunities of 2D materials in the biomedical field and the challenges to be addressed.

NIR-II Fluorescence Imaging Reveals Bone Marrow Retention of Small Polymer Nanoparticles.

The concept that systemically administered nanoparticles are highly accumulated into the liver, spleen and kidney is a central paradigm in the field of nanomedicine. Here, we report that bone is an important organ for retention of small polymer nanoparticles using in vivo fluorescence imaging in the second near-infrared (NIR-II) window. We prepared different sized polymer nanoparticles with both visible and NIR-II fluorescence. NIR-II imaging reveals that the behavior of nanoparticle distribution in bone was largely dependent on the particle size. Small polymer nanoparticles of ∼15 nm diameter showed fast accumulation and long-term retention in bone, while the nanoparticles larger than ∼25 nm were dominantly distributed in liver. Confocal microscopy of bone sections indicated that the nanoparticles were largely distributed in the endothelial cells of sinusoidal vessels in bone marrow. The study provides promising opportunities for bone imaging and treatment of bone-related disease.

Short-Wave Infrared Emitting Nanocomposites for Fluorescence-Guided Surgery.

Fluorescence-guided surgery (FGS) is an emerging technique for tissue visualization during surgical procedures. Structures of interest are labeled with exogenous probes whose fluorescent emissions are acquired and viewed in real-time with optical imaging systems. This study investigated rare-earth-doped albumin-encapsulated nanocomposites (REANCs) as short-wave infrared emitting contrast agents for FGS. Experiments were conducted using an animal model of 4T1 breast cancer. The signal-to-background ratio (SBR) obtained with REANCs was compared to values obtained using indocyanine green (ICG), a near-infrared dye used in clinical practice. Prior to resection, the SBR for tumors following intratumoral administration of REANCs was significantly higher than for tumors injected with ICG. Following FGS, evaluation of fluorescence intensity levels in excised tumors and at the surgical bed demonstrated higher contrast between tissues at these sites with REANC contrast than ICG. REANCs also demonstrated excellent photostability over 2 hours of continuous illumination, as well as the ability to perform FGS under ambient lighting, establishing these nanocomposites as a promising contrast agent for FGS applications.

Shortwave infrared emitting multicolored nanoprobes for biomarker-specific cancer imaging in vivo.

BACKGROUND: The ability to detect tumor-specific biomarkers in real-time using optical imaging plays a critical role in preclinical studies aimed at evaluating drug safety and treatment response. In this study, we engineered an imaging platform capable of targeting different tumor biomarkers using a multi-colored library of nanoprobes. These probes contain rare-earth elements that emit light in the short-wave infrared (SWIR) wavelength region (900-1700 nm), which exhibits reduced absorption and scattering compared to visible and NIR, and are rendered biocompatible by encapsulation in human serum albumin. The spectrally distinct emissions of the holmium (Ho), erbium (Er), and thulium (Tm) cations that constitute the cores of these nanoprobes make them attractive candidates for optical molecular imaging of multiple disease biomarkers. METHODS: SWIR-emitting rare-earth-doped albumin nanocomposites (ReANCs) were synthesized using controlled coacervation, with visible light-emitting fluorophores additionally incorporated during the crosslinking phase for validation purposes. Specifically, HoANCs, ErANCs, and TmANCs were co-labeled with rhodamine-B, FITC, and Alexa Fluor 647 dyes respectively. These Rh-HoANCs, FITC-ErANCs, and 647-TmANCs were further conjugated with the targeting ligands daidzein, AMD3100, and folic acid respectively. Binding specificities of each nanoprobe to distinct cellular subsets were established by in vitro uptake studies. Quantitative whole-body SWIR imaging of subcutaneous tumor bearing mice was used to validate the in vivo targeting ability of these nanoprobes. RESULTS: Each of the three ligand-functionalized nanoprobes showed significantly higher uptake in the targeted cell line compared to untargeted probes. Increased accumulation of tumor-specific nanoprobes was also measured relative to untargeted probes in subcutaneous tumor models of breast (4175 and MCF-7) and ovarian cancer (SKOV3). Preferential accumulation of tumor-specific nanoprobes was also observed in tumors overexpressing targeted biomarkers in mice bearing molecularly-distinct bilateral subcutaneous tumors, as evidenced by significantly higher signal intensities on SWIR imaging. CONCLUSIONS: The results from this study show that tumors can be detected in vivo using a set of targeted multispectral SWIR-emitting nanoprobes. Significantly, these nanoprobes enabled imaging of biomarkers in mice bearing bilateral tumors with distinct molecular phenotypes. The findings from this study provide a foundation for optical molecular imaging of heterogeneous tumors and for studying the response of these complex lesions to targeted therapy.

High Affinity to Skeleton Rare Earth Doped Nanoparticles for Near-Infrared II Imaging.

As a newly noninvasive emerging modality, NIR-II fluorescence imaging (1000-1700 nm) has many advantages over conventional visible and NIR-I imaging (700-900 nm). Unfortunately, only a few NIR-II fluorophores are suitable for bone imaging. Here, we report an NIR-II fluorophore based on DSPE-mPEG encapsulated rare earth doped nanoparticles (RENPs@DSPE-mPEG), which shows inherent affinity to bone without linking any targeting ligands, and thus, it provides an alternative noninvasive and nonradiation strategy for skeletal system mapping and bone disease diagnoses. Interestingly, within the NIR-II window, imaging at a longer wavelength (1345 nm) provides a higher resolution and signal-to-noise ratio than imaging at 1064 nm, even though the quantum yield at 1064 nm is 2-fold higher than that at 1345 nm. Besides bone imaging, RENPs@DSPE-mPEG show an imaging application in blood vessels and lymph nodes. Importantly, RENPs@DSPE-mPEG can be internalized by circulating white blood cells. This finding may open a window to increase efficient nanoparticle delivery in the fields such as immunotherapy and improve the diagnostic and therapeutic efficacy of cancer-targeted nanoparticles in clinical applications.

Fluorination Enhances NIR-II Fluorescence of Polymer Dots for Quantitative Brain Tumor Imaging.

Here, we describe a fluorination strategy for semiconducting polymers for the development of highly bright second near-infrared region (NIR-II) probes. Tetrafluorination yielded a fluorescence QY of 3.2 % for the polymer dots (Pdots), over a 3-fold enhancement compared to non-fluorinated counterparts. The fluorescence enhancement was attributable to a nanoscale fluorous effect in the Pdots that maintained the molecular planarity and minimized the structure distortion between the excited state and ground state, thus reducing the nonradiative relaxations. By performing through-skull and through-scalp imaging of the brain vasculature of live mice, we quantitatively analyzed the vascular morphology of transgenic brain tumors in terms of the vessel lengths, vessel branches, and vessel symmetry, which showed statistically significant differences from the wild type animals. The bright NIR-II Pdots obtained through fluorination chemistry provide insightful information for precise diagnosis of the malignancy of the brain tumor.

Semiconducting Polymer Dots with Dual-Enhanced NIR-IIa Fluorescence for Through-Skull Mouse-Brain Imaging.

Fluorescence probes in the NIR-IIa region show drastically improved imaging owing to the reduced photon scattering and autofluorescence in biological tissues. Now, NIR-IIa polymer dots (Pdots) are developed with a dual fluorescence enhancement mechanism. First, the aggregation induced emission of phenothiazine was used to reduce the nonradiative decay pathways of the polymers in condensed states. Second, fluorescence quenching was minimized by different levels of steric hindrance to further boost the fluorescence. The resulting Pdots displayed a fluorescence QY of ca. 1.7 % in aqueous solution, suggesting an enhancement of ca. 21 times in comparison with the original polymer in tetrahydrofuran (THF) solution. Small-animal imaging by using the NIR-IIa Pdots exhibited a remarkable improvement in penetration depth and signal to background ratio, as confirmed by through-skull and through-scalp fluorescent imaging of the cerebral vasculature of live mice.

Hierarchically Nanostructured Hybrid Platform for Tumor Delineation and Image-Guided Surgery via NIR-II Fluorescence and PET Bimodal Imaging.

Bimodal imaging with fluorescence in the second near infrared window (NIR-II) and positron emission tomography (PET) has important significance for tumor diagnosis and management because of complementary advantages. It remains challenging to develop NIR-II/PET bimodal probes with high fluorescent brightness. Herein, bioinspired nanomaterials (melanin dot, mesoporous silica nanoparticle, and supported lipid bilayer), NIR-II dye CH-4T, and PET radionuclide 64 Cu are integrated into a hybrid NIR-II/PET bimodal nanoprobe. The resultant nanoprobe exhibits attractive properties such as highly uniform tunable size, effective payload encapsulation, high stability, dispersibility, and biocompatibility. Interestingly, the incorporation of CH-4T into the nanoparticle leads to 4.27-fold fluorescence enhancement, resulting in brighter NIR-II imaging for phantoms in vitro and in situ. Benefiting from the fluorescence enhancement, NIR-II imaging with the nanoprobe is carried out to precisely delineate and resect tumors. Additionally, the nanoprobe is successfully applied in tumor PET imaging, showing the accumulation of the nanoprobe in a tumor with a clear contrast from 2 to 24 h postinjection. Overall, this hierarchically nanostructured platform is able to dramatically enhance fluorescent brightness of NIR-II dye, detect tumors with NIR-II/PET imaging, and guide intraoperative resection. The NIR-II/PET bimodal nanoprobe has high potential for sensitive preoperative tumor diagnosis and precise intraoperative image-guided surgery.

Crucial breakthrough of second near-infrared biological window fluorophores: design and synthesis toward multimodal imaging and theranostics.

The development of fluorophores and molecular probes for the second near-infrared biological window (NIR-II, 1000-1700 nm) represents an important, newly emerging and dynamic field in molecular imaging, chemical biology and materials chemistry. Because of reduced scattering, minimal absorption and negligible autofluorescence, NIR-II imaging provides high resolution, a high signal-to-noise ratio, and deep tissue penetration capability. Among various state-of-the-art bioimaging modalities, one of the greatest challenges in developing novel probes is to achieve both high resolution and sensitivity. The chemical design and synthesis of NIR-II fluorophores suitable for multimodal imaging is thus emerging as a new and powerful strategy for obtaining high-definition images. NIR-II fluorophores may convert NIR-II photons into heat for photothermal therapy and be excited by NIR-II light to produce singlet oxygen for photodynamic therapy. The presence of simultaneous diagnostic and therapeutic capabilities in a single probe can be used for precise treatment. In this review, we have focused on recent advances in the chemical design and synthesis of NIR-II fluorophores from small organic molecules to organic and inorganic nanoparticles, and we have further discussed recent advances and key operational differences in reported NIR-II imaging systems and biomedical applications based on NIR-II imaging, such as multimodal imaging, photothermal and photodynamic therapy, guidance for intraoperative surgery, and drug delivery.

Time-Aware Service Ranking Prediction in the Internet of Things Environment.

With the rapid development of the Internet of things (IoT), building IoT systems with high quality of service (QoS) has become an urgent requirement in both academia and industry. During the procedures of building IoT systems, QoS-aware service selection is an important concern, which requires the ranking of a set of functionally similar services according to their QoS values. In reality, however, it is quite expensive and even impractical to evaluate all geographically-dispersed IoT services at a single client to obtain such a ranking. Nevertheless, distributed measurement and ranking aggregation have to deal with the high dynamics of QoS values and the inconsistency of partial rankings. To address these challenges, we propose a time-aware service ranking prediction approach named TSRPred for obtaining the global ranking from the collection of partial rankings. Specifically, a pairwise comparison model is constructed to describe the relationships between different services, where the partial rankings are obtained by time series forecasting on QoS values. The comparisons of IoT services are formulated by random walks, and thus, the global ranking can be obtained by sorting the steady-state probabilities of the underlying Markov chain. Finally, the efficacy of TSRPred is validated by simulation experiments based on large-scale real-world datasets.

"Spark" PtMnIr Nanozymes for Electrodynamic-Boosted Multienzymatic Tumor Immunotherapy.

Multienzyme-mimicking redox nanozymes capable of efficient reactive oxygen species (ROS) generation and cellular homeostasis disruption are highly pursued for cancer therapy. However, it still faces challenges from the complicate tumor microenvironment (TME) and high chance for tumor metastasis. Herein, well-dispersed PtMnIr nanozymes are designed with multiple enzymatic activities, including catalase (CAT), oxidase (OXD), superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GPx), which continuously produce ROS and deplete glutathione (GSH) concurrently in an "inner catalytic loop" way. With the help of electrodynamic stimulus, highly active "spark" species (Ir3+ and Mn3+) are significantly increased, resulting in an effective cascade enzymatic and electrodynamic therapy. Moreover, the cyclic generation of ROS can also facilitate ferroptosis and apoptosis in tumor cells, boosting synergistic therapy. Importantly, lung metastasis inhibition is found, which confirms efficient immunotherapy by the combined effect of immunogenic cell death (ICD) and Mn2+-induced cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (cGAS-STING) pathway, contributing great potential in the treatment of malignant tumors.

The role of crm-1 in ionizing radiation-induced nervous system dysfunction in Caenorhabditis elegans.

Ionizing radiation can cause changes in nervous system function. However, the underlying mechanism remains unclear. In this study, Caenorhabditis elegans (C. elegans) was irradiated with 75 Gy of 60Co whole-body γ radiation. Behavioral indicators (head thrashes, touch avoidance, and foraging), and the development of dopaminergic neurons related to behavioral function, were evaluated to assess the effects of ionizing radiation on nervous system function in C. elegans. Various behaviors were impaired after whole-body irradiation and degeneration of dopamine neurons was observed. This suggests that 75 Gy of γ radiation is sufficient to induce nervous system dysfunction. The genes nhr-76 and crm-1, which are reported to be related to nervous system function in human and mouse, were screened by transcriptome sequencing and bioinformatics analysis after irradiation or sham irradiation. The expression levels of these two genes were increased after radiation. Next, RNAi technology was used to inhibit the expression of crm-1, a gene whose homologs are associated with motor neuron development in other species. Downregulation of crm-1 expression effectively alleviated the deleterious effects of ionizing radiation on head thrashes and touch avoidance. It was also found that the expression level of crm-1 was regulated by the nuclear receptor gene nhr-76. The results of this study suggest that knocking down the expression level of nhr-76 can reduce the expression level of crm-1, while down-regulating the expression level of crm-1 can alleviate behavioral disorders induced by ionizing radiation. Therefore, inhibition of crm-1 may be of interest as a potential therapeutic target for ionizing radiation-induced neurological dysfunction.

Palladium nanoparticle based smart hydrogels for NIR light-triggered photothermal/photodynamic therapy and drug release with wound healing capability.

Tumor recurrence and wound repair are two major challenges following cancer surgical resection that can be addressed through precision nanomedicine. Herein, palladium nanoparticles (Pd NPs) with photothermal and photodynamic therapy (PTT/PDT) capacity were successfully synthesized. The Pd NPs were loaded with chemotherapeutic doxorubicin (DOX) to form hydrogels (Pd/DOX@hydrogel) as a smart anti-tumor platform. The hydrogels were composed of clinically approved agarose and chitosan, with excellent biocompatibility and wound healing ability. Pd/DOX@hydrogel can be used for both PTT and PDT with a synergistic effect to kill tumor cells. Additionally, the photothermal effect of Pd/DOX@hydrogel allowed the photo-triggered drug release of DOX. Therefore, Pd/DOX@hydrogel can be used for near-infrared (NIR)-triggered PTT and PDT as well as for photo-induced chemotherapy, efficiently inhibiting tumor growth. Furthermore, Pd/DOX@hydrogel can be used as a temporary biomimetic skin to block the invasion of foreign harmful substances, promote angiogenesis, and accelerate wound repair and new skin formation. Thus, the as-prepared smart Pd/DOX@hydrogel is expected to provide a feasible therapeutic solution following tumor resection.

Dual enzyme-like Co-FeSe2 nanoflowers with GSH degradation capability for NIR II-enhanced catalytic tumor therapy.

Nanozymes mediated catalytic therapy can produce toxic reactive oxygen species (ROS) and destroy the metabolic balance of tumor cells, providing a new direction for cancer treatment. However, the catalytic efficiency of a single nanozyme is limited by the complexity of the tumor microenvironment (hypoxia, GSH overexpression, etc.). In order to overcome these problems, we designed flower-like Co-doped FeSe2 (Co-FeSe2) nanozymes by a simple wet chemistry method. Co-FeSe2 nanozymes not only exhibit high POD and OXD-mimicking activities for facile kinetics, but also effectively consume over-expressed glutathione (GSH), inhibiting the consumption of generated ROS and destroying the metabolic balance of the tumor microenvironment. These catalytic reactions trigger cell death through apoptosis and ferroptosis dual pathways. More importantly, under the NIR II laser irradiation, the catalytic activities of Co-FeSe2 nanozymes are boosted, confirming the photothermal and catalytic synergistic tumor therapy. This study takes advantage of self-cascading engineering that offers new ideas for designing efficient redox nanozymes and promoting their clinical translation.

Under-5, infant, and neonatal mortality trends and causes of death, 1991-2022: Findings from death surveillance in Xicheng district of Beijing, China.

Overall, China has made substantial progress in improving child survival over the past few decades, but a detailed understanding of child mortality trend at local level is limited. This study aimed to present a comprehensive analysis of under-5, infant, and neonatal mortality rates and its trend in Xicheng district of Beijing, China. We used the surveillance data of under-5 children reported by Preventive Health Department of Xicheng District Community Health Service Center from 1991 to 2022. The data was collected based on the Child Death Reporting Card of the Beijing Under-5 Mortality Rate Surveillance Network. Data check was performed by each community health service center and related medical institutions. We extracted data included maternal age, date of death, date of birth, gender, census register, classification of any causes of death, and utilization of healthcare services before death and doubly input it in the Excel 2016 program. Categorization of the causes of death was adapted by the International Categorization of Diseases (ICD-10). Mortality rates and distribution of the leading causes of death were analyzed with descriptive statistics and the Pearson's Chi-square test using SAS 14.0 software. The Chi-square trend test was used to explore the trends in mortality. Interrupted time series analysis (ITSA) was conducted to assess the impact of the two-child policy on mortality using STATA statistical packages. From 1991 to 2022, totally, there were 166,061 live births and 793 (4.78 ‰) under-5 deaths. The mortality rates of under-5 children, infants and neonates in Xicheng district decreased from 14.75 ‰, 11.25 ‰ and 8.00 ‰ to 1.03 ‰, 0.83 ‰ and 0.41 ‰ respectively. All mortality rates showed an overall significant decline trend (χ2 trend for neonatal = -15.8136, P trend for neonatal < 0.001; χ2 trend for infant = -17.6652, P trend for infant < 0.001; χ2 trend for under-5 = -18.9103, P trend for under-5 < 0.001). The leading causes of death among under-5 children were congenital heart disease (1.65 ‰), birth asphyxia (1.44 ‰), and other congenital abnormalities (except congenital heart disease and down's syndrome) (1.36 ‰). ITSA results showed that the two-child policy did not change the overall decreased trend of child mortality rates. Future preventive measures for child healthcare should give a priority for congenital heart disease, birth asphyxia, and other congenital abnormalities.

Mechanism Study on Radiosensitization Effect of Curcumin in Bladder Cancer Cells Regulated by Filamin A.

Objective: To study the radiosensitization effect of curcumin, a natural product with anti-inflammatory and anti-cancer properties, in bladder cancer cells and identify the specific role of FLNA gene in that process. Methods: CCK-8 method was initially adopted to identify the proper interventional concentration of curcumin. T24 bladder cancer cells were subjected to CCK-8, flow cytometry, and colony formation assay to study the cell biological behaviors under different interventions. γ-H2AX test was performed to test the level of damage in T24 cells. RT-qPCR and Western blot were conducted to measure FLNA mRNA and protein levels. Results: Low-dose curcumin (10, 20 µM) following X-ray exposure resulted in increased DNA damage, augmented apoptosis, and reduced proliferation of T24 cells. Certain radiosensitization was demonstrated when curcumin was applied at 10 µM. Additionally, elevation of FLNA gene and protein levels was also indicated upon combination treatment. Conclusion: Low-dose curcumin has certain radiosensitization effect in bladder cancer, where FLNA plays a certain regulatory role.

A facile synthesis of PEGylated Cu2O@SiO2/MnO2 nanocomposite as efficient photo-Fenton-like catalysts for methylene blue treatment.

The removal of toxic organic dyes from wastewater has received much attention from the perspective of environmental protection. Metal oxides see wide use in pollutant degradation due to their chemical stability, low cost, and broader light absorption spectrum. In this work, a Cu2O-centered nanocomposite Cu2O@SiO2/MnO2-PEG with an average diameter of 52 nm was prepared for the first time via a wet chemical route. In addition, highly dispersed MnO2 particles and PEG modification were realized simultaneously in one step, meanwhile, Cu2O was successfully protected under a dense SiO2 shell against oxidation. The obtained Cu2O@SiO2/MnO2-PEG showed excellent and stable photo-Fenton-like catalytic activity, attributed to integration of visible light-responsive Cu2O and H2O2-responsive MnO2. A degradation rate of 92.5% and a rate constant of 0.086 min-1 were obtained for methylene blue (MB) degradation in the presence of H2O2 under visible light for 30 min. Additionally, large amounts of •OH and 1O2 species played active roles in MB degradation. Considering the enhanced degradation of MB, this stable composite provides an efficient catalytic system for the selective removal of organic contaminants in wastewater.

Analysis of circRNA-miRNA-mRNA Regulatory Network in Peripheral Blood of Radiation Workers.

The health of radiation workers has always been our focus. Epidemiological investigation shows that long-term exposure to low-dose ionizing radiation can affect human health, especially cancer and cardiovascular disease, and there are many studies on it. However, up to now, there have been few reports on the research of blood and biological samples from radiation workers. In this study, radiation workers and healthy control groups were strictly screened, and the transcriptome of mRNA and circRNA was sequenced by extracting their peripheral venous blood. At the same time, appropriate data sets were selected in the GEO database for bioinformatics analysis, and circRNA-miRNA-mRNA network was constructed. We identified 9 different circular ribonucleic acids, 3 tiny ribonucleic acids, and 2 central genes (NOD 2 and IRF 7). These differentially expressed genes and non-coding RNA are closely related to ionizing radiation damage, and play an important role as biological markers. In conclusion, this study may provide new insights into the role of the circRNA-miRNA-mRNA regulatory network in the health of radiation workers, and provides a new strategy for the future study of radiation biology.

Effect of Rice Protein Meal Replacement of Fish Meal on Growth, Anti-Oxidation Capacity, and Non-Specific Immunity for Juvenile Shrimp Litopenaeus vannamei.

This study assessed the effect of rice protein meal replacement for fish meal on the growth, nonspecific immunity, and disease resistance on juvenile shrimp Litopenaeus vannamei. Six groups of iso-nitrogenous and iso-lipid feeds named FM, R10, R20, R40, R60, and R80 were prepared by replacing 0%, 10%, 20%, 40%, 60%, and 80% in FM protein with RPM, respectively, and then fed to the shrimps (0.54 ± 0.01 g). An amount of 720 healthy and evenly sized shrimps were allocated to six groups (three replicates per group) and fed four times a day (7:00, 11:00, 17:00 and 21:00) for eight weeks. Results revealed no significant differences in WG, FCR, and SGR of shrimps after replacing FM with 10% RPM (p > 0.05). In the R10 and R20 groups, SOD and T-AOC activities were significantly higher than those in the FM group, whereas the opposite was observed for MDA content (p < 0.05). CAT, ACP, and LZM were all significantly higher in the R10, R20, and R40 groups than in the FM group (p < 0.05). GSH-Px activity in the R10 group was significantly higher than the activity in the FM group (p < 0.05). AKP, PO, TYS, GPT, and GOT activities were significantly higher in the R10 group than in the FM group (p < 0.05). Compared to the FM group, the eukaryotic translation initiation factor 3K (eif3k) gene was significantly up-regulated in the R10 group, whereas the penaiedin 3a (pen 3a) and anti-lipopolysaccharide factor (alf) genes were significantly up-regulated in the R10 and R20 groups (p < 0.05). The crustin a (cru a), immune deficiency (imd), and lysozyme (lzm) mRNA levels were significantly higher in the R10, R20, and R40 groups than in the other groups (p < 0.05). The prophenoloxidase (PO) mRNA levels in the R20 group were significantly higher than those in the FM group (p < 0.05). The replacement of 10−40% of FM with RPM improved the gut flora composition of shrimps, increasing beneficial bacteria (Bacteroidetes) abundance and reducing harmful bacteria (Aspergillus and Vibrio) abundance. After the challenge test of Vibrio parahaemolyticus (7 days), the cumulative mortality in the R10 group significantly decreased (p < 0.05). In conclusion, replacement of 10% FM by RPM significantly improved digestibility, protein synthesis, antioxidant capacity, and disease resistance in L. vannamei.

Synergistic strategy of rare-earth doped nanoparticles for NIR-II biomedical imaging.

Featuring simultaneous multicolor imaging for multiple targets, a synergistic strategy has become promising for fluorescence imaging applications. Visible and first near infrared (NIR-I, 700-900 nm) fluorophores have been explored for multicolor imaging to achieve good multi-target capacity, but they are largely hampered by the narrow imaging bands available (400-900 nm, bandwidth 500 nm), the broad emission spectra of many fluorophores, shallow tissue penetration and scattering loss. With attractive characteristic emission peaks in the second NIR window (NIR-II, 1000-1700 nm), a narrow emission spectrum, and deeper tissue penetration capability, rare-earth doped nanoparticles (RENPs) have been considered by us to be outstanding candidates for multicolor bioimaging. Herein, two RENPs, NaYF4:Yb20Er2@NaYF4 and NaYF4:Nd5@NaYF4, were prepared and modified with polyethylene glycol (PEG) to explore simultaneous imaging in the NIR-IIb (1530 nm, under 980 nm laser excitation) and the NIR-II (1060 nm, under 808 nm laser excitation) windows. The PEGylated-RENPs (RENPs@PEG) were able to simultaneously visualize the circulatory system, trace the lymphatic system, and evaluate the skeletal system. Our study demonstrates that RENPs have high synergistic imaging capability in multifunctional biomedical applications using their NIR-II fluorescence. Importantly, the two RENPs@PEG are complementary to each other for higher temporal resolution in NaYF4:Nd5@NaYF4@PEG and higher spatial resolution in NaYF4:Yb20Er2@NaYF4@PEG, which may provide more comprehensive and accurate imaging diagnosis. In conclusion, RENPs are highly promising nanomaterials for multicolor imaging in the NIR-II window.