Wybutosine hypomodification of tRNAphe activates HERVK and impairs neuronal differentiation.

We previously reported that loss of function of TYW1 led to cerebral palsy with severe intellectual disability through reduced neural proliferation. However, whether TYW1 loss affects neural differentiation is unknown. In this study, we first demonstrated that TYW1 loss blocked the formation of OHyW in tRNAphe and therefore affected the translation efficiency of UUU codon. Using the brain organoid model, we showed impaired neuron differentiation when TYW1 was depleted. Interestingly, retrotransposons were differentially regulated in TYW1-/- hESCs (human embryonic stem cells). In particular, one kind of human-specific endogenous retrovirus-K (HERVK/HML2), whose reactivation impaired human neurodevelopment, was significantly up-regulated in TYW1-/- hESCs. Consistently, a UUU codon-enriched protein, SMARCAD1, which was a key factor in controlling endogenous retroviruses, was reduced. Taken together, TYW1 loss leads to up-regulation of HERVK in hESCs by down-regulated SMARCAD1, thus impairing neuron differentiation.

Consistency label-activated region generating network for weakly supervised medical image segmentation.

The current methods of auto-segmenting medical images are limited due to insufficient and ambiguous pathonmorphological labeling. In clinical practice, rough classification labels (such as disease or normal) are more commonly used than precise segmentation masks. However, there is still much to be explored regarding utilizing these weak clinical labels to accurately determine the lesion mask and guide medical image segmentation. In this paper, we proposed a weakly supervised medical image segmentation model to directly generate the lesion mask through a class activation map (CAM) guided cycle-consistency label-activated region transferring network. Cycle-consistency enforces that the mappings between the two domains should be reversible, which ensures that the original image can be reconstructed from the translated image. We developed a complementary branches fusion module to address the issue of blurry boundaries in CAM-guided segmentation. The complementary branch preserves the original semantic information of the non-lesion region and perfectly fuses the transferred feature of the lesion region with a complementary mask-constrained fake image generation process to clear the boundary of the lesion and non-lesion regions. This module allows the class transformation to focus solely on the label-activated region, resulting in more explicit segmentation. This model can accurately identify different region of medical images at the pixel-level while preserving the overall semantic structure semantion. It organizes disease labels and corresponding regions during image synthesis. Our method utilizes a joint discrimination strategy that significantly enhances the precision of the produced lesion mask. Extensive experiments of the proposed method on BraTs, ISIC and COVID-19 datasets demonstrate superior performance over existing state-of-the-art methods. The code and datasets are available at: https://github.com/mlcb-jlu/MedImgSeg.

Incidence, clinical features, and survival outcomes of primary malignant lacrimal gland tumors: A population-based analysis.

BACKGROUND: Studies on the epidemiological information and prognosis of primary malignant lacrimal gland tumors (MLGTs) are rare for its low occurrence. The goal of our research was to investigate the epidemiological characteristics and survival outcomes of patients with MLGTs. METHODS: Incidence and demographic information of patients with MLGTs were collected from the Surveillance, Epidemiology, and End Results (SEER) database. To identify independent prognostic factors for disease-specific survival (DSS) and overall survival (OS), univariate and multivariate Cox regression analysis were performed. RESULTS: The overall incidence of primary MLGTs from 1975 to 2020 was 0.413/1,000,000 (according to the 2000 American standard population), with a steadily increasing incidence over years. A total of 964 patients with primary MLGTs were diagnosed, with an average age of 59.3 years. Of these, 53.2% were aged ≥60 years, 57.4% were female, and 77.1% were whites. Multivariate Cox regression analysis demonstrated that year of diagnosis, age, sex, histological type, SEER stage, surgery, and chemotherapy were independent prognostic factors of DSS or OS. CONCLUSIONS: Although primary MLGT is rare, its incidence has steadily increased in the past 46 years, and surgery was related to a better prognosis.

Long Noncoding RNA ZBED5-AS1 Facilitates Tumor Progression and Metastasis in Lung Adenocarcinoma via ZNF146/ATR/Chk1 Axis.

Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis, including lung adenocarcinoma (LUAD). However, the functional and regulatory mechanisms of lncRNAs in LUAD remain poorly understood. In this study, we investigated the role of lncRNA ZBED5-AS1 in LUAD. We found that ZBED5-AS1 was upregulated in LUAD specimens and overexpressed in LUAD cell lines. ZBED5-AS1 promoted LUAD cell proliferation, migration, and invasion in vitro and promoted LUAD cell growth in vivo. ZBED5-AS1 promoted ZNF146 expression, activating the ATR/Chk1 pathway and leading to LUAD progression. We observed that exosomes from LUAD cells have a higher expression of ZBED5-AS1 compared with exosomes from the normal cell line BEAS-2B. Coculture experiments with exosomes showed that ZBED5-AS1 expression was downregulated after coculture with Si-ZBED5-AS1 exosomes, and coculture with exosomes with low ZBED5-AS1 expression inhibited proliferation and invasion of LUAD cells. Our results indicate that ZBED5-AS1 functions as an oncogenic factor in LUAD cells by targeting the ZNF146/ATR/Chk1 axis.

Preparation of Gd-doped AuNBP@mSiO2 nanocomposites for the MR imaging, drug delivery and chemo-photothermal synergistic killing of breast cancer cells.

Under near-infrared (NIR) light, gold nanobipyramids (AuNBPs) exhibit a high photothermal conversion rate and photothermal stability, making them ideal mediators for photothermal therapy (PTT). In this study, highly purified AuNBPs are prepared, followed by coating their surfaces with mesoporous silica (mSiO2). The obtained AuNBP@mSiO2 nanocomplex exhibits an ellipsoidal shape with a relatively large specific surface, pore diameter and pore volume. To achieve MRI guided chemo-photothermal therapy of breast cancer cells, the nanocomplex is further coupled with the MRI contrast agent Gd-DTTA and the chemotherapeutic drug doxorubicin (DOX). The results indicated that under NIR light irradiation, AuNBPs exhibited promising PTT effects, while the cumulative release rate of DOX was significantly enhanced to 81.40%. Moreover, the chemo-photothermal therapy approach effectively eradicated 4T1 breast cancer cells. This work successfully confirms that chemo-photothermal synergistic therapy is an effective tumor treatment strategy and demonstrates the potential application of AuNBP@mSiO2 as a nano-drug delivery platform. Additionally, it introduces new ideas for the integrated study of breast cancer diagnosis and treatment.

A Facile Raman Spectroscopy Method for Online Monitoring of Crystal Plane Orientation of Favipiravir.

The efficiency of pharmacotherapy is significantly influenced by the crystal habit and polymorphic form of the drugs. Especially due to the anisotropy of different facets in crystalline material, crystal habit impacts the physicochemical properties and behaviors of a drug, which has been rarely reported. This paper describes a facile method for online monitoring of crystal plane orientation of favipiravir (T-705) by Raman spectroscopy. Firstly, we investigated the synergy of multiple physicochemical fields (solvation, agitated flow fields, etc.), and then prepared favipiravir crystals with different orientations in a controllable manner. Secondly, to establish the connection between crystal planes and Raman spectra, the favipiravir crystals were theoretically analyzed at the molecular and structural levels using density functional theory (DFT) and three dimensional (3D) visualization tools. Finally, we based on standard samples and applied it to 12 actual samples to evaluate the crystal habit of favipiravir. The results are similar to the classical X-ray diffraction (XRD) method. Additionally, the XRD method is difficult to be monitored online, while the Raman method is non-contact, fast, and requires no sample preparation, showing a great application prospect in the pharmaceutical process.

Retrospective screening of serum IgG glycosylation biomarker for primary Sjögren's syndrome using lectin microarray.

Background: Primary Sjögren's syndrome (PSS) is a systemic autoimmune disease resulting in significant loss of systemic gland secretory function. IgG glycosylation abnormalities had been found to play important roles in autoimmune diseases. Here, we aim to explore the specific changes of IgG glycosylation in PSS patient serum that could serve as potential biomarkers for disease diagnosis and differential diagnosis. Method: From 2012 to 2018, patients diagnosed with PSS or primary biliary cholangitis (PBC) admitted consecutively to the department of Rheumatology at Peking Union Medical College Hospital were retrospectively included in this study. Glycan profiles of serum IgG from 40 PSS patients, 50 PBC patients, and 38 healthy controls were detected with lectin microarray containing 56 lectins. Lectins with significantly different signal intensity among groups were selected and validated by lectin blot assay. Results: Lectin microarray analysis revealed that binding levels of Amaranthus Caudatus Lectin (ACL, prefers glycan Galß3GalNAc, P = 0.011), Morniga M Lectin (MNA-M, prefers glycan mannose. P = 0.013), and Lens Culinaris Agglutinin (LCA, prefers glycan fucose) were significantly increased, while Salvia sclarea Agglutinin (SSA, prefers glycan sialylation, P = 0.001) was significantly decreased in PSS patients compared to PBC group. Compared to healthy controls, MNA-M (P = 0.001) and LCA (P = 0.028) were also significantly increased, while Phaseolus Vulgaris Erythroagglutinin and Phaseolus Vulgaris Leucoagglutinin (PHA-E and PHA-L, prefer glycan galactose, P = 0.004 and 0.006) were significantly decreased in PSS patients. The results of LCA and MNA-M were further confirmed using lectin blot assay. Conclusion: Changes in serum IgG glycosylation in PSS increased binding levels of LCA and MNA-M lectins using microarray techniques compared to PBC patients and healthy controls, which could provide potential diagnostic value. Increased core fucose and mannose alteration of IgG may play important roles in PSS disease.

Graphene Microheater Chips for In Situ TEM.

Low-dimensional materials are bringing significant innovations to in situ TEM characterization. Here a new graphene microheater chip for TEM was developed by stacking graphene on a suspended SiNx membrane as the Joule heating element. It could be heated up to 800 °C within 26.31 ms with a low power consumption of 0.025 mW/1000 µm2. The bulging was only ∼50 nm at 650 °C, which is 2 orders of magnitude smaller than those of conventional MEMS heaters at similar temperatures. The performances benefit from the employment of graphene, since its monolayer structure greatly reduces the heat capacity, and the vdW contact significantly reduces the interfacial interaction. The TEM observation on the Sn melting process verifies its great potential in resolving thermodynamic processes. Moreover, more multifunctional in situ chips could be developed by integrating other stimuli to such chips. This work opens a new frontier for both graphene and in situ characterization techniques.

Comparison of temporomandibular joint disc, meniscus, and intervertebral disc in fundamental characteristics and tissue engineering.

The temporomandibular joint (TMJ) disc, meniscus and intervertebral disc (IVD) are three fibrocartilage discs, which play critical roles in our daily life. Their degeneration contributes to diseases such as TMJ disorders, osteoarthritis and degenerative disc disease, affecting patients' quality of life and causing substantial morbidity and mortality. Interestingly, similar in some aspects of fundamental characteristics, they exhibit differences in other aspects such as biomechanical properties. Highlighting these similarities and differences can not only benefit a comprehensive understanding of them and their pathology but also assist in future research of tissue engineering. Likewise, comparing their tissue engineering in cell sources, scaffold and stimuli can guide imitation and improvement of their engineered discs. However, the anatomical structure, function, and biomechanical characteristics of the IVD, TMJ, and Meniscus have not been compared in any meaningful depth needed to advance current tissue engineering research on these joints, resulting in incomplete understanding of them and their pathology and ultimately limiting future research of tissue engineering. This review, for the first time, comprehensively compares three fibrocartilage discs in those aspects to cast light on their similarities and differences.

Relationship between Structure and Properties of Nonstoichiometric Protic Ionic Liquids: n-Butylammonium Butyrate System.

Nonstoichiometric protic ionic liquids have drawn much attention in applications, including fuel cells, batteries, and reaction media. An understanding of the relationship between their structure and properties is instructive for further applications. However, there are only a few studies on nonstoichiometric protic ionic liquids. Herein, the density, viscosity, and conductivity of nonstoichiometric n-butylammonium butyrate protic ionic liquids were measured, and we used small/wide-angle scattering (S/WAXS), electron paramagnetic resonance (EPR), and molecular dynamics (MD) simulation to explore the effect of mesostructure on their properties. It is found that the hydrogen bonds drive excess N-butyric acid (PrCOOH) molecules to wrap around ion clusters, resulting in the higher density and viscosity of PrCOOH-rich PILs. The microenvironments around various radicals differ significantly in BuNH2-rich and PrCOOH-rich PILs because of the distinct molecular arrangements. This research provided a link between the physicochemical properties and structures of nonstoichiometric PILs, which is essential for their applications in electrolytes and organic reactions.

A new self-passivating template with the phosphorothioate strategy to effectively improve the detection limit and applicability of exponential amplification reaction.

Exponential amplification reaction (EXPAR) has attracted much attention due to its simple primers and high amplification efficiency, but its applications are hindered by severe non-specificity amplification. Convenient exogenous chemical modification methods modified the entire template while inhibiting both non-specific and specific amplification. In this paper, we proposed a new self-passivating template with the phosphorothioate strategy to effectively improve the detection limit and applicability of EXPAR. We phosphorothioated several bases where the sequence was prone to form transient intermolecular 3'-end hybridization, thereby inhibiting the non-specific interactions and preventing the extension of templates by DNA polymerase. The melting temperature (Tm) curve and density functional theory (DFT) proved that the stability of hydrogen bonds between phosphorothioated bases did decrease. Benefitting from this strategy, the detection limit had been improved by 3 orders of magnitude. Moreover, due to the antioxidation property of phosphorothioate, this strategy showed good stability in serum, reflecting its excellent prospects in clinical sampling and detection.

Use of historical and contemporary distribution of mammals in China to inform conservation.

A systematic understanding of dynamic animal extinction trajectories for different regions in a nation like China is critically important to developing practical conservation strategies. We explored historical and contemporary changes in terrestrial mammalian diversity to determine how diversity in each of the 5 regions in China has changed over time and to examine the conservation potential of these regions. We used records from databases on Pleistocene mammalian fossils and historical distribution records (1175-2020) for Primates (as a case study) to reconstruct evolutionary and historical distribution trajectories of the 11 orders of terrestrial mammals and to predict their prospective survival based on the national conservation strategy applied. The results indicated that since the Pleistocene, 4-5 mammalian orders have been lost in the northeast, 3 in central China, 2 along the coast, and 1 in the northwest. In the southwest, all 11 orders were maintained. Contemporarily, the coast and southwest had the highest and second-highest species densities. The southwest region and southeastern sections of the northwest region were the most historically and contemporarily diverse areas, which suggests that they should be the first priority for protected area (PA) designation. The central and coastal areas should be secondarily prioritized. In these 2 regions, conservation should focus on human coexistence with nature. Less attention should be paid to the PA in the northeast and western northwest because in these areas ecosystems are depauperate and the climate is harsh. Conservation in these areas should focus principally on avoiding further human encroachment on natural areas. Article impact statement: Historical and contemporary patterns of extinction can be a basis for mammalian conservation strategies.

Uso de la Distribución Histórica y Contemporánea de los Mamíferos en China para Orientar a la Conservación Resumen El entendimiento sistemático de las trayectorias de extinción dinámica de los animales para diferentes regiones en un país como en China es de importancia crítica para poder desarrollar estrategias de conservación prácticas. Exploramos los cambios históricos y contemporáneos en la diversidad de mamíferos terrestres para determinar cómo ha cambiado con el tiempo la diversidad en cada una de las cinco regiones de China y para examinar el potencial de conservación de aquellas regiones. Usamos registros tomados de bases de datos con información sobre los fósiles de mamíferos del Pleistoceno y registros de la distribución histórica (1175 - 2020) de los primates (como estudio de caso) para reconstruir las trayectorias de distribución históricas y contemporáneas de los once órdenes de mamíferos terrestres presentes en China. También utilizamos esta información para predecir la supervivencia potencial de estos órdenes con base en la estrategia nacional de conservación aplicada. Los resultados indicaron que, desde el Pleistoceno, entre cuatro y cinco órdenes de mamíferos se han perdido en el noreste de China, tres en la zona central, dos a lo largo de la costa y uno en el noroeste. En el suroeste del país se han mantenido los once órdenes. Actualmente, la costa y el suroeste tienen la primera y segunda densidad más alta de especies. La región del suroeste y las secciones al sureste de la región del noroeste son las áreas con la mayor diversidad histórica y contemporánea, lo que sugiere que deberían ser de primera prioridad para la designación de áreas protegidas (AP). Las áreas de la costa y el centro deberían ser las de segunda prioridad por la misma razón. En estas dos últimas regiones, la conservación debería enfocarse en la coexistencia entre los humanos y la naturaleza. Se les debería prestar una menor atención a las AP en el noreste y en la zona oeste del noroeste porque en estas áreas los ecosistemas son paupérrimos y el clima es hostil. La conservación en estas áreas debería enfocarse principalmente en evitar más invasiones humanas dentro de las áreas naturales.

Changes of Serum IgG Glycosylation Patterns in Primary Biliary Cholangitis Patients.

Objective: Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease whose diagnosis is based significantly on autoantibody detection. This study aims to investigate the glycosylation profile of serum IgG in PBC patients using high-throughput lectin microarrays technology. Method: Lectin microarray containing 56 lectins was used to detect and analyze the expression of serum IgG glycosylation in 99 PBC patients, 70 disease controls (DCs), and 38 healthy controls (HCs). Significant differences in PBC from control groups as well as across PBC subgroups positive for various autoantibodies were explored and verified by lectin blot technique. Results: Lectin microarray detection revealed that compared to DC and HC groups, the specific glycan level of serum IgG sialic acid in PBC patients was increased. For each PBC subgroup, glycan levels of IgG mannose and galactose were decreased in AMA-M2 positive PBC patients compared to the AMA-M2 negative group. IgG N-Acetylgalactosamine (GalNAc) and fucose were decreased in anti-sp100 positive patients. IgG galactose was increased in anti-gp210 positive patients. IgG mannose was decreased in ACA-positive patients. Although the difference in overall sialic acid level was not observed using lectin blot, all results among the above PBC subgroups were consistent with the results of the technique. Conclusion: Lectin microarray is an effective and reliable technique for analyzing glycan structure. PBC patients positive for different autoantibody exhibits distinct glycan profile. Altered levels of glycosylation may be related to the occurrence and development of the disease, which could provide a direction for new biomarker identification.

NIR/photoacoustic imaging of multitype gallbladder cancer using carboxyl/amino functionalized polymer dots.

Gallbladder cancer has high incidence and mortality and a low early diagnosis rate and requires rapid and efficient diagnosis. Herein, carboxyl/amino functionalized polymer dots (Pdots) were designed to enhance cellular internalization and tumor accumulation. The prepared Pdots were 40-50 nm in diameter, contained no toxic metal, exhibited long circulation time and high stability, and produced strong NIR emission and photoacoustic signals. Different cellular uptake and distribution of functionalized Pdots in eight gallbladder cell lines were quantitatively investigated using flow cytometry and super-resolution microscopy. In vivo NIR fluorescence imaging showed that the functional Pdots had high accumulation in the tumor after 30 minutes of injection and remained there for up to 6 days. In addition, photoacoustic imaging found that the abundant blood vessels around the tumor microenvironment and Pdots entered the tumor through the blood vessels. Furthermore, a high heterogeneity of vascular networks was visualized in real-time and high resolution by probe-based confocal laser endomicroscopy imaging. These results offer a new avenue for the development of functional Pdots as a probe for multi-modal and multi-scale imaging of gallbladder cancer in small animals.

The Effect of Polymer Dots During Mammalian Early Embryo Development and Their Biocompatibility on Maternal Health.

Conjugated polymer dots have excellent fluorescence properties in terms of their structural diversity and functional design, showing broad application prospects in the fields of biological imaging and biosensing. Polymer dots contain no heavy metals and are thought to be of low toxicity and good biocompatibility. Therefore, systematic studies on their potential toxicity are needed. Herein, the biocompatibility of poly[(9,9-dioctylfluorenyl-2,7diyl)-co-(1,4-benzo-{2,1',3}-thiadiazole)],10% benzothiadiazole(y) (PFBT) and poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) polymer dots on early embryo development as well as maternal health is studied in detail. The results show that prepared polymer dots are dose-dependently toxic to preimplantation embryos, and low-dose polymer dots can be used for cell labeling of early embryos without affecting the normal development of embryos into blastocysts. In addition, the in vivo distribution data show that the polymer dots accumulate mainly in the maternal liver, spleen, kidney, placenta, ovary, and lymph nodes of the pregnant mice. Histopathological examination and blood biochemical tests demonstrate that exposure of the maternal body to polymer dots at a dosage of 14 µg g-1 does not affect the normal function of the maternal organs and early fetal development. The research provides a safe basis for the wide application of polymer dots.

Toxicity, uptake and transport mechanisms of dual-modal polymer dots in penny grass (Hydrocotyle vulgaris L.).

The use of polymers such as plastic has become an important part of daily life, and in aqueous environments, these polymers are considered as pollutants. When macropolymers are reduced to the nanoscale, their small particle size and large specific surface area facilitate their uptake by plants, which has a significant impact on aquatic plants. Therefore, it is essential to study the pollution of nanoscale polymers in the aquatic environment. In this work, we prepared nanoscale polymer dots (Pdots) and explored their toxicity, uptake and transport mechanisms in penny grass. From toxicological studies, in the absence of other nutrients, the cell structure, physiological parameters (total soluble protein and chlorophyll) and biochemical parameters (malondialdehyde) do not show significant changes over at least five days. Through in vivo fluorescence and photoacoustic (PA) imaging, the transport location can be visually detected accurately, and the transport rate can be analyzed without destroying the plants. Moreover, through ex vivo fluorescence imaging, we found that different types of Pdots have various uptake and transport mechanisms in stems and blades. It may be due to the differences in ligands, particle sizes, and oil-water partition coefficients of Pdots. By understanding how Pdots interact with plants, a corresponding method can be developed to prevent them from entering plants, thus avoiding the toxicity from accumulation. Therefore, the results of this study also provide the basis for subsequent prevention work.

Genetic Structure and Evolutionary History of Rhinopithecus roxellana in Qinling Mountains, Central China.

The Qinling mountainous region is one of the world's biodiversity hotspots and provides refuges for many endangered endemic animals. The golden snub-nosed monkeys (Rhinopithecus roxellana) are considered as a flagship species in this area. Here, we depicted the genetic structure and evolutionary history via microsatellite markers and combination with the ecological niche models (ENMs) to elucidate the intraspecific divergent and the impacts of the population demography on our focal species. Our results revealed three distinct subpopulations of R. roxellana and also uncovered asymmetric historical and symmetric contemporary gene flow that existed. Our evolutionary dynamics analyses based on diyabc suggested that the intraspecific divergence accompanied with effective population sizes changes. The ENM result implied that the distribution range of this species experienced expansion during the last glacial maximum (LGM). Our results highlighted that geological factors could contribute to the high genetic differentiation within the R. roxellana in the Qinling Mountains. We also provided a new insight into conservation management plans with endangered species in this region.

Urban drought challenge to 2030 sustainable development goals.

In the first two decades of the 21st century, 79 global big cities have suffered extensively from drought disaster. Meanwhile, climate change has magnified urban drought in both frequency and severity, putting tremendous pressure on a city's water supply. Therefore, tackling the challenges of urban drought is an integral part of achieving the targets set in at least 5 different Sustainable Development Goals (SDGs). Yet, the current literatures on drought have not placed sufficient emphasis on urban drought challenge in achieving the United Nations' 2030 Agenda for Sustainable Development. This review is intended to fill this knowledge gap by identifying the key concepts behind urban drought, including the definition, occurrence, characteristics, formation, and impacts. Then, four sub-categories of urban drought are proposed, including precipitation-induced, runoff-induced, pollution-induced, and demand-induced urban droughts. These sub-categories can support city stakeholders in taking drought mitigation actions and advancing the following SDGs: SDG 6 "Clean water and sanitation", SDG 11 "Sustainable cities and communities", SDG 12 "Responsible production and consumption", SDG 13 "Climate actions", and SDG 15 "Life on land". To further support cities in taking concrete actions in reaching the listed SDGs, this perspective proposes five actions that city stakeholders can undertake in enhancing drought resilience and preparedness:1) Raising public awareness on water right and water saving; 2) Fostering flexible reliable, and integrated urban water supply; 3) Improving efficiency of urban water management; 4) Investing in sustainability science research for urban drought; and 5) Strengthening resilience efforts via international cooperation. In short, this review contains a wealth of insights on urban drought and highlights the intrinsic connections between drought resilience and the 2030 SDGs. It also proposes five action steps for policymakers and city stakeholders that would support them in taking the first step to combat and mitigate the impacts of urban droughts.

Fluorescent Polymer Dots for Tracking SKOV3 Cells in Living Mice with Probe-Based Confocal Laser Endomicroscopy.

PURPOSE: Probe-based confocal laser endomicroscopy (pCLE) is a novel technique allowing real-time and high-resolution imaging in vivo. It provides microscopic images and increases the penetration depth of tissues compared with conventional white light endoscopy. The aim of the present study was to track ovarian cancer cells in organs by fluorescent polymer dots based on pCLE. PROCEDURES: SKOV3-mCherry cells were incubated with polymer dots for 24 h in a serum-free culture medium. Labeled cells were administrated to nude mice via intravenous, intraperitoneal, and lymph node injection. The fluorescent signals of labeled cells in organs were observed by pCLE. Furthermore, the results were confirmed by frozen section analysis. RESULTS: pCLE displayed fluorescence signals of labeled cells in the vessels of organs. Besides, the accumulations of labeled cells visualized in detoxification organs like the spleen and kidney were increased with time. CONCLUSIONS: In this article, we present a real-time and convenient method for tracking SKOV3-mCherry in living mice by combined fluorescent polymer dots with pCLE.