CD11b + CD43 hi Ly6C lo splenocyte-derived macrophages exacerbate liver fibrosis via spleen-liver axis.

BACKGROUND AND AIMS: Monocyte-derived macrophages (MoMFs), a dominant population of hepatic macrophages under inflammation, play a crucial role in liver fibrosis progression. The spleen serves as an extra monocyte reservoir in inflammatory conditions; however, the precise mechanisms of involvement of the spleen in the pathogenesis of liver fibrosis remain unclear. APPROACH AND RESULTS: By splenectomy and splenocyte transfusion, it was observed that splenic CD11b + cells accumulated intrahepatically as Ly6C lo MoMFs to exacerbate CCl 4 -induced liver fibrosis. The splenocyte migration into the fibrotic liver was further directly visualized by spleen-specific photoconversion with KikGR mice and confirmed by CD45.1 + /CD45.2 + spleen transplantation. Spleen-derived CD11b + cells purified from fibrotic livers were then annotated by single-cell RNA sequencing, and a subtype of CD11b + CD43 hi Ly6C lo splenic monocytes (sM-1s) was identified, which was markedly expanded in both spleens and livers of mice with liver fibrosis. sM-1s exhibited mature feature with high expressions of F4/80, produced much ROS, and manifested preferential migration into livers. Once recruited, sM-1s underwent sequential transformation to sM-2s (highly expressed Mif , Msr1 , Clec4d , and Cstb ) and then to spleen-derived macrophages (sMφs) with macrophage features of higher expressions of CX 3 CR1, F4/80, MHC class II, and CD64 in the fibrotic hepatic milieu. Furthermore, sM-2s and sMφs were demonstrated capable of activating hepatic stellate cells and thus exacerbating liver fibrosis. CONCLUSIONS: CD11b + CD43 hi Ly6C lo splenic monocytes migrate into the liver and shift to macrophages, which account for the exacerbation of liver fibrosis. These findings reveal precise mechanisms of spleen-liver axis in hepatic pathogenesis and shed light on the potential of sM-1 as candidate target for controlling liver diseases.

Inward Flow of Intervening Liquid Films Driven by the Marangoni Effect during Bubble-Solid Collisions in Ethyl Alcohol-NaCl Aqueous Solutions.

The drainage dynamics of confined thin liquid films between an air bubble and a freshly cleaved mica surface were investigated in ethyl alcohol aqueous solutions. Focus was given to the holding stage, in which an unexpected increase in the thickness of a few hundred nanometers at the center of the film was captured by interferometry in ethyl alcohol-500 mM NaCl aqueous solutions. Such an increase in film thickness occurred when the ethyl alcohol concentration exceeded the critical value at a bubble approach velocity of 100 µm/s. For a given ethyl alcohol concentration, the increase in thickness at the center of the film did not happen when the bubble approach velocity was decreased to 10 µm/s. Compared to the cases in ethyl alcohol-500 mM NaCl solutions, no increase in thickness at the center of the film was observed in ethyl alcohol-water solutions under the same ethyl alcohol concentration and bubble approach velocity. The phenomenon of the increasing thickness at the center of the film was attributed to the net inward flow in the film, resulting from competition between the inward Marangoni flow and the outward drainage flow that was hindered by the narrow channel at the barrier rim of the film under a high electrolyte concentration. The inward Marangoni flow was achieved by a concentration gradient of ethyl alcohol between the film and the bulk solution resulting from the mobile air-liquid interface in the initial approaching period.

Contributions of van der Waals Interactions and Hydrophobic Attraction to Molecular Adhesions on a Hydrophobic MoS2 Surface in Water.

Pushing the boundaries of the investigation of hydrophobic attraction (HA) to the molecular scale readily ensures the collection of experimental results free of secondary effects, thereby facilitating the unraveling of the underlying mechanism by providing clean experimental results that truly reflect the hydrophobic attraction. Regardless of the feasibility of this approach, investigations using this promising method are stagnant due to the difficulties in determining the individual contributions of HA and van der Waals (vdW) interactions at the molecular scale. Here, a novel approach was proposed for the first time to determine the individual contributions of vdW interactions and HA by studying the single-molecule adhesion forces of a neutral oligo ethylene glycol methacrylate copolymer on a MoS2 crystal exposed to different water chemistry. The anisotropic surface properties of MoS2 enabled the partitioning of vdW interactions and hydrophobic attraction in total single-molecule adhesion forces and also enabled determining the contribution of electrostatic interaction (ESI). When the presence of ESI is excluded, the study of single-molecule adhesion forces using single-molecule force spectroscopy (SMFS) revealed that the contribution of vdW interactions to total molecular interactions was smaller than 9 pN. The strong single-molecule adhesion forces of oligo ethylene glycol copolymer on the hydrophobic basal surface of MoS2 demonstrated that HA plays a dominant role with contribution up to 89% to the total single-molecule adhesion force. By utilizing the derived theoretical model, we quantified the individual contribution of each fundamental interaction under a variety of conditions. This study proposed a facile approach to quantitatively clarify the roles of vdW interactions and HA at the molecular scale, which may help assist future experimental and theoretical investigations of hydrophobic (solvophobic) effects and vdW interactions in aqueous solutions.

Probing Boundary Conditions at Hydrophobic Solid-Water Interfaces by Dynamic Film Drainage Measurement.

A newly developed dynamic force apparatus was used to determine hydrodynamic boundary conditions of a liquid on a hydrophobic silica surface. For a given approach velocity of bubble to solid surfaces in an electrolyte solution, a reduced dimple formation and faster film drainage were observed by increasing the hydrophobicity of silica surfaces, indicating a significant change in hydrodynamic boundary conditions of water molecules from an immobile to a mobile water-hydrophobic silica interface. By comparing the measured film profiles with the predictions from the Stokes-Reynolds-Young-Laplace model, the slippage boundary condition of water on the hydrophobic silica surface of surface nanoroughness was quantified. Increasing the surface hydrophobicity was found to increase the mobility of water in the thin liquid film, promoting faster drainage of the liquid. For a given hydrophobicity of solids, the mobility of water occurred only above a critical bubble approach velocity and increased with increasing bubble approach velocity. In contrast, similar experiments with hydrophobized mica surfaces showed no-slip boundary condition of water at the molecularly smooth hydrophobic surface. The results collectively suggest that the observed mobility of water with more than 100 nm in thickness on the studied hydrophobic silica surfaces was due to the nanoroughness of hydrophobic surfaces. Such finding sheds light on one possible way of reducing the friction of water on hydrophobic solid surfaces by creating nanostructured surface of nanoroughness.

Dynamic Interaction between a Millimeter-Sized Bubble and Surface Microbubbles in Water.

The coalescence between microbubbles and millimeter-sized bubbles is an elementary process in various industrial applications such as froth flotation and wastewater treatment. Fundamental understanding of the coalescence behavior between two colliding bubbles requires knowledge of water drainage from the thin liquid film between the deformable air-water surfaces, a simple phenomenon with high complexity in physics because of the interplay of surface forces, hydrodynamic drainage, and surface rheology. In this work, we performed simultaneous measurements of the interaction force and spatial thin-film thickness during the collision between a millimeter-sized bubble (radius 1.2 mm) and surface microbubbles (radii between 30 and 700 µm) using our recently developed dynamic force apparatus. The interaction force during the collision agrees well with the prediction from the Stokes-Reynolds-Young-Laplace model with the tangentially immobile boundary condition at the air-liquid interface. However, the measured coalescence times for different bubble sizes are shorter than the model predictions, possibly caused by a rapid drainage behavior along with the loss of symmetry of the thin liquid film. In dozens of experimental runs, the bubbles coalesced at a critical film thickness of 25 ± 15 nm, which agrees reasonably well with the predicted rupture thickness using attractive van der Waals interaction force. These results suggest that the nonsymmetric drainage process, rather than the rupture thickness, contributes to the scattering of the experimental coalescence time between two fast-colliding air bubbles. Furthermore, our results suggest that smaller surface bubbles (30-100 µm) are more effective for the attachment onto a large bubble as the coalescence time decreases considerably when the microbubbles are smaller than 100 µm.

Genome-Wide Identification and Analysis of HAK/KUP/KT Potassium Transporters Gene Family in Wheat (Triticum aestivum L.).

In plants, the HAK (high-affinity K⁺)/KUP (K⁺ uptake)/KT (K⁺ transporter) family represents a large group of potassium transporters that play important roles in plant growth and environmental adaptation. Although HAK/KUP/KT genes have been extensively investigated in many plant species, they remain uncharacterized in wheat, especially those involved in the response to environmental stresses. In this study, 56 wheat HAK/KUP/KT (hereafter called TaHAKs) genes were identified by a genome-wide search using recently released wheat genomic data. Phylogenetic analysis grouped these genes into four clusters (Ι, II, III, IV), containing 22, 19, 7 and 8 genes, respectively. Chromosomal distribution, gene structure, and conserved motif analyses of the 56 TaHAK genes were subsequently performed. In silico RNA-seq data analysis revealed that TaHAKs from clusters II and III are constitutively expressed in various wheat tissues, while most genes from clusters I and IV have very low expression levels in the examined tissues at different developmental stages. qRT-PCR analysis showed that expression levels of TaHAK genes in wheat seedlings were significantly up- or downregulated when seedlings were exposed to K⁺ deficiency, high salinity, or dehydration. Furthermore, we functionally characterized TaHAK1b-2BL and showed that it facilitates K⁺ transport in yeast. Collectively, these results provide valuable information for further functional studies of TaHAKs, and contribute to a better understanding of the molecular basis of wheat development and stress tolerance.

Probing Single-Molecule Adhesion of a Stimuli Responsive Oligo(ethylene glycol) Methacrylate Copolymer on a Molecularly Smooth Hydrophobic MoS2 Basal Plane Surface.

Molybdenum disulfide (MoS2) has been receiving increasing attention in scientific research due to its unique properties. Up to now, several techniques have been developed to prepare exfoliated nanosize MoS2 dispersions to facilitate its applications. To improve its desired performance, as-prepared MoS2 dispersion needs further appropriate modification by polymers. Thus, understanding polymer-MoS2 interaction is of great scientific importance and practical interest. Here, we report our results on molecular interactions of a biocompatible stimuli-responsive copolymer with the basal plane surface of MoS2 determined using single molecule force spectroscopy (SMFS). Under isothermal conditions, the single-molecule adhesion force of oligo(ethylene glycol) methacrylate copolymer was found to increase from 50 to 75 pN with increasing NaCl concentration from 1 mM to 2 M, as a result of increasing hydrophobicity of the polymers. The theoretical analysis demonstrated that single-molecule adhesion force is determined by two contributions: the adhesion energy per monomer and the entropic free energy of the stretched polymer chain. Further data analysis revealed a significant increase in the adhesion energy per monomer with a negligible change in the other contribution with increasing salt concentration. The hydrophobic attraction (HA) was found to be the main contribution for the higher adhesion energy in electrolyte solutions of higher NaCl concentrations where the zero-frequency of van der Waals interaction were effectively screened. The results illustrate that oligo(ethylene glycol) methacrylate copolymer is a promising polymer for functionalizing MoS2 and that one can simply change the salt concentration to modulate the single-molecule interactions for desired applications.

Simultaneous measurement of dynamic force and spatial thin film thickness between deformable and solid surfaces by integrated thin liquid film force apparatus.

Interactions involving deformable surfaces reveal a number of distinguishing physicochemical characteristics that do not exist in interactions between rigid solid surfaces. A unique fully custom-designed instrument, referred to as integrated thin liquid film force apparatus (ITLFFA), was developed to study the interactions between one deformable and one solid surface in liquid. Incorporating a bimorph force sensor with interferometry, this device allows for the simultaneous measurement of the time-dependent interaction force and the corresponding spatiotemporal film thickness of the intervening liquid film. The ITLFFA possesses the specific feature of conducting measurement under a wide range of hydrodynamic conditions, with a displacement velocity of deformable surfaces ranging from 2 µm s-1 to 50 mm s-1. Equipped with a high speed camera, the results of a bubble interacting with hydrophilic and partially hydrophobic surfaces in aqueous solutions indicated that ITLFFA can provide information on interaction forces and thin liquid film drainage dynamics not only in a stable film but also in films of the quick rupture process. The weak interaction force was extracted from a measured film profile. Because of its well-characterized experimental conditions, ITLFFA permits the accurate and quantitative comparison/validation between measured and calculated interaction forces and temporal film profiles.

Interaction between Air Bubbles and Superhydrophobic Surfaces in Aqueous Solutions.

Superhydrophobic surfaces are usually characterized by a high apparent contact angle of water drops in air. Here we analyze the inverse situation: Rather than focusing on water repellency in air, we measure the attractive interaction of air bubbles and superhydrophobic surfaces in water. Forces were measured between microbubbles with radii R of 40-90 µm attached to an atomic force microscope cantilever and submerged superhydrophobic surfaces. In addition, forces between macroscopic bubbles (R = 1.2 mm) at the end of capillaries and superhydrophobic surfaces were measured. As superhydrophobic surfaces we applied soot-templated surfaces, nanofilament surfaces, micropillar arrays with flat top faces, and decorated micropillars. Depending on the specific structure of the superhydrophobic surfaces and the presence and amount of entrapped air, different interactions were observed. Soot-templated surfaces in the Cassie state showed superaerophilic behavior: Once the electrostatic double-layer force and a hydrodynamic repulsion were overcome, bubbles jumped onto the surface and fully merged with the entrapped air. On nanofilaments and micropillar arrays we observed in addition the formation of sessile bubbles with finite contact angles below 90° or the attachment of bubbles, which retained their spherical shape.

Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect.

Bystander effects can be induced through cellular communication between irradiated cells and non-irradiated cells. The signals that mediate this cellular communication, such as cytokines, reactive oxygen species, nitric oxide and even microRNAs, can be transferred between cells via gap junctions or extracellular medium. We have previously reported that miR-21, a well described DDR (DNA damage response) microRNA, is involved in radiation-induced bystander effects through a medium-mediated way. However, the mechanisms of the microRNA transfer have not been elucidated in details. In the present study, it was found that exosomes isolated from irradiated conditioned medium could induce bystander effects. Furthermore, we demonstrated plenty of evidences that miR-21, which is up-regulated as a result of mimic transfection or irradiation, can be transferred from donor or irradiated cells into extracellular medium and subsequently get access to the recipient or bystander cells through exosomes to induce bystander effects. Inhibiting the miR-21 expression in advance can offset the bystander effects to some extent. From all of these results, it can be concluded that the exosome-mediated microRNA transfer plays an important role in the radiation-induced bystander effects. These findings provide new insights into the functions of microRNAs and the cellular communication between the directly irradiated cells and the non-irradiated cells.

MiR-21 is involved in radiation-induced bystander effects.

Radiation-induced bystander effects are well-established phenomena, in which DNA damage responses are induced not only in the directly irradiated cells but also in the non-irradiated bystander cells through intercellular signal transmission. Recent studies hint that bystander effects are possibly mediated via small non-coding RNAs, especially microRNAs. Thus, more details about the roles of microRNA in bystander effects are urgently needed to be elucidated. Here we demonstrated that bystander effects were induced in human fetal lung MRC-5 fibroblasts through medium-mediated way by different types of radiation. We identified a set of differentially expressed microRNAs in the cell culture medium after irradiation, among which the up-regulation of miR-21 was further verified with qRT-PCR. In addition, we found significant upregulation of miR-21 in both directly irradiated cells and bystander cells, which was confirmed by the expression of miR-21 precursor and its target genes. Transfection of miR-21 mimics into non-irradiated MRC-5 cells caused bystander-like effects. Taken together, our data reveals that miR-21 is involved in radiation-induced bystander effects. Elucidation of such a miRNA-mediated bystander effect is of utmost importance in understanding the biological processes related to ionizing radiation and cell-to-cell communication.

Real-time mapping of rat stomach lymph nodes by quantum dots.

OBJECTIVE: To develop a real-time imaging method to identify the rat stomach lymph node basin with quantum dots (Qdots). MATERIAL AND METHODS: Six Sprague-Dawley rats received injections of 0.05 ml Qdots (1 mg/ml) in the subserosal layer in the lesser curvature of the gastric antrum. Subsequently, draining lymphatic channels and lymph nodes were visualized with a near-infrared fluorescence imaging system. Histological examination was required to confirm the presence of lymph nodes. Additionally, rats received injections of Qdots and underwent 2 weeks of observation to confirm if there was any abnormality. The distribution of Qdots was measured by inductively coupled plasma-mass spectrometry. RESULTS: After injection of the Qdots, the gastric sentinel lymph nodes were visualized 15 min later. The fluorescence then began to spread. The intensity of fluorescence increased in the perigastric area at 60 min, and declined at 360 min. Histological analysis of the fluorescent tissue confirmed the presence of nodal tissue. The results of a cadmium assay showed that Qdots were mainly distributed in the liver, spleen and kidney of the rats. No apparent toxicity could be seen during the 2 weeks of observation. CONCLUSIONS: NIR fluorescence imaging of lymph nodes with Qdots is a novel and reliable real-time technique that can be used to assist with identification and resection of stomach lymph nodes. The optimal observation time of perigastric SLNs was 15 min after the injection, and the optimal observation time of perigastric lymph nodes beyond the SLNs was 60-120 min after the injection.

Symbiont-Induced Phagosome Changes Rather than Extracellular Discrimination Contribute to the Formation of Social Amoeba Farming Symbiosis.

Symbiont recognition is essential in many symbiotic relationships, especially for horizontally transferred symbionts. Therefore, how to find the right partner is a crucial challenge in these symbiotic relationships. Previous studies have demonstrated that both animals and plants have evolved various mechanisms to recognize their symbionts. However, studies about the mechanistic basis of establishing protist-bacterium symbioses are scarce. This study investigated this question using a social amoeba Dictyostelium discoideum and their Burkholderia symbionts. We found no evidence that D. discoideum hosts could distinguish different Burkholderia extracellularly in chemotaxis assays. Instead, symbiont-induced phagosome biogenesis contributed to the formation of social amoeba symbiosis, and D. discoideum hosts have a higher phagosome pH when carrying symbiotic Burkholderia than nonsymbiotic Burkholderia. In conclusion, the establishment of social amoeba symbiosis is not linked with extracellular discrimination but related to symbiont-induced phagosome biogenesis, which provides new insights into the mechanisms of endosymbiosis formation between protists and their symbionts. IMPORTANCE Protists are single-celled, extremely diverse eukaryotic microbes. Like animals and plants, they live with bacterial symbionts and have complex relationships. In protist-bacterium symbiosis, while some symbionts are strictly vertically transmitted, others need to reestablish and acquire symbionts from the environment frequently. However, the mechanistic basis of establishing protist-bacterium symbioses is mostly unclear. This study uses a novel amoeba-symbiont system to show that the establishment of this symbiosis is not linked with extracellular discrimination. Instead, symbiont-induced phagosome biogenesis contributes to the formation of social amoeba-bacterium symbiosis. This study increases our understanding of the mechanistic basis of establishing protist-bacterium symbioses.

Valorization of fluid petroleum coke for efficient catalytic destruction of biomass gasification tar.

Large volumes of waste petroleum coke stockpiled in open yard not only represent a huge loss of valuable material but also pose a significant risk to the environment. This work proposed an innovative strategy for waste petroleum coke valorization by exploring its catalytic performance of biomass gasification tar destruction. Waste petroleum coke was firstly activated by potassium hydroxide (KOH) to obtain high specific surface area as well as low sulfur and ash contents. Petroleum coke derived catalyst showed superior performance than a commercial activated carbon derived catalyst for destruction of naphthalene as the tar model compound. The petroleum coke derived catalyst exhibited 99.1% naphthalene destruction efficiency at 800 °C but deactivated quickly under N2 atmosphere. Under H2 and steam atmospheres, the catalytic activities were 98.6% and 96.5% for 8 h, respectively. To study the correlation between catalytic performance and the structure of carbon catalyst, elemental analysis, scanning electron microscope (SEM) analysis, transmission electron microscope (TEM) analysis, X-ray powder diffraction (XRD) analysis, Brunauer-Emmett-Teller method (BET) analysis, Fourier transform infrared (FTIR) spectroscopy, temperature programmed oxidation (TPO) analysis and Raman spectroscopy were performed on both fresh and spent catalysts. Results demonstrated that the hydrogen-rich groups (small rings and amorphous carbon) and oxygen-containing groups may account for the good resistance to coke deposition under H2 and steam atmospheres.

Achieving high selectivity towards electro-conversion of CO2 using In-doped Bi derived from metal-organic frameworks.

Metal-organic frameworks (MOFs) and their derivatives have shown great potential as electrocatalysts, in virtue of their ease of functionalization and abundance of active sites. Here, we report a series of indium-doped bismuth MOF-derived composites (BiInX-Y@C) for the direct conversion of carbon dioxide (CO2) to hydrocarbon derivatives. Amongst the catalysts studied, BiIn5-500@C demonstrated high selectivity for the production of formate and intrinsic activity in a wide potential window, ranging from - 1.16 to - 0.76 V vs. RHE (VRHE). At - 0.86 VRHE, the Faradaic efficiency and total current density were determined as 97.5% and - 13.5 mA cm-2, respectively. In addition, a 15-h stability test shows no obvious signs of deactivation. Complementary density functional theory (DFT) calculations revealed that the In-doped Bi2O3 are the predominant active centers for HCOOH production in the reduction of CO2 under the action of the BiInX-Y@C catalyst. This work provides new detailed insights into reaction mechanism, and selectivity for reduction of CO2via MOFs, which are expected to inspire and guide the design of novel, selective and efficient catalysts.

Comparison of arsenic fractions and health risks in PM2.5 before and after coal-gas replacement.

Coal-Gas replacement project has been implemented to decrease haze pollution in China in recent years. Airborne arsenic (As) mostly originates from coal burning processes. It is noteworthy to compare the distribution of arsenic fraction in PM2.5 before and after coal-gas replacement. Eighty PM2.5 samples were collected in Baoding in December 2016 (coal dominated year) and December 2017 (gas dominated year) at different functional areas including residential area (RA), industrial area (IA), suburb (SB), roadside (ST) and Botanical Garden Park (BG). The fraction, bioavailability and health risk of As in the PM2.5 samples were investigated and compared between these two years. Arsenic was mainly distributed in the non-specifically sorbed fraction (F1) and the residual fraction (F5). However, the proportion of F1 to the total As in 2017 was higher than that in 2016, while the proportion of As in the amorphous and poorly-crystalline hydrous oxides of Fe and Al fraction (F3) in 2017 was lower. The distributions of fraction and bioavailability showed temporal and spatial characteristics. The total concentration and bioavailability of As in SB and IA were significantly higher than those in RA, ST and BG. The BF (Bioavailability Factor) values of As ranged from 0.30 to 0.61. Health risk assessment indicated that the hazard quotient (HQ) and carcinogenic risk (CR) of As in PM2.5 significantly decreased after coal-gas replacement.

Bubbles with tunable mobility of surfaces in ethanol-NaCl aqueous solutions.

The mobility of bubble surfaces in aqueous solutions can be hindered by even a trace amount of contaminants at the air-liquid interface. Adding ethanol into an aqueous solution is expected to modify the activity of the contaminants and hence their level at the air-liquid interface, which can possibly tune the mobility of the bubble surface. The mobility of the bubble surface was characterized by measuring dynamic interactions between a millimeter-size air bubble and a flat mica surface in ethanol-NaCl aqueous solutions using the newly developed dynamic force apparatus and quantified by the Stokes-Reynolds-Young-Laplace model. For a given bubble approach velocity, the hydrodynamic boundary condition at the air-liquid interface deviated from a tangentially immobile boundary at a critical ethanol concentration and converged gradually to fully mobile boundary with further increasing the ethanol concentration. Increasing the bubble approach velocity was found to reduce the critical ethanol concentration that was needed to change the mobility of the bubble surface. By adding surfactants to the system of high ethanol concentration and fully mobile air-liquid interface, the boundary condition became immobile when the amount of surfactant reached a critical concentration. This study introduced a method to control the hydrodynamic boundary condition at the air-liquid interface in mixed liquids.

Serum microRNAs as Early Indicators for Estimation of Exposure Degree in Response to Ionizing Irradiation.

Exposure to ionizing radiation from nuclear devices, spaceflights or terrorist attacks represents a major threat to human health and public security. After a radiological incident, noninvasive biomarkers that can facilitate rapid assessment of exposure risk in the early stages are urgently needed for optimal medical treatment. Serum microRNAs (miRNAs) are ideal biomarkers because they are stable in response to environmental changes, they are common among different species and are easily collected. Here, we performed miRNA PCR arrays to analyze miRNA expression profiles at 24 h postirradiation. Blood samples were collected from animals that received 0.5-2 Gy total-body carbon-ion irradiation. A specific signature with 12 radiosensitive miRNAs was selected for further validation. After exposure to 0.1-2 Gy of carbon-ion, iron-ion or X-ray radiations, five miRNAs that showed a significant response to these radiation types were selected for further observation of dose- and time-dependent changes: miR-183-5p, miR-9-3p, miR-200b-5p, miR-342-3p and miR-574-5p. We developed a universal model using these five miRNAs to predict the degree of exposure to different radiation types with high sensitivity and specificity. In conclusion, we have identified a set of miRNAs that are quite sensitive to different radiation types in the early stages after exposure, demonstrating their potential use as effective indicators to predict the degree of exposure.

Both Complexity and Location of DNA Damage Contribute to Cellular Senescence Induced by Ionizing Radiation.

Persistent DNA damage is considered as a main cause of cellular senescence induced by ionizing radiation. However, the molecular bases of the DNA damage and their contribution to cellular senescence are not completely clear. In this study, we found that both heavy ions and X-rays induced senescence in human uveal melanoma 92-1 cells. By measuring senescence associated-ß-galactosidase and cell proliferation, we identified that heavy ions were more effective at inducing senescence than X-rays. We observed less efficient repair when DNA damage was induced by heavy ions compared with X-rays and most of the irreparable damage was complex of single strand breaks and double strand breaks, while DNA damage induced by X-rays was mostly repaired in 24 hours and the remained damage was preferentially associated with telomeric DNA. Our results suggest that DNA damage induced by heavy ion is often complex and difficult to repair, thus presents as persistent DNA damage and pushes the cell into senescence. In contrast, persistent DNA damage induced by X-rays is preferentially associated with telomeric DNA and the telomere-favored persistent DNA damage contributes to X-rays induced cellular senescence. These findings provide new insight into the understanding of high relative biological effectiveness of heavy ions relevant to cancer therapy and space radiation research.

Synthesis of CdTe quantum dot-conjugated CC49 and their application for in vitro imaging of gastric adenocarcinoma cells.

The purpose of this experiment was to investigate the visible imaging of gastric adenocarcinoma cells in vitro by targeting tumor-associated glycoprotein 72 (TAG-72) with near-infrared quantum dots (QDs). QDs with an emission wavelength of about 550 to 780 nm were conjugated to CC49 monoclonal antibodies against TAG-72, resulting in a probe named as CC49-QDs. A gastric adenocarcinoma cell line (MGC80-3) expressing high levels of TAG-72 was cultured for fluorescence imaging, and a gastric epithelial cell line (GES-1) was used for the negative control group. Transmission electron microscopy indicated that the average diameter of CC49-QDs was 0.2 nm higher compared with that of the primary QDs. Also, fluorescence spectrum analysis indicated that the CC49-QDs did not have different optical properties compared to the primary QDs. Immunohistochemical examination and in vitro fluorescence imaging of the tumors showed that the CC49-QDs probe could bind TAG-72 expressed on MGC80-3 cells.