A deep red ratiometric fluorescent probe for accurate detection of peroxynitrite in mitochondria.

Peroxynitrite (ONOO-) is widespread within living organisms and has been implicated in many physiological and pathological processes. Since ONOO- is mainly produced in mitochondria, accurate detection of ONOO- in mitochondria can help us understand its specific mechanism of action in the organism. Rather than single-wavelength emissive mitochondrial probes, ratiometric fluorescent probes with longer emission wavelength, large emission shift, and specific mitochondrial targeting properties are more likely to obtain a more accurate ONOO- content in mitochondria. To further avoid the interference by cytoplasmic ONOO-, we constructed a fluorescent probe MXMP with deep red emission and ratio properties, and it will be forbidden to enter the mitochondria after oxidation. In addition to its excellent selectivity and sensitivity, it shifted its fluorescence emission by up to 130 nm, with a detection limit of 84 nM.

Defective Ag-In-S/ZnS quantum dots: an oxygen-derived free radical scavenger for mitigating macrophage inflammation.

Oxidative stress plays an important role in the development of inflammatory diseases including allergy, heart disease, diabetes and cancer. Nanomaterial-mediated antioxidant therapy is regarded as a promising strategy to treat oxidative stress-mediated inflammation. Herein, defective Ag-In-S/ZnS quantum dots (AIS/ZnS QDs) with oxygen-derived radical-scavenging capabilities are developed. Owing to their intrinsic defects and abundant surface functional groups, these quantum dots exhibit excellent oxygen-derived free radical removal efficiency in vitro. In macrophages, AIS/ZnS QDs can eliminate intracellular excessive ROS stimulated by either H2O2 or lipopolysaccharide (LPS), thus can effectively protect macrophages against ROS-induced oxidative injury. Moreover, in the model of LPS-triggered macrophage inflammation, they exhibit benign anti-inflammatory ability by inhibiting the expression of related proinflammatory cytokines (e.g., TNF-α and IL-6). These findings indicate that AIS/ZnS QDs hold great potential for the treatment of ROS-related inflammatory disorders.

Off-On Squalene Epoxidase-Specific Fluorescent Probe for Fast Imaging in Living Cells.

SQLE (squalene epoxidase) is a cell membrane-bound enzyme. It is a target of fungicides and may become a new target for cancer therapy. Therefore, monitoring the content and distribution of the key enzyme in living cells is very challenging. To achieve this goal, tetraphenyl ethylene-Ter (TPE-Ter) was first designed as a new fluorescent probe to SQLE based on its active cavity. Spectral experiments discovered that SQLE/TPE-Ter shows stronger emission with fast response time and low interference from other analytes. Molecular dynamics simulation clearly confirmed the complex structure of SQLE/TPE-Ter, and the key residues contribute to restriction of TPE-Ter single-molecular motion in the cavity. TPE-Ter-specific response to SQLE is successfully demonstrated in living cells such as LO2, HepG2, and fungi. Imaging of TPE-Ter-treated fungi indicates that it can be used to rapidly assess antifungal drug susceptibility (30 min at least). The present work provides a powerful tool to detect content and distribution of SQLE in living cells.

A simple dual-response fluorescent probe for imaging of viscosity and ONOO- through different fluorescence signals in living cells and zebrafish.

Cellular viscosity is a prominent micro-environmental parameter and peroxynitrite is an essential reactive oxygen special, both of which are involved in various pathological and physiological processes. When the intracellular viscosity is abnormal or the ONOO- concentration is irregular, the normal function of cells will be disturbed. Herein, we rationally designed and synthesized a novel multichannel fluorescent probe (probe 1) for multichannel imaging of viscosity and peroxynitrite. Probe 1 displayed about 108-fold enhancement as the viscosity increased from 1.005 cP to 1090 cP. Moreover, the fluorescence intensity at 540 nm was quickly increased after adding ONOO-. It should be noted that probe 1 has high sensitivity, selectivity and low cytotoxicity, which can be successfully employed for the visualization of exogenous and endogenous ONOO- and imaging viscosity changes in HeLa cells by different fluorescent signals. Furthermore, probe 1 could monitor the change of ONOO- induced by LPS (lipopolysaccharide) and IFN-γ (interferon-γ) in zebrafish. This result reveals that probe 1 may inspire more diagnostic and therapeutic programs for viscosity-peroxynitrite related diseases shortly.

Polydopamine nanodots-based cost-effective nanoprobe for glucose detection and intracellular imaging.

The cellular glucose detection remains a vital topic, which could provide some essential information about the glucose-based pathological and physiological processes. In this study, a smart polydopamine nanodots-based cost-effective fluorescence turn-on nanoprobe (denoted as PDA-Ag-GOx) for intracellular glucose detection is established. Silver nanoparticles (AgNPs) are directly formed in one step by the reduction of fluorescent polydopamine nanodots (PDADs) which have much phenolic hydroxyls on the surface. The fluorescence of PDADs could be quenched by AgNPs through surface plasmon-enhanced energy transfer (SPEET) from donor PDADs to acceptor AgNPs. Glucose oxidase (GOx) is modified on the PDA-Ag NPs by covalent bond. In the presence of glucose, GOx could catalyze glucose to produce H2O2 and gluconic acid. The generated acid and H2O2 would degrade AgNPs into Ag+, the PDADs release and restore its fluorescence. The proposed nanoprobe has some advantages, such as cost-effective, easy preparation, and excellent selectivity toward glucose, which could be successfully utilized to intracellular glucose imaging.

A dual-functional biomimetic-mineralized nanoplatform for glucose detection and therapy with cancer cells in vitro.

Glucose detection is a crucial topic in the diagnosis of numerous diseases, such as hypoglycemia or diabetes mellitus. Research indicates that people with diabetes mellitus are at a higher risk of developing various types of cancer. A nanoplatform that combines both diabetes diagnosis and cancer therapy might be regarded as a more effective way to solve the above-mentioned problem. However, none of the known sensors has a smart strategy that can work as a fluorescent glucose sensor and a cancer therapeutic platform simultaneously. Here, we developed a pH responsive biomimetic-mineralized nanoplatform (denoted as CaCO3-PDA@DOX-GOx) for glucose detection in serum samples and applied it to treat the tumor cells combined chemotherapy with the starvation therapy in vitro. Doxorubicin (DOX) and glucose oxidase (GOx) were loaded through the mesoporous CaCO3-PDA nanoparticles (m-CaCO3-PDA NPs). The fluorescence of DOX is quenched as a result of fluorescence resonance energy transfer (FRET) caused by the broad absorption of m-CaCO3-PDA NPs. The nanoplatform would recover fluorescence under lower pH values due to the catalytic reaction of GOx with glucose or tumor microenvironment (TME), which leads to the elimination of FRET. Its application as a glucose sensor is indicated with a linear relationship in the range of 0.01-1.0 mM of glucose and limit of detection is calculated by 6 µM. This nanoplatform also has a TME-responsive antitumor effect and fluorescence imaging functionality, which provide a new idea for cancer therapy together with glucose monitoring in diabetes.

An Endoplasmic Reticulum-Targeted Ratiometric Fluorescent Probe for the Sensing of Hydrogen Sulfide in Living Cells and Zebrafish.

Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule in many physiological processes. Relevant investigations indicated that H2S plays a cytoprotective effect under endoplasmic reticulum stress. Currently, it is still a challenge to design effective methods for ratio detection of endoplasmic reticulum H2S. Herein we are the first to construct a ratiometric near-infrared fluorescent probe (M-H2S) for sensing H2S in the endoplasmic reticulum. M-H2S has high selectivity and sensitivity toward H2S (LOD = 39.1 nM). Additionally, M-H2S possessed an excellent endoplasmic reticulum targeting ability. Moreover, M-H2S was successfully utilized to visualize exogenous/endogenous H2S in HeLa cells and zebrafish. Particularly important, endogenously produced H2S was observed under endoplasmic reticulum stress induced by tunicamycin.

Geographical Environment Factors and Risk Assessment of Tick-Borne Encephalitis in Hulunbuir, Northeastern China.

Tick-borne encephalitis (TBE) is one of natural foci diseases transmitted by ticks. Its distribution and transmission are closely related to geographic and environmental factors. Identification of environmental determinates of TBE is of great importance to understanding the general distribution of existing and potential TBE natural foci. Hulunbuir, one of the most severe endemic areas of the disease, is selected as the study area. Statistical analysis, global and local spatial autocorrelation analysis, and regression methods were applied to detect the spatiotemporal characteristics, compare the impact degree of associated factors, and model the risk distribution using the heterogeneity. The statistical analysis of gridded geographic and environmental factors and TBE incidence show that the TBE patients mainly occurred during spring and summer and that there is a significant positive spatial autocorrelation between the distribution of TBE cases and environmental characteristics. The impact degree of these factors on TBE risks has the following descending order: temperature, relative humidity, vegetation coverage, precipitation and topography. A high-risk area with a triangle shape was determined in the central part of Hulunbuir; the low-risk area is located in the two belts next to the outside edge of the central triangle. The TBE risk distribution revealed that the impact of the geographic factors changed depending on the heterogeneity.

Evolutionary, epidemiological, demographical, and geographical dissection of porcine bocavirus in China and America.

Porcine bocavirus was first discovered in Swedish pigs with post-weaning multisystemic wasting syndrome (PMWS) in 2009. Many efforts have been implemented to investigate the porcine bocavirus, but it remains enigmatic. In the current study, we utilized data from both China and the USA. The China-derived data included 403 pig samples collected from five provinces, 122 gene sequences from the GenBank database, and 637 old porcine bocavirus (PBoV) cases. The USA-derived data comprised 181 pig samples from 18 states, 39 new gene sequences, and 85 new emerging cases. First, we executed a comprehensive analysis of the disease's prevalence, phylogenetics, evolutionary distances, mutation network, geographical distribution, occurrence frequency, and phylogeographical estimation in both China and the USA. The results showed that the positive rates of PBoV (42.0%, 76/181) in American samples were significantly higher than those (11.4%, 46/403) in the Chinese samples. All PBoV cases from these countries can be divided into six groups: PBoV1 (group 1), PBoV2 (group 2), PBoV3C (group 3), PBoV5 (group 4), PBoV3/4 (group 5), and PBoV6V7V (group 6). PBoV1 and PBoV2 were epidemic strains from 2006 to 2011 in China, whereas the PBoV3 subtypes were epidemic from 2010 to 2012 in China and the USA. At present, PBoV3C (group 3), PBoV5 (group 4), and PBoV3/4 (group 5) are epidemic viruses and co-exist in China and the USA. The geographical distribution of PBoV mainly lies in the east and south coastal areas of China and the central states of the USA. Jiangsu Province and the state of Minnesota were the centers of high occurrence frequency of PBoV with six outbreaks. The old PBoV cases involved 14 provinces and regions of China and North Carolina in the USA, whereas the new emerging cases involved five provinces in China and 13 states in the USA, of which two provinces and 12 states reported for the first time that piglets were infected by PBoV. Hong Kong, Hebei, and Jiangsu Provinces and the states of Minnesota and North Carolina were possibly geographical origins of PBoV in China and America, respectively. These data can help us systematically understand porcine bocavirus in China and America and find effective strategies for its treatment.

The novel H1N1 Influenza A global airline transmission and early warning without travel containments.

A novel influenza A (H1N1) has been spreading worldwide. Early studies implied that international air travels might be key cause of a severe potential pandemic without appropriate containments. In this study, early outbreaks in Mexico and some cities of United States were used to estimate the preliminary epidemic parameters by applying adjusted SEIR epidemiological model, indicating transmissibility infectivity of the virus. According to the findings, a new spatial allocation model totally based on the real-time airline data was established to assess the potential spreading of H1N1 from Mexico to the world. Our estimates find the basic reproductive number R0 of H1N1 is around 3.4, and the effective reproductive number fall sharply by effective containment strategies. The finding also implies Spain, Canada, France, Panama, Peru are the most possible country to be involved in severe endemic H1N1 spreading.

Risk analysis for the highly pathogenic avian influenza in Mainland China using meta-modeling.

A logistic model was employed to correlate the outbreak of highly pathogenic avian influenza (HPAI) with related environmental factors and the migration of birds. Based on MODIS data of the normalized difference vegetation index, environmental factors were considered in generating a probability map with the aid of logistic regression. A Bayesian maximum entropy model was employed to explore the spatial and temporal correlations of HPAI incidence. The results show that proximity to water bodies and national highways was statistically relevant to the occurrence of HPAI. Migratory birds, mainly waterfowl, were important infection sources in HPAI transmission. In addition, the HPAI outbreaks had high spatiotemporal autocorrelation. This epidemic spatial range fluctuated 45 km owing to different distribution patterns of cities and water bodies. Furthermore, two outbreaks were likely to occur with a period of 22 d. The potential risk of occurrence of HPAI in Mainland China for the period from January 23 to February 17, 2004 was simulated based on these findings, providing a useful meta-model framework for the application of environmental factors in the prediction of HPAI risk.