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Ultrasmall luminescent nanoprobes have shown some unique imaging advantages and application scenarios. In this review, we present a comprehensive summary and discussion of ultrasmall luminescent nanoprobes towards in vivo PL bioimaging.

Cell temperature monitoring is of great importance to uncover temperature-dependent intracellular events and regulate cellular functions. However, it remains a great challenge to precisely probe the localized temperature status in living cells. Herein, we report a strategy for in situ temperature mapping on an immune cell membrane for the first time, which was achieved by using the lanthanide-doped upconversion nanoparticles. The nanothermometer was designed to label the cell membrane by combining metabolic labeling and click chemistry and can leverage ratiometric upconversion luminescence signals to in situ sensitively monitor temperature variation (1.4% K

Current X-ray imaging technologies involving flat-panel detectors have difficulty in imaging three-dimensional objects because fabrication of large-area, flexible, silicon-based photodetectors on highly curved surfaces remains a challenge1–3. Here we demonstrate ultralong-lived X-ray trapping for flat-panel-free, high-resolution, three-dimensional imaging using a series of solution-processable, lanthanide-doped nanoscintillators. Corroborated by quantum mechanical simulations of defect formation and electronic structures, our experimental characterizations reveal that slow hopping of trapped electrons due to radiation-triggered anionic migration in host lattices can induce more than 30 days of persistent radioluminescence. We further demonstrate X-ray luminescence extension imaging with resolution greater than 20 line pairs per millimetre and optical memory longer than 15 days. These findings provide insight into mechanisms underlying X-ray energy conversion through enduring electron trapping and offer a paradigm to motivate future research in wearable X-ray detectors for patient-centred radiography and mammography, imaging-guided therapeutics, high-energy physics and deep learning in radiology. Using lanthanide-doped nanomaterials and flexible substrates, an approach that enables flat-panel-free, high-resolution, three-dimensional imaging is demonstrated and termed X-ray luminescence extension imaging.

The design of bright NIR-II luminescent nanomaterials that enable efficient labelling of proteins without disturbing their physiological properties in vivo is challenging. We developed an efficient strategy to synthesize bright NIR-II gold nanoclusters (Au NCs) protected by biocompatible cyclodextrin (CD). Leveraging the ultrasmall size of Au NCs (

Gas therapy has emerged as a forceful strategy for augmenting the effects of chemotherapeutic drugs against cancer cells. However, it remains extremely challenging to effectively deliver gas into tissues of interest and unravel its underlying mechanisms. Herein, we designed a near-infrared (NIR) light-switchable nitric oxide (NO) delivery nanosystem for high-efficacy multidrug resistance (MDR) reversal in cancer therapy based on a yolk-shell upconverting nanoparticles@magnesium silica (UCNP@MgSiO3). The internal hollow cavity and flower-like mesoporous shell of UCNPs@MgSiO3 not only enabled a significantly high encapsulation capacity for the NO precursor (BNN6) and doxorubicin (DOX) but also allowed the enhanced cellular uptake, resulting in NIR-triggered NO generation and low pH-triggered DOX release in cancer cells. Mechanistically, intracellular NO can downregulate the drug efflux-related P-glycoprotein and adenosine 5'-triphosphate-binding cassette transporters, thereby increasing the DOX accumulation in the cell nuclei. Such combination therapy of NO and DOX induced the apoptosis of MDR cells and completely inhibited in vivo MDR tumor growth. We further elucidated the therapy mechanism via proteomic profiling, showcasing the downregulation of the ubiquitin-proteasome pathway and nuclear factor kappa-B signaling pathway in the NO-treated MDR cells. Therefore, our findings develop a promising nanoscale gas/drug delivery paradigm for fighting MDR tumors and providing molecular insights into cancer therapy.

Ultrasmall gold nanoclusters (AuNCs) are emerging as promising luminescent nanoprobes for bioimaging due to their fantastic photoluminescence (PL) and renal-clearable ability. However, it remains a great challenge to design them for in vivo sensitive molecular imaging in desired tissues. Herein, we have developed a strategy to tailor the PL and biofate of near-infrared II (NIR-II)-emitting AuNCs via ligand anchoring for improved bioimaging. By optimizing the ligand types in AuNCs and using Er

Extensively drug-resistant Acinetobacter baumannii (XDR-AB) has raised considerable concerns due to its mortal damage to humans and its high transmission rate of infections in hospitals. However, current antibiotics not only show poor anti-infection effects in vivo but also frequently cause high nephrotoxicity and neurotoxicity. Herein, we report a near-infrared (NIR) light-initiated antimicrobial photodynamic therapy (aPDT) to effectively treat in vivo XDR-AB infections based on photosensitizer (PS) loaded upconversion nanoparticles (UCNPs, LiYF4:Yb/Er). Such nanoagents feature robust NIR triggered UC luminescence and high-efficiency energy transfer from UCNPs to the loaded PS, thereby allowing NIR-triggered generation of reactive oxygen species (ROS) for destroying the bacterial cell membrane. This strategy permits a high antibacterial activity against XDR-AB, resulting in a decline of 4.72 log10 in viability at a dose of 50 μg mL-1 UCNPs-PVP-RB with 980 nm laser irradiation (1 W cm-2). More significantly, we can achieve excellent therapeutic efficacy against deep-tissue (about 5 mm) XDR-AB infections without causing any side effects in the murine model. In brief, such NIR-activated aPDT may open up new avenues for treating various deep-tissue intractable infections.

The synthesis of hydrophilic lanthanide-doped nanocrystals (Ln3+ -NCs) with molecular recognition ability for bioimaging currently remains a challenge. Herein, we present an effective strategy to circumvent this bottleneck by encapsulating Ln3+ -NCs in graphene oxide (NCs@GO). Monodisperse NCs@GO was prepared by optimizing GO size and core-shell structure of NaYF4 :Yb,Er@NaYF4 , thus combining the intense visible/near-infrared II (NIR-II) luminescence of NCs and the unique surface properties and biomedical functions of GO. Such nanostructures not only feature broad solvent dispersibility, efficient cell uptake, and excellent biocompatibility but also enable further modifications with various agents such as DNA, proteins, or nanoparticles without tedious procedures. Moreover, we demonstrate in proof-of-concept experiments that NCs@GO can realize simultaneous intracellular tracking and microRNA-21 visualization, as well as highly sensitive in vivo tumor-targeted NIR-II imaging at 1525 nm.

The detection of circulating tumor cells (CTCs) is crucial to early cancer diagnosis and the evaluation of cancer metastasis. However, it remains challenging due to the scarcity of CTCs in the blood. Herein, we report an ultrasensitive platform for the direct detection of CTCs using luminescent lanthanide nanoprobes. These were designed to recognize the epithelial cell adhesion molecules on cancer cells, allowing signal amplification through dissolution-enhanced time-resolved photoluminescence (TRPL) and the elimination of short-lived autofluorescence interference. This enabled the direct detection of blood breast-cancer cells with a limit of detection down to 1 cell/well of a 96-well plate. Moreover, blood CTCs (≥10 cells mL-1 ) can be detected in cancer patients with a detection rate of 93.9 % (14/15 patients). We envision that this ultrasensitive detection platform with excellent practicality may provide an effective strategy for early cancer diagnosis and prognosis evaluation.

Background Photodynamic therapy (PDT), a clinical anticancer therapeutic modality, has a long history in clinical cancer treatments since the 1970s. However, PDT has not been widely used largely because of metabolic problems and off-target phototoxicities of the current clinical photosensitizers. Purpose The objective of the study is to develop a high-efficiency and high-specificity carrier to precisely deliver photosensitizers to tumor sites, aiming at addressing metabolic problems, as well as the systemic damages current clinical photosensitizers are known to cause. Methods We synthesized a polydopamine (PDA)-based carrier with the modification of folic acid (FA), which is to target the overexpressed folate receptors on tumor surfaces. We used this carrier to load a cationic phthalocyanine-type photosensitizer (Pc) and generated a PDA-FA-Pc nanomedicine. We determined the antitumor effects and the specificity to tumor cell lines in vitro. In addition, we established human cancer-xenografted mice models to evaluate the tumor-targeting property and anticancer efficacies in vivo. Results Our PDA-FA-Pc nanomedicine demonstrated a high stability in normal physiological conditions, however, could specifically release photosensitizers in acidic conditions, eg, tumor microenvironment and lysosomes in cancer cells. Additionally, PDA-FA-Pc nanomedicine demonstrated a much higher cellular uptake and phototoxicity in cancer cell lines than in healthy cell lines. Moreover, the in vivo imaging data indicated excellent tumor-targeting properties of PDA-FA-Pc nanomedicine in human cancer-xenografted mice. Lastly, PDA-FA-Pc nanomedicine was found to significantly suppress tumor growth within two human cancer-xenografted mice models. Conclusion Our current study not only demonstrates PDA-FA-Pc nanomedicine as a highly potent and specific anticancer agent, but also suggests a strategy to address the metabolic and specificity problems of clinical photosensitizers.

CuInS2 semiconductor nanocrystals (NCs) exhibit large absorption coefficient, size-dependent photoluminescence and low toxicity, making them excellent candidates in a variety of bioapplications. However, precise control of both their composition and morphology to improve the luminescent efficiency remains a great challenge via conventional direct synthesis. Herein, we present a novel low-temperature template synthesis of highly efficient luminescent CuInS2 nanoprobes from In2S3 NCs via a facile cation exchange strategy. The proposed strategy enables synthesis of a series of CuInS2 NCs with broad size tunability from 2.2 to 29.6 nm. Through rationally manipulating the stoichiometry of Cu/In, highly efficient luminescence of CuInS2 with the maximum quantum yield of 28.6% has been achieved, which is about one order of magnitude improvement relative to that of directly synthesized NCs. By virtue of the intense emission of CuInS2 nanoprobes, we exemplify their application in sensitive homogeneous biodetection for an important biomolecule of adenosine triphosphate (ATP) with the limit of detection down to 49.3 nM. Moreover, the CulnS2 nanoprobes are explored for ATP-targeted cancer cell imaging, thus revealing their great potentials in the field of cancer diagnosis and prognosis.

Current X-ray imaging technologies involving flat-panel detectors have difficulty in imaging three-dimensional objects because fabrication of large-area, flexible, silicon-based photodetectors on highly curved surfaces remains a challenge

The presence of phenolic substances in sugarcane juice seriously affects the color value of sugar products. Magnetic chitosan (MCS) was prepared using an ionic cross-linking technique, and then was modified with arginine to prepare arginine-modified magnetic chitosan (AMCS) for use as a new sucrose clarifying adsorbent. Gallic acid (GA) is a representative phenolic substance and was used to test the adsorption properties of the prepared AMCS. The adsorption kinetics indicated that the adsorption of GA on AMCS conformed to the pseudo-second-order model, the main adsorption mechanism was chemisorption. The Langmuir equation fit well and with good linearity, and indicated a maximum adsorption capacity of 48.38 mg g−1. The adsorption process was consistent with monolayer adsorption and spontaneous endothermic process. The prepared AMCS exhibited excellent regenerability, and can effectively remove GA in sugarcane juice to improve product safety.

In this study, diatomite was refined by a simple purification method consisting of calcination combined with acid washing. Optimal purification conditions were the focus, including the influence of conditions on diatomite morphology, structure, and specific surface area. The results showed that the optimal conditions were a 550 °C carbonization temperature and 25 wt% HCl. This purified diatomite was then employed to adsorb gallic acid (GA) from molasses wastewater in a series of adsorption experiments, which illustrated that (ḭ) GA adsorption fitted a pseudo-second-order model and the Freundlich equation better with GA adsorption by purified diatomite; (ḭḭ) the adsorption process was physical, nonspontaneous, and endothermic; (ḭḭḭ) the maximum GA adsorption capacity by purified diatomite was 19.852 mg g−1. This study reported the examination of a promising material for sugar mill wastewater pretreatment.

Gas therapy has emerged as a forceful strategy for augmenting the effects of chemotherapeutic drugs against cancer cells. However, it remains extremely challenging to effectively deliver gas into tissues of interest and unravel its underlying mechanisms. Herein, we designed a near-infrared (NIR) light-switchable nitric oxide (NO) delivery nanosystem for high-efficacy multidrug resistance (MDR) reversal in cancer therapy based on a yolk-shell upconverting nanoparticles@magnesium silica (UCNP@MgSiO

The promising potential of photodynamic therapy (PDT) has fueled the development of minimally invasive therapeutic approaches for cancer therapy. However, overcoming limitations in PDT efficacy in the hypoxic tumor environment and light penetration depth remains a challenge. We report the engineering of tungsten carbide nanoparticles (W2C NPs) for 1,064 nm laser-activated dual-type PDT and combined theranostics. The synthesized W2C NPs allow the robust generation of dual-type reactive oxygen species, including hydroxyl radicals (type I) and singlet oxygen (type II), using only single 1,064 nm laser activation, enabling effective PDT even in the hypoxic tumor environment. The W2C NPs also possess high photothermal performance under 1,064 nm laser irradiation, thus enabling synergistically enhanced cancer therapeutic efficacy of PDT and photothermal therapy. Additionally, the photoacoustic and X-ray computed tomography bioimaging properties of W2C NPs facilitate the integration of tumor diagnosis and therapy. The developed W2C based theranostic nanoagents increase the generation of reactive oxygen species in hypoxic tumors, improve the light penetration depth, and facilitate combined photothermal therapy and photoacoustic/computed tomography dual-mode bioimaging. These attributes could spur the exploration of transition metal carbides for advanced biomedical applications.

Lanthanide (Ln3+)-doped NaREF4 (RE = rare earth) nanocrystals (NCs) are one of the most widely studied upconversion and downshifting luminescent nanoprobes. However, the size and optical performance of the Ln3+-doped NaREF4 NCs produced by the available lab-scale synthesis may vary from batch to batch, which inevitably limits their practical bioapplications. Herein, we report the synthesis of uniform Ln3+-doped NaREF4 NCs via a facile solid-liquid-thermal-decomposition (SLTD) method by directly employing NaHF2 powder as a fluoride and sodium precursor. The proposed SLTD strategy is easy to perform, time-saving and cost-effective, making it ideal for scale-up syntheses. Particularly, over 63 g of β-NaGdF4:Yb,Er@NaYF4 core/shell NCs with narrow size variation (

Multifunctional nanomedicines are highly demanded in the development of new cancer theranostic approaches to achieve more effective and safer treatment. Herein, we designed a polydopamine (PDA) nanoparticle by loading with cell cycle inhibitor nocodazole (NOC) and photosensitizer ZnPc(TAP)412+ (ZnPc12+) for simultaneous tumor imaging and efficient synergistic therapy. It was found that the loaded NOC can facilitate enhanced nuclear uptake of ZnPc12+ in MCF-7 cells, resulting in PDA-NOC–ZnPc12+ nanoparticles not only inhibiting cell proliferation and inducing cell cycle G2/M arrest, but also improving photodynamic therapy (PDT) efficacy. Compared with the respective single anticancer action, PDA-NOC–ZnPc12+ nanoparticles exhibited better anticancer efficacy in tumor-bearing mice, demonstrating the synergistic effect of combination therapy with a cell cycle inhibitor and photosensitizer. Particularly, PDA-NOC–ZnPc12+ resulted in a high accumulation of ZnPc12+ in tumors but low retention in livers, without rendering distinct toxicity to the treated animals. Such PDA-based nanocarriers functionalized with dual-drug loading and bioimaging may have great potential for diagnosis and combination therapy of cancer.

In recent years, photodynamic therapy (PDT) studies have gained considerable attention as a non-invasive method used to fight cancer. In this study, a series of structurally similar photosensitizers (PSs) with incremental positive electric charges (ZnPc-4, 8 and 12) was investigated via in vitro and in vivo experiments. Photodynamic antitumor studies of these PSs, including phototoxicities, cellular uptake, the production of reactive oxygen species (ROSs) and the process of apoptosis, were conducted in the murine breast carcinoma cell line 4T1. The results indicated that the amount of positive electric charges in PSs is a key factor in influencing the efficacy of PDT. Furthermore, we established a hepatocellular carcinoma (H22) tumor-bearing mouse model to detect the antitumor activities of three PSs. ZnPc-4, 8 and 12 demonstrated significant antitumor effects and no obvious systemic damages in vivo (PDT effects: ZnPc-4 > ZnPc-8 > ZnPc-12), suggesting that the amount of positive electric charges was important to PSs, as well as the PDT effects. Our study not only indicates that ZnPc-4, 8 and 12 were highly potent anticancer PSs, but also suggests that adjusting the amount of positive electric charges is able to promote the PDT effects in cancer therapy.

Solution-processed metal-halide perovskites hold great promise in developing next-generation low-cost, high-performance photodetectors. However, the weak absorption of perovskites beyond the near-infrared spectral region posts a stringent limitation on their use for broadband photodetectors. Here, the rational design and synthesis of an upconversion nanoparticles (UCNPs)-perovskite nanotransducer are presented, namely UCNPs@mSiO2 @MAPbX3 (X = Cl, Br, or I), for broadband photon detection spanning from X-rays, UV, to NIR. It is demonstrated that, by in situ crystallization and deliberately tuning the material composition in the lanthanide core and perovskites, the nanotransducers allow for a high stability and show a wide linear response to X-rays of various dose rates, as well as UV/NIR photons of various power densities. The findings provide an opportunity to explore the next-generation broadband photodetectors in the field of high-quality imaging and optoelectronic devices.

Persistent luminescent nanoparticles (PLNPs) have emerged as important nanomaterials for biological imaging as a result of complete avoidance of tissue auto-fluorescence. However, the imaging sensitivity and long-term in vivo imaging are still limited due to the persistent luminescence that is rapidly decayed in vivo after an ex vivo excitation. To address this limitation, in vivo activation of PLNPs is highly desired. Herein, we present a new strategy for the activation of PLNPs (SrAl2O4:Eu2+) by using soft X-ray excitation. Importantly, as the soft X-ray light source possesses the advantage of deep tissue penetration, the PLNPs can be reactivated in vivo through living tissue using soft X-ray excitation. Furthermore, X-ray/persistent luminescence dual-modal imaging can be achieved to empower this strategy with high sensitivity. Our results suggest that this new strategy of in vivo energy charging in PLNPs would bring new insights for deep tissue and long-term bioimaging in living animals, and provide new perspectives for persistent luminescence bioimaging and therapeutic applications.

As the effective photothermal agent, NIR cyanine dye has shown great promise in cancer therapy due to its distinct NIR absorbance and excellent thermal conversion superiority. Up to date, various nanosystems have been developed as the delivery carrier for NIR dye in order to overcome the inherent issues such as poor stability, low bioavailability and insufficient therapy efficacy. However, the huge obstacle of current nanocarriers for NIR dye encapsulation frequently lies in high leakage risk, complicated preparation and poor biocompatibility, which significantly hinder their further application in cancer therapy. To make up for these deficiencies, we developed a facile and universal strategy to fabricate a novel nanoscale coordination polymers (NCPs) through the co-coordination driven assembly of cypate and carboxyl ligand with Gd3+. Through this design, cypate can be effectively introduced into the interior of NCPs through the coordination between its carboxyl group and Gd3+, resulting in the enhanced stability, reduced leakage risk, and improved therapeutic efficacy. The fabricated NCPs have exhibited multimodal imaging guided tumor targeting chemo-photothermal property. After accumulation in tumor site, rapid drug release can be effectively triggered by NIR laser induced hyperthermia and acidic endo/lysosomal microenvironment, which fundamentally improved the synergistic chemo-photothermal efficacy for tumor killing. The newly fabricated NCP system can exert distinctively chemo-photothermal synergistic efficacy for cancer therapy and will pave a new avenue for the application of NCPs in biomedical field.

Biosensing of circulating tumor cells (CTCs) is of vital significance in cancer theranostics. Thus, the development of highly efficient luminescent nano-bioprobes is imperative to meet the growing demand of CTCs-related clinical diagnosis and biomedical research. Herein, we exquisitely manipulate the stoichiometry of Se/In to synthesize CuInSe2 (CISe) quantum dots (QDs) with near-infrared (NIR) emission peak tunable from 920 to 1224 nm. Meanwhile, the excitation band of these CISe QDs spans from ultraviolet to NIR regions, which is highly desired for various bioapplications. Through surface coating of thin ZnS shell, an absolute NIR-II photoluminescence quantum yield of 21.8% can be achieve, which is the highest among Pb/Cd-free QDs reported so far. By virtue of their intense NIR-II emission, we demonstrate the application of CISe nanoprobes for autofluorescence-free bioassay of CTCs (e.g., human breast cancer MCF-7 cells) spiked in whole blood samples, with the limit of detection down to 12 cell/well of a 96-well plate. Furthermore, the CISe@ZnS nanoprobes are exploited for tumor-targeted bioimaging in live mice with a signal-to-noise ratio of 5.8. These findings reveal the great potentials of the novel NIR-II luminescent CuInSe2 nanoprobes in the field of cancer diagnosis and imaging-guided surgery.

The phenolic substances in sugar cane juice affect the color value of white sugar. A magnetic chitosan-modified-diatomite (MCMD), as a new type of clarifying agent for sugar, prepared via a co-precipitation method combined with cross-linking treatment was firstly used to adsorb two primary phenolic acids of sugarcane juice: gallic acid (GA) and caffeic acid (CA). The maximum adsorption capacities for GA and CA by MCMD were 31.949 mg g–1 and 27.640 mg g–1, respectively. Additionally, our results showed that adsorption of GA and CA on MCMD fitted well with the pseudo-second-order model and Langmuir equation, respectively. The adsorption, a physical spontaneous endothermic process, might have involved electrostatic attraction and micropore filling. Importantly, MCMD has good regenerability and achieves better sulfur-free clarification of sugar cane juice and improves more significantly the food safety of white sugar than the traditional decolorization method.

The exploitation of gas therapy platforms holds great promise as a “green” approach for selective cancer therapy, however, it is often associated with some challenges, such as uncontrolled or insufficient gas generation and unclear therapeutic mechanisms. In this work, a gas therapy approach based on near-infrared (NIR) light-triggered sulfur dioxide (SO2) generation was developed, and the therapeutic mechanism as well as in vivo antitumor therapeutic efficacy was demonstrated. A SO2 prodrug-loaded rattle-structured upconversion@silica nanoparticles (RUCSNs) was constructed to enable high loading capacity without obvious leakage and to convert NIR light into ultraviolet light so as to activate the prodrug for SO2 generation. In addition, SO2 prodrug-loaded RUCSNs showed high cell uptake, good biocompatibility, intracellular tracking ability, and high NIR light-triggered cytotoxicity. Furthermore, the cytotoxic SO2 was found to induce cell apoptosis accompanied by the increase of intracellular reactive oxy...

Lanthanide (Ln3+)-doped NaREF4 (RE = rare earth) nanocrystals (NCs) are one of the most widely studied upconversion and downshifting luminescent nanoprobes. However, the size and optical performance of the Ln3+-doped NaREF4 NCs produced by the available lab-scale synthesis may vary from batch to batch, which inevitably limits their practical bioapplications. Herein, we report the synthesis of uniform Ln3+-doped NaREF4 NCs via a facile solid-liquid-thermal-decomposition (SLTD) method by directly employing NaHF2 powder as a fluoride and sodium precursor. The proposed SLTD strategy is easy to perform, time-saving and cost-effective, making it ideal for scale-up syntheses. Particularly, over 63 g of β-NaGdF4:Yb,Er@NaYF4 core/shell NCs with narrow size variation (7%) were synthesized via a one-pot reaction. By virtue of their superior upconversion and downshifting luminescence, we employed the synthesized core/shell nanoprobes for the in vitro detection of prostate-specific antigen with a limit of detection down to 1.8 ng mL-1, and for in vivo near-infrared imaging with a high signal-to-noise ratio of 12. These findings may pave the way for the commercialization of Ln3+-doped nanoprobes in bioassay kits for versatile clinical applications.

Theranostic nanomedicines that integrate diagnostic and therapeutic moieties into a single nanoscale platform are playing an increasingly important role in fighting cancer. Here, a facile and green synthetic strategy for hollow CoPt alloy nanoparticles (HCPA-NPs) using plant polyphenols as assisted agents is reported for the first time. This novel strategy enables size-controlled synthesis of HCPA-NPs through the control of the molecular sizes of polyphenols. It is also a versatile strategy for synthesizing other hollow alloy nanoparticles with various metal compositions due to the diverse metal-chelating ability of the polyphenols. Further studies show that HCPA-NPs have good biocompatibility and can be successfully implemented for magnetic resonance and photoacoustic dual-modal imaging guided photothermal therapy. This work brings new insights for the green synthesis of hollow nanoparticles and extends these biocompatible nanoparticles for theranostic applications.

As microRNAs (miRNAs) are aberrantly expressed in a variety of cancers, detecting them precisely is of great importance. Here we constructed a sensitive and selective enzyme-free sensing platform for miRNA detection based on target-catalyzed hairpin assembly and magnesium ion-dependent deoxyribozyme (Mg2+-dependent DNAzyme). This sensing method introduces two amplification circuits simultaneously and shows a low detection limit of 1 pmol/L. This enzyme-free method is especially preferred because of its facility and economy. Furthermore, this amplified sensor shows high selectivity for discriminating perfectly complementary target and other mismatched RNAs. Therefore, the established strategy could be used as a simple, sensitive and selective method for target miRNA detection.

Photodynamic therapy (PDT) is a new therapeutic approach for cancer treatment. Its mechanism relies on three elements: photosensitizer, light and oxygen. Under aerobic conditions, a suitable wavelength of light activates the photosensitizer that results in the formation of reactive oxygen species (ROS). We herein report that PDT with a zinc phthalocyanine (ZnPc) photosensitizer coupled with 2,4,6-tris (N, N-dimethylaminomethyl) phenoxy (TAP), termed as ZnPc(TAP)4, has the ability to photodegrade DNA in tumor cells via hydroxyl radicals produced under the red light irradiation, resulting in effective elimination of tumor cells. Furthermore, the high-efficient anti-tumor effect of ZnPc(TAP)4 was verified in a human breast adenocarcinoma cell line MCF-7 tumor-bearing animal model. To the best of our knowledge, this is the first time that destructive effects of hydroxyl radicals produced by PDT on DNA of tumor cells has been documented, which may open up new avenues of antitumor therapy on eliminating the DNA of tumor cells.

As one of food-borne parasitic diseases, toxoplasmosis entails the risk of developing reactivation in immunocompromised patients. The synthetic dipeptide pidotimod is a potent immunostimulating agent that improves the immunodefenses in immunodepression. To investigate the efficacy of pidotimod as a preventive treatment, we used a murine model of reactivated toxoplasmosis with cyclophosphamide (CY)-induced immunosuppression. Pidotimod administration significantly restored the body weight and spleen organ index, increased survival time (from 70 to 90 %), and decreased the parasitemia (from 80 to 35 %) of CY-induced mice with reactivated toxoplasmosis. Cytokine profiles and CD4+ T cells subpopulation analyses by Cytometric Bead Array and flow cytometry demonstrated that pidotimod treatment resulted in a significant upregulation of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-2) and Th1 cells (from 3.73 ± 0.39 to 5.88 ± 0.46 %) after CY induction in infected mice. Additionally, histological findings and parasite DNA quantification revealed that mice administered with pidotimod had a remarkable reduction of parasite burden (two-log) and amelioration of histopathology in the brains. The in vitro studies showed that pidotimod significantly restored concanavalin A-induced splenocyte proliferation and pro-inflammatory cytokines in the supernatants of splenocyte culture. It could be concluded that the administration of pidotimod in immunocompromised mice significantly increases the Th1-biased immune response, prolongs survival time, and ameliorates the load of parasites in the blood. This is the first report of the preventive effect of pidotimod on reactivated toxoplasmosis.

Smart assemblies have attracted increased interest in various areas, especially in developing novel stimuli-responsive theranostics. Herein, commercially available, natural tannic acid (TA) and iron oxide nanoparticles (Fe3 O4 NPs) are utilized as models to construct smart magnetic assemblies based on polyphenol-inspired NPs-phenolic self-assembly between NPs and TA. Interestingly, the magnetic assemblies can be specially disassembled by adenosine triphosphate, which shows a stronger affinity to Fe3 O4 NPs than that of TA and partly replaces the surface coordinated TA. The disassembly can further be facilitated by the acidic environment hence causing the remarkable change of the transverse relaxivity and potent "turn-on" of fluorescence (FL) signals. Therefore, the assemblies for specific and sensitive tumor magnetic resonance and FL dual-modal imaging and photothermal therapy after intravenous injection of the assemblies are successfully employed. This work not only provides understandings on the self-assembly between NPs and polyphenols, but also will open new insights for facilely constructing versatile assemblies and extending their biomedical applications.

T cell immunoglobulin domain and mucin domain (Tim) family, a new gene that expresses on the surface of T cells, plays a critical role in regulation of T cells response. Previous data have shown that Tim-3 expressed on Th1 cells promotes itself apoptosis. Tim-2 is preferentially up-regulated during Th2 differentiation and functions as a potent costimulatory molecule for T-cell immunity. The present study aims to learn whether Tims are responsible for Th2-biased response evoked by Schistosoma japonicum infection. The expressions of Tim-2 and Tim-3 in spleen lymphocytes from S. japonicum-infected mice were examined, and the possible role of galectin-9-Tim-3 pathway in Th2-biased response triggered by schistosome infection was discussed. Our results showed that Tim-2 mRNAs were up-regulated in the spleen of schistosome-infected mice, which coincided with elevated IL-4 gene expression. Administration of galectin-9 significantly induced apoptosis of naïve spleen lymphocytes with down-regulation IFN-γexpression in vitro. Additionally, Tim-3-Fc fusion protein notably enhanced Th1 cells and decreased Th2 cells in vitro. Thus, we concluded that pro-apoptotic effects on Th1 population through galectin-9-Tim-3 pathway and the up-regulation of Tim-2 on Th2 cells might be critical to Th2-biased response of host with schistosomiasis japonica.

A simple and highly sensitive homogeneous aptasensor is developed, which relies on nicking enzyme. The sensitivity of this newly proposed aptasensor is about three orders of magnitude higher than that of traditional homogeneous aptasensors. Furthermore, it is capable of detecting target protein in real samples.

A simple turn-on and homogeneous aptasensor, which relies on target induced formation of silver nanoclusters (Ag NCs), was developed for the determination of platelet-derived growth factor B-chain homodimer (PDGF-BB). The aptasensor contains two hairpin DNA probes termed as P1 and P2. P1 consists of the aptamer sequence of PDGF-BB. Meanwhile, P2 contains the Ag NCs nucleation sequence, which is blocked by the hairpin stem region. P1 and P2 can co-exist metastably in the absence of PDGF-BB and maintain hairpin structure. However, in the presence of PDGF-BB, the binding of PDGF-BB with aptamer will result in the hybridization between P1 and P2, and release the Ag NCs nucleation sequence. In this case, Ag NCs can be formed via the reduction of Ag + by NaBH 4 . By monitoring the increase in fluorescence intensity, we could detect the target protein with high sensitivity. The detection limit of this aptasensor is 0.37 nM, which is comparable with that of other reported aptasensors. Furthermore, this proposed aptasensor shows high selectivity toward its target protein. Thus, the proposed aptasensor based on target induced formation of Ag NCs could be used as a sensitive and selective platform for the detection of target protein.

Schistosomiasis remains a major parasitic disease, with 200 million people infected and 779 million people at risk worldwide. The lack of reliable diagnostic techniques makes this disease difficult to control. In an attempt to discover useful candidates for the diagnosis of schistosomiasis, proteomics in combination with western blotting were employed in this study. This serological proteome assay yielded more than 30 immunodominant spots. Ten of these spots were precisely matched with a homologous two-dimensional electrophoresis (2-DE) gel and successfully identified by LC/MS-MS as corresponding to four different proteins. Of these proteins, SjLAP and SjFBPA were successfully expressed, and their recombinant protein products were further applied in the diagnosis of human Schistosomiasis japonica using ELISA. The ELISA results revealed sensitivities of 98.1% and 87.8% for acute and chronic schistosomiasis with rSjLAP and 100% and 84.7% with rSjFBPA, whereas the assays showed a specificity of 96.7% with both recombinant proteins. After treatment with praziquantel, the titres of the antibodies against both antigens declined significantly (P0.001). Our data therefore suggest that these antibody-oriented recombinant proteins had a high efficacy for the diagnosis of S. japonica, and 2-DE based screening followed by LC/MS-MS has promising potential in the screening of candidate antigens for the diagnosis of schistosomiasis.

Background Recent population structure studies of T. gondii revealed that a few major clonal lineages predominated in different geographical regions. T. gondii in South America is genetically and biologically divergent, whereas this parasite is remarkably clonal in North America and Europe with a few major lineages including Types I, II and III. Information on genotypes and mouse virulence of T. gondii isolates from China is scarce and insufficient to investigate its population structure, evolution, and transmission. Methodology/Principal Findings Genotyping of 23 T. gondii isolates from different hosts using 10 markers for PCR-restriction fragment length polymorphism analyses (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) revealed five genotypes; among them three genotypes were atypical and two were archetypal. Fifteen strains belong to the Chinese 1 lineage, which has been previously reported as a widespread lineage from swine, cats, and humans in China. Two human isolates fall into the type I and II lineages and the remaining isolates belong to two new atypical genotypes (ToxoDB#204 and #205) which has never been reported in China. Our results show that these genotypes of T. gondii isolates are intermediately or highly virulent in mice except for the strain TgCtwh6, which maintained parasitemia in mice for 35 days post infection although it possesses the uniform genotype of Chinese 1. Additionally, phylogenetic network analyses of all isolates of genotype Chinese 1 are identical, and there is no variation based on the sequence data generated for four introns (EF1, HP2, UPRT1 and UPRT7) and two dense granule proteins (GRA6 and GRA7). Conclusion/Significance A limited genetic diversity was found and genotype Chinese 1 (ToxoDB#9) is dominantly circulating in mainland China. The results will provide a useful profile for deep insight to the population structure, epidemiology and biological characteristics of T. gondii in China.

A GO-based molecular beacon assay was developed for rapid, sensitive and cost-efficient detection of transcription factor proteins. Furthermore, this assay can be employed for screening inhibitors of transcription factor proteins.

A simple, highly sensitive and enzyme-free DNAzyme sensor based on target-catalyzed hairpin assembly is developed, which permits detection of 0.1 pM target DNA. Furthermore, this DNAzyme sensor is capable of detecting target DNA in real samples because of its high selectivity.

BACKGROUND: The hygiene hypothesis suggests that helminth infections prevent a range of autoimmune diseases. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the effects of S. japonicum infection on collagen-induced arthritis (CIA), male DBA/1 mice were challenged with unisexual or bisexual S. japonicum cercariae two weeks prior to bovine type II collagen (CII) immunization or at the onset of CIA. S. japonicum infection prior to CII immunization significantly reduced the severity of CIA. ELISA (enzyme linked immunosorbent assay) showed that the levels of anti-CII IgG and IgG2a were reduced in prior schistosome-infected mice, while anti-CII IgG1 was elevated. Splenocyte proliferation against both polyclonal and antigen-specific stimuli was reduced by prior schistosome infection as measured by tritiated thymidine incorporation ((3)H-TdR). Cytokine profiles and CD4(+) T cells subpopulation analysis by ELISA and flow cytometry (FCM) demonstrated that prior schistosome infection resulted in a significant down-regulation of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β and IL-6) and Th1 cells, together with up-regulation of the anti-inflammatory cytokine IL-10 and Th2 cells. Interestingly, the expansion of Treg cells and the reduction of Th17 cells were only observed in bisexually infected mice. In addition, prior schistosome infection notably reduced the expression of pro-inflammatory cytokines and receptor activator of NF-κB ligand (RANKL) in the inflamed joint. However, the disease was exacerbated at one week after infection when established CIA mice were challenged with bisexual cercariae. CONCLUSION/SIGNIFICANCE: Our data provide direct evidence that the Th2 response evoked by prior S. japonicum infection can suppress the Th1 response and pro-inflammatory mediator and that bisexual infection with egg-laying up-regulates the Treg response and down-regulates the Th17 response, resulting in an amelioration of autoimmune arthritis. The beneficial effects might depend on the establishment of a Th2-dominant response rather than the presence of the eggs. Our results suggest that anti-inflammatory molecules from the parasite could treat autoimmune diseases.

In this article, we present a new method for the multiplex detection of nucleases by using graphene oxide (GO) as a platform. We introduce a Y-shaped DNA (Y-DNA) as the multiplex probe. The 5′ termini of the Y-DNA are labeled with carboxy fluorescein (FAM), 6-carboxy-X-rhodamine (ROX) and cyanine 5 (Cy5) and they include three nuclease cleavage sites corresponding to PvuII, EcoRV and HaeIII, respectively. Upon the addition of nucleases, the nucleases cleave the corresponding sites in Y-DNA. Then, short dsDNA fragments containing fluorophores were released from the Y-DNA. These dsDNA fragments were unstable and easy to unwind into two short ssDNAs. They were then adsorbed onto the GO surface. Because of the excellent electronic transference of GO, the fluorescence intensity of the fluorophores can be quenched efficiently. Therefore, by monitoring the fluorophores’ fluorescence change before and after the addition of the nucleases, it is easy to establish a platform of a Y-DNA/GO complex for the simultaneous multiplex detection of nucleases.