Ligand-Mediated Magnetism-Conversion Nanoprobes for Activatable Ultra-High Field Magnetic Resonance Imaging.

Ultra-high field (UHF) magnetic resonance imaging (MRI) has emerged as a focal point of interest in the field of cancer diagnosis. Despite the ability of current paramagnetic or superparamagnetic smart MRI contrast agents to selectively enhance tumor signals in low-field MRI, their effectiveness at UHF remains inadequate due to inherent magnetism. Here, we report a ligand-mediated magnetism-conversion nanoprobe (MCNP) composed of 3-mercaptopropionic acid ligand-coated silver-gadolinium bimetallic nanoparticles. The MCNP exhibits a pH-dependent magnetism conversion from ferromagnetism to diamagnetism, facilitating tunable nanomagnetism for pH-activatable UHF MRI. Under neutral pH, the thiolate (-S- ) ligands lead to short τ'm and increased magnetization of the MCNPs. Conversely, in the acidic tumor microenvironment, the thiolate ligands are protonated and transform into thiol (-SH) ligands, resulting in prolonged τ'm and decreased magnetization of the MCNP, thereby enhancing longitudinal relaxivity (r1) values at UHF MRI. Notably, under a 9 T MRI field, the pH-sensitive changes in Ag-S binding affinity of the MCNP lead to a remarkable (>10-fold) r1 increase in an acidic medium (pH 5.0). In vivo studies demonstrate the capability of MCNPs to amplify MRI signal of hepatic tumors, suggesting their potential as a next-generation UHF-tailored smart MRI contrast agent.

Morphology and Ultrastructure of the Female Reproductive Apparatus of an Asexual Strain of the Endoparasitoid Meteorus pulchricornis (Wesmael) (Hymenoptera, Braconidae).

Meteorus pulchricornis (Wesmael) is a solitary endoparasitoid of lepidopteran pests and a good candidate for the control of Spodoptera frugiperda. To elucidate the structure of the female reproductive apparatus, which may play a role in facilitating successful parasitism, we presented the description of the morphology and ultrastructure of the whole female reproductive system in a thelytokous strain of M. pulchricornis. Its reproductive system includes a pair of ovaries without specialized ovarian tissues, a branched venom gland, a venom reservoir, and a single Dufour gland. Each ovariole contains follicles and oocytes at different stages of maturation. A fibrous layer, possibly an egg surface protector, coats the surface of mature eggs. The venom gland consists of secretory units (including secretory cells and ducts) with abundant mitochondria, vesicles and end apparatuses in the cytoplasm, and a lumen. The venom reservoir is comprised of a muscular sheath, epidermal cells with few end apparatuses and mitochondria, and a large lumen. Furthermore, venosomes are produced by secretory cells and delivered into the lumen via the ducts. As a result, myriad venosomes are observed in the venom gland filaments and the venom reservoir, suggesting that they may function as a parasitic factor and have important roles in effective parasitism.

Inorganic ion-sensitive imaging probes for biomedical applications.

Inorganic ions are indispensable substances in living systems, and are widely involved in many essential biological processes. Increasing evidence has shown that the disruption of ion homeostasis is closely related to health problems; thus, the in situ evaluation of ion levels and monitoring their dynamic changes in the living body are critical for precise diagnosis and therapy of diseases. Currently, along with the development of advanced imaging probes, optical imaging and magnetic resonance imaging (MRI) are becoming two major imaging approaches for the identification of ion dynamics. In this review, the design and fabrication of ion-sensitive fluorescent/MRI probes are introduced from the perspective of imaging principles. Furthermore, the recent advances in dynamic imaging of ion levels in living organisms, as well as understanding of ion dyshomeostasis related progression and early diagnosis of diseases, are summarized. Finally, the future perspectives of state-of-the-art ion-sensitive probes for biomedical applications are briefly discussed.

An activatable fluorescent probe enables in vivo evaluation of peroxynitrite levels in rheumatoid arthritis.

An activatable probe able to detect RONS level underlying the development of rheumatoid arthritis (RA) would be far-reaching for the diagnosis and drug efficacy assessment of RA. Despite more and more evidence suggests that ONOO- is an important signaling molecule participating in the RA disease, only rare fluorescent probes can detect ONOO- in this disease with satisfying performance. To this end, we designed and synthesized a novel activatable AIE fluorescent probe (DPPO-PN) for the detection of ONOO- levels in RA. The probe linearly responds to 0-10 µM ONOO- with a significant far-red fluorescence enhancement at 632 nm in 30 s (F/F0 = 161-fold, LOD = 10 nM) upon the excitation of 490 nm, elucidating excellent sensing abilities for ONOO- in cuvettes. Moreover, the fluctuations of intracellular ONOO- levels caused by adscititious adding or stimulant provoking could be real-time captured and visualized with this probe by confocal imaging. Further, the intravital imaging of ONOO- in LPS-induced and CFA-induced RA mouse models also can be achieved with the aid of the probe, substantiating the burst of ONOO- in the RA process. Therefore, this work not only offers an auxiliary tool for the diagnosis of RA but also would benefit our understanding of the ONOO-'s roles in RA.

An Activity-Based Fluorescent Probe for Imaging Fluctuations of Peroxynitrite (ONOO- ) in the Alzheimer's Disease Brain.

Peroxynitrite (ONOO- ) plays a critical role in Alzheimer's disease (AD). To reveal the ONOO- influx in AD brains, an activatable activity-based fluorescence probe Rd-DPA3 was designed by a structure-modulated strategy. Taking advantage of ONOO- -initiated two-step cascade reactions of a novel chemical trigger, Rd-DPA3 specifically responds to ONOO- in 0.3 mM of other reactive oxygen species (ROS) and varied proteins, and gives an intensive fluorescence enhancement (F/F0 =50). Moreover, with its mitochondria-targeting ability, Rd-DPA3 can be used to efficiently monitor the alternations of intracellular ONOO- levels in cerebral cells during oxidative stress. Significantly, due to NIR emission and good blood-brain barrier (BBB) crossing ability, Rd-DPA3 is suitable for in vivo imaging of cerebral ONOO- influx and illustrating an age-dependent accumulation of ONOO- in AD mice brains.

Highly Sensitive Near-Infrared Imaging of Peroxynitrite Fluxes in Inflammation Progress.

Inflammation is an important protection reaction in living organisms associated with many diseases. Since peroxynitrite (ONOO-) is engaged in the inflammatory processes, illustrating the key nexus between ONOO- and inflammation is significant. Due to the lack of sensitive ONOO- in vivo detection methods, the research still remains at its infancy. Herein, a highly sensitive NIR fluorescence probe DDAO-PN for in vivo detection of ONOO- in inflammation progress was reported. The probe responded to ONOO- with significant NIR fluorescence enhancement at 657 nm (84-fold) within 30 s in solution. Intracellular imaging of exogenous ONOO- with the probe demonstrated a 68-fold fluorescence increase (F/F0). Impressively, the probe can in vivo detect ONOO- fluxes in LPS-induced rear leg inflammation with a 4.0-fold fluorescence increase and LPS-induced peritonitis with an 8.0-fold fluorescence increase The remarkable fluorescence enhancement and quick response enabled real-time tracking of in vivo ONOO- with a large signal-to-noise (S/N) ratio. These results clearly denoted that DDAO-PN was able to be a NIR fluorescence probe for in vivo detection and high-fidelity imaging of ONOO- with high sensitivity and will boost the research of inflammation-related diseases.

A cell-based high-throughput protocol to screen entry inhibitors of highly pathogenic viruses with Traditional Chinese Medicines.

Emerging viruses such as Ebola virus (EBOV), Lassa virus (LASV), and avian influenza virus H5N1 (AIV) are global health concerns. Since there is very limited options (either vaccine or specific therapy) approved for humans against these viruses, there is an urgent need to develop prophylactic and therapeutic treatments. Previously we reported a high-throughput screening (HTS) protocol to identify entry inhibitors for three highly pathogenic viruses (EBOV, LASV, and AIV) using a human immunodeficiency virus-based pseudotyping platform which allows us to perform the screening in a BSL-2 facility. In this report, we have adopted this screening protocol to evaluate traditional Chinese Medicines (TCMs) in an effort to discover entry inhibitors against these viruses. Here we show that extracts of the following Chinese medicinal herbs exhibit potent anti-Ebola viral activities: Gardenia jasminoides Ellis, Citrus aurantium L., Viola yedoensis Makino, Prunella vulgaris L., Coix lacryma-jobi L. var. mayuen (Roman.) Stapf, Pinellia ternata (Thunb.) Breit., and Morus alba L. This study represents a proof-of-principle investigation supporting the suitability of this assay for rapid screening TCMs and identifying putative entry inhibitors for these viruses. J. Med. Virol. 89:908-916, 2017. © 2016 Wiley Periodicals, Inc.