Injectable Black Phosphorus Nanosheets for Wireless Nongenetic Neural Stimulation.

Neurons can be modified to express light-sensitive proteins for enabling stimulation with a high spatial and temporal resolution, but such techniques require gene transfection and systematical implantation. Here, a black phosphorus nanosheet-based injectable strategy is described for wireless neural stimulation both in vitro and in vivo without cell modifications. These nanosheets, with minimal invasiveness, high biocompatibility, and biodegradability, are anchored on cell membranes as miniature near-infrared (NIR) light transducers to create local heating for neural activity excitation. Based on cultured multielectrode-array recording, in vivo electrophysiology analysis, and open field behavioral tests, it is demonstrated that remotely applied NIR illumination can reliably trigger spiking activity in cultured neurons and rat brains. Excitingly, reliable regulation of brain function to control animal behaviors is also described. Moreover, this approach has shown its potential for future clinical use by successful high-frequency stimulation in cells and animals in this proof-of-concept study. It is believed that this new method will offer a powerful alternative to other neural stimulation solutions and potentially be of independent value to the healthcare system.

High-throughput brain activity mapping and machine learning as a foundation for systems neuropharmacology.

Technologies for mapping the spatial and temporal patterns of neural activity have advanced our understanding of brain function in both health and disease. An important application of these technologies is the discovery of next-generation neurotherapeutics for neurological and psychiatric disorders. Here, we describe an in vivo drug screening strategy that combines high-throughput technology to generate large-scale brain activity maps (BAMs) with machine learning for predictive analysis. This platform enables evaluation of compounds' mechanisms of action and potential therapeutic uses based on information-rich BAMs derived from drug-treated zebrafish larvae. From a screen of clinically used drugs, we found intrinsically coherent drug clusters that are associated with known therapeutic categories. Using BAM-based clusters as a functional classifier, we identify anti-seizure-like drug leads from non-clinical compounds and validate their therapeutic effects in the pentylenetetrazole zebrafish seizure model. Collectively, this study provides a framework to advance the field of systems neuropharmacology.

Self-Monitoring and Self-Delivery of Photosensitizer-Doped Nanoparticles for Highly Effective Combination Cancer Therapy in Vitro and in Vivo.

Theranostic nanomedicine is capable of diagnosis, therapy, and monitoring the delivery and distribution of drug molecules and has received growing interest. Herein, a self-monitored and self-delivered photosensitizer-doped FRET nanoparticle (NP) drug delivery system (DDS) is designed for this purpose. During preparation, a donor/acceptor pair of perylene and 5,10,15,20-tetro (4-pyridyl) porphyrin (H2TPyP) is co-doped into a chemotherapeutic anticancer drug curcumin (Cur) matrix. In the system, Cur works as a chemotherapeutic agent. In the meantime, the green fluorescence of Cur molecules is quenched (OFF) in the form of NPs and can be subsequently recovered (ON) upon release in tumor cells, which enables additional imaging and real-time self-monitoring capabilities. H2TPyP is employed as a photodynamic therapeutic drug, but it also emits efficient NIR fluorescence for diagnosis via FRET from perylene. By exploiting the emission characteristics of these two emitters, the combinatorial drugs provide a real-time dual-fluorescent imaging/tracking system in vitro and in vivo, and this has not been reported before in self-delivered DDS which simultaneously shows a high drug loading capacity (77.6%Cur). Overall, our carrier-free DDS is able to achieve chemotherapy (Cur), photodynamic therapy (H2TPyP), and real-time self-monitoring of the release and distribution of the nanomedicine (Cur and H2TPyP). More importantly, the as-prepared NPs show high cancer therapeutic efficiency both in vitro and in vivo. We expect that the present real-time self-monitored and self-delivered DDS with multiple-therapeutic and multiple-fluorescent ability will have broad applications in future cancer therapy.

[Clinical study on treatment of HIV infected persons based on viral load detection and CD4+ T lymphocyte counting].

OBJECTIVE: To study the usage of viral load and CD4+ cell count methods in evaluating the effects of clinical treatment in HIV infected people. METHODS: Totally 73 cases of HIV infected persons were studied with clinical observation and laboratory examinations, six cases were treated with cocktail therapy, 36 cases with chinese herbs and the other 31 cases were untreated. RESULTS: The results indicated that the viral load levels in cocktail therapy group were significantly lower than the other two groups within 3 months and then kept at very low level. The CD4+ T lymphocyte levels showed a significant increase after 3 months and kept rising up. The chinese herb group, however, had no significant difference in viral load level and CD4+ T lymphocyte level as compared with untreated group. But in clinical observation chinese herbs showed the effect of improving clinical status in some cases. CONCLUSIONS: The authors conclude that the viral load and CD4+ count are efficient methods in clinical evaluation of HIV treatment, especially in routine anti-HIV therapy. As for the chinese herbs treatment, these two monitors did not reflect changes in clinical status.