Physical and chemical technologies have been continuously progressing advances in neuroscience research. The development of research tools for closed-loop control and monitoring neural activities in behaving animals is highly desirable. In this paper, we introduce a wirelessly operated, miniaturized microprobe system for optical interrogation and neurochemical sensing in the deep brain. Via epitaxial liftoff and transfer printing, microscale light-emitting diodes (micro-LEDs) as light sources and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)-coated diamond films as electrochemical sensors are vertically assembled to form implantable optoelectrochemical probes for real-time optogenetic stimulation and dopamine detection capabilities. A customized, lightweight circuit module is employed for untethered, remote signal control, and data acquisition. After the probe is injected into the ventral tegmental area (VTA) of freely behaving mice, in vivo experiments clearly demonstrate the utilities of the multifunctional optoelectrochemical microprobe system for optogenetic interference of place preferences and detection of dopamine release. The presented options for material and device integrations provide a practical route to simultaneous optical control and electrochemical sensing of complex nervous systems.

Lysyl oxidase-like 2 (LOXL2) participates in every stage of cancer progression and promotes invasion and metastasis. In this study, we identified a novel alternative splicing isoform of LOXL2, namely LOXL2 Δe13, which lacked exon 13. Deletion of exon 13 caused an open reading frame shift and produced a truncated protein. LOXL2 Δe13 was expressed ubiquitously in cell lines and tissues and was mainly localized to the cytoplasm. Although it showed impaired deamination enzymatic activity compared with full-length LOXL2, LOXL2 Δe13 promoted the cell mobility and invasion of esophageal squamous cell carcinoma (ESCC) cells to greater degrees. In further research on the mechanisms, gene expression profiling and signaling pathway analysis revealed that LOXL2 Δe13 induced the expression of MAPK8 without affecting the FAK, AKT, and ERK signaling pathways. RNAi-mediated knockdown of MAPK8 could block the cell migration promoted by LOXL2De13, but it had little effect on that of full-length LOXL2. Our data suggest that LOXL2 Δe13 modulates the effects of cancer cell migration and invasion through a different mechanism from that of full-length LOXL2 and that it may play a very important role in tumor carcinogenesis and progression.

Medulloblastoma is the most common malignant brain tumor in children. Despite remarkable advances over previous decades, the long-term survival of patients with medulloblastoma remains poor due to the frequent metastatic nature of this malignancy. The aim of the present study was to examine the role of tripartite motif containing 59 (TRIM59) in cell metastasis in medulloblastoma. It was initially demonstrated that TRIM59 expression was significantly increased in clinical medulloblastoma tissues compared with adjacent non-cancerous tissues and differentially expressed in a series of medulloblastoma cell lines. The knockdown of TRIM59 in D283 cells resulted in epithelial-to-mesenchymal transition (EMT), and decreased cell migratory and invasive capacities. By contrast, the overexpression of TRIM59 in Daoy cells was able to inhibit the EMT process and increase migratory and invasive capacities of the cells. Notably, the knockdown of TRIM59 was able to decrease the protein level of matrix metalloproteinase (MMP)-2 without altering the levels of MMP-9, and conversely the overexpression of TRIM59 was able to increase the protein level of MMP-2. Importantly, the downregulation of TRIM59 in D283 cells was able to inhibit the levels of phosphorylated (p)-AKT (Ser473), glycogen synthase kinase 3 β(GSK3β; Ser9) and phosphoinositide 3-kinase (PI3K) p85 (Tyr458) without altering the levels of total protein. The data from the present study suggest that TRIM59 induces epithelial-to-mesenchymal transition and promotes migration and invasion by PI3K/AKT signaling pathway in medulloblastoma. This data may provide novel insight into tumor metastasis and pave the way for the development of therapeutic strategies for the treatment of medulloblastoma in the clinic.

As nitric oxide (NO) plays significant roles in a variety of physiological processes, the capability for real-time and accurate detection of NO in live organisms is in great demand. Traditional assessments of NO rely on indirect colorimetric techniques or electrochemical sensors that often comprise rigid constituent materials and can hardly satisfy sensitivity and spatial resolution simultaneously. Here, we report a flexible and highly sensitive biosensor based on organic electrochemical transistors (OECTs) capable of continuous and wireless detection of NO in biological systems. By modifying the geometry of the active channel and the gate electrodes of OECTs, devices achieve optimum signal amplification of NO. The sensor exhibits a low response limit, a wide linear range, high sensitivity, and excellent selectivity, with a miniaturized active sensing region compared with a conventional electrochemical sensor. The device demonstrates continuous detection of the nanomolar range of NO in cultured cells for hours without significant signal drift. Real-time and wireless measurement of NO is accomplished for 8 d in the articular cavity of New Zealand White rabbits with anterior cruciate ligament (ACL) rupture injuries. The observed high level of NO is associated with the onset of osteoarthritis (OA) at the later stage. The proposed device platform could provide critical information for the early diagnosis of chronic diseases and timely medical intervention to optimize therapeutic efficacy.

No abstract