A flexible and highly sensitive organic electrochemical transistor-based biosensor for continuous and wireless nitric oxide detection.

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.

A multiscale attribution framework for separating the effects of cascade and individual reservoirs on runoff.

Climate change and human activities have great impacts on runoff. With the gradual development of cascade hydropower in the watershed, the reservoirs have increasingly impacted runoff. However, the current study mainly focuses on quantifying the impacts of human activities and climate change on runoff, lacking the exploration of the impacts of cascade reservoirs, and the attribution results are relatively rough. Therefore, this study utilized data-driven models to establish a runoff attribution framework with the basic steps of "interval runoff prediction and scheduling rule extraction", which achieved the spatial scale separation of the impacts of cascade and individual reservoirs on the runoff, and the analysis of the impacts of each factor at multiple time scales. Taking the upper reaches of the Yangtze River mainstem as an example, we verified the applicability and accuracy of the framework, explored the impacts of climate change, human activities (without reservoir scheduling), and reservoir scheduling on runoff during the period 1980-2018. The research found: (1) Compared to the base period 1980-2005, the average multi-year runoff changes at Pingshan Station (during 2013-2018), Yichang Station (during 2006-2012) and Yichang Station (during 2013-2018) were - 2.61 %, -4.33 % and - 0.89 %, respectively, with decreasing, increasing, and flattening trends over time. (2) Reservoir scheduling is the main factor leading to runoff change, showing negative impacts during flood season and positive impacts during non-flood season. (3) Under the control domain of single and cascade reservoirs, the annual scale impacts of climate change, human activities, and reservoir scheduling on runoff accounted for approximately 1:1:8 and 2:2:6, respectively, showing a complex nonlinear relationship between the impacts of single and cascade reservoirs on runoff. This study provides ideas for quantitatively assessing the impacts of cascade reservoirs on runoff and provide a basis for comprehensively assessing the ecosystem and socio-economic impacts of reservoirs on future runoff changes.

[Corrigendum] Hsp90 inhibitor 17­AAG inhibits stem cell­like properties and chemoresistance in osteosarcoma cells via the Hedgehog signaling pathway.

Following the publication of the article, a concerned reader drew to the authors' attention that, in Fig. 1B and C on p. 316, two pairs of the data panels showing the results from invasion and migration assay experiments appeared to be overlapping, such that they would have been derived from the same original sources where they were intended to show the results from different experiments; moreover, on p. 1698, the '17­AAG / MG­63' data panels in Fig. 3B and C were also overlapping, albeit the images were presented at a different scale and in a slightly different orientation. After having examined their original data, the authors have realized that these figures were inadvertently assembled incorrectly. The corrected versions of Figs. 1 and 3, now showing the correct data in Fig. 1C (where the errors made in compiling the figure had occurred) and the correct data for the '17­AAG / MG­63' data panel in Fig. 3C, are shown on the next two pages. These corrections do not grossly affect either the results or the conclusions reported in this work. The authors all agree to the publication of this Corrigendum, and are grateful to the Editor of Oncology Reports for granting them the opportunity to correct the errors that were made during the assembly of these figures. Lastly, the authors apologize to the readership for any inconvenience these errors may have caused. [Oncology Reports 44: 313­324, 2020; DOI: 10.3892/or.2020.7597].

Hsp90 inhibitor 17­AAG inhibits stem cell­like properties and chemoresistance in osteosarcoma cells via the Hedgehog signaling pathway.

Multiple drug resistance is a major obstacle to the successful treatment of osteosarcoma (OS). Recent studies have demonstrated that a subset of cells, referred to as OS stem cells (OSCs), play a crucial role in the acquisition of multiple drug resistance. Therefore, an improved understanding of OS biology and pathogenesis is required to advance the development of targeted therapies aimed at eradicating this particular subset of cells in order to reverse acquired chemoresistance in OS. The aim of the present study was to assess the anti­OSC effects of 17­AAG and determine the underlying molecular mechanism. Heat shock protein 90 expression was found to be increased in sarcosphere cells and was positively associated with cancer stem cell characteristics. In addition, 17­AAG was able to suppress the stem cell­like phenotype of OS cells. Mechanistically, 17­AAG inhibited OSC­like properties and chemoresistance through glycogen synthase kinase (GSK) 3ß inactivation­mediated repression of the Hedgehog signaling pathway. The findings of the present study provided comprehensive evidence for the inhibition of OSC properties and chemoresistance by 17­AAG through repression of the GSK3ß/Hedgehog signaling pathway, suggesting that 17­AAG may be a promising therapeutic agent for targeting OSCs.

A flexible and physically transient electrochemical sensor for real-time wireless nitric oxide monitoring.

Real-time sensing of nitric oxide (NO) in physiological environments is critically important in monitoring neurotransmission, inflammatory responses, cardiovascular systems, etc. Conventional approaches for NO detection relying on indirect colorimetric measurement or built with rigid and permanent materials cannot provide continuous monitoring and/or require additional surgical retrieval of the implants, which comes with increased risks and hospital cost. Herein, we report a flexible, biologically degradable and wirelessly operated electrochemical sensor for real-time NO detection with a low detection limit (3.97 nmol), a wide sensing range (0.01-100 µM), and desirable anti-interference characteristics. The device successfully captures NO evolution in cultured cells and organs, with results comparable to those obtained from the standard Griess assay. Incorporated with a wireless circuit, the sensor platform achieves continuous sensing of NO levels in living mammals for several days. The work may provide essential diagnostic and therapeutic information for health assessment, treatment optimization and postsurgical monitoring.

[PREPARATION OF ACELLULAR DERMAL MATRIX AS A KIND OF SCAFFOLD FOR CARTILAGE TISSUE ENGINEERING AND ITS BIOCOMPATIBILITY].

OBJECTIVE: To study the preparation method of acellular dermal matrix (ADM) for cartilage tissue engineering and analyze its biocompatibility. METHODS: The dermal tissues of the calf back were harvested, and decelluarized with 0.5% SDS, and the ADM was reconstructed with 0.5% trypsin, cross-linked with formaldehyde, and modified with 0.5% chondroitin sulfate which can promote the proliferation of chondrocytes. And the porosity, cytotoxicity, and biocompatibility were determined. Co-cultured 2nd passage chondrocytes and bone marrow stromal cells in a proportion of 3 to 7 were used as seed cells. The cells were seeded on ADM (experimental group) for 48 hours to observe the cell adhesion. The expressions of mRNA and protein of collagen type II were tested by RT-PCR and Western blot methods, respectively. And the expressions were compared between the cells seeded on the scaffold and cultured in monolayer (control group). RESULTS: After modification of 0.5% trypsin, the surface of ADM was smooth and had uniform pores; the porosity (85.4% ± 2.8%) was significantly higher than that without modification (72.8% ± 5.8%) (t = -4.384, P = 0.005). The cell toxicity was grade 1, which accords to the requirements for cartilage tissue engineering scaffolds. With time passing, the number of inflammatory cells decreased after implanted in the back of the rats (P < 0.05). The scanning electron microscope observation showed that lots of seed cells adhered to the scaffold, the cells were well stacked, displaying surface microvilli and secretion. The expressions of mRNA and protein of collagen type II were not significantly different between experimental and control groups (t = 1.265, P = 0.235; t = 0.935, P = 0.372). CONCLUSION: The ADM prepared by acellular treatment, reconstruction, cross-linking, and modification shows perfect characters. And the seed cells maintain chondrogenic phenotype on the scaffold. So it is a proper choice for cartilage tissue engineering.