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Stretchable electrodes have a crucial impact on the development of flexible electronic systems. Most conventionally blended nanocomposite electrodes are incapable of achieving high stretchability, breathability, or durability. In this work, a highly conductive, breathable, and stretchable epidermal electrode (SEE) is demonstrated by designing a hierarchically interactive nano-network that is composed of elastic polymer nano-fibers and multi-level silver nano-wires (AgNWs). The elastic polymer nano-fibers act as a continuous scaffold, and multi-level AgNWs embedded in the nano-fibers form branched conductive pathways. This structure enables high conductivity of the SEE at 4800 S cm-1 (at a significantly low AgNW content of 1.59 vt%), with high stretchability and excellent durability. For example, the SEE remained conductive even at a high strain of 500%, and it also maintained its initial resistance even after 30 000 cycles of strain at 50% or being washed with water for 100 000 cycles. The SEE was prepared by a facile in situ nonequilibrium fabrication process, and can easily be produced into an elastic circuit on a large scale, which provides a foundation for integrated and multifunctional electronic skins. The SEE possesses superior mechanical conformability and permeability of gas and liquid, and therefore, it was successfully applied in measuring electrocardiogram signals and thermal therapy, and exhibited highly robust and comfortable performances even while being washed with water or undergoing complex deformations.

Finely tuned mitogen-activated protein kinase (MAPK) signaling is important for cancer cell survival. Perturbations that push cells out of the MAPK fitness zone result in cell death. Previously, in a screen of the North China Pharmaceutical Group Corporation’s pure compound library of microbial origin, we identified elaiophylin as an autophagy inhibitor. Here, we demonstrated a new role for elaiophylin in inducing excessive endoplasmic reticulum (ER) stress, ER-derived cytoplasmic vacuolization, and consequent paraptosis by hyperactivating the MAPK pathway in multiple cancer cells. Genome-wide CRISPR/Cas9 knockout library screening identified SHP2, an upstream intermediary of the MAPK pathway, as a critical target in elaiophylin-induced paraptosis. The cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) assay further confirmed the direct binding between the SHP2 and elaiophylin. Inhibition of the SHP2/SOS1/MAPK pathway through SHP2 knockdown or pharmacological inhibitors distinctly attenuated elaiophylin-induced paraptosis and autophagy inhibition. Interestingly, elaiophylin markedly increased the already-elevated MAPK levels and preferentially killed drug-resistant cells with enhanced basal MAPK levels. Elaiophylin overcame drug resistance by triggering paraptosis in multiple tumor-bearing mouse models resistant to platinum, taxane, or PARPi, suggesting that elaiophylin might offer a reasonable therapeutic strategy for refractory ovarian cancer.

A method for the simultaneous determination of aspartic acid (Asp), glutamic acid (Glu), glycine (Gly), taurine (Tau) and gamma-aminobutyric acid (GABA) in animal blood and brain by two-dimensional liquid chromatography (2D-LC) combined with ultraviolet detection was established for the first time. First, the amino acid neurotransmitters (AANTs) were labeled on the corresponding fluorescent derivatives with 4-fluoro-7-nitrobenzofurazan (NBD-F), enriched on the extraction column and automatically transferred to the analytical column to achieve on-line extraction and complete separation of the target components. This method exhibited good selectivity, and the correlation coefficients for the analyte calibration curves of were > 0.99. The intra- and inter-day precisions were ≤ 16.03, and the accuracies were in the range of 70.59–116.20%. The system realizes the rapid detection and stability quantification of the five AANTs, which proves that the alternative dilution method is feasible. The results show that the system has high loading capacity, excellent resolution, and good peak shape and is not affected by other endogenous substances. Moreover, the developed method has been successfully applied to the analysis of biological samples in the blood and whole brain of rats and pigs. The content of AANTs in the hippocampus and cortex of rats was higher than that in those of pigs. This method is expected to provide applicability for the determination of AANTs in pharmacological, pharmaceutical and clinical research in nervous science.

Rationale Gelsemium elegans (G. elegans) is highly toxic to humans and rats but has insecticidal and growth-promoting effects on pigs and goats. However, the mechanisms behind the toxicity differences of G. elegans are unclear. Gelsenicine, isolated from G. elegans, has been reported to be a toxic alkaloid. Methods In this study, the in vitro metabolism of gelsenicine was investigated and compared for the first time using human (HLM), pig (PLM), goat (GLM) and rat (RLM) liver microsomes and high-performance liquid chromatography/mass spectrometry (HPLC/MS). Results In total, eight metabolites (M1-M8) were identified by using high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS). Two main metabolic pathways were found in the liver microsomes of the four species: demethylation at the methoxy group on the indole nitrogen (M1) and oxidation at different positions (M2-M8). M8 was identified only in the GLM. The degradation ratio of gelsenicine and the relative percentage of metabolites produced during metabolism were determined by high-performance liquid chromatography/tandem mass spectrometry (HPLC/QqQ-MS/MS). The degradation ratio of gelsenicine in liver microsomes decreased in the following order: PLM ≥ GLM > HLM > RLM. The production of M1 decreased in the order of GLM > PLM > RLM > HLM, the production of M2 was similar among the four species, and the production of M3 was higher in the HLM than in the liver microsomes of the other three species. Conclusions Based on these results, demethylation was speculated to be the main gelsenicine detoxification pathway, providing vital information to better understand the metabolism and toxicity differences of G. elegans among different species.

Ethnopharmacological relevance Herbal medicine contains hundreds of natural products, and studying their absorption, metabolism, distribution, and elimination presents great challenges. Gelsemium elegans (G. elegans) is a flowering plants in the Loganiaceae family. The plant is known to be toxic and has been used for many years as a traditional Chinese herbal medicine for the treatment of rheumatoid arthritis, neuropathic pain, spasticity, skin ulcers and cancer. It was also used as veterinary drugs for deworming, promoting animal growth, and pesticides. At present, studies on the metabolism of G. elegans have primarily focused on only a few single available reference ingredients, such as koumine, gelsemine and gelsedine. Material and methods The goal of this work is to elucidate the overall metabolism of whole G. elegans powder in goats using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS). Results Analyses of plasma, urine and fecal samples identified or tentatively characterized a total of 44 absorbed natural products and 27 related produced metabolites. Gelsedine-type, sarpagine-type and gelsemine-type alkaloids were the compounds with the highest metabolite formation. In the present study, most natural products identified in G. elegans were metabolized through glucuronidation and oxidation. Hydrogenation, dehydrogenation and demethylation also occurred. Conclusion To our knowledge, this is the first report of the metabolite profiling of the G. elegans crude extract in goats, which is of great significance for a safer and more rational application of this herbal medicine.

In this work, a novel solid-liquid interfacing triboelectric field based electroluminescence (SL-TEL) was proposed. When a droplet impacting on the SL-TEL device surface, specific textured green SL-TEL emit on the two cross-overlapped areas. As a coupling effect of solid-liquid interfacing triboelectrification and electroluminescence, the SL-TEL is essentially a type of electroluminescence excited by changing triboelectric field of droplet impact or wave scour. It relies on converting mechanical energy of liquid to visual light energy utilizing an intermediate triboelectric field without any electric power consumption. The SL-TEL device simply consist of three thin flexible layers, which is greatly simplifying the electroluminescent device structure and showing strong advantages of simple structure such as easy to integration and excellent stability. Experiments show that sequential liquid motions of droplet impinging on solid surface excite a corresponding dynamic series of electroluminescence patterns. The features of the electroluminescence also reveal the characteristics of liquid and the solid surface, such as contour edge of liquid spreading, capillary convergence of liquid at the apex (advancing and receding), and so on, which is capable of both sensing liquid leakage and displaying the dynamic information of droplets impacting motions.

Wearable and portable electronics for water environment application are of paramount significance, however restricted by its power source component. It remains a great challenge to simultaneously achieve ultra stretchability and high electric output performance for most energy harvesters in water. Herein, we report a high-performance stretchable liquid-solid contact electrification-based nanogenerator (S-LSNG) that enables water wave energy harvesting and subtle motion monitoring in water by an in-situ charged nanocomposite membrane. Notably, the effectively charged PTFE nanoparticles (100 nm) in this novel membrane can highly promote the output of S-LSNG. For the first time, the excellent stretchability (tensile strain, 200%), high output performance (open-circuit voltage of 120 V and short-circuit current of 18 μA) and ultra-thin device structure (300 μm) were achieved simultaneously for a liquid-solid contact electrification-based nanogenerator. Besides, the output performance of S-LSNG barely changed even after 100000 submerging-emerging cycles. In addition, the application of motion monitoring for human body in water was also demonstrated, such as single finger motion sensing and complex motion sensing of multiple-fingers. Because of the excellent stretchability, output performance and durability, the S-LSNG would be extensively applied to a sustainable energy supplier for the stretchable and wearable electronics in water.

Harvesting water wave energy presents a significantly practical route to energy supply for self-powered wireless sensing networks. Here we report a networked integrated triboelectric nanogenerator (NI-TENG) as a highly adaptive means of harvesting energy from interfacing interactions with various types of water waves. Having an arrayed networking structure, the NI-TENG can accommodate diverse water wave motions and generate stable electric output regardless of how random the water wave is. Nanoscaled surface morphology consisting of dense nanowire arrays is the key for obtaining high electric output. A NI-TENG having an area of 100 × 70 mm2 can produce a stable short-circuit current of 13.5 μA and corresponding electric power of 1.03 mW at a water wave height of 12 cm. This merit promises practical applications of the NI-TENG in real circumstances, where water waves are highly variable and unpredictable. After energy storage, the generated electric energy can drive wireless sensing by autonomously transmi...

Triboelectric nanogenerator (TENG) is a newly emerged technology for harvesting mechanical energy, which has the promise for various practical applications. Here, we introduce a new principle of TENG in which induced current is generated between two coplanar electrodes because of different dielectric fillers of distinct permittivities. The manipulation of permittivity of dielectric materials for TENG is first reported, demonstrating a novel route in designing high-performance TENGs. When repeatedly contacting with an object, a TENG having lateral dimensions of 21 mm × 10 mm can produce an open-circuit voltage of 58.5 V and a short-circuit current of 44.7 μA. The instantaneous output power density can reach up to 708 μW. Besides, the new design incorporates all electrodes into a single plane, greatly simplifying the structure, promoting robustness, and providing a viable solution for device miniaturization.

A mathematic model of the electric servo system was founded in this paper and several groups of data collection and data processing were executed to check up the model veracity. This paper described the data processing steps and analyzed the contrast of test and simulation results. This model is effectual to describe the performance of this kind of servo in respect that the results are mainly consentaneous.

We investigate the nonvolatile holographic storage characteristics of near-stoichiometric LiNbO3:Fe:Mn crystals with different Li2O contents. Experimental results indicate that the optimal value of Li2O content is about 49.6 mol%. Nonvolatile sensitivity S′ considerably improved to 0.15 cm/J because of the use of near-stoichiometric LiNbO3:Fe:Mn with 49.6 mol% Li2O.

We report a flexible and area-scalable energy-harvesting technique for converting kinetic wave energy. Triboelectrification as a result of direct interaction between a dynamic wave and a large-area nanostructured solid surface produces an induced current among an array of electrodes. An integration method ensures that the induced current between any pair of electrodes can be constructively added up, which enables significant enhancement in output power and realizes area-scalable integration of electrode arrays. Internal and external factors that affect the electric output are comprehensively discussed. The produced electricity not only drives small electronics but also achieves effective impressed current cathodic protection. This type of thin-film-based device is a potentially practical solution of on-site sustained power supply at either coastal or off-shore sites wherever a dynamic wave is available. Potential applications include corrosion protection, pollution degradation, water desalination, and wireless sensing for marine surveillance.

This study was purposed to establish a retrovirus-mediated murine model with MLL-AF9 leukemia, so as to provide a basis for further investigation of the pathogenesis and therapeutic strategy of MLL associated leukemia. Murine (CD45.2) primary hematopoietic precursor positively selected for expression of the progenitor marker c-Kit by means of MACS were transduced with a retrovirus carrying MLL-AF9 fusion gene. After cultured in vitro, the transduced cells were injected intravenously through the tail vein into the lethally irradiated mice (CD45.1). PCR, flow cytometry and morphological observation were employed to evaluate the murine leukemia model system. The results showed that MLL-AF9 fusion gene was expressed in the infected cells, and the cells had a dramatically enhanced potential to generate myeloid colonies with primitive and immature morphology. Flow cytometric analysis revealed that the immortalized cells highly expressed myeloid lineage surface markers Gr-1 and Mac-1. Moreover, the expression levels of Hoxa9 and Meis1 mRNA were significantly higher in the MLL-AF9 cells than that in control. The mice transplanted with MLL-AF9 cells displayed typical signs of leukemia within 6-12 weeks. Extensive infiltration leukemic cells was observed in the Wright-Giemsa stained peripheral blood smear and bone marrow, and also in the histology of liver and spleen. Flow cytometric analysis of the bone marrow and spleen cells demonstrated that the CD45.2 populations expressed highly myeloid markers Gr-1 and Mac-1. The leukemic mice died within 12 weeks. It is concluded that the retrovirus-mediated murine model with MLL-AF9 leukemia is successfully established, which can be applied in the subsequent researches.

Xingnaojing (XNJ) is an effective clinical drug used to treat acute stroke. Compared with injection administration, its nasal administration has better brain targeting. Therefore, through nasal administration, XNJ microemulsion could help solve the drug load of compound components of different polarities contained in large-dose and high-concentration traditional Chinese medicines, and reduce irritation to nasal mucosa In this study, the modified volume correction method and the improved rat in situ nasal perfusion model were adopted to compare the nasal absorption of geniposide contained in different XNJ preparations. The results showed that the constant absorption rate of geniposide (GE) in XNJ-D was (2.95 +/- 0.25) x 10(-3) min(-1), whereas the constant absorption rate of GE in XNJ-M was (2.16 +/- 0.21) x 10(-3) min(-1). This indicated that the rat nasal absorption of GE in different XNJ preparations complied with the first-order process and could be considered as passive absorption. GE in XNJ-D was absorbed faster than that in XNJ-M, which provided basis for the development of nasal preparations of XNJ.

A biocide-free antifouling method on wetted insulating surfaces, enabled by the oscillation of electric potential generated by an integrated triboelectric wave harvester (I-TEWH) is reported. Distinct from previous studies that reported antifouling on conducting surfaces by applying an additional power source, this method achieves antifouling on insulating surfaces with zero-power consumption. The electric potential in the vicinity of a protected surface oscillates in large amplitude as a result of periodically accumulated free electrons on an underlying electrode. The dynamic flow of the free electrons is driven by the I-TEWH that converts ambient wave energy by solid–liquid interface triboelectrification. As a consequence, the oscillating electric potential disturbs the inherent charge distribution on microbes due to electrostatic induction, preventing their initial adhesion onto the protected surface and thus prohibiting the subsequent formation of macroorganisms. Significant anti-adhesion efficiencies of as high as 99.3%, 99.1%, and 96.0% are achieved for negative-gram bacteria (Escherichia coli), positive-gram bacteria (Staphylococcus aureus), and diatoms (bacillariophyceze), respectively, on a smooth surface. The antifouling efficiency on a roughened surface with micro/nanostructures can be further enhanced by another 75%. This approach can be potentially utilized in coastal constructions, offshore facilities, and vessels that are either moving or stationary in port.

It has been suggested to use LiNbO3:Fe, Mn crystal for solving the problem of information volatility during the read-out process with all-optical facilities, but the minute order response time is far from the requirements for the real-time information processing. We present the nonvolatile holographic storage properties of LiNbO3:Hf, Fe, Mn. The response time is shortened to 5.0 s, and the sensitivity S' is enhanced to 0.22 cm/J in this triply doped crystal. The experimental results show that the HfO2 doping threshold is 5.0 mol.%. Thus it seems that we have found a useful tetravalent dopant for LiNbO3:Fe, Mn that can obviously improve the nonvolatile holographic recording sensitivity.

We propose a method for reconstructing a complex field from a series of its near-field diffraction patterns. This method is based on the paraxial Fresnel diffraction equation without making further approximations. Numerical simulations are presented showing that a complex field can even be reconstructed with moderate qualities from its two near-field diffraction patterns and almost exact reconstructions can be obtained when three or more diffraction patterns are used. We also show by numerical simulation that the correct diffraction distances can be recovered in case only coarsely measured values are available. This method may be applied to phase imaging of weak-absorption objects.