Ultralow-resistance electrochemical capacitor for integrable line filtering.

Electrochemical capacitors are expected to replace conventional electrolytic capacitors in line filtering for integrated circuits and portable electronics1-8. However, practical implementation of electrochemical capacitors into line-filtering circuits has not yet been achieved owing to the difficulty in synergistic accomplishment of fast responses, high specific capacitance, miniaturization and circuit-compatible integration1,4,5,9-12. Here we propose an electric-field enhancement strategy to promote frequency characteristics and capacitance simultaneously. By downscaling the channel width with femtosecond-laser scribing, a miniaturized narrow-channel in-plane electrochemical capacitor shows drastically reduced ionic resistances within both the electrode material and the electrolyte, leading to an ultralow series resistance of 39 mΩ cm2 at 120 Hz. As a consequence, an ultrahigh areal capacitance of up to 5.2 mF cm-2 is achieved with a phase angle of -80° at 120 Hz, twice as large as one of the highest reported previously4,13,14, and little degradation is observed over 1,000,000 cycles. Scalable integration of this electrochemical capacitor into microcircuitry shows a high integration density of 80 cells cm-2 and on-demand customization of capacitance and voltage. In light of excellent filtering performances and circuit compatibility, this work presents an important step of line-filtering electrochemical capacitors towards practical applications in integrated circuits and flexible electronics.

Microribbons composed of directionally self-assembled nanoflakes as highly stretchable ionic neural electrodes.

Many natural materials possess built-in structural variation, endowing them with superior performance. However, it is challenging to realize programmable structural variation in self-assembled synthetic materials since self-assembly processes usually generate uniform and ordered structures. Here, we report the formation of asymmetric microribbons composed of directionally self-assembled two-dimensional nanoflakes in a polymeric matrix during three-dimensional direct-ink printing. The printed ribbons with embedded structural variations show site-specific variance in their mechanical properties. Remarkably, the ribbons can spontaneously transform into ultrastretchable springs with controllable helical architecture upon stimulation. Such springs also exhibit superior nanoscale transport behavior as nanofluidic ionic conductors under even ultralarge tensile strains (>1,000%). Furthermore, to show possible real-world uses of such materials, we demonstrate in vivo neural recording and stimulation using such springs in a bullfrog animal model. Thus, such springs can be used as neural electrodes compatible with soft and dynamic biological tissues.

Graphene Ionogel Ultra-Fast Filter Supercapacitor with 4 V Workable Window and 150 °C Operable Temperature.

The filtering capacitor plays an essential role in the ever-increasing electronics for current stability in complicated environments. However, because of the low specific capacitance and bulky volume, current filtering devices have difficulty satisfying the harsh temperature environment and small size for supercomputers, electric vehicles, aircraft and so on. Therefore, an ultra-fast electrochemical capacitor is developed on the basis of vertically oriented graphene iongel electrodes (GI-EC), which demonstrates excellent alternate current line-filtering performance with both hot tolerance of up to 150 °C and a wide voltage window of 4 V. Because of the particularly oriented graphene nanosheets induced fast ion transport, this ionic electrochemical capacitor displays a high areal specific energy density of 1784 µF V2  cm-2 with a phase angle of -80.0° (120 Hz) at 150 °C, which is greater than most of the reported electrochemical capacitors. Moreover, it can filter arbitrary waveforms to smooth direct current signals and works well with a wide frequency range from 10 to 104  Hz. The easy integration of GI-ECs in series or parallel can also further deliver desired capacitances or high voltages. The GI-EC with high-rate performance, wide voltage window, and high-temperature adaptability presents a great promise for universally applicable filtering capacitors.

Novel Strategy for the Investigation on Chirality Selection of Single-Walled Carbon Nanotubes with DNA by Electrochemical Characterization.

There is a correlation between specific bases of DNA molecules and the chirality of single-walled carbon nanotubes (SWNTs), which contributes the recognition ability of DNA toward partner species of chiral SWNTs. A novel strategy of electrochemical characterization is reported here for the investigation on chirality selection of (7,6) and (6,5) SWNTs with various DNA sequences, and it is found that both DNA strand length and sequence composition significantly affected the interaction of chiral SWNTs with DNA. Then (7,6) and (6,5) SWNTs were distinguished from each other with DNA sequences chosen by electrochemical methods, which demonstrated an effective and excellent feasibility for the strategy and presented a new insight into DNA-SWNT applications. This strategy can also be applied to more chiral SWNTs and DNA sequence recognition and may serve as a prescreening method for the recognition and separation of single-chirality SWNTs, which would be a new contribution to the further development of DNA-SWNT hybrids.

Cell Membrane Camouflaged Biomimetic Nanoparticles as a Versatile Platform for Brain Diseases Treatment.

Although there are various advancements in biomedical in the past few decades, there are still challenges in the treatment of brain diseases. The main difficulties are the inability to deliver a therapeutic dose of the drug to the brain through the blood-brain barrier (BBB) and the serious side effects of the drug. Thus, it is essential to select biocompatible drug carriers and novel therapeutic tools to better enhance the effect of brain disease treatment. In recent years, biomimetic nanoparticles (BNPs) based on natural cell membranes, which have excellent biocompatibility and low immunogenicity, are widely used in the treatment of brain diseases to enable the drug to successfully cross the BBB and target brain lesions. BNPs can prolong the circulation time in vivo, are more conducive to drug aggregation in brain lesions. Cell membranes (CMs) from cancer cells (CCs), red blood cells (RBCs), white blood cells (WBCs), and so on are used as biomimetic coatings for nanoparticles (NPs) to achieve the ability to target, evade clearance, or stimulate the immune system. This review summarizes the application of different cell sources as BNPs coatings in the treatment of brain diseases and discusses the possibilities and challenges of clinical translation.

Engineering Nanomedicine for Non-Viral RNA-Based Gene Therapy of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common type of malignant tumor of the central nervous system, characterized by aggressiveness, genetic instability, heterogenesis, and unpredictable clinical behavior. Disappointing results from the current clinical therapeutic methods have fueled a search for new therapeutic targets and treatment modalities. GBM is characterized by various genetic alterations, and RNA-based gene therapy has raised particular attention in GBM therapy. Here, we review the recent advances in engineered non-viral nanocarriers for RNA drug delivery to treat GBM. Therapeutic strategies concerning the brain-targeted delivery of various RNA drugs involving siRNA, microRNA, mRNA, ASO, and short-length RNA and the therapeutical mechanisms of these drugs to tackle the challenges of chemo-/radiotherapy resistance, recurrence, and incurable stem cell-like tumor cells of GBM are herein outlined. We also highlight the progress, prospects, and remaining challenges of non-viral nanocarriers-mediated RNA-based gene therapy.

Robustly and Intrinsically Stretchable Ionic Gel-Based Moisture-Enabled Power Generator with High Human Body Conformality.

Direct harvesting of energy from moist air will be a promising route to supply electricity for booming wearable and distributed electronics, with the recent rapid development of the moisture-enabled electricity generator (MEG). However, the easy spatial distortion of rigid MEG materials under severe deformation extremely inconveniences the human body with intense physical activity, seriously hindering the desirable applications. Here, an intrinsically stretchable moisture-enabled electricity generator (s-MEG) is developed based on a well-fabricated stretchable functional ionic gel (SIG) with a flexible double-network structure and reversible cross-linking interactions, demonstrating stable electricity output performance even when stretched up to 150% strain and high human body conformality. This SIG exhibits ultrahigh tensile strain (∼600%), and a 1 cm × 1 cm SIG film-based s-MEG can generate a voltage of ∼0.4 V and a current of ∼5.7 µA when absorbing water from humidity air. Based on the strong adhesion and the excellent interface combination of SIG and rough fabric electrodes induced by the fabrication process, s-MEG is able to realize bending or twisting deformation and shows outstanding electricity output stability with ∼90% performance retention after 5000 cycles of bending tests. By connecting s-MEG units in series or parallel, an integrated device of "moisture-powered wristband" is developed to wear on the wrist of humans and drive a flexible sensor for tracking finger motions. Additionally, a comfortable "moisture-powered sheath" based on s-MEGs is created, which can be worn like clothing on human arms to generate energy while walking and flexing the elbow, which is promising in the field of wearable electronics.

Multistage coupling water-enabled electric generator with customizable energy output.

Constant water circulation between land, ocean and atmosphere contains great and sustainable energy, which has been successfully employed to generate electricity by the burgeoning water-enabled electric generator. However, water in various forms (e.g. liquid, moisture) is inevitably discharged after one-time use in current single-stage water-enabled electric generators, resulting in the huge waste of inherent energy within water circulation. Herein, a multistage coupling water-enabled electric generator is proposed, which utilizes the internal liquid flow and subsequently generated moisture to produce electricity synchronously, achieving a maximum output power density of ~92 mW m-2 (~11 W m-3). Furthermore, a distributary design for internal water in different forms enables the integration of water-flow-enabled and moisture-diffusion-enabled electricity generation layers into mc-WEG by a "flexible building blocks" strategy. Through a three-stage adjustment process encompassing size control, space optimization, and large-scale integration, the multistage coupling water-enabled electric generator realizes the customized electricity output for diverse electronics. Twenty-two units connected in series can deliver ~10 V and ~280 µA, which can directly lighten a table lamp for 30 min without aforehand capacitor charging. In addition, multistage coupling water-enabled electric generators exhibit excellent flexibility and environmental adaptability, providing a way for the development of water-enabled electric generators.

Discovery of (S)-N-(3-isopropylphenyl)-2-(5-phenylthiazol-2-yl)pyrrolidine-1-carboxamide as potent and brain-penetrant TRPV1 antagonist.

Transient receptor potential vanilloid 1 (TRPV1) antagonists can inhibit the transmission of nociceptive signals from the peripheral to the central nervous system (CNS), providing a new strategy for pain relief. In this work, in order to develop potent, CNS-penetrant, and orally available TRPV1 antagonists, three series of novel molecules based on the key pharmacophore structures of classic TRPV1 ligands SB-705498 and MDR-652 were designed and synthesized. Through systematic in vitro and in vivo bioassays, (S)-N-(3-isopropylphenyl)-2-(5-phenylthiazol-2-yl)pyrrolidine-1-carboxamide (7q) was finally identified, which had enhanced TRPV1 antagonistic activity (IC50 (capsaicin) = 2.66 nM), excellent CNS penetration (brain/plasma ratio = 1.66), favorable mode-selectivity, good bioavailability, and no side effects of hyperthermia. Molecular docking and dynamics studies indicated that the high binding affinity of compound 7q to TRPV1 was related to multiple interactions, which resulted in significant conformational changes of TRPV1. Overall, our findings have led to a potent, mode-selective, and CNS-penetrant TRPV1 antagonist as a valuable lead for development of novel TRPV1 antagonists.

Brain-Targeted Codelivery of Bcl-2/Bcl-xl and Mcl-1 Inhibitors by Biomimetic Nanoparticles for Orthotopic Glioblastoma Therapy.

Glioblastoma (GBM) is among the most treatment-resistant solid tumors and often recurrs after resection. One of the mechanisms through which GBM escapes various treatment modalities is the overexpression of anti-apoptotic Bcl-2 family proteins (e.g., Bcl-2, Bcl-xl, and Mcl-1) in tumor cells. Small-molecule inhibitors such as ABT-263 (ABT), which can promote mitochondrial-mediated cell apoptosis by selectively inhibiting the function of Bcl-2 and Bcl-xl, have been proven to be promising anticancer agents in clinical trials. However, the therapeutic prospects of ABT for GBM treatment are hampered by its limited blood-brain barrier (BBB) penetration, dose-dependent thrombocytopenia, and the drug resistance driven by Mcl-1, which is overexpressed in GBM cells and further upregulated upon treatment with ABT. Herein, we reported that the Mcl-1-specific inhibitor A-1210477 (A12) can act synergistically with ABT to induce potent cell apoptosis in U87 MG cells, drug-resistant U251 cells, and patient-derived GBM cancer stem cells. We further designed a biomimetic nanomedicine, based on the apolipoprotein E (ApoE) peptide-decorated red blood cell membrane and pH-sensitive dextran nanoparticles, for the brain-targeted delivery of ABT and A12. The synergistic anti-GBM effect was retained after encapsulation in the nanomedicine. Additionally, the obtained nanomedicine possessed good biocompatibility, exhibited efficient BBB penetration, and could effectively suppress tumor growth and prolong the survival time of mice bearing orthotopic GBM xenografts without inducing detectable adverse effects.

Biomimetic Dp44mT-nanoparticles selectively induce apoptosis in Cu-loaded glioblastoma resulting in potent growth inhibition.

Selective targeting of elevated copper (Cu) in cancer cells by chelators to induce tumor-toxic reactive oxygen species (ROS) may be a promising approach in the treatment of glioblastoma multiforme (GBM). Previously, the Cu chelator di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) attracted much interest due to its potent anti-tumor activity mediated by the formation of a highly redox-active Cu-Dp44mT complex. However, its translational potential was limited by the development of toxicity in murine models of cancer reflecting poor selectivity. Here, we overcame the limitations of Dp44mT by incorporating it in new biomimetic nanoparticles (NPs) optimized for GBM therapy. Biomimetic design elements enhancing selectivity included angiopeptide-2 functionalized red blood cell membrane (Ang-M) camouflaging of the NPs carrier. Co-loading Dp44mT with regadenoson (Reg), that transiently opens the blood-brain-barrier (BBB), yielded biomimetic Ang-MNPs@(Dp44mT/Reg) NPs that actively targeted and traversed the BBB delivering Dp44mT specifically to GBM cells. To further improve selectivity, we innovatively pre-loaded GBM tumors with Cu. Oral dosing of U87MG-Luc tumor bearing mice with diacetyl-bis(4-methylthiosemicarbazonato)-copperII (Cu(II)-ATSM), significantly enhanced Cu-level in GBM tumor. Subsequent treatment of mice bearing Cu-enriched orthotopic U87MG-Luc GBM with Ang-MNPs@(Dp44mT/Reg) substantially prevented orthotopic GBM growth and led to maximal increases in median survival time. These results highlighted the importance of both angiopeptide-2 functionalization and tumor Cu-loading required for greater selective cytotoxicity. Targeting Ang-MNPs@(Dp44mT/Reg) NPs also down-regulated antiapoptotic Bcl-2, but up-regulated pro-apoptotic Bax and cleaved-caspase-3, demonstrating the involvement of the apoptotic pathway in GBM suppression. Notably, Ang-MNPs@(Dp44mT/Reg) showed negligible systemic drug toxicity in mice, further indicating therapeutic potential that could be adapted for other central nervous system disorders.

Stable and Biocompatible Carbon Nanotube Ink Mediated by Silk Protein for Printed Electronics.

Ink-based processes, which enable scalable fabrication of flexible devices based on nanomaterials, are one of the practical approaches for the production of wearable electronics. However, carbon nanotubes (CNTs), which possess great potential for flexible electronics, are facing challenges for use in inks due to their low dispersity in most solvents and suspicious cytotoxicity. Here, a stable and biocompatible CNT ink, which is stabilized by sustainable silk sericin and free from any artificial chemicals, is reported. The ink shows stability up to months, which can be attributed to the formation of sericin-CNT (SSCNT) hybrid through non-covalent interactions. It is demonstrated that the SSCNT ink can be used for fabricating versatile circuits on textile, paper, and plastic films through various techniques. As proofs of concept, electrocardiogram electrodes, breath sensors, and electrochemical sensors for monitoring human health and activity are fabricated, demonstrating the great potential of the SSCNT ink for smart wearables.

Integrated textile sensor patch for real-time and multiplex sweat analysis.

Wearable sweat analysis devices for monitoring of multiple health-related biomarkers with high sensitivity are highly desired for noninvasive and real-time monitoring of human health. Here, we report a flexible sweat analysis patch based on a silk fabric-derived carbon textile for simultaneous detection of six health-related biomarkers. The intrinsically N-doped graphitic structure and the hierarchical woven, porous structure provided the carbon textile good electrical conductivity, rich active sites, and good water wettability for efficient electron transmission and abundant access to reactants, enabling it to serve as an excellent working electrode in electrochemical sensors. On the basis of the above, we fabricated a multiplex sweat analysis patch that is capable of simultaneous detection of glucose, lactate, ascorbic acid, uric acid, Na+, and K+. The integration of selective detectors with signal collection and transmission components in this device has enabled us to realize real-time analysis of sweat.

Hollow core-sheath nanocarbon spheres grown on carbonized silk fabrics for self-supported and nonenzymatic glucose sensing.

Flexible enzymatic glucose sensors have been investigated extensively for health monitoring systems. However, enzymatic glucose sensors have some problems, such as poor stability and complicated immobilization procedures. Rational and controllable design of nanomaterials with a unique structure, high activity and good electrochemical performance for nonenzymatic glucose sensors is desired critically. In this paper, we synthesize cuprous oxide nanoparticles embedded in carbon spheres directly on carbonized silk fabrics (Cu2O NPs@CSs/CSF), which is further used for the fabrication of a flexible and self-supported non-enzymatic glucose sensor. The Cu2O NPs@CSs/CSF shows good electrical conductivity due to the large contact area and the stable connection between the carbonized silk fabrics and carbon spheres. We demonstrate that the as-obtained non-enzymatic glucose sensor possesses high sensitivity and good stability, indicating its potential for practical applications. This strategy diversifies the toolbox available to the field of nonenzymatic glucose sensors and holds promise for flexible electronic devices.

Plasmonic titanium nitride nanoparticles for in vivo photoacoustic tomography imaging and photothermal cancer therapy.

Titanium nitride, an alternative plasmonic material to gold with unique physiochemical properties, has been widely used in microelectronics, biomedical devices and food-contact applications. However, its potential application in the area of biomedicine has not been effectively explored. With the spectral match of their plasmon resonance band and the biological transparency window as well as good biocompatibility, titanium nitride nanoparticles (TiN NPs) are promising photoabsorbing agents for photothermal therapy (PTT) and photoacoustic imaging. Nevertheless, the photothermal performance of TiN NPs has not been investigated until now. Here, we presented the investigation of employing TiN NPs as photoabsorbing agents for in vivo photoacoustic tomography (PAT) imaging-guided photothermal cancer therapy. Our experimental results showed that TiN NPs could strongly absorb the NIR light and provided up to 48% photothermal conversion efficiency. After PEGylation, the resultant nanoparticles demonstrated improved physiological stability and extensive blood retention. Following intravenously administration, they could simultaneously enhance the photoacoustic signals of the tumor region and destroy tumors in the tumor-bearing mouse model by taking advantage of the photothermal effect of the TiN NPs. Our findings highlighted the great potential of plasmonic TiN NPs in detection and treatment of cancer.

Electrochemical sensor based on carbon-supported NiCoO2 nanoparticles for selective detection of ascorbic acid.

An electrochemical sensor for selective detection of ascorbic acid (AA) in the presence of dopamine (DA) and uric acid (UA) was fabricated by modifying the glassy carbon electrode (GCE) with carbon-supported NiCoO2 (NiCoO2/C) nanoparticles. The electrochemical impedance spectroscopic (EIS) studies reveal the little charge transfer resistance for the modified electrode. The electrocatalytic activity of the modified electrode for the oxidation of AA was investigated. The current sensitivity of AA was enhanced to about five times upon modification. The voltammetric response of AA was well resolved from the responses of DA and UA, and the oxidation potential of AA was negatively shifted to -0.20 V. The biosensor tolerated a wide linear concentration range for AA, from 1.0 × 10(-5)M to 2.63 × 10(-3)M (R(2)=0.9929), with a detection limit of 0.5 µM (S/N = 3). Our results demonstrate that the NiCoO2/C nanomaterials has excellent AA sensing capability, including a fast response time, high reproducibility and stability, with great promise in the quantification of AA in real samples. That makes it a unique electrochemical sensor for the detection of AA which is free from the interference of DA, UA and other interferents.

Misconceptions toward methadone maintenance treatment (MMT) and associated factors among new MMT users in Guangzhou, China.

The methadone maintenance treatment (MMT) program is scaling up in China, but little is known about drug users' cognitions of MMT. To investigate the prevalence and associated factors of MMT-related misconceptions, a totally of 300 newly admitted MMT users were interviewed in three MMT clinics in Guangzhou. Four statements were used to assess MMT-related misconceptions. The results showed that the majority of participants misconceived that MMT is intended primarily for detoxification (92.3%), that one could be completely detoxified and quit using methadone after using it for 2-3months (64.2%), that MMT is not a long-term or even lifetime treatment (77.9%); and that one should attempt to reduce its treatment dosage as methadone is harmful to one's health (84.3%); 48.5% of the respondents possessed all four types of misconceptions. Prior experience of methadone use in voluntary drug detoxification centers (OR=1.82 to 2.55, p<0.05) was associated with some misconception items, whilst being introduced by some peer drug users or community members to use MMT (versus not being introduced by anyone; OR=0.38 to 0.50, p<0.05), having taken up HIV voluntary counseling and testing prior to admission (OR=0.52, p<0.05), and a higher HIV-related knowledge level (OR=0.38, p<0.05) were associated with lower likelihoods for possessing some of the misconceptions. The findings suggested that MMT-related misconceptions were very prevalent among newly recruited MMT users in China. Misconceptions are potential factors causing drop-outs. Interventions targeting such misconceptions are greatly warranted.