An Artificial Tactile Neuron Enabling Spiking Representation of Stiffness and Disease Diagnosis.

Mechanical properties of biological systems provide useful information about the biochemical status of cells and tissues. Here, an artificial tactile neuron enabling spiking representation of stiffness and spiking neural network (SNN)-based learning for disease diagnosis is reported. An artificial spiking tactile neuron based on an ovonic threshold switch serving as an artificial soma and a piezoresistive sensor as an artificial mechanoreceptor is developed and shown to encode the elastic stiffness of pressed materials into spike frequency evolution patterns. SNN-based learning of ultrasound elastography images abstracted by spike frequency evolution rate enables the classification of malignancy status of breast tumors with a recognition accuracy up to 95.8%. The stiffness-encoding artificial tactile neuron and learning of spiking-represented stiffness patterns hold a great promise for the identification and classification of tumors for disease diagnosis and robot-assisted surgery with low power consumption, low latency, and yet high accuracy.

Self-Healing Graphene-Templated Platinum-Nickel Oxide Heterostructures for Overall Water Splitting.

Electrocatalysts with dramatically enhanced water splitting efficiency, derived from controlled structures, phase transitions, functional activation, etc., have been developed recently. Herein, we report an in situ observation of graphene-based self-healing, in which this functional activation is induced by a redox reaction. Specifically, graphene on stainless steel (SUS) switches between graphene (C-C) and graphene oxide (C-O) coordination via an electrical redox reaction to activate water splitting. A heterostructure comprising Pt-NiO thin films on single-layer graphene directly grown on a SUS substrate (Pt-NiO/Gr-SUS) was also synthesized by electrodeposition. Pt-NiO/Gr-SUS exhibited water splitting activity with low Pt loading (<1 wt %). The findings provide valuable insight for designing robust electrodes based on reversible redox-induced self-healable graphene to develop more efficient catalysts.

3D motion tracking display enabled by magneto-interactive electroluminescence.

Development of a human-interactive display enabling the simultaneous sensing, visualisation, and memorisation of a magnetic field remains a challenge. Here we report a skin-patchable magneto-interactive electroluminescent display, which is capable of sensing, visualising, and storing magnetic field information, thereby enabling 3D motion tracking. A magnetic field-dependent conductive gate is employed in an alternating current electroluminescent display, which is used to produce non-volatile and rewritable magnetic field-dependent display. By constructing mechanically flexible arrays of magneto-interactive displays, a spin-patchable and pixelated platform is realised. The magnetic field varying along the z-axis enables the 3D motion tracking (monitoring and memorisation) on 2D pixelated display. This 3D motion tracking display is successfully used as a non-destructive surgery-path guiding, wherein a pathway for a surgical robotic arm with a magnetic probe is visualised and recorded on a display patched on the abdominal skin of a rat, thereby helping the robotic arm to find an optimal pathway.

Highly luminescent biocompatible CsPbBr3@SiO2 core-shell nanoprobes for bioimaging and drug delivery.

The encapsulation of lead halide perovskite nanocrystals (PNCs) with an inert protective layer against moisture and the environment is a promising approach to overcome hinderances for their practical use in optoelectronic and biomedical applications. Herein, a facile method for synthesizing highly luminescent and biocompatible CsPbBr3@SiO2 core-shell PNCs with a controlled SiO2 thickness, which are suitable for both cell imaging and drug delivery, is reported. The synthesized CsPbBr3@SiO2 core-shell PNCs exhibit bright green emission at 518 nm upon excitation of 374 nm. Interestingly, a significant increase in the photoluminescence intensity is observed with an increase in the SiO2 shell thickness, which varies with the increasing reaction time. Cytotoxicity results indicate that the CsPbBr3@SiO2 core-shell PNCs are nontoxic, making them suitable for in vitro cell imaging using HeLa cells. Furthermore, doxorubicin physically adsorbed on the surface of CsPbBr3@SiO2 core-shell PNCs is efficiently released in cells when the drug-loaded perovskite nanoprobes are injected in the cells, indicating that these core-shell nanoparticles can be used for drug loading and delivery. The results of this study suggest that the CsPbBr3@SiO2 core-shell PNCs can pave the way for new biomedical applications and processes.

High-Performance Field-Effect Transistor and Logic Gates Based on GaS-MoS2 van der Waals Heterostructure.

This work demonstrates a high-performance and hysteresis-free field-effect transistor based on two-dimensional (2D) semiconductors featuring a van der Waals heterostructure, MoS2 channel, and GaS gate insulator. The transistor exhibits a subthreshold swing of 63 mV/dec, an on/off ratio over 106 within a gate voltage of 0.4 V, and peak mobility of 83 cm2/(V s) at room temperature. The low-frequency noise characteristics were investigated and described by the Hooge mobility fluctuation model. The results suggest that the van der Waals heterostructure of 2D semiconductors can produce a high-performing interface without dangling bonds and defects caused by lattice mismatch. Furthermore, a logic inverter and a NAND gate are demonstrated, with an inverter voltage gain of 14.5, which is higher than previously reported by MoS2-based transistors with oxide dielectrics. Therefore, this transistor based on van der Waals heterostructure exhibits considerable potential in digital logic applications with low-power integrated circuits.

Strategic Design of 2,2'-Bipyridine Derivatives to Modulate Metal-Amyloid-ß Aggregation.

The complexity of Alzheimer's disease (AD) stems from the inter-relation of multiple pathological factors upon initiation and progression of the disease. To identify the involvement of metal-bound amyloid-ß (metal-Aß) aggregation in AD pathology, among the pathogenic features found in the AD-affected brain, small molecules as chemical tools capable of controlling metal-Aß aggregation were developed. Herein, we report a new class of 2,2'-bipyridine (bpy) derivatives (1-4) rationally designed to be chemical modulators toward metal-Aß aggregation over metal-free Aß analogue. The bpy derivatives were constructed through a rational design strategy employing straightforward structural variations onto the backbone of a metal chelator, bpy: (i) incorporation of an Aß interacting moiety; (ii) introduction of a methyl group at different positions. The newly prepared bpy derivatives were observed to bind to metal ions [i.e., Cu(II) and Zn(II)] and interact with metal-Aß over metal-free Aß to varying degrees. Distinguishable from bpy, the bpy derivatives (1-3) were indicated to noticeably modulate the aggregation pathways of Cu(II)-Aß and Zn(II)-Aß over metal-free Aß. Overall, our studies of the bpy derivatives demonstrate that the alteration of metal binding properties as well as the installation of an Aß interacting capability onto a metal chelating framework, devised via the rational structure-based design, were able to achieve evident modulating reactivity against metal-Aß aggregation. Obviating the need for complicated structures, our design approach, presented in this work, could be appropriately utilized for inventing small molecules as chemical tools for studying desired metal-related targets in biological systems.

Gas-driven ultrafast reversible switching of super-hydrophobic adhesion on palladium-coated silicon nanowires.

A gas-driven ultrafast adhesion switching of water droplets on palladium-coated Si nanowire arrays is demonstrated. By regulating the gas-ambient between the atmosphere and H2 , the super-hydrophobic adhesion is repeatedly switched between water-repellent and water-adhesive. The capability of modulating the super-hydrophobic adhesion on a super-hydrophobic surface with a non-contact mode could be applicable to novel functional lab-on-a-chip platforms.

ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets.

Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are key regulators of the apoptotic process. This family comprises proapoptotic and prosurvival proteins, and shifting the balance toward the latter is an established mechanism whereby cancer cells evade apoptosis. The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2-like 1 (BCL-X(L)), which has shown clinical efficacy in some BCL-2-dependent hematological cancers. However, concomitant on-target thrombocytopenia caused by BCL-X(L) inhibition limits the efficacy achievable with this agent. Here we report the re-engineering of navitoclax to create a highly potent, orally bioavailable and BCL-2-selective inhibitor, ABT-199. This compound inhibits the growth of BCL-2-dependent tumors in vivo and spares human platelets. A single dose of ABT-199 in three patients with refractory chronic lymphocytic leukemia resulted in tumor lysis within 24 h. These data indicate that selective pharmacological inhibition of BCL-2 shows promise for the treatment of BCL-2-dependent hematological cancers.

Compression of cross-linked poly(vinylidene fluoride-co-trifluoro ethylene) films for facile ferroelectric polarization.

In this study, we demonstrated a facile route for enhancing the ferroelectric polarization of a chemically cross-linked poly(vinylidene fluoride-co-trifluoro ethylene) (PVDF-TrFE) film. Our method is based on thermally induced cross-linking of a PVDF-TrFE film with a 2,2,4-trimethyl-1,6-hexanediamine (THDA) agent under compression. The remanent polarization (P(r)) of a metal/ferroelectric/metal capacitor containing a cross-linked PVDF-TrFE film increased with pressure up to a certain value, whereas no change in the P(r) value was observed in the absence of THDA. A film cross-linked with 10 wt % THDA with respect to PVDF-TrFE under a pressure of 100 kPa exhibited a P(r) of approximately 5.61 µC/cm(2), which is 1.6 times higher than that in the absence of pressure. The enhanced ferroelectric polarization was attributed to highly ordered 20-nm-thick edge-on crystalline lamellae whose c-axes are aligned parallel to the substrate. The lamellae were effective for ferroelectric switching of the PVDF-TrFE when a cross-linked film was recrystallized under pressure. Furthermore, compression of a PVDF-TrFE film with a topographically prepatterned poly(dimethyl siloxane) mold gave rise to a chemically cross-linked micropattern in which edge-on crystalline lamellae were globally oriented over a very large area.

Ordered nanostructure of PS-b-PEO copolymer by solvent annealing with mixture of benzene/water vapor and its micropattern fabrication.

We investigate the effect of water/benzene co-solvent vapor on the ordering of poly(styrene-b-ethylene oxide) (PS-b-PEO) copolymer thin film on silicon substrate upon solvent annealing. In-plane cylindrical PEO microdomains were observed after exposure of benzene vapor. The addition of water vapor dominantly produced the cylindrical PEO domains aligned perpendicular to the substrate. The best ordering of the cylinders was obtained at the water fraction of approximately 0.05. The degree of ordering decreases while the periodicity of haxagonally packed PEO cylinders increases with the amount of water in the vapor mixture. The average center-to-center distance of hexagonally packed cylindrical PEO microdomains increases with the water fraction from approximately 25 nm to 40 nm. As one way of utilizing the dewetting of thin films inevitable during solvent annealing, PS-b-PEO micropatterns prepared by microcontact printing were treated with co-solvent vapor, which allows us to fabricate the controlled dewet structures guided by the micropatterns. Cylinder-to-sphere phase transition of PEO microdomains also occurred upon solvent annealing in the micropatterned PS-b-PEO films.

N-aryl-benzimidazolones as novel small molecule HSP90 inhibitors.

We describe the development of a novel series of N-aryl-benzimidazolone HSP90 inhibitors (9) targeting the N-terminal ATP-ase site. SAR development was influenced by structure-based design based around X-ray structures of ligand bound HSP90 complexes. Lead compounds exhibited high binding affinities, ATP-ase inhibition and cellular client protein degradation.

Discovery of a potent and selective Bcl-2 inhibitor using SAR by NMR.

The Bcl-2 family of proteins plays a major role in the regulation of apoptosis, or programmed cell death. Overexpression of the anti-apoptotic members of this family (Bcl-2, Bcl-x(L), and Mcl-1) can render cancer cells resistant to chemotherapeutic agents and therefore these proteins are important targets for the development of new anti-cancer agents. Here we describe the discovery of a potent, highly selective, Bcl-2 inhibitor using SAR by NMR and structure-based drug design which could serve as a starting point for the development of a Bcl-2 selective anti-cancer agent. Such an agent would potentially overcome the Bcl-x(L) mediated thrombocytopenia observed with ABT-263.

Discovery of an orally bioavailable small molecule inhibitor of prosurvival B-cell lymphoma 2 proteins.

Overexpression of prosurvival proteins such as Bcl-2 and Bcl-X L has been correlated with tumorigenesis and resistance to chemotherapy, and thus, the development of antagonists of these proteins may provide a novel means for the treatment of cancer. We recently described the discovery of 1 (ABT-737), which binds Bcl-2, Bcl-X L, and Bcl-w with high affinity, shows robust antitumor activity in murine tumor xenograft models, but is not orally bioavailable. Herein, we report that targeted modifications at three key positions of 1 resulted in a 20-fold improvement in the pharmacokinetic/pharmacodynamic relationship (PK/PD) between oral exposure (AUC) and in vitro efficacy in human tumor cell lines (EC 50). The resulting compound, 2 (ABT-263), is orally efficacious in an established xenograft model of human small cell lung cancer, inducing complete tumor regressions in all animals. Compound 2 is currently in multiple phase 1 clinical trials in patients with small cell lung cancer and hematological malignancies.

Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL.

Overexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide.