Improvement of Therapeutic Effect via Inducing Non-Apoptotic Cell Death Using mRNA-Protection Nanocage.

Necroptosis, a cell death mechanism with the characteristics of both apoptosis and necrosis, is proposed as a promising therapeutic approach for cancer therapy. Induction of necroptosis for cancer therapy may be possible through the regulation of the expression of a key factor gene receptor-interacting protein kinase-3 (RIPK3) via in vitro transcription (IVT) mRNA delivery. However, mRNA is susceptible to degradation and has a low delivery efficiency, which highlights the requirement of a proper delivery vehicle for intracellular delivery. Therefore, a new mRNA delivery system based on the nanostructured silica nanoparticles, termed mRNA-protective nanocage (mPN) has been developed. High-efficiency expression of RIPK3 and induction of necroptosis is achieved through delivery of RIPK3 IVT mRNA with mPN in vitro and in vivo models. Importantly, the mPN carrying RIPK3 mRNA distributed locally in tumors upon intravascular injection, and successfully induced necroptosis and immune cell infiltration, a hallmark of necroptosis. the suppression of tumor growth in a murine cancer model, demonstrating the synergistic effect of RIPK3 mRNA- and immune cell-mediated therapy is also observed. These findings suggest the potential for anticancer therapy through necroptosis induction and provide a strategy for the development of mRNA-based nanomedicine.

Highly Luminescent Shell-Less Indium Phosphide Quantum Dots Enabled by Atomistically Tailored Surface States.

Contrary to the prevailing notion that shell structures arise from the intricate chemistry and surface defects of InP quantum dots (QDs), an innovative strategy that remarkably enhances the luminescence efficiency of core-only InP QDs to over 90% is introduced. This paradigm shift is achieved through the concurrent utilization of group 2 and 3 metal-derived ligands, providing an effective remedy for surface defects and facilitating charge recombination. Specifically, a combination of Zn carboxylate and Ga chloride is employed to address the undercoordination issues associated with In and P atoms, leading to the alleviation of in-gap trap states. The intricate interplay and proportional ratio between Ga- and Zn-containing ligands play pivotal roles in attaining record-high luminescence efficiency in core-only InP QDs, as successfully demonstrated across various sizes and color emissions. Moreover, the fabrication of electroluminescent devices relying solely on InP core emission opens a new direction in optoelectronics, demonstrating the potential of the approach not only in optoelectronic applications but also in catalysis or energy conversion by charge transfer.

Colloidal Synthesis of P-Type Zn3As2 Nanocrystals.

Zinc pnictides, particularly Zn3As2, hold significant promise for optoelectronic applications owing to their intrinsic p-type behavior and appropriate bandgaps. However, despite the outstanding properties of colloidal Zn3As2 nanocrystals, research in this area is lacking because of the absence of suitable precursors, occurrence of surface oxidation, and intricacy of the crystal structures. In this study, a novel and facile solution-based synthetic approach is presented for obtaining highly crystalline p-type Zn3As2 nanocrystals with accurate stoichiometry. By carefully controlling the feed ratio and reaction temperature, colloidal Zn3As2 nanocrystals are successfully obtained. Moreover, the mechanism underlying the conversion of As precursors in the initial phases of Zn3As2 synthesis is elucidated. Furthermore, these nanocrystals are employed as active layers in field-effect transistors that exhibit inherent p-type characteristics with native surface ligands. To enhance the charge transport properties, a dual passivation strategy is introduced via phase-transfer ligand exchange, leading to enhanced hole mobilities as high as 0.089 cm2 V-1 s-1. This study not only contributes to the advancement of nanocrystal synthesis, but also opens up new possibilities for previously underexplored p-type nanocrystal research.

Ion trap and release dynamics enables nonintrusive tactile augmentation in monolithic sensory neuron.

An iontronic-based artificial tactile nerve is a promising technology for emulating the tactile recognition and learning of human skin with low power consumption. However, its weak tactile memory and complex integration structure remain challenging. We present an ion trap and release dynamics (iTRD)-driven, neuro-inspired monolithic artificial tactile neuron (NeuroMAT) that can achieve tactile perception and memory consolidation in a single device. Through the tactile-driven release of ions initially trapped within iTRD-iongel, NeuroMAT only generates nonintrusive synaptic memory signals when mechanical stress is applied under voltage stimulation. The induced tactile memory is augmented by auxiliary voltage pulses independent of tactile sensing signals. We integrate NeuroMAT with an anthropomorphic robotic hand system to imitate memory-based human motion; the robust tactile memory of NeuroMAT enables the hand to consistently perform reliable gripping motion.

Physically defined long-term and short-term synapses for the development of reconfigurable analog-type operators capable of performing health care tasks.

Extracting valuable information from the overflowing data is a critical yet challenging task. Dealing with high volumes of biometric data, which are often unstructured, nonstatic, and ambiguous, requires extensive computer resources and data specialists. Emerging neuromorphic computing technologies that mimic the data processing properties of biological neural networks offer a promising solution for handling overflowing data. Here, the development of an electrolyte-gated organic transistor featuring a selective transition from short-term to long-term plasticity of the biological synapse is presented. The memory behaviors of the synaptic device were precisely modulated by restricting ion penetration through an organic channel via photochemical reactions of the cross-linking molecules. Furthermore, the applicability of the memory-controlled synaptic device was verified by constructing a reconfigurable synaptic logic gate for implementing a medical algorithm without further weight-update process. Last, the presented neuromorphic device demonstrated feasibility to handle biometric information with various update periods and perform health care tasks.

Does the Sound of a Singing Bowl Synchronize Meditational Brainwaves in the Listeners?

This study aims to verify if the beating sound of a singing bowl synchronizes and activates brain waves during listening. The singing bowl used in this experiment produce beats at a frequency of 6.68 Hz, while it decays exponentially and lasts for about 50 s. Brain waves were measured for 5 min in the F3 and F4 regions of seventeen participants (eight males and nine females, average age 25.2) who heard the beating singing bowl sounds. The experimental results showed that the increases (up to ~251%) in the spectral magnitudes of the brain waves were dominant at the beat frequency compared to those of any other clinical brain wave frequency bands. The observed synchronized activation of the brain waves at the beating sound frequency supports that the singing bowl sound may effectively facilitate meditation and relaxation, considering that the beat frequency belongs to the theta wave region which increases in the relaxed meditation state.

Ligand-Crosslinking Strategy for Efficient Quantum Dot Light-Emitting Diodes via Thiol-Ene Click Chemistry.

While solution-processable colloidal quantum dots (QDs) offer cost-effective and large-scale manufacturing, they can be susceptible to subsequent solution processes, making continuous processing challenging. To enable complex and integrated device architectures, robust QD films with subsequent patterning are necessary. Here, we report a facile ligand-crosslinking strategy based on thiol-ene click chemistry. Thiol molecules added to QD films react with UV light to form radicals that crosslink with QD ligands containing carbon double bonds, enabling microscale photo-patterning of QD films and enhancing their solvent resistance. This strategy can also be extended to other ligand-capped nanocrystals. It is found that the swelling of QD films during the process of binding with the thiol molecules placed between the ligands contributes to the improvement of photoluminescence and electroluminescence properties. These results suggest that the thiol-ene crosslinking modifies the optoelectronic properties and enables direct optical patterning, expanding the potential applications of QDs.

Battery-Free, Wireless, Cuff-Type, Multimodal Physical Sensor for Continuous Temperature and Strain Monitoring of Nerve.

Peripheral nerve injuries cause various disabilities related to loss of motor and sensory functions. The treatment of these injuries typically requires surgical operations for improving functional recovery of the nerve. However, capabilities for continuous nerve monitoring remain a challenge. Herein, a battery-free, wireless, cuff-type, implantable, multimodal physical sensing platform for continuous in vivo monitoring of temperature and strain from the injured nerve is introduced. The thin, soft temperature, and strain sensors wrapped around the nerve exhibit good sensitivity, excellent stability, high linearity, and minimum hysteresis in relevant ranges. In particular, the strain sensor integrated with circuits for temperature compensation provides reliable, accurate strain monitoring with negligible temperature dependence. The system enables power harvesting and data communication to wireless, multiple implanted devices wrapped around the nerve. Experimental evaluations, verified by numerical simulations, with animal tests, demonstrate the feasibility and stability of the sensor system, which has great potential for continuous in vivo nerve monitoring from an early stage to complete regeneration.

Ultrasensitive Near-Infrared InAs Colloidal Quantum Dot-ZnON Hybrid Phototransistor Based on a Gradated Band Structure.

Amorphous metal oxide semiconductor phototransistors (MOTPs) integrated with colloidal quantum dots (QDs) (QD-MOTPs) are promising infrared photodetectors owing to their high photoconductive gain, low off-current level, and high compatibility with pixel circuits. However, to date, the poor mobility of conventional MOTPs, such as indium gallium zinc oxide (IGZO), and the toxicity of lead (Pb)-based QDs, such as lead sulfide and lead selenide, has limited the commercial applications of QD-MOTPs. Herein, an ultrasensitive QD-MOTP fabricated by integrating a high-mobility zinc oxynitride (ZnON)-based MOTP and lead-free indium arsenide (InAs) QDs is demonstrated. A new gradated bandgap structure is introduced in the InAs QD layer that absorbs infrared light, which prevents carriers from moving backward and effectively reduces electron-hole recombination. Chemical, optical, and structural analyses confirm the movement of the photoexcited carriers in the graded band structure. The novel QD-MOTP exhibits an outstanding performance with a responsivity of 1.15 × 105 A W-1 and detectivity of 5.32 × 1016 Jones at a light power density of 2 µW cm-2 under illumination at 905 nm.

Biocompatible and Oxidation-Resistant Ti3 C2 Tx MXene with Halogen-Free Surface Terminations.

Surface chemistry influences not only physicochemical properties but also safety and applications of MXene nanomaterials. Fluorinated Ti3 C2 Tx MXene, synthesized using conventional HF-based etchants, raises concerns regarding harmful effects on electronics and toxicity to living organisms. In this study, well-delaminated halogen-free Ti3 C2 Tx flakes are synthesized using NaOH-based etching solution. The transversal surface plasmon mode of halogen-free Ti3 C2 Tx MXene (833 nm) confirmed red-shift compared to conventional Ti3 C2 Tx (752 nm), and the halogen-free Ti3 C2 Tx MXene has a different density of state by the high proportion of -O and -OH terminations. The synthesized halogen-free Ti3 C2 Tx exhibits a lower water contact angle (34.5°) and work function (3.6 eV) than those of fluorinated Ti3 C2 Tx (49.8° and 4.14 eV, respectively). The synthesized halogen-free Ti3 C2 Tx exhibits high biocompatibility with the living cells, as evidenced by no noticeable cytotoxicity, even at very high concentrations (2000 µg mL⁻1 ), at which fluorinated Ti3 C2 Tx caused ≈50% reduction in cell viability upon its oxidation. Additionally, the oxidation stability of halogen-free Ti3 C2 Tx is enhanced unexpectedly, which cumulatively provides a good rationale for pursuing the halogen-free routes for synthesizing MXene materials for their uses in biomedical and therapeutic applications.

Isotropic conductive paste for bioresorbable electronics.

Bioresorbable implantable medical devices can be employed in versatile clinical scenarios that burden patients with complications and surgical removal of conventional devices. However, a shortage of suitable electricalinterconnection materials limits the development of bioresorbable electronic systems. Therefore, this study highlights a highly conductive, naturally resorbable paste exhibiting enhanced electrical conductivity and mechanical stability that can solve the existing problems of bioresorbable interconnections. Multifaceted experiments on electrical and physical properties were used to optimize the composition of pastes containing beeswax, submicron tungstenparticles, and glycofurol. These pastes embody isotropic conductive paths for three-dimensional interconnects and function as antennas, sensors, and contact pads for bioresorbable electronic devices. The degradation behavior in aqueous solutions was used to assess its stability and ability to retain electrical conductance (∼7 â€‹kS/m) and structural form over the requisite dissolution period. In vitro and in vivo biocompatibility tests clarified the safety of the paste as an implantable material.

Graphene barristors for de novo optoelectronics.

Graphene-based vertical Schottky-barrier transistors (SBTs), renowned as graphene barristors, have emerged as a feasible candidate to fundamentally expand the horizon of conventional transistor technology. The remote tunability of graphene's electronic properties could endorse multi-stimuli responsive functionalities for a broad range of electronic and optoelectronic applications of transistors, with the capability of incorporating nanochannel architecture with dramatically reduced footprints from the vertical integrations. In this Feature Article, we provide a comprehensive overview of the progress made in the field of SBTs over the last 10 years, starting from the operating principles, materials evolution, and processing developments. Depending on the types of stimuli such as electrical, optical, and mechanical stresses, various fields of applications from conventional digital logic circuits to sensory technologies are highlighted. Finally, more advanced applications toward beyond-Moore electronics are discussed, featuring recent advancements in neuromorphic devices based on SBTs.

Humanlike spontaneous motion coordination of robotic fingers through spatial multi-input spike signal multiplexing.

With advances in robotic technology, the complexity of control of robot has been increasing owing to fundamental signal bottlenecks and limited expressible logic state of the von Neumann architecture. Here, we demonstrate coordinated movement by a fully parallel-processable synaptic array with reduced control complexity. The synaptic array was fabricated by connecting eight ion-gel-based synaptic transistors to an ion gel dielectric. Parallel signal processing and multi-actuation control could be achieved by modulating the ionic movement. Through the integration of the synaptic array and a robotic hand, coordinated movement of the fingers was achieved with reduced control complexity by exploiting the advantages of parallel multiplexing and analog logic. The proposed synaptic control system provides considerable scope for the advancement of robotic control systems.

The human ribosome-associated complex suppresses prion formation in yeast.

Many human diseases are associated with the misfolding of amyloidogenic proteins. Understanding the mechanisms cells employ to ensure the integrity of the proteome is therefore a crucial step in the development of potential therapeutic interventions. Yeast cells possess numerous prion-forming proteins capable of adopting amyloid conformations, possibly as an epigenetic mechanism to cope with changing environmental conditions. The ribosome-associated complex (RAC), which docks near the ribosomal polypeptide exit tunnel and recruits the Hsp70 Ssb to chaperone nascent chains, can moderate the acquisition of these amyloid conformations in yeast. Here we examine the ability of the human RAC chaperone proteins Mpp11 and Hsp70L1 to function in place of their yeast RAC orthologues Zuo1 and Ssz1 in yeast lacking endogenous RAC and investigate the extent to which the human orthologues can perform RAC chaperone activities in yeast. We found that the Mpp11/Hsp70L1 complex can partially correct the growth defect seen in RAC-deficient yeast cells, although yeast/human hetero species complexes were variable in this ability. The proportion of cells in which the Sup35 protein undergoes spontaneous conversion to a [PSI+ ] prion conformation, which is increased in the absence of RAC, was reduced by the presence of the human RAC complex. However, the toxicity in yeast from expression of a pathogenically expanded polyQ protein was unable to be countered by the human RAC chaperones. This yeast system can serve as a facile model for studying the extent to which the human RAC chaperones contribute to combating cotranslational misfolding of other mammalian disease-associated proteins.

Multiplexed Complementary Signal Transmission for a Self-Regulating Artificial Nervous System.

Neuromorphic engineering has emerged as a promising research field that can enable efficient and sophisticated signal transmission by mimicking the biological nervous system. This paper presents an artificial nervous system capable of facile self-regulation via multiplexed complementary signals. Based on the tunable nature of the Schottky barrier of a complementary signal integration circuit, a pair of complementary signals is successfully integrated to realize efficient signal transmission. As a proof of concept, a feedback-based blood glucose level control system is constructed by incorporating a glucose/insulin sensor, a complementary signal integration circuit, an artificial synapse, and an artificial neuron circuit. Certain amounts of glucose and insulin in the initial state are detected by each sensor and reflected as positive and negative amplitudes of the multiplexed presynaptic pulses, respectively. Subsequently, the pulses are converted to postsynaptic current, which triggered the injection of glucose or insulin in a way that confined the glucose level to a desirable range. The proposed artificial nervous system demonstrates the notable potential of practical advances in complementary control engineering.

3D microengineered vascularized tumor spheroids for drug delivery and efficacy testing.

Tumor angiogenesis is regarded as a promising target for limiting cancer progression because tumor-associated vasculature supplies blood and provides a path for metastasis. Thus, in vitro recapitulation of vascularized tumors is critical to understand the pathology of cancer and identify the mechanisms by which tumor cells proliferate, metastasize, and respond to drugs. In this study, we microengineered a vascularized tumor spheroid (VTS) model to reproduce the pathological features of solid tumors. We first generated tumor-EC hybrid spheroids with self-assembled intratumoral vessels, which enhanced the uniformity of the spheroids and peritumoral angiogenic capacity compared to spheroids composed only with cancer cells. Notably, the hybrid spheroids also exhibited expression profiles associated with aggressive behavior. The blood vessels sprouting around the hybrid spheroids on the VTS chip displayed the distinctive characteristics of leaky tumor vessels. With the VTS chip showing a progressive tumor phenotype, we validated the suppressive effects of axitinib on tumor growth and angiogenesis, which depended on exposure dose and time, highlighting the significance of tumor vascularization to predict the efficacy of anticancer drugs. Ultimately, we effectively induced both lymphangiogenesis and angiogenesis around the tumor spheroid by promoting interstitial flow. Thus, our VTS model is a valuable platform with which to investigate the interactions between tumor microenvironments and explore therapeutic strategies in cancer. STATEMENT OF SIGNIFICANCE: We conducted an integrative study within a vascularized tumor spheroid (VTS) model. We first generated tumor-EC hybrid spheroids with self-assembled intratumoral vessels, which enhanced the uniformity of the spheroids and peritumoral angiogenic capacity compared to spheroids composed only with cancer cells. Through RNA sequencing, we elucidated that the tumor-EC hybrid spheroids exhibited expression profiles associated with aggressive behavior such as cancer progression, invasion and metastasis. The blood vessels sprouting around the hybrid spheroids on the VTS chip displayed the distinctive characteristics of leaky tumor vessels. We further validated the suppressive effects of axitinib on tumor growth and angiogenesis, depending on exposure dose and time. Ultimately, we effectively induced both lymphangiogenesis and angiogenesis around the tumor spheroid by promoting interstitial flow.

Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins through In Vivo Delivery Based on Absorptive Silica Nanoconstruct.

Key to the widespread and secure application of genome editing tools is the safe and effective delivery of multiple components of ribonucleoproteins (RNPs) into single cells, which remains a biological barrier to their clinical application. To overcome this issue, a robust RNP delivery platform based on a biocompatible sponge-like silica nanoconstruct (SN) for storing and directly delivering therapeutic RNPs, including Cas9 nuclease RNP (Cas9-RNP) and base editor RNP (BE-RNP) is designed. Compared with commercialized material such as lipid-based methods, up to 50-fold gene deletion and 10-fold base substitution efficiency is obtained with a low off-target efficiency by targeting various cells and genes. In particular, gene correction is successfully induced by SN-based delivery through intravenous injection in an in vivo solid-tumor model and through subretinal injection in mouse eye. Moreover, because of its low toxicity and high biodegradability, SN has negligible effect on cellular function of organs. As the engineered SN can overcome practical challenges associated with therapeutic RNP application, it is strongly expected this platform to be a modular RNPs delivery system, facilitating in vivo gene deletion and editing.

A Cost-Effective Reusable Tissue Mimicking Phantom for High Intensity Focused Ultrasonic Liver Surgery.

A polyacrylamide polysaccharide hydrogel (PASG) containing a nonionic surfactant of the polyoxyethylene nonylphenyl ethers series (NP14) has been adapted to the fabrication of a reusable cost-effective ultrasonic tissue-mimicking phantom for real-time visualization of the thermal lesions by high intensity focused ultrasound (HIFU) irradiation. The constructed NP14 (40% in w/v) PASG is optically transparent at room temperatures, and it turns out to be opaque white as heated over the clouding points of about 55 °C and returns to its original transparent state after cooling. The acoustic property of the proposed phantom is similar to those of human liver tissues, which includes the acoustic impedance of 1.68 Mrayls, the speed of sound of 1595 ± 5 m/s, the attenuation coefficient of 0.52 ± 0.05 dB cm-1 (at 1 MHz), the backscatter coefficient of 0.21 ± 0.09 × 10-3 sr-1 cm-1 (at 1 MHz), and the nonlinear parameter B/A of 6.4 ± 0.2. The NP14-PASG was tested to assess the characteristic information (sizes, shapes, and locations) of the thermal lesions visualized when exposed to typical HIFU fields (1.1 MHz, focal pressure up to 20.1 MPa, focal intensity 4075 W/cm2). The proposed NP14-PASG is expected to replace the existing costly BSA-PASG used for more effective testing of the performance of therapeutic ultrasonic devices based on thermal mechanisms.

A biomimetic ocular prosthesis system: emulating autonomic pupil and corneal reflections.

The human light modulation response allows humans to perceive objects clearly by receiving the appropriate amount of light from the environment. This paper proposes a biomimetic ocular prosthesis system that mimics the human light modulation response capable of pupil and corneal reflections. First, photoinduced synaptic properties of the quantum dot embedded photonic synapse and its biosimilar signal transmission is confirmed. Subsequently, the pupillary light reflex is emulated by incorporating the quantum dot embedded photonic synapse, electrochromic device, and CMOS components. Moreover, a solenoid-based eyelid is connected to the pupillary light reflex system to emulate the corneal reflex. The proposed ocular prosthesis system represents a platform for biomimetic prosthesis that can accommodate an appropriate amount of stimulus by self-regulating the intensity of external stimuli.

Neurorobotic approaches to emulate human motor control with the integration of artificial synapse.

The advancement of electronic devices has enabled researchers to successfully emulate human synapses, thereby promoting the development of the research field of artificial synapse integrated soft robots. This paper proposes an artificial reciprocal inhibition system that can successfully emulate the human motor control mechanism through the integration of artificial synapses. The proposed system is composed of artificial synapses, load transistors, voltage/current amplifiers, and a soft actuator to demonstrate the muscle movement. The speed, range, and direction of the soft actuator movement can be precisely controlled via the preset input voltages with different amplitudes, numbers, and signs (positive or negative). The artificial reciprocal inhibition system can impart lifelike motion to soft robots and is a promising tool to enable the successful integration of soft robots or prostheses in a living body.