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.

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.

Commensurate Assembly of C60 on Black Phosphorus for Mixed-Dimensional van der Waals Transistors.

2D crystals can serve as templates for the realization of new van der Waals (vdW) heterostructures via controlled assembly of low-dimensional functional components. Among available 2D crystals, black phosphorus (BP) is unique due to its puckered atomic surface topography, which may lead to strong epitaxial phenomena through guided vdW assembly. Here, it is demonstrated that a BP template can induce highly oriented assembly of C60 molecular crystals. Transmission electron microscopy and theoretical analysis of the C60 /BP vdW heterostructure clearly confirm that the BP template results in oriented C60 assembly with higher-order commensurism. Lateral and vertical devices with C60 /BP junctions are fabricated via a lithography-free clean process, which allows one to investigate the ideal electrical properties of pristine C60 /BP junctions. Effective tuning of the C60 /BP junction barrier from 0.2 to 0.5 eV and maximum on-current density higher than 104  mA cm-2 are achieved with graphite/C60 /BP vertical vdW transistors. Due to the formation of high-quality C60 film and the semitransparent graphite top-electrode, the vertical transistors show high photoresponsivities up to ≈100 A W-1 as well as a fast response time under visible light illumination.

Percolation-Limited Dual Charge Transport in Vertical p-n Heterojunction Schottky Barrier Transistors.

Solution-processed, high-speed, and polarity-selective organic vertical Schottky barrier (SB) transistors and logic gates are presented. The organic layer, which is a bulk heterojunction (BHJ) composed of PBDB-T and PC71BM, is employed to simultaneously realize vertical electron and hole transports through the separate p-channel and n-channel. The gate-modulated graphene work functions enable broad modulation of SB heights at both the graphene-PBDB-T and graphene-PC71BM heterointerfaces. Interestingly, the fine-tuned energy-level alignment enables an exclusive injection of holes or electrons unlike conventional BHJ-based ambipolar transistors, leading to a clear transition between p-channel and n-channel single-carrier-like transistor characteristics. Furthermore, the improved percolation-limited dual charge transport in vertical architecture results in high charge carrier density and high-speed on-off switching characteristics, providing a high on-off current ratio exceeding 105 and an operation speed of 100 kHz. Solution-based on-substrate fabrications of low-power complementary logic gates such as NOT, NOR, and NAND are also successfully performed.

Barrier to autointegration factor 1, procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3, and splicing factor 3b subunit 4 as early-stage cancer decision markers and drivers of hepatocellular carcinoma.

An accurate tool enabling early diagnosis of hepatocellular carcinoma (HCC) is clinically important, given that early detection of HCC markedly improves survival. We aimed to investigate the molecular markers underlying early progression of HCC that can be detected in precancerous lesions. We designed a gene selection strategy to identify potential driver genes by integrative analysis of transcriptome and clinicopathological data of human multistage HCC tissues, including precancerous lesions, low- and high-grade dysplastic nodules. The gene selection process was guided by detecting the selected molecules in both HCC and precancerous lesion. Using various computational approaches, we selected 10 gene elements as a candidate and, through immunohistochemical staining, showed that barrier to autointegration factor 1 (BANF1), procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3), and splicing factor 3b subunit 4 (SF3B4) are HCC decision markers with superior capability to diagnose early-stage HCC in a large cohort of HCC patients, as compared to the currently popular trio of HCC diagnostic markers: glypican 3, glutamine synthetase, and heat-shock protein 70. Targeted inactivation of BANF1, PLOD3, and SF3B4 inhibits in vitro and in vivo liver tumorigenesis by selectively modulating epithelial-mesenchymal transition and cell-cycle proteins. Treatment of nanoparticles containing small-interfering RNAs of the three genes suppressed liver tumor incidence as well as tumor growth rates in a spontaneous mouse HCC model. We also demonstrated that SF3B4 overexpression triggers SF3b complex to splice tumor suppressor KLF4 transcript to nonfunctional skipped exon transcripts. This contributes to malignant transformation and growth of hepatocyte through transcriptional inactivation of p27Kip1 and simultaneously activation of Slug genes. CONCLUSION: The findings suggest molecular markers of BANF1, PLOD3, and SF3B4 indicating early-stage HCC in precancerous lesion, and also suggest drivers for understanding the development of hepatocarcinogenesis. (Hepatology 2018;67:1360-1377).

MAP4-regulated dynein-dependent trafficking of BTN3A1 controls the TBK1-IRF3 signaling axis.

The innate immune system detects viral nucleic acids and induces type I interferon (IFN) responses. The RNA- and DNA-sensing pathways converge on the protein kinase TANK-binding kinase 1 (TBK1) and the transcription factor IFN-regulatory factor 3 (IRF3). Activation of the IFN signaling pathway is known to trigger the redistribution of key signaling molecules to punctate perinuclear structures, but the mediators of this spatiotemporal regulation have yet to be defined. Here we identify butyrophilin 3A1 (BTN3A1) as a positive regulator of nucleic acid-mediated type I IFN signaling. Depletion of BTN3A1 inhibits the cytoplasmic nucleic acid- or virus-triggered activation of IFN-ß production. In the resting state, BTN3A1 is constitutively associated with TBK1. Stimulation with nucleic acids induces the redistribution of the BTN3A1-TBK1 complex to the perinuclear region, where BTN3A1 mediates the interaction between TBK1 and IRF3, leading to the phosphorylation of IRF3. Furthermore, we show that microtubule-associated protein 4 (MAP4) controls the dynein-dependent transport of BTN3A1 in response to nucleic acid stimulation, thereby identifying MAP4 as an upstream regulator of BTN3A1. Thus, the depletion of either MAP4 or BTN3A1 impairs cytosolic DNA- or RNA-mediated type I IFN responses. Our findings demonstrate a critical role for MAP4 and BTN3A1 in the spatiotemporal regulation of TBK1, a central player in the intracellular nucleic acid-sensing pathways involved in antiviral signaling.

Synthesis of Fluorescent Au Nanocrystals-Silica Hybrid Nanocomposite (FLASH) with Enhanced Optical Features for Bioimaging and Photodynamic Activity.

Fluorescent Au nanocrystals (AuNCs)-silica hybrid nanocomposite (FLASH) was synthesized by co-condensation of surface-modified AuNCs. Present FLASH nanocomposite exhibited four times the enhanced photoluminescence and photocatalytic activity compared to single nanocrystals. On the basis of these enhanced optical features, we successfully demonstrated in vitro fluorescence bioimaging of introduced FLASH to human cervical cancer cell line (HeLa). Beyond the confirmation of photocatalytic activity from the photodegradation of methylene blue as a model compound, the regional selective photodynamic therapy of HeLa cells under UV irradiation was also presented. Taken together the enhanced optical features and further potential in theranostic applications, we expect that the present FLASH can be a promising tool for nanobiotechnology field.

Bone Mineral Density and Osteoporotic Vertebral Fractures in Traditional, Unassisted, Free-Diving Women (Haenyeos).

BACKGROUND: Water pressure and muscle contraction may influence bone mineral density (BMD) in a positive way. However, divers experience weightlessness, which has a negative effect on BMD. The present study investigated BMD difference in normal controls and woman free-divers with vertebral fracture and with no fracture. METHODS: Between January 2010 and December 2014, traditional woman divers (known as Haenyeo in Korean), and non-diving women were investigated. The study population was divided into osteoporotic vertebral fracture and non-fracture groups. The BMD of the lumbar spine and femoral neck was measured. The radiological parameters for global spinal sagittal balance were measured. RESULTS: Thirty free-diving women and thirty-three non-diving women were enrolled in this study. The mean age of the divers was 72.1 ± 4.7 years and that of the controls was 72.7 ± 4.0 years (P = 0.61). There was no statistical difference in BMD between the divers and controls. In divers, cervical lordosis and pelvic tilt were significantly increased in the fracture subgroup compared to the non-fracture subgroup (P = 0.028 and P = 0.008, respectively). Sagittal vertical axis was statistically significantly correlated with cervical lordosis (Spearman's rho R = 0.41, P = 0.03), and pelvic tilt (Spearman's rho R = 0.46, P = 0.01) in divers. CONCLUSION: BMD did not differ significantly between divers and controls during their postmenopausal period. When osteoporotic spinal fractures develop, compensation mechanisms, such as increased cervical lordosis and pelvic tilt, was more evident in traditional woman divers. This may be due to the superior back muscle strength and spinal mobility of this group of women.

Large-Area CVD-Grown Sub-2 V ReS2 Transistors and Logic Gates.

We demonstrated the fabrication of large-area ReS2 transistors and logic gates composed of a chemical vapor deposition (CVD)-grown multilayer ReS2 semiconductor channel and graphene electrodes. Single-layer graphene was used as the source/drain and coplanar gate electrodes. An ion gel with an ultrahigh capacitance effectively gated the ReS2 channel at a low voltage, below 2 V, through a coplanar gate. The contact resistance of the ion gel-gated ReS2 transistors with graphene electrodes decreased dramatically compared with the SiO2-devices prepared with Cr electrodes. The resulting transistors exhibited good device performances, including a maximum electron mobility of 0.9 cm2/(V s) and an on/off current ratio exceeding 104. NMOS logic devices, such as NOT, NAND, and NOR gates, were assembled using the resulting transistors as a proof of concept demonstration of the applicability of the devices to complex logic circuits. The large-area synthesis of ReS2 semiconductors and graphene electrodes and their applications in logic devices open up new opportunities for realizing future flexible electronics based on 2D nanomaterials.

One-pot synthesis of multifunctional Au@graphene oxide nanocolloid core@shell nanoparticles for Raman bioimaging, photothermal, and photodynamic therapy.

The paper reports a facile one-pot synthesis of core@shell nanoparticles (NPs) composed of Au core and graphene oxide nanocolloid (GON) shell. Unique properties of Au NPs and GON can be incorporated into a single nanohybrid structure to provide desirable functions for theranosis such as localized surface plasmon resonance, Raman scattering, amphiphilic surface, and photothermal conversion. Synthesis of Au@GON NPs is achieved by simple one-pot reaction in aqueous phase utilizing GON as a reducing and stabilizing agent without any additional reducing agent. The zinc phthalocyanine, a photosensitizer, loaded Au@GON NPs show excellent multifunctional properties for combinational treatment of photothermal and photodynamic therapy in addition to Raman bioimaging with low cytotoxicity.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.