Unlocking the Potential of Porous Bi2Te3-Based Thermoelectrics Using Precise Interface Engineering through Atomic Layer Deposition.

Porous thermoelectric materials offer exciting prospects for improving the thermoelectric performance by significantly reducing the thermal conductivity. Nevertheless, porous structures are affected by issues, including restricted enhancements in performance attributed to decreased electronic conductivity and degraded mechanical strength. This study introduces an innovative strategy for overcoming these challenges using porous Bi0.4Sb1.6Te3 (BST) by combining porous structuring and interface engineering via atomic layer deposition (ALD). Porous BST powder was produced by selectively dissolving KCl in a milled mixture of BST and KCl; the interfaces were engineered by coating ZnO films through ALD. This novel architecture remarkably reduced the thermal conductivity owing to the presence of several nanopores and ZnO/BST heterointerfaces, promoting efficient phonon scattering. Additionally, the ZnO coating mitigated the high resistivity associated with the porous structure, resulting in an improved power factor. Consequently, the ZnO-coated porous BST demonstrated a remarkable enhancement in thermoelectric efficiency, with a maximum zT of approximately 1.53 in the temperature range of 333-353 K, and a zT of 1.44 at 298 K. Furthermore, this approach plays a significant role in enhancing the mechanical strength, effectively mitigating a critical limitation of porous structures. These findings open new avenues for the development of advanced porous thermoelectric materials and highlight their potential for precise interface engineering through the ALD.

Homotypic SCOTIN assemblies form ER-endosome membrane contacts and regulate endosome dynamics.

The ER regulates the spatiotemporal organization of endolysosomal systems by membrane contact. In addition to tethering via heterotypic interactions on both organelles, we present a novel ER-endosome tethering mechanism mediated by homotypic interactions. The single-pass transmembrane protein SCOTIN is detected in the membrane of the ER and endosomes. In SCOTIN-knockout (KO) cells, the ER-late endosome contacts are reduced, and the perinuclear positioning of endosomes is disturbed. The cytosolic proline-rich domain (PRD) of SCOTIN forms homotypic assemblies in vitro and is necessary for ER-endosome membrane tethering in cells. A region of 28 amino acids spanning 150-177 within the SCOTIN PRD is essential to elicit membrane tethering and endosomal dynamics, as verified by reconstitution in SCOTIN-KO cells. The assembly of SCOTIN (PRD) is sufficient to mediate membrane tethering, as purified SCOTIN (PRD), but not SCOTIN (PRDΔ150-177), brings two different liposomes closer in vitro. Using organelle-specific targeting of a chimeric PRD domain shows that only the presence on both organellar membranes enables the ER-endosome membrane contact, indicating that the assembly of SCOTIN on heterologous membranes mediates organelle tethering.

Complexation of drug and hapten-conjugated aptamer with universal hapten antibody for pancreatic cancer treatment.

Owing to a lack of reliable markers and therapeutic targets, pancreatic ductal adenocarcinoma (PDAC) remains the most lethal malignant tumor despite numerous therapeutic advances. In this study, we utilized cell-SELEX to isolate a DNA aptamer recognizing the natural conformation of the target on the cell surface. PAp7T8, an aptamer optimized by size and chemical modification, exhibited specific targeting to pancreatic cancer cells and orthotopic xenograft pancreatic tumors. To confer therapeutic functions to the aptamer, we adopted a drug-conjugated oligobody (DOligobody) strategy. Monomethyl auristatin E was used as a cytotoxic drug, digoxigenin acted as a hapten, and the humanized anti-digoxigenin antibody served as a universal carrier of the aptamer. The resulting PAp7T8-DOligobody showed extended in vivo half-life and markedly inhibited tumor growth in an orthotopic pancreatic cancer xenograft model without causing significant toxicity. Therefore, PAp7T8-DOligobody represents a promising novel therapeutic delivery platform for PDAC.

Selective Dissolution-Derived Nanoporous Design of Impurity-Free Bi2 Te3 Alloys with High Thermoelectric Performance.

Thermoelectric technology, which has been receiving attention as a sustainable energy source, has limited applications because of its relatively low conversion efficiency. To broaden their application scope, thermoelectric materials require a high dimensionless figure of merit (ZT). Porous structuring of a thermoelectric material is a promising approach to enhance ZT by reducing its thermal conductivity. However, nanopores do not form in thermoelectric materials in a straightforward manner; impurities are also likely to be present in thermoelectric materials. Here, a simple but effective way to synthesize impurity-free nanoporous Bi0.4 Sb1.6 Te3 via the use of nanoporous raw powder, which is scalably formed by the selective dissolution of KCl after collision between Bi0.4 Sb1.6 Te3 and KCl powders, is proposed. This approach creates abundant nanopores, which effectively scatter phonons, thereby reducing the lattice thermal conductivity by 33% from 0.55 to 0.37 W m-1 K-1 . Benefitting from the optimized porous structure, porous Bi0.4 Sb1.6 Te3 achieves a high ZT of 1.41 in the temperature range of 333-373 K, and an excellent average ZT of 1.34 over a wide temperature range of 298-473 K. This study provides a facile and scalable method for developing high thermoelectric performance Bi2 Te3 -based alloys that can be further applied to other thermoelectric materials.

Epitaxial Growth of ß-Ga2O3 Thin Films on Si with YSZ Buffer Layer.

We report the epitaxial growth of (2̅01)-oriented ß-Ga2O3 thin films on a (001) Si substrate using the pulsed laser deposition technique employing epitaxial yttria-stabilized zirconia (YSZ) buffer layers. Epitaxial ß-Ga2O3 thin films possess a biaxial compressive strain on YSZ single-crystal substrates while they exhibit a biaxial tensile strain on YSZ-buffered Si substrates. Post-annealing improves the crystalline quality of ß-Ga2O3 thin films. High-resolution X-ray diffraction analyses reveal that the epitaxial (2̅01) ß-Ga2O3 thin films on Si have eight in-plane domain variants to accommodate the large difference in the crystal structure between monoclinic ß-Ga2O3 and cubic YSZ. The results provide a pathway to integrate epitaxial ß-Ga2O3 thin films on a Si gold standard substrate, which will expand the application scope beyond high-power electronics.

Phenylboronic acid-based core-shell drug delivery platform clasping 1,3-dicarbonyl compounds by a coordinate interaction.

Along with the successful commercialization of chemotherapeutics, such as doxorubicin and paclitaxel, numerous natural compounds have been investigated for clinical applications. Recently, curcumin (CUR), a natural compound with various therapeutic effects, has attracted attention for cancer immunotherapy. Most chemotherapeutics, however, have poor water solubility due to their hydrophobicity, which makes them less suited to biomedical applications; CUR is no exception because of its low bioavailability and extremely high hydrophobicity. In the present study, we developed an easy but effective strategy using the interaction between the 1,3-dicarbonyl groups of drugs and phenylboronic acid (PBA) to solubilize hydrophobic drugs. First, we verified the coordinate interaction between 1,3-dicarbonyl and PBA using 3,5-heptanedione as a model compound, followed by CUR as a model drug. A PBA-grafted hydrophilic polymer was used to form a nanoconstruct by coordination bonding with CUR, which then made direct administration of the nanoparticles possible. The nanoconstruct exhibited remarkable loading capability, uniform size, colloidal stability, and pH-responsive drug release, attributed to the formation of core-shell nanoconstructs by coordinate interaction. The therapeutic nanoconstructs successfully showed both chemotherapeutic and anti-PD-L1 anticancer effects in cellular and animal models. Furthermore, we demonstrated the applicability of this technique to other 1,3-dicarbonyl compounds. Overall, our findings suggest a facile, but expandable strategy by applying the coordinate interaction between 1,3-dicarbonyl and PBA, which enables high drug loading and stimuli-responsive drug release.

Quadruple ultrasound, photoacoustic, optical coherence, and fluorescence fusion imaging with a transparent ultrasound transducer.

Ultrasound and optical imagers are used widely in a variety of biological and medical applications. In particular, multimodal implementations combining light and sound have been actively investigated to improve imaging quality. However, the integration of optical sensors with opaque ultrasound transducers suffers from low signal-to-noise ratios, high complexity, and bulky form factors, significantly limiting its applications. Here, we demonstrate a quadruple fusion imaging system using a spherically focused transparent ultrasound transducer that enables seamless integration of ultrasound imaging with photoacoustic imaging, optical coherence tomography, and fluorescence imaging. As a first application, we comprehensively monitored multiparametric responses to chemical and suture injuries in rats' eyes in vivo, such as corneal neovascularization, structural changes, cataracts, and inflammation. As a second application, we successfully performed multimodal imaging of tumors in vivo, visualizing melanomas without using labels and visualizing 4T1 mammary carcinomas using PEGylated gold nanorods. We strongly believe that the seamlessly integrated multimodal system can be used not only in ophthalmology and oncology but also in other healthcare applications with broad impact and interest.

Phenylboronic-acid-based nanocomplex as a feasible delivery platform of immune checkpoint inhibitor for potent cancer immunotherapy.

Inspired by our previous study, we report a simple yet effective platform for therapeutic antibody delivery. A polymeric phenylboronic acid (pPBA)-antibody nanocomplex was simply formulated by mixing pPBA and antibody, derived by the formation of a pH-responsive phenylboronic ester between the PBA group on pPBA and diol on the inherent glycosylation site of the antibody. We focused on the basic prerequisites for a successful delivery, protection from degradation during the circulation, and release at the target lesion. To evaluate the antibody delivery system, anti-PD-L1, one of the most common antibody therapeutics in immuno-oncology, and mouse colon cancer model with an MC-38 cell line were used. Several in-vitro assays reveal the outstanding protective effect of the nanocomplexes as well as the pH-responsive release of antibodies. Moreover, the anti-PD-L1 nanocomplex exhibited an enhanced circulation as well as a better accumulation in tumor lesions after administration in vivo, which led to a significant antitumor effect in comparison to that of a free antibody. Our nanocomplex platform is a promising antibody delivery system for application in conventional antibody-mediated therapies.

The psychology of luxury consumption.

This review synthesizes the latest advances in the psychology behind consumption of luxury objects and experiences to which people typically feel strongly attached. We discuss novel drivers, forms, and consequences of luxury consumption from recent research. We propose that the psychology of luxury consumption is governed by a set of tensions between what luxury means to the self and the external forces that define luxury consumption. These tensions shape consumer behavior, from the level of desire for luxury products and services, to the types of signals viewed as luxury and acquired and displayed as such, and to post-consumption consequences of consuming luxury. We discuss how this tension-based framework offers future opportunities for the study of the drivers, forms, and consequences of luxury consumption.

Polymeric Nanoparticles Controlled by On-Chip Self-Assembly Enhance Cancer Treatment Effectiveness.

Nanoparticle (NP)-based drug delivery systems or nanomedicines have broadened the horizon of translational research for decades. Conventional bulk mixing synthesis methods have impeded successful clinical translations of nanomedicines due to the limited ability of the controlled, scalable production with high uniformity. Herein, an on-chip preparation of self-assembled, drug-encapsulated polymeric NPs is presented for their improved uniformity and homogeneity that results in enhanced anti-cancer effect in vitro and in vivo. The NPs are formulated through rapid convective mixing of two aqueous solutions of a hydrophilic polymer and an anti-cancer drug, doxorubicin (DOX), in the swirling microvortex reactor (SMR). Compared to conventional bulk-mixed NPs (BMPs), the microvortex-synthesized NPs (MVPs) exhibit narrower size distributions and better size tunability. It is found that the improved uniformity and homogeneity of the MVPs not only enhance cellular uptake and anti-cancer effect with pH-responsive drug release in vitro, but also result in an improved tumor regression and decreased side effects at off-targeted organs in vivo. The findings demonstrate that uniformly designed NPs with more homogeneous properties can induce a significant enhancement of an anti-cancer effect in vivo. The results show the potential of a high-speed on-chip synthesis as a scalable manufacturing platform for reliable clinical translations of nanomedicines.

In vivo self-degradable graphene nanomedicine operated by DNAzyme and photo-switch for controlled anticancer therapy.

Although graphene oxide (GO) possesses many beneficial functionalities for biomedical usage as itself, modification of GO surface with several polymers or protein is inevitable for in vivo applications; however, such modification limits the degradability of GO due to the steric hindrance. In that context, designing of a surface modified GO carrier that is going to be degraded after its biological function (i.e., drug delivery) is highly desired, especially at complex in vivo level. Herein, we design an unprecedented "catalytic GO nanomedicine" by applying the catalytic DNA, achieving self-degradation of GO in systemic level in the body after the therapy following surface modification. Once the catalytic GO nanomedicines are taken up by mucin1 (MUC1) aptamer-facilitated endocytosis, a photo-switch triggers the release of doxorubicin from the DNA. The single stranded G-quadruplex sequence on the surface of GO forms a quartet structure and becomes DNAzyme by binding with hemin on the GO surface, exhibiting peroxidase effect. Due to the high H2O2 concentration in cancer cells, the catalytic GO nanomedicine generates sufficient amount of strong oxidant, hypochlorous acid (HOCl), inducing GO degradation into small fragments for potential clearance. We demonstrate the potential of our catalytic GO nanomedicine for both therapy and degradation at cellular and complex in vivo environment.

A Pt(iv)-mediated polymer architecture for facile and stimuli-responsive intracellular gene silencing with chemotherapy.

Conventional chemotherapy has been impeded by the inherent characteristics of cancer including fast mutagenesis and drug resistance; thus a combination therapy consisting of multiple therapeutic strategies has attracted much attention. However, the loading processes of multiple therapeutic molecules affect each other; thus the development of a nanocarrier that enables independent loading of the cargo molecules has been demanded. Herein, we report an ingeniously designed Pt(iv)-mediated polymeric architecture (Pt-PA) for combinatorial gene and chemotherapy to address the issue, prepared by crosslinking a cationic polymer (polyethylenimine, PEI) with a Pt(iv) prodrug. Therapeutic siRNA (anti-BCL2) was simply loaded by electrostatic interaction to form a stable nanocomplex. In the cellular study, the simultaneous release of both the active Pt(ii) drug and siRNA was monitored under the intracellular reducing environment, driven by dissociation of the polymer architecture due to an inherent characteristic of the Pt(iv) crosslinker. Therefore, an enhanced gene silencing effect and an anticancer effect were observed. Furthermore, in the animal study, an improved therapeutic effect of the nanocomplex was observed, which can be explained by tumor targeting via the EPR effect, and enhanced drug and siRNA release at the intracellular environment simultaneously. Taken together, the overall results from in vitro and in vivo studies strongly suggest the therapeutic potential of our precisely designed Pt(iv)-mediated polymer architecture.

Functional-DNA-Driven Dynamic Nanoconstructs for Biomolecule Capture and Drug Delivery.

The discovery of sequence-specific hybridization has allowed the development of DNA nanotechnology, which is divided into two categories: 1) structural DNA nanotechnology, which utilizes DNA as a biopolymer; and 2) dynamic DNA nanotechnology, which focuses on the catalytic reactions or displacement of DNA structures. Recently, numerous attempts have been made to combine DNA nanotechnologies with functional DNAs such as aptamers, DNAzymes, amplified DNA, polymer-conjugated DNA, and DNA loaded on functional nanoparticles for various applications; thus, the new interdisciplinary research field of "functional DNA nanotechnology" is initiated. In particular, a fine-tuned nanostructure composed of functional DNAs has shown immense potential as a programmable nanomachine by controlling DNA dynamics triggered by specific environments. Moreover, the programmability and predictability of functional DNA have enabled the use of DNA nanostructures as nanomedicines for various biomedical applications, such as cargo delivery and molecular drugs via stimuli-mediated dynamic structural changes of functional DNAs. Here, the concepts and recent case studies of functional DNA nanotechnology and nanostructures in nanomedicine are reviewed, and future prospects of functional DNA for nanomedicine are indicated.

Programmed Nanoparticle-Loaded Nanoparticles for Deep-Penetrating 3D Cancer Therapy.

Tumors are 3D, composed of cellular agglomerations and blood vessels. Therapies involving nanoparticles utilize specific accumulations due to the leaky vascular structures. However, systemically injected nanoparticles are mostly uptaken by cells located on the surfaces of cancer tissues, lacking deep penetration into the core cancer regions. Herein, an unprecedented strategy, described as injecting "nanoparticle-loaded nanoparticles" to address the long-lasting problem is reported for effective surface-to-core drug delivery in entire 3D tumors. The "nanoparticle-loaded nanoparticle" is a silica nanoparticle (≈150 nm) with well-developed, interconnected channels (diameter of ≈30 nm), in which small gold nanoparticles (AuNPs) (≈15 nm) with programmable DNA are located. The nanoparticle (AuNPs)-loaded nanoparticles (silica): (1) can accumulate in tumors through leaky vascular structures by protecting the inner therapeutic AuNPs during blood circulation, and then (2) allow diffusion of the AuNPs for penetration into the entire surface-to-core tumor tissues, and finally (3) release a drug triggered by cancer-characteristic pH gradients. The hierarchical "nanoparticle-loaded nanoparticle" can be a rational design for cancer therapies because the outer large nanoparticles are effective in blood circulation and in protection of the therapeutic nanoparticles inside, allowing the loaded small nanoparticles to penetrate deeply into 3D tumors with anticancer drugs.

Low-Power Low-Noise Amplifier Using Attenuation-Adaptive Noise Control for Ultrasound Imaging Systems.

This paper presents a low-noise amplifier (LNA) using attenuation-adaptive noise control (AANC) for ultrasound imaging systems. The proposed AANC reduces unnecessary power consumption of the LNA, which arises from useless noise floor, by controlling the noise floor of the LNA with respect to the attenuation of the ultrasound. In addition, a current feedback amplifier with a source-degenerated input stage reduces variations of the bandwidth and the closed loop gain, which are caused by the AANC. The proposed LNA was fabricated using a 0.18-[Formula: see text] CMOS process. The input-referred voltage noise density of the fabricated LNA is 1.01 [Formula: see text] at the frequency of 5 MHz. The second harmonic distortion is -53.5 dB when the input signal frequency is 5 MHz and the output voltage swing is 2 [Formula: see text]. The power consumption of the LNA using the AANC is 16.2 mW at the supply voltage of 1.8 V, which is reduced to 64% of that without using the AANC. The noise efficiency factor (NEF) of the proposed LNA is 3.69, to our knowledge, which is the lowest NEF compared with previous LNAs for ultrasound imaging.

A Readout IC Using Two-Step Fastest Signal Identification for Compact Data Acquisition of PET Systems.

A readout integrated circuit (ROIC) using two-step fastest signal identification (FSI) is proposed to reduce the number of input channels of a data acquisition (DAQ) block with a high-channel reduction ratio. The two-step FSI enables the proposed ROIC to filter out useless input signals that arise from scattering and electrical noise without using complex and bulky circuits. In addition, an asynchronous fastest signal identifier and a self-trimmed comparator are proposed to identify the fastest signal without using a high-frequency clock and to reduce misidentification, respectively. The channel reduction ratio of the proposed ROIC is 16:1 and can be extended to 16 × N:1 using N ROICs. To verify the performance of the two-step FSI, the proposed ROIC was implemented into a gamma photon detector module using a Geiger-mode avalanche photodiode with a lutetium-yttrium oxyorthosilicate array. The measured minimum detectable time is 1 ns. The difference of the measured energy and timing resolution between with and without the two-step FSI are 0.8% and 0.2 ns, respectively, which are negligibly small. These measurement results show that the proposed ROIC using the two-step FSI reduces the number of input channels of the DAQ block without sacrificing the performance of the positron emission tomography (PET) systems.

Additional effects of transcranial direct-current stimulation and trigger-point injection for treatment of myofascial pain syndrome: a pilot study with randomized, single-blinded trial.

BACKGROUND: Chronic pain caused by myofascial pain syndrome (MPS) results in generalized and debilitating conditions. Trigger-point injection (TPI) is the mainstay of MPS management to reduce acute and localized pain. Other adjunctive intervention to modulate the central pain pathway might be helpful if they are combined with TPI. Transcranial direct-current stimulation (tDCS), which is a form of neurostimulation, has been reported to be safe and effective in treating chronic pain by changing cortical excitability. OBJECTIVES: To determine whether there is an additional effect of tDCS and TPI to reduce pain in patients with MPS. PATIENTS: Twenty-one patients with newly diagnosed MPS of shoulder girdle muscles. INTERVENTIONS: Patients were randomly assigned into 1 of 3 groups (2 active and 1 sham stimulation groups) and received TPI. Immediately after TPI, tDCS (2 mA for 20 minutes on 5 consecutive days) was administered. For the active stimulation groups, tDCS was applied over 2 different locations (primary motor cortex and dorsolateral prefrontal cortex [DLPFC]). OUTCOME MEASURES: Visual analogue scale (VAS), Pain Threshold Test, and short form of the McGill Pain Questionnaire were measured before and immediately after stimulation for 5 consecutive days. RESULTS: The mean VAS values were decreased in all three groups after 5 days. There was a significant change between before and after stimulation only in the DLPFC group. The significant change in the mean VAS value was shown from after the second stimulation session (p=0.031), and this remained significant until the last stimulation session (p=0.027). CONCLUSION: This study suggests that tDCS over DLPFC may have additional effects with TPI to reduce pain in patients with MPS. tDCS over DLPFC can be used to reverse central pain pathway by modulating cortical plasticity.

Strain-assisted, low-temperature synthesis of high-performance thermoelectric materials.

Utilizing internal energy artificially implemented by cold-pressing in the specimens, we demonstrate a way to synthesize high-quality bulk thermoelectric materials at otherwise too low a temperature to approach to an equilibrium state. This low-temperature synthesis technique will provide a new opportunity to integrate high-performance thermoelectric materials into various electronic devices for a built-in energy source, as well as to develop low-cost fabrication methods.