A Cold-Sensing Receptor Encoded by a Glutamate Receptor Gene.

In search of the molecular identities of cold-sensing receptors, we carried out an unbiased genetic screen for cold-sensing mutants in C. elegans and isolated a mutant allele of glr-3 gene that encodes a kainate-type glutamate receptor. While glutamate receptors are best known to transmit chemical synaptic signals in the CNS, we show that GLR-3 senses cold in the peripheral sensory neuron ASER to trigger cold-avoidance behavior. GLR-3 transmits cold signals via G protein signaling independently of its glutamate-gated channel function, suggesting GLR-3 as a metabotropic cold receptor. The vertebrate GLR-3 homolog GluK2 from zebrafish, mouse, and human can all function as a cold receptor in heterologous systems. Mouse DRG sensory neurons express GluK2, and GluK2 knockdown in these neurons suppresses their sensitivity to cold but not cool temperatures. Our study identifies an evolutionarily conserved cold receptor, revealing that a central chemical receptor unexpectedly functions as a thermal receptor in the periphery.

Concurrent self-assembly of RGB microLEDs for next-generation displays.

MicroLED displays have been in the spotlight as the next-generation displays owing to their various advantages, including long lifetime and high brightness compared with organic light-emitting diode (OLED) displays. As a result, microLED technology1,2 is being commercialized for large-screen displays such as digital signage and active R&D programmes are being carried out for other applications, such as augmented reality3, flexible displays4 and biological imaging5. However, substantial obstacles in transfer technology, namely, high throughput, high yield and production scalability up to Generation 10+ (2,940 × 3,370 mm2) glass sizes, need to be overcome so that microLEDs can enter mainstream product markets and compete with liquid-crystal displays and OLED displays. Here we present a new transfer method based on fluidic self-assembly (FSA) technology, named magnetic-force-assisted dielectrophoretic self-assembly technology (MDSAT), which combines magnetic and dielectrophoresis (DEP) forces to achieve a simultaneous red, green and blue (RGB) LED transfer yield of 99.99% within 15 min. By embedding nickel, a ferromagnetic material, in the microLEDs, their movements were controlled by using magnets, and by applying localized DEP force centred around the receptor holes, these microLEDs were effectively captured and assembled in the receptor site. Furthermore, concurrent assembly of RGB LEDs were demonstrated through shape matching between microLEDs and receptors. Finally, a light-emitting panel was fabricated, showing damage-free transfer characteristics and uniform RGB electroluminescence emission, demonstrating our MDSAT method to be an excellent transfer technology candidate for high-volume production of mainstream commercial products.

Split-face comparative trial of 785-nm picosecond neodymium:yttrium-aluminum-garnet laser and precision cryotherapy combination treatment for facial benign pigmented lesions.

Cryotherapy (or cryosurgery) has been performed to treat various skin lesions in the field of dermatology; however, to the best of our knowledge, no study has investigated its efficacy and safety for benign pigmented lesions. Therefore, we conducted a split-face study to evaluate the efficacy and safety of cryotherapy in the treatment of benign pigmented lesions. A total of five subjects were included. Picosecond laser therapy was performed to treat the whole face and cryotherapy for half the face. Four weeks after completing the treatment sessions, patients showed more clinical improvement on the laser and cryotherapy combination treatment side than on the laser-only side, with no adverse events. Our study demonstrated that cryotherapy is a potential adjuvant therapeutic modality for benign pigmented lesions.

Photoactive Antiviral Face Mask with Self-Sterilization and Reusability.

Since the emergence of the COVID-19 pandemic outbreak, the increasing demand and disposal of surgical masks has resulted in significant economic costs and environmental impacts. Here, we applied a dual-channel spray-assisted nanocoating hybrid of shellac/copper nanoparticles (CuNPs) to a nonwoven surgical mask, thereby increasing the hydrophobicity of the surface and repelling aqueous droplets. The resulting surface showed outstanding photoactivity (combined photocatalytic and photothermal properties) for antimicrobial action, conferring reusability and self-sterilizing ability to the masks. Under solar illumination, the temperature of this photoactive antiviral mask (PAM) rapidly increased to >70 °C, generating a high level of free radicals that disrupted the membrane of nanosized (∼100 nm) virus-like particles and made the masks self-cleaning and reusable. This PAM design can provide significant protection against the transmission of viral aerosols in the fight against the COVID-19 pandemic.

Combined Effects of Zeta-potential and Temperature of Nanopores on Diffusioosmotic Ion Transport.

Diffusioosmosis (DO) results from ion transport near charged surfaces in the presence of electrolyte gradients and is critical in nanofluidic systems. However, DO has not yet been comprehensively studied because nanofabrication materials have limitations of low throughput and difficult quantification. Herein, we describe a self-assembled particle membrane (SAPM)-integrated microfluidic platform that can modulate the material properties (e.g., zeta-potential) and transport flux of nanopores. We quantify the effect of the zeta-potential on DO by measuring the electrical signals across three different nanopores/nanochannels of the SAPM. We then empirically quantify the effects of the temperature and ionic strength of the electrolytes on DO and reveal a nonlinear relationship with DO-driven ion transport; the ionic strengths govern the DO- or diffusion-effective ion transport phenomena. Finally, we demonstrate DO-driven electric power generation with enhanced performance as a potential application under optimized experimental conditions.

High thermal conductivity in amorphous polymer blends by engineered interchain interactions.

Thermal conductivity is an important property for polymers, as it often affects product reliability (for example, electronics packaging), functionality (for example, thermal interface materials) and/or manufacturing cost. However, polymer thermal conductivities primarily fall within a relatively narrow range (0.1-0.5 W m(-1) K(-1)) and are largely unexplored. Here, we show that a blend of two polymers with high miscibility and appropriately chosen linker structure can yield a dense and homogeneously distributed thermal network. A sharp increase in cross-plane thermal conductivity is observed under these conditions, reaching over 1.5 W m(-1) K(-1) in typical spin-cast polymer blend films of nanoscale thickness, which is approximately an order of magnitude larger than that of other amorphous polymers.

Single nanowire resistive nano-heater for highly localized thermo-chemical reactions: localized hierarchical heterojunction nanowire growth.

A single nanowire resistive nano-heater (RNH) is fabricated, and it is demonstrated that the RNH can induce highly localized temperature fields, which can trigger highly localized thermo-chemical reactions to grow hierarchical nanowires directly at the desired specific spot such as ZnO nanowire branch growth on a single Ag nanowire.

A Preliminary Study of a Prototype Cryoablation Needle on Porcine Livers for Pancreatic Cancer Treatment.

Background and Aims: Despite its relatively low incidence rate compared to others, pancreatic cancer has a poor prognosis owing to its late detection and poor response to systemic chemotherapy. Because the effectiveness of chemotherapy is still restricted, the need for locoregional treatment is increasing. Cryoablation is an effective and minimally invasive treatment for some cancers, but its efficiency in pancreatic cancer is limited. Despite recent reports about promising outcomes, the optimal method and conditions of treatment are not known. In this preliminary study, we aimed to develop a cryoablation needle which can control the ablated area considering application through endoscopic ultrasonography. Methods: Here, we used a novel cryoneedle cooling system which can adjust the ablation range based on a liquid carbon dioxide refrigerant. Applied to the livers of swine, the cryoablation needle rapidly reached -60 °C within 30 s and cryoablation was performed for approximately 240 s. Based on the distance and depth, we collected real-time temperature data during the procedure. To compare the extent of cell death over time, tissue samples were collected hourly from 3 to 6 h after the procedure. Results: Approximately 4-5 mm of tissue was ablated via cryoablation, and cell death progressed over time after cryoablation. Moreover, the ablated lesions could be regulated using an insulating agent on the needle. Conclusions: This preliminary study on a novel surgical cooling needle system compatible with endoscopic ultrasound for cryoablation-based pancreatic cancer treatment confirmed the efficacy of cryoablation and identified the conditions necessary to induce necrosis. Additionally, this study evaluated the effectiveness of the insulation component of the system in protecting normal cells and assessed the extent of necrosis over time after the procedure.

Evaluation of cryoablation using a prototype cryoablation needle in swine liver.

BACKGROUND/AIMS: Pancreatic cancer poses significant challenges due to its tendency for late-stage diagnosis and high mortality rates. Cryoablation, a technique used to treat various types of cancer, has shown potential in enhancing the prognosis of pancreatic cancer when combined with other therapies. However, its implementation is often limited by the need for lengthy procedures and specialized equipment. This study aims to develop a cryoablation needle optimized for endoscopic ultrasonography to simplify its application in treating pancreatic cancer. METHODS: The study involved conducting cryoablation experiments on swine liver tissue. It utilized cryo-needles to evaluate the extent of cell death across various temperatures and durations of cryoablation. RESULTS: The cryoablation system, which employed liquid carbon dioxide, achieved rapid cooling, reaching temperatures below -60 °C within 30 seconds and maintained the cryoablation process for 200 seconds. These conditions resulted in necrosis of the liver tissue. Notable cellular changes were observed up to 15 mm away from the cryoablation needle. CONCLUSIONS: This experimental study successfully demonstrated the efficacy of using a cryo-needle for cryoablation in swine liver tissue. Further trials involving pancreatic tissue are expected to verify its effectiveness, underscoring the importance of continued research to establish its role as a complementary therapy in pancreatic cancer treatment.

Diagnostic Accuracy of Transient Elastography for Staging Liver Fibrosis in Autoimmune Liver Diseases: A Systematic Review and Meta-Analysis.

Background/Aims: The assessment of liver fibrosis is crucial for managing autoimmune liver diseases such as primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). However, data on the efficacy of noninvasive tests (NITs) for these diseases are limited. This meta-analysis evaluated the diagnostic accuracy of vibration-controlled transient elastography (VCTE) for staging fibrosis in patients with autoimmune liver disease. Methods: Searches were conducted in PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases to assess the diagnostic accuracy of VCTE against histology as the reference standard in adult patients with autoimmune liver disease. The summary area under the curve (sAUC) and diagnostic odds ratio were calculated for significant fibrosis (SF), advanced fibrosis (AF), and cirrhosis, defined as METAVIR stages F≥2, F≥3, and F=4, respectively, according to liver biopsy. Results: Fourteen articles were included, comprising 559 PBC patients from six studies, 388 AIH patients from five studies, and 151 PSC patients from three studies. VCTE demonstrated good performance for fibrosis staging in PBC, AIH, and PSC. In PBC, sAUCs of VCTE were 0.87 (95% confidence interval, 0.80-0.94), 0.89 (0.85-0.94), and 0.99 (0.96-1.00) for staging SF, AF, and cirrhosis, respectively. In AIH, the sAUCs were 0.88 (0.84-0.92), 0.88 (0.83-0.93), and 0.92 (0.88-0.96), respectively, while in PSC, they were 0.88 (0.82-0.95), 0.95 (0.90-1.00), and 0.92 (0.84-0.99), respectively. The cutoff values for AF were 7.5-17.9 kPa in PBC, 8.18-12.1 kPa in AIH, and 9.6 kPa in PSC. Conclusions: VCTE shows high diagnostic accuracy for staging liver fibrosis in patients with autoimmune liver diseases such as PBC, AIH, and PSC. This non-invasive and reliable method serves as a valuable tool for the evaluation and monitoring of fibrosis in these lifelong diseases.

Microscale acoustic metamaterials as conformal sonotransparent skull prostheses.

Functional ultrasound imaging enables sensitive, high-resolution imaging of neural activity in freely behaving animals and human patients. However, the skull acts as an aberrating and absorbing layer for sound waves, leading to most functional ultrasound experiments being conducted after skull removal. In pre-clinical settings, craniotomies are often covered with a polymethylpentene film, which offers limited longitudinal imaging, due to the film's poor conformability, and limited mechanical protection, due to the film's low stiffness. Here, we introduce a skull replacement consisting of a microstructured, conformal acoustic window based on mechanical metamaterials, designed to offer high stiffness-to-density ratio and sonotransparency. We test the acoustic window in vivo, via terminal and survival experiments on small animals. Long-term biocompatibility and lasting signal sensitivity are demonstrated over a long period of time (> 4 months) by conducting ultrasound imaging in mouse models implanted with the metamaterial skull prosthesis.

Sensing of sound pressure gradients by C. elegans drives phonotaxis behavior.

Despite lacking ears, the nematode C. elegans senses airborne sound and engages in phonotaxis behavior, enabling it to locate and avoid sound sources.1 How worms sense sound, however, is not well understood. Here, we report an interesting observation that worms respond only to sounds emitted by small but not large speakers, indicating that they preferentially respond to localized sound sources. Notably, sounds emitted by small speakers form a sharp sound pressure gradient across the worm body, while sounds from large speakers do not, suggesting that worms sense sound pressure gradients rather than absolute sound pressure. Analysis of phonotaxis behavior, sound-evoked skin vibration, and sound-sensitive neuron activities further support this model. We suggest that the ability to sense sound pressure gradients provides a potential mechanism for worms to distinguish sounds generated by their predators, which are typically small animals, from those produced by large animals or background noise. As vertebrate cochlea and some insect ears can also detect sound pressure gradients, our results reveal that sensing of sound pressure gradients may represent a common mechanism in auditory sensation across animal phyla. VIDEO ABSTRACT.

Cold anesthesia for pain reduction during intralesional steroid injection for nodulocystic acne.

BACKGROUND: In any dermatologic procedure, patient acceptance of treatment is heavily influenced by intraprocedural pain. Intralesional triamcinolone injections are very important in keloid scar and nodulocystic acne treatment. However, the main problem of needle-stick procedures is pain. Cryoanesthesia is ideally intended to cool only the epidermis during treatment and has advantage which did not require application time. AIMS: The aim of this study was to investigate the pain-reducing effect and safety of CryoVIVE® (newly introduced cryoanesthesia device) during triamcinolone injections for nodulocystic acne in actual clinical settings. PATIENTS/METHODS: In this two-staged, non-randomized clinical trial, a total of 64 subjects underwent intralesional triamcinolone injections for their acne lesions with cold anesthesia using CryoVIVE®. The pain intensity was assessed with Visual Analogue Scale (VAS) scores. Safety profile was also evaluated. RESULTS: The mean pain VAS scores on the lesion with and without cold anesthesia were 3.667 and 5.933, respectively (p = 0.0001). No side effects, discoloration, and scarring were observed. CONCLUSION: In conclusion, the anesthetic use of CryoVIVE® with intralesional corticosteroid injections is a practical and well-tolerated modality.

Effect of a Precision Cryotherapy Device with Temperature Adjustability on Pigmentation.

Background: Pigmentary skin disorders impair the quality of life, leading to the development of therapeutic modalities. However, these treatments should focus more on effectiveness and safety. Aims and Objectives: To evaluate the effect of a temperature-adjustable cryotherapy device on the expression of pigmentation-related biomarkers. Methods and Results: A temperature- and time-adjustable cryotherapy device was employed to improve 200 mJ UVB-induced pigmentation on mice at -5°C (for 5, 10 or 20 s), 0°C (for 5, 10 or 20 s), 5°C (for 5, 10 or 20 s), or 10°C (for 5, 10 or 20 s). Expression of pigmentation-related biomarkers, such as tyrosinase, c-kit, melanocortin 1 receptor and microphthalmia-associated transcription factor before and after treatment with the cryotherapy device was investigated with real-time polymerase chain reaction and immunohistochemistry. Results: Expression of pigmentation-related biomarkers was decreased after the treatment of the temperature-adjustable cryotherapy device. Gene expression of the pigmentation-related biomarkers was decreased under the above conditions with some exception. Protein expression of the pigmentation-related biomarkers showed decreased tendency under the conditions with some exceptions. Conclusion: The temperature-adjustable cryotherapy device used in this study reduced the expression of pigmentation-related biomarkers on mice and may be used to treat patients with skin pigmentation.

Cooling Anesthesia for Intravitreal Injection: Results of the Prospective Open-Label, Dose-Ranging COOL-1 Trial.

PURPOSE: To evaluate the safety and efficacy of a novel medical device to provide cooling anesthesia to the eye as local anesthesia for intravitreal injections. STUDY DESIGN: First in human, open-label study of 43 subjects assessed at three different doses: -10°C for 20 seconds (group 1), -15°C for 15 seconds (group 2), and -15°C for 20 seconds (group 3). Main outcome measures were safety and pain of injection using a numeric rating scale (NRS). RESULTS: Cooling anesthesia did not result in any serious ocular adverse events. One grade 1 adverse event was a vasovagal response during cooling administration which resolved immediately after cooling. Mean NRS scores at the time of injection for each group ranged from 2.5 to 4.3 There was a statistically significant difference between pain scores of the 3 groups at injection in aggregate but not in pairwise comparisons (P value = 0.047). There was a statistically significant decrease in pain from injection to 5 minutes post injection in all groups (P value = 0.00008, 0.003, 0.0005 for groups 1, 2, 3, respectively) as well as from 5 minutes to 24-48 hours (P value = 0.00001, 0.018, and 0.0545 for groups 1, 2, 3, respectively). CONCLUSION: The rapid cooling anesthesia device was well tolerated for achieving local anesthesia among patients receiving intravitreal injections with no serious ocular adverse events.

Enhanced Mechanical and Antibacterial Properties of Nanocomposites Based on Poly(vinyl Alcohol) and Biopolymer-Derived Reduced Graphene Oxide.

Functionalized graphene-polymer nanocomposites have gained significant attention for their enhanced mechanical, thermal, and antibacterial properties, but the requirement of multi-step processes or hazardous reducing agents to functionalize graphene limits their current applications. Here, we present a single-step synthesis of thermally reduced graphene oxide (TrGO) based on shellac, which is a low-cost biopolymer that can be employed to produce poly(vinyl alcohol) (PVA)/TrGO nanocomposites (PVA-TrGO). The concentration of TrGO varied from 0.1 to 2.0 wt.%, and the critical concentration of homogeneous TrGO dispersion was observed to be 1.5 wt.%, below which strong interfacial molecular interactions between the TrGO and the PVA matrix resulted in improved thermal and mechanical properties. At 1.5 wt.% filler loading, the tensile strength and modulus of the PVA-TrGO nanocomposite were increased by 98.7% and 97.4%, respectively, while the storage modulus was increased by 69%. Furthermore, the nanocomposite was 96% more effective in preventing bacterial colonization relative to the neat PVA matrix. The present findings indicate that TrGO can be considered a promising material for potential applications in biomedical devices.

A general approach to composites containing nonmetallic fillers and liquid gallium.

We report a versatile method to make liquid metal composites by vigorously mixing gallium (Ga) with non-metallic particles of graphene oxide (G-O), graphite, diamond, and silicon carbide that display either paste or putty-like behavior depending on the volume fraction. Unlike Ga, the putty-like mixtures can be kneaded and rolled on any surface without leaving residue. By changing temperature, these materials can be stiffened, softened, and, for the G-O-containing composite, even made porous. The gallium putty (GalP) containing reduced G-O (rG-O) has excellent electromagnetic interference shielding effectiveness. GalP with diamond filler has excellent thermal conductivity and heat transfer superior to a commercial liquid metal-based thermal paste. Composites can also be formed from eutectic alloys of Ga including Ga-In (EGaIn), Ga-Sn (EGaSn), and Ga-In-Sn (EGaInSn or Galinstan). The versatility of our approach allows a variety of fillers to be incorporated in liquid metals, potentially allowing filler-specific "fit for purpose" materials.

Low cost synthesis of reduced graphene oxide using biopolymer for influenza virus sensor.

A biocompatible, cost-effective, and scalable reduced graphene oxide (rGO) film was obtained from shellac using thermal treatment and its structural, chemical, and electrical properties were investigated. This thermally-decomposed rGO (TrGO) film exhibited good crystallinity, low sheet resistance, and high carbon content. TrGO flakes obtained from the film were dispersed and drop cast onto indium tin oxide/glass electrodes to fabricate label-free electrochemical immunosensors for the quantitative detection of the influenza virus H1N1 via electrochemical impedance spectroscopy. These sensors exhibited high stability and reproducibility, both possibly ascribable to the high adhesion of TrGO due to its phenolic-OH moiety; the limits of detection were 26 and 33 plaque-forming units, respectively, in phosphate-buffered saline and diluted saliva. These cost-effective TrGO-based sensors showed great potential as reliable and robust nanomaterial-based biosensors for widespread clinical applications.

High Efficiency Doping of Conjugated Polymer for Investigation of Intercorrelation of Thermoelectric Effects with Electrical and Morphological Properties.

Intercorrelation of thermoelectric properties of a doped conjugated semiconducting polymer (PIDF-BT) with charge carrier density, conductive morphology, and crystallinity are systematically investigated. Upon being doped with F4-TCNQ by the sequential doping method, PIDF-BT exhibited a high electrical conductivity over 210 S cm-1. The significant enhancement of electrical conductivity resulted from a high charge carrier density, which is attributed to the effective charge-transfer-based integer doping between PIDF-BT and dopant molecules. Based on the systemic characterization on the optical, electrical, and structural properties of doped PIDF-BT annealed at different temperatures, we investigated the characteristic correlations between thermoelectric properties of PIDF-BT films and their four-probe electrical conductivity, charge carrier density, and charge carrier mobility obtained from AC Hall effect measurements. This study revealed that exercising fine control over the crystallinity and conductive migration of the conjugated polymer films can be a strategic approach to suppressing the degradation of the Seebeck coefficient at high charge carrier density and ultimately to maximizing the power factors of organic thermoelectric devices.