Optical neuromodulation at all scales: from nanomaterials to wireless optoelectronics and integrated systems.

Light-based neuromodulation systems offer exceptional spatiotemporal resolution combined with the elimination of physical tether to communicate with neurons. Currently, optical neuromodulation systems ranging from the nano to the centimeter scale enable neural activity control from the single cell to the organ level in retina, heart, spinal cord, and brain, facilitating a wide range of experiments in intact and freely moving animals in different contexts, such as during social interactions and behavioral tasks. Nanotransducers (e.g., metallic nanoparticles, silicon nanowires, and polymeric nanoparticles) and microfabricated photodiodes convert light to electrical, thermal, and mechanical stimuli that can allow remote and non-contact stimulation of neurons. Moreover, integrated devices composed of nano and microscale optoelectronic components comprise fully implantable and wirelessly powered smart optoelectronic systems that exhibit multimodal and closed-loop operation. In this review, we first discuss the material platforms, stimulation mechanisms, and applications of passive systems, i.e., nanotransducers and microphotodiodes. Then, we review the use of organic and inorganic light-emitting diodes for optogenetics and implantable wireless optoelectronic systems that enable closed-loop optogenetic neuromodulation through the use of light-emitting diodes, wireless power transfer circuits, and feedback loops. Exploration of materials and mechanisms together with the presented applications from both research and clinical perspectives in this review provides a comprehensive understanding of the optical neuromodulation field with its advantages and challenges to build superior systems in the future.

pH-sensitive gallol-rich chitosan hydrogel beads for on-off controlled drug delivery.

Malignant tumors have emerged as a serious health issue, and the interest in developing pH-sensitive polymers for site-specific drug delivery has increased. The physical and/or chemical properties of pH-sensitive polymers depend on the pH, and thus, drugs can be released by cleaving dynamic covalent and/or noncovalent bonds. In this study, gallic acid (GA) was conjugated to chitosan (CS) to prepare self-crosslinked hydrogel beads containing Schiff base (imine bond) crosslinks. The CS-GA hydrogel beads were formed by the dropwise addition of the CS-GA conjugate solution into a Tris-HCl buffer solution (TBS, pH 8.5). The pH-sensitivity of pristine CS was significantly enhanced following the introduction of GA moiety, and as a result, the CS-GA hydrogel beads swelled more than approximately 5000 % at pH 4.0, indicating an excellent swelling/deswelling ability of the beads at different pH (pH 4.0 and 8.5). The reversible breakage/recovery of the imine crosslinks in the CS-GA hydrogel beads was confirmed through X-ray photoelectron spectroscopic and rheological studies. Finally, Rhodamine B was loaded onto the hydrogel beads as a model drug to investigate the pH-sensitive drug release behavior. At pH 4, the drug was released up to approximately 83 % within 12 h. The findings indicate that the CS-GA hydrogel beads have great potential as a drug delivery system that is sensitive to acidic tumor sites in the body.

Highly gallol-substituted, rapidly self-crosslinkable, and robust chitosan hydrogel for 3D bioprinting.

Although three-dimensional (3D) bioprinting is a promising technology for reconstructing artificial tissues and organs using bioink, there is a lack of a bioink that satisfies all requirements, including printability, gelation, mechanical properties, and cytocompatibility, Herein, a novel self-crosslinkable bioink derived from chitosan (CS) and gallic acid (GA) is presented. 3D printed scaffolds with excellent shape fidelity are realized by systematically analyzing the self-crosslinking mechanism of hydrogel formation from CS-GA conjugates and by optimizing various parameters of the printing process. The CS-GA hydrogel forms rapidly in a physiological pH without any chemical crosslinking agent. In addition, the CS-GA hydrogel exhibited various physical and chemical intermolecular interactions, fast gelation rates, and excellent mechanical properties (>337 kPa). Moreover, the CS-GA hydrogel singificantly improves the cell viability (>92 %) and proliferation of the bioink. Therefore, the self-crosslinkable CS-GA bioink has great potential to overcome the limitations of conventional bioinks.

Hyaluronic acid/tannic acid hydrogel sunscreen with excellent anti-UV, antioxidant, and cooling effects.

Excessive exposure to UV radiation is one of the major factors that causes skin aging, erythema, burns, and skin cancer. Recently, the usage of sunscreens for skin protection has increased because the amount of UV radiation reaching the Earth's surface has increased owing to the destruction of the ozone layer that blocks UV radiation. Hydrogels with a three-dimensional network structure exhibit physical and chemical properties that are similar to those of the extracellular matrix in the human body, a high water content, flexibility, and biocompatibility. Therefore, they are applied in a wide range of fields, such as in cosmetics, medicines, and pharmaceuticals. However, conventional hydrogel-based sunscreens have drawbacks such as complicated process conditions, high cost, and low biocompatibility. In this study, a novel hydrogel-type sunscreen with excellent UV protection and cooling effects was prepared by a very simple process using two natural materials, hyaluronic acid (HA) and tannic acid (TA). The HA/TA hydrogels exhibited broad-spectrum UV protection in the UVA and UVB regions (280-360 nm). In addition, they showed excellent adhesion to the skin surface, antioxidative activity, cooling effect, and high moisture content, demonstrating great application potential as a hydrogel-type sunscreen.

Effect of tannic acid on the mechanical and adhesive properties of catechol-modified hyaluronic acid hydrogels.

Hyaluronic acid (HA) is applied in various fields, including pharmaceutical science, owing to its favorable biological properties such as moisture retention, non-toxicity, biodegradability, biocompatibility and biodegradability. In particular, many studies have aimed at its application in the form of a hydrogel. However, the applications of HA hydrogels are limited owing to their poor mechanical properties. In this study, an HA-catechol conjugate (HA-Cat) was synthesized by reacting the HA polymer with dopamine to improve its adhesion to various substrates. The HA-Cat hydrogel was prepared via oxidative crosslinking using a small amount of NaIO4 as the oxidant, and the hydrogel formation was investigated by rheological and mechanical studies. Further, the effect of tannic acid (TA) on the adhesive strength and compressive strength of the HA-Cat/TA hydrogels was examined according to the amount of NaIO4 used for crosslinking and the TA contents. Both the adhesive and compressive properties of the HA-Cat hydrogels were improved with the addition of TA. The HA-based hydrogels containing TA have great potential as cost-effective and biocompatible medical adhesives.

Gut-Brain Connection: Microbiome, Gut Barrier, and Environmental Sensors.

The gut is an important organ with digestive and immune regulatory function which consistently harbors microbiome ecosystem. The gut microbiome cooperates with the host to regulate the development and function of the immune, metabolic, and nervous systems. It can influence disease processes in the gut as well as extra-intestinal organs, including the brain. The gut closely connects with the central nervous system through dynamic bidirectional communication along the gut-brain axis. The connection between gut environment and brain may affect host mood and behaviors. Disruptions in microbial communities have been implicated in several neurological disorders. A link between the gut microbiota and the brain has long been described, but recent studies have started to reveal the underlying mechanism of the impact of the gut microbiota and gut barrier integrity on the brain and behavior. Here, we summarized the gut barrier environment and the 4 main gut-brain axis pathways. We focused on the important function of gut barrier on neurological diseases such as stress responses and ischemic stroke. Finally, we described the impact of representative environmental sensors generated by gut bacteria on acute neurological disease via the gut-brain axis.

Self-crosslinkable hyaluronate-based hydrogels as a soft tissue filler.

With increasing interest in aging and skin care, the use of fillers to increase the volume of soft tissue volume is increasing globally. However, the side effects caused by the residual chemical crosslinking agents present in these fillers limit the effective application of commercialized filler products. Therefore, the development of a novel crosslinking system with a non-toxic chemical crosslinking agent is required to overcome the limitations of commercial hyaluronate (HA)-based fillers. In this paper, a new injectable hydrogel with enhanced mechanical properties, tissue adhesion, injectability, and biocompatibility is reported. The HA derivatives modified with catechol groups (HA-DA) were crosslinked by self-oxidation under in vivo physiological conditions (pH 7.4) without chemical crosslinkers to form hydrogels, which can be further accelerated by the dissolved oxygen in the body. The fabricated HA-DA filler showed excellent mechanical properties and could be easily injected with a low injection force. Further, the HA-DA filler stably attached to the injection site due to the tissue adhesion properties of the catechol groups, thus leading to an improved displacement stability. In addition, the HA-DA filler showed excellent cell viability, cell proliferation, and biocompatibility. Therefore, the HA-DA hydrogel is a novel soft tissue filler with great potential to overcome the limitations of commercial soft tissue fillers.

Using reflectance confocal microscopy to observe in vivo melanolysis after treatment with the picosecond alexandrite laser and Q-switched Nd:YAG laser in melasma.

OBJECTIVES: Melasma is an acquired type of hyperpigmentation that is characterized by the appearance of scattered light- to dark-brown macules and patches on the face. Recently, several lasers have been proposed as treatment options for melasma. In particular, the picosecond alexandrite laser is an ideal laser for selective photothermal melanolysis. The aim of our study was to compare the effectiveness in melanolysis of a single treatment of the picosecond alexandrite laser with that of the Q-switched Nd:YAG laser using reflectance confocal microscopy imaging of the melasma lesions. MATERIALS AND METHODS: We performed a spilt-face study using the picosecond alexandrite laser and Q-switched Nd:YAG laser in eight patients with melasma. Both melasma lesions and surrounding normal skin were examined under reflectance confocal microscopy 1 and 24 hours after treatment. The melanin intensity of each skin layer was investigated. RESULTS: At baseline, melasma has irregular melanin distribution and a higher melanin density than surrounding normal skin under reflectance confocal microscopy. After a single treatment with either the picosecond alexandrite laser or the Q-switched Nd:YAG laser, both melanin-induced reflectance and melanin index decreased. CONCLUSION: Our findings suggest that it is feasible to assess the distribution of melanin by reflectance confocal microscopy and observe the melanolysis in melasma lesion after laser treatment. Lasers Surg. Med. 51:423-429, 2019. © 2018 Wiley Periodicals, Inc.

Efficacy and durability of hyaluronic acid fillers for malar enhancement: A prospective, randomized, split-face clinical controlled trial.

Various hyaluronic acid fillers can be used for facial attenuation and rejuvenation. The efficacy and durability of hyaluronic acid fillers are of major concern to dermatologists and patients. This study aimed to evaluate three-dimensional morphology, tissue distribution, and changes in volume after injection of two different hyaluronic acid fillers. Ten Korean women were enrolled in this study. Each subject was injected with monophasic hyaluronic acid filler in one malar area and biphasic filler in the other. Clinical outcome was measured before and after injection, and after 2, 4, 6, 8, 12, and 24 weeks, using the Global Aesthetic Improvement Scale, photographs and Moire's topography. Facial magnetic resonance imaging (MRI) was performed twice over six months. Both products showed good results after injection and demonstrated good durability over time. MRI was a useful modality for assessing tissue distribution and volume changes. The effects and durability after injection of monophasic hyaluronic acid filler and biphasic hyaluronic acid filler are generally comparable.

Imaging of the Finger Vein and Blood Flow for Anti-Spoofing Authentication Using a Laser and a MEMS Scanner.

A new authentication method employing a laser and a scanner is proposed to improve image contrast of the finger vein and to extract blood flow pattern for liveness detection. A micromirror reflects a laser beam and performs a uniform raster scan. Transmissive vein images were obtained, and compared with those of an LED. Blood flow patterns were also obtained based on speckle images in perfusion and occlusion. Curvature ratios of the finger vein and blood flow intensities were found to be nearly constant, regardless of the vein size, which validated the high repeatability of this scheme for identity authentication with anti-spoofing.

Polymeric cantilever integrated with PDMS/graphene composite strain sensor.

This paper describes the mechanical and electrical characteristics of a polydimethylsiloxane (PDMS) cantilever integrated with a high-sensitivity strain sensor. The strain sensor is fabricated using PDMS and graphene flakes that are uniformly distributed in the PDMS. In order to prepare PDMS/graphene composite with uniform resistance, a tetrahydrofuran solution is used to decrease the viscosity of a PDMS base polymer solution. A horn-type sonicator is then used to mix the base polymer with graphene flakes. Low viscosity of the base polymer solution improves the reliability and reproducibility of the PDMS/graphene composite for strain sensor applications. After dicing the composite into the desired sensor shape, a tensile test is performed. The experimental results show that the composite with a concentration of 30 wt.% exhibits a linear response up to a strain rate of 9%. The graphene concentration of the prepared materials affects the gauge factor, which at 20% graphene concentration reaches about 50, and with increasing graphene concentration to 30% decreases to 9. Furthermore, photolithography, PDMS casting, and a stencil process are used to fabricate a PDMS cantilever with an integrated strain sensor. The change in resistance of the integrated PDMS/graphene sensor is characterized with respect to the displacement of the cantilever of within 500 µm. The experimental results confirmed that the prepared PDMS/graphene based sensor has the potential for high-sensitive biosensor applications.

Initial serum lactate level is associated with inpatient mortality in patients with community-acquired pneumonia.

STUDY OBJECTIVE: The aim of the present study was to investigate the prognostic value of the initial serum lactate level in patients with community-acquired pneumonia (CAP). METHODS: We collected data on hospitalized adult patients with CAP via the study hospital emergency department between October 2012 and September 2013. Demographics, comorbidities, and physiologic and laboratory variables including initial C-reactive protein (CRP) and serum lactate level were extracted from the electronic medical record. The primary outcome was inpatient mortality. Comparisons between survivors and nonsurvivors were performed, and multivariable logistic regression analyses were constructed as dependent variables of both continuous and categorical varieties. RESULTS: A total of 397 patients were enrolled, and the mortality cases were 46 (11.6%). The mean lactate level was 1.7 ± 1.4 mmol/L and was significantly higher in the nonsurvivor group than in the survivor group (2.4 ± 2.2 mmol/L vs 1.6 ± 1.2 mmol/L). In the multivariable logistic regression model for inpatient mortality constructed using lactate, CRP, and laboratory variables of pneumonia severity index (PSI), lactate and CRP remained as significant factors, but laboratory variables of PSI were not. In other multivariable logistic regression models for the outcome constructed using collected laboratory variables and PSI, lactate remained as a significant factor (adjusted odds ratio, 1.24; 95% confidence interval, 1.01-1.53; P = .042 by continuous variable; adjusted odds ratio of third tertile, 2.60; 95% confidence interval, 1.02-6.66; P = .046 by category variable). C-reactive protein and albumin were also left as significant factors. CONCLUSIONS: The initial serum lactate level is independently associated with mortality in hospitalized patients with CAP. However, laboratory variables of PSI or others were not, except CRP and albumin.

Regional Bias of Intratumoral Genetic Heterogeneity of Apoptosis-Related Genes BAX, APAF1, and FLASH in Colon Cancers with High Microsatellite Instability.

BACKGROUND: Apoptosis inactivation and intratumoral heterogeneity (ITH) are common features of cancers, including colorectal cancer (CRC). Inactivation of apoptosis prolongs cancer cell survival, and ITH may contribute to CRC progression. AIM: To examine the presence and extent of mutational ITH in the pro-apoptotic genes APAF1, BAX, and FLASH and the association of mutational ITH with pathologic parameters of CRC. METHODS: The ITH of mutations in the mononucleotide repeats of APAF1, BAX and FLASH in different tumors were analyzed in 16 cases of CRC with high microsatellite instability (MSI-H) and 41 cases of CRC with stable MSI/low MSI (MSS/MSI-L) by single-strand conformation polymorphism and DNA sequencing analyses. RESULTS: Frameshift mutations of APAF1, BAX, and FLASH were identified in 19, 31, and 6 % of CRC with MSI-H, respectively, but also in cases of CRC with MSS/MSI-L. All but one CRC with a mutation (8/9) harbored regional ITH of the APAF1, BAX and FLASH frameshift mutations. ITH, however, was not associated with histopathologic features of CRC with MSI-H, suggesting that ITH might not be related to development of the MSI-H phenotype itself, but rather to disease progression. CONCLUSIONS: Our results indicate that the APAF1, BAX, and FLASH genes not only harbor frameshift mutations but also demonstrate mutational ITH, which together might play a role in the tumorigenesis of CRC with MSI-H by affecting the apoptosis of cancer cells. Our data also suggest that multiregional mutation analysis is needed for a better evaluation of the mutation status in CRC.