Molecular Design of SERTlight: A Fluorescent Serotonin Probe for Neuronal Labeling in the Brain.

The serotonergic transmitter system plays fundamental roles in the nervous system in neurotransmission, synaptic plasticity, pathological processes, and therapeutic effects of antidepressants and psychedelics, as well as in the gastrointestinal and circulatory systems. We introduce a novel small molecule fluorescent agent, termed SERTlight, that specifically labels serotonergic neuronal cell bodies, dendrites, and axonal projections as a serotonin transporter (SERT) fluorescent substrate. SERTlight was developed by an iterative molecular design process, based on an aminoethyl-quinolone system, to integrate structural elements that impart SERT substrate activity, sufficient fluorescent brightness, and a broad absence of pharmacological activity, including at serotonin (5-hydroxytryptamine, 5HT) receptors, other G protein-coupled receptors (GPCRs), ion channels, and monoamine transporters. The high labeling selectivity is not achieved by high affinity binding to SERT itself but rather by a sufficient rate of SERT-mediated transport of SERTlight, resulting in accumulation of these molecules in 5HT neurons and yielding a robust and selective optical signal in the mammalian brain. SERTlight provides a stable signal, as it is not released via exocytosis nor by reverse SERT transport induced by 5HT releasers such as MDMA. SERTlight is optically, pharmacologically, and operationally orthogonal to a wide range of genetically encoded sensors, enabling multiplexed imaging. SERTlight enables labeling of distal 5HT axonal projections and simultaneous imaging of the release of endogenous 5HT using the GRAB5HT sensor, providing a new versatile molecular tool for the study of the serotonergic system.

Kawasaki Disease with Hepatobiliary Manifestations.

Background and Objectives: Kawasaki Disease (KD) incidence has been on the rise globally throughout the years, particularly in the Asia Pacific region. KD can be diagnosed based on several clinical criteria. Due to its systemic inflammatory nature, multi-organ involvement has been observed, making the diagnosis of KD more challenging. Notably, several studies have reported KD patients presenting with hepatobiliary abnormalities. Nonetheless, comprehensive data regarding the hepatobiliary manifestations of KD are limited in Malaysia, justifying a more in-depth study of the disease in this country. Thus, in this article, we aim to discuss KD patients in Malaysia with hepatobiliary manifestations. Materials and Methods: A total of six KD patients with hepatobiliary findings who presented at Hospital Canselor Tuanku Muhriz (HCTM) from 2004 to 2021 were selected and included. Variables including the initial presenting signs and symptoms, clinical progress, laboratory investigations such as liver function test (LFT), and ultrasound findings of hepatobiliary system were reviewed and analyzed. Results: Out of these six KD patients, there were two patients complicated with hepatitis and one patient with gallbladder hydrops. Different clinical features including jaundice (n = 3) and hepatomegaly (n = 4) were also observed. All patients received both aspirin and intravenous immunoglobulin (IVIG) as their first-line treatment and all of them responded well to IVIG. The majority of them (n = 5) had a complete recovery and did not have any cardiovascular and hepatobiliary sequelae. Conclusions: Despite KD mostly being diagnosed with the classical clinical criteria, patients with atypical presentations should always alert physicians of KD as one of the possible differential diagnoses. This study discovered that hepatobiliary manifestations in KD patients were not uncommon. More awareness on the epidemiology, diagnosis, and management of KD patients with hepatobiliary manifestations are required to allow for the initiation of prompt treatment, thus preventing further complications.

Lorentz-Boost-Driven Magneto-Optics in a Dirac Nodal-Line Semimetal.

Optical response of crystalline solids is to a large extent driven by excitations that promote electrons among individual bands. This allows one to apply optical and magneto-optical methods to determine experimentally the energy band gap -a fundamental property crucial to our understanding of any solid-with a great precision. Here it is shown that such conventional methods, applied with great success to many materials in the past, do not work in topological Dirac semimetals with a dispersive nodal line. There, the optically deduced band gap depends on how the magnetic field is oriented with respect to the crystal axes. Such highly unusual behavior is explained in terms of band-gap renormalization driven by Lorentz boosts which results from the Lorentz-covariant form of the Dirac Hamiltonian relevant for the nodal line at low energies.

Development of a Dual Fluorescent and Magnetic Resonance False Neurotransmitter That Reports Accumulation and Release from Dopaminergic Synaptic Vesicles.

Myriad neuropsychiatric disorders are due to dopamine dysfunction. However, understanding these disorders is limited by our ability to measure dopamine storage and release. Fluorescent false neurotransmitters (FFNs), small-molecule dyes that co-transit through the synaptic vesicle cycle, have allowed us to image dopamine in cell culture and acute brain slice, but in vivo microscopy is constrained by the biopenetrance of light. Here, we adapt FFNs into magnetic resonance false neurotransmitters (MFNs). The design principles guiding MFNs are (1) the molecule is a valid false neurotransmitter and (2) it has a 19F-substituent near a pH-sensing functional group, which (3) has pKa close to 6 so that the probe within vesicles is protonated. We demonstrate that MFN103 meets these criteria. While a magnetic resonance spectroscopy (MRS) signal was too low for measurement in vivo with the current technology, in principle, MFNs can quantify neurotransmitters within and without synaptic vesicles, which may underlie noninvasive in vivo analysis of dopamine neurotransmission.

High-sensitivity of initial SrO growth on the residual resistivity in epitaxial thin films of SrRuO[Formula: see text] on SrTiO[Formula: see text] (001).

The growth of SrRuO[Formula: see text] (SRO) thin film with high-crystallinity and low residual resistivity (RR) is essential to explore its intrinsic properties. Here, utilizing the adsorption-controlled growth technique, the growth condition of initial SrO layer on TiO[Formula: see text]-terminated SrTiO[Formula: see text] (STO) (001) substrate was found to be crucial for achieving a low RR in the resulting SRO film grown afterward. The optimized initial SrO layer shows a c(2 [Formula: see text] 2) superstructure that was characterized by electron diffraction, and a series of SRO films with different thicknesses (ts) were then grown. The resulting SRO films exhibit excellent crystallinity with orthorhombic-phase down to [Formula: see text] 4.3 nm, which was confirmed by high resolution X-ray measurements. From X-ray azimuthal scan across SRO orthorhombic (02 ± 1) reflections, we uncover four structural domains with a dominant domain of orthorhombic SRO [001] along cubic STO [010] direction. The dominant domain population depends on t, STO miscut angle ([Formula: see text]), and miscut direction ([Formula: see text]), giving a volume fraction of about 92 [Formula: see text] for [Formula: see text] 26.6 nm and [Formula: see text] (0.14[Formula: see text], 5[Formula: see text]). On the other hand, metallic and ferromagnetic properties were well preserved down to t [Formula: see text] 1.2 nm. Residual resistivity ratio (RRR = [Formula: see text]/[Formula: see text]) reduces from 77.1 for t [Formula: see text] 28.5 nm to 2.5 for t [Formula: see text] 1.2 nm, while [Formula: see text] increases from 2.5 [Formula: see text]cm for t [Formula: see text] 28.5 nm to 131.0 [Formula: see text]cm for t [Formula: see text] 1.2 nm. The ferromagnetic onset temperature ([Formula: see text]) of around 151 K remains nearly unchanged down to t [Formula: see text] 9.0 nm and decreases to 90 K for t [Formula: see text] 1.2 nm. Our finding thus provides a practical guideline to achieve high crystallinity and low RR in ultra-thin SRO films by simply adjusting the growth of initial SrO layer.

A Clinical Study Evaluating the Efficacy of Topical Bakuchiol (UP256) Cream on Facial Acne.

Acne vulgaris is a common skin disease that manifests clinically as comedones, papules, nodules, and cysts. In this single center, open-label pilot study (ISRCTN13992386), we aimed to evaluate the effectiveness of UP256 cream, a newly patented topical product containing 0.5% bakuchiol, on facial acne and acne-related post-inflammatory hyperpigmentation (PIH). A series of 13 subjects enriched for Fitzpatrick skin types III–VI with mild or moderate acne received treatment with UP256 twice daily for 12 weeks. Efficacy assessments included changes in inflammatory and non-inflammatory lesions as well as a reduction in Evaluator Global Severity Score (EGSS) assessments of acne severity and PIH. Safety, adverse events, and cutaneous tolerability were evaluated throughout the study. UP256 significantly reduced the number of inflammatory lesions and improved existing PIH. UP256 was also cosmetically acceptable and well tolerated by all study subjects. Overall, our results demonstrate that monotherapy with UP256 improves mild to moderate acne and may be particularly well suited for individuals with skin of color. J Drugs Dermatol. 2021;20(3):307-310. doi:10.36849/JDD.5655.

A propellant-free superconducting solenoid thruster driven by geomagnetic field.

INTRODUCTION: Space travel nowadays relies on physical ejection of propellants, which is challenged by reachable distance of a vehicle in desirable time. In contrast, electromagnetic propulsion was proposed to be a potential solution without need of carrying bulky mass of propellants, by using force interaction of local magnetic dipoles with the external natural magnetic field. Further development of this technique, however, has been daunted by extremely small magnetic induction that can be obtained. OBJECTIVES: To generate a significant thrust by a system with a reasonable scale, we propose an alternative concept of design, based on the variation of local magnetic dipole moments that has not been considered. METHODS: A magnetic dipole is created by wrapping a solenoid around an iron core. It is varied spatially by changing the cross-sectional area of the solenoid, hence giving a gradient of magnetic dipole moment. The interaction force is measured by an in-house force sensor based on a cantilever, which has a high sensitivity of one micro-Newton. In addition, numerical simulation is used to calculate the magnetic field and created force via the Maxwell stress tensor. RESULTS: As shown by experimental measurements and numerical simulations, a substantially larger magnitude of force is obtained on the solenoid with varying cross-sectional area, indicating a much stronger interaction with the geomagnetic field. Furthermore, to enhance electric current with negligible dissipation, a superconducting solenoid can be adopted at low temperature in space. With readily attainable conditions of operation, we demonstrate generation of a thrust comparable to that of present electric propulsion thrusters which are deemed as the most promising techniques for long-term space travel. CONCLUSIONS: By incorporating supplementary means, we provide a breakthrough solution for constructing an efficient thruster with minimal energy consumption and nearly null propellant load for near-Earth transportation and deep-space exploration.

Nanostructured Free-Form Objects via a Synergy of 3D Printing and Thermal Nanoimprinting.

High-resolution surface patterning has garnered interests as a nonchemical-based surface engineering approach for creating functional surfaces. Applications in consumer products, parts for transportation vehicles, optics, and biomedical technologies demand topographic patterning on 3D net shape objects. Through a hybrid approach, high-resolution surface texture is incorporated onto 3D-printed polymers via direct thermal nanoimprinting process. The synergy of geometry design freedom in 3D printing and the high spatial resolution in nanoimprinting is demonstrated to be a versatile fabrication of high-fidelity surface pattern (from 2 µm to 200 nm resolution) on convex, concave semicylindrical, and hemispherical objects spanning a range of surface curvatures. The novel hybrid fabrication is further extended to achieve a high-resolution curved mold insert for rapid prototyping via injection molding. The versatility of the fabrication strategies reported here not only provides a post-3D printing process that enhances the surface properties of 3D-printed objects but also opens a new pathway to enable future study on the effects of combining microscale and nanoscale surface texture with macroscopic curvature. Both have been known, individually, as an effective approach to tune surface functionalities.

Crystal Growth and Magnetic Properties of Topological Nodal-Line Semimetal GdSbTe with Antiferromagnetic Spin Ordering.

We report crystal growth, AC and DC magnetic susceptibilities [χ(T, H)], magnetization [M(T, H)], and heat capacity [CP(T, H)] measurement results of GdSbTe single crystal. GdSbTe is isostructural to the confirmed nonmagnetic nodal-line semimetal ZrSiS of noncentrosymmetric tetragonal crystal structure in space group P4/nmm (No. 129), but it shows additional long-range antiferromagnetic spin ordering for the Gd spins of S = 7/2 below TN. Both χ(T, H) and CP(T, H) measurements confirm the existence of a long-range antiferromagnetic (AFM) spin ordering of Gd spins below TN ∼ 12 K, and an additional spin reorientation/recovery (sr) behavior is identified from the change of on-site spin anisotropy between Tsr1 ∼ 7 and Tsr2 ∼ 4 K. The anisotropic magnetic susceptibilities of χ(T, H) below TN clearly demonstrate that the AFM long-range spin ordering of GdSbTe has an easy axis parallel to the ab-plane direction. The field- and orientation-dependent magnetization of M(T, H) at 2 K shows two plateaus to indicate the spin-flop transition for H||ab near ∼2.1 T and a metamagnetic state near ∼5.9 T having ∼1/3 of the fully polarized magnetization by the applied field. The heat capacity measurement results yield Sommerfeld coefficient of γ ∼ 7.6(4) mJ/mol K2 and θD ∼ 195(2) K being less than half of that for the nonmagnetic ZrSiS. A three-dimensional (3D) AFM spin structure is supported by the ab initio calculations for Gd having magnetic moment of 7.1 µB and the calculated AFM band structure indicates that GdSbTe is a semimetal with bare density of states (0.36 states/eV fu) at the Fermi level, which is 10 times smaller than the measured one to suggest strong spin-fluctuation.

A copper(ii)-dipicolylamine-coumarin sensor for maltosyltransferase assay.

A Cu(ii)-[di(2-methylpyridyl)methylamino]coumarin fluorescence turn-on sensor (Cu-1b) is designed to detect phosphate ions with Kass = 1.4 × 105 M-1 in HEPES buffer. Cu-1b is applied to probe the GlgE-catalyzed maltose-transfer reaction of α-maltose-1-phosphate to α-1,4-glucan with concomitant release of phosphate ions in Mycobacterium tuberculosis.

Anisotropic magnetotransport and extremely large magnetoresistance in NbAs2 single crystals.

We report the extremely large magnetoresistance and anisotropic magnetoresistance in a non-magnetic semimetallic NbAs2 single crystal. Unsaturated transverse XMR with quadratic field dependence has been observed to be ~3 × 105 % at 2 K and 15 T. Up to 12.5 K, clear Shubnikov de Haas (SdH) quantum oscillations were observed from which two distinct Fermi pockets were identified. The corresponding quantum electronic parameters such as effective cyclotron mass and Dingle temperature were obtained using Lifshitz-Kosevich formula. From the field dependent Hall resistivity at 2 K, carrier concentrations n e (n h ) = 6.7691 (6.4352) × 1025 m-3 and mobilities µ e (µ h ) = 5.6676 (7.6947) m2 V-1 s-1 for electrons (e) and holes (h) were extracted using semiclassical two-band model fitting. We observed large anisotropic magnetoresistance about 84%, 75%, and 12% at 0.75 T and 6 K for three different orientations γ, θ and ϕ, respectively, similar to that in several topological semimetallic systems. Magnetic properties of NbAs2 are similar to the case of graphite, without any phase transition in the temperature range from 5 K to 300 K.

Off-Stoichiometry Driven Carrier Density Variation at the Interface of LaAlO3/SrTiO3.

The interface between LaAlO3 (LAO) and SrTiO3 (STO) has attracted enormous interests due to its rich physical phenomena, such as metallic nature, magnetism and superconductivity. In this work, we report our experimental investigations on the influence of the LAO stoichiometry to the metallic interface. Taking advantage of the oxide molecular beam epitaxy (MBE) technique, a series of high quality LAO films with different nominal La/Al ratios and LAO thicknesses were grown on the TiO2-terminated STO substrates, where systematic variations of the LAO lattice constant and transport property were observed. In particular, the sheet density can be largely reduced by nearly an order of magnitude with merely about 20% increase in the nominal La/Al ratio. Our finding provides an effective method on tuning the electron density of the two-dimensional electron liquid (2DEL) at the LAO/STO interface.

Divergent and Ultrahigh Thermal Conductivity in Millimeter-Long Nanotubes.

Low-dimensional materials could display anomalous thermal conduction that the thermal conductivity (κ) diverges with increasing lengths, in ways inconceivable in any bulk materials. However, previous theoretical or experimental investigations were plagued with many finite-size effects, rendering the results either indirect or inconclusive. Indeed, investigations on the anomalous thermal conduction must demand the sample length to be sufficiently long so that the phenomena could emerge from unwanted finite-size effects. Here we report experimental observations that the κ's of single-wall carbon nanotubes continuously increase with their lengths over 1 mm, reaching at least 8640 W/mK at room temperature. Remarkably, the anomalous thermal conduction persists even with the presence of defects, isotopic disorders, impurities, and surface absorbates. Thus, we demonstrate that the anomalous thermal conduction in real materials can persist over much longer distances than previously thought. The finding would open new regimes for wave engineering of heat as well as manipulating phonons at macroscopic scales.

Geometry-dependent compressive responses in nanoimprinted submicron-structured shape memory polyurethane.

High resolution surface textures, when rationally designed, provide an attractive surface engineering approach to enhance surface functionalities. Designing smart surfaces by coupling surface texture with shape memory polymers has garnered attention in achieving tunable mechanical properties. We investigate the structure-mechanical property relationships for programmable, shape-memorizing submicron-scale pillar arrays subjected to flat-punch compression. The geometrically-dependent deformation of structured surfaces with two different aspect ratios (250 nm-pillars 1 : 1 and 550 nm-pillars 2.4 : 1) were investigated, and their moduli were found to be lower than that of non-patterned surface. From finite element analysis, the pillar deformation is correlated to a mechanistic transition from a discrete, unidirectional compression of 250 nm-pillars to lateral constraints caused by interpillar contact in 550 nm-pillars. This lateral pillar-pillar contact in the 550 nm-pillars resulted in an increased and maximum strain-dependent modulus but lower elastic recovery and energy dissipation as compared with the 250 nm-pillars. Furthermore, the compressive responses of temporarily shaped pillars (programmed by stretching) were compared with the permanently shaped pillars. The extent of lateral constraints controlled by pillar shape and spacing in 550 nm-pillars was responsible for the modulus differences between the original and stretched patterns, whereas the modulus of 250 nm-pillars remained as a constant value with different levels of stretching. This study provides mechanistic insights into how the mechanical behavior can be modulated by designing the aspect ratio of shape memory pillar arrays and by programming the surface geometry, thus revealing the potential of developing ingenious designs of responsive surfaces sensitive to mechanical deformation.

Anisotropic superconducting property studies of single crystal PbTaSe2.

The anisotropic superconducting properties of PbTaSe2 single crystal is reported. Superconductivity with T c = 3.83 ± 0.02 K has been characterized fully with electrical resistivity ρ(T), magnetic susceptibility χ(T), and specific heat C p (T) measurements using single crystal samples. The superconductivity is type-II with lower critical field H c1 and upper critical field H c2 of 65 and 450 Oe (H⊥ to the ab-plane), 140 and 1500 Oe (H|| to the ab-plane), respectively. These results indicate that the superconductivity of PbTaSe2 is anisotropic. The superconducting anisotropy, electron-phonon coupling λ ep, superconducting energy gap Δ0, and the specific heat jump ΔC/γT c at T c confirms that PbTaSe2 can be categorized as a bulk superconductor.

Osmogen-Mediated One-Step Technique of Fabricating Hollow Microparticles for Encapsulation and Delivery of Bioactive Molecules.

Microparticulate systems composed of biodegradable polymers, such as poly(d,l-lactic-co-glycolic acid) (PLGA), are widely used for controlled release of bioactive molecules. However, the acidic microenvironment within these microparticles, as they degrade, has been reported to perturb the configuration of most encapsulated proteins. In addition, these polymer particles are also reported to suffer from unrealistically slow and incomplete release of proteins. To address these drawbacks, hollow PLGA microparticles are fabricated through a novel one-step oil-in-water emulsion solvent evaporation technique, by capitalizing on the osmotic property of an osmogen. The effects of fabrication para-meters on particle size and morphology, i.e., volume space of hollow cavity and shell thickness, are also studied. These hollow microparticles are subsequently loaded with bovine insulin microcrystals. It is shown that insulin release profiles can be tuned by simply changing the amount of osmogen in the formulation. At the same time, these hollow microparticles are shown to be effective in maintaining the bioactivity of the encapsulated protein.

Unusual imaging properties of superresolution microspheres.

We employ a self-assembly method to fabricate dielectric microsphere arrays that can be transferred to any desired positions. The arrays not only enable far-field, broad-band, high-speed, large-area, and wide-angle field of views but also achieve superresolution reaching λ/6.4. We also find that many proposed theories are insufficient to explain the imaging properties; including the achieved superresolution, effects of immersion, and unusual size-dependent magnification. The half-immersed microspheres certainly do not behave like any ordinary solid immersion lenses and new mechanisms must be incorporated to explain their unusual imaging properties.

Large transverse Hall-like signal in topological Dirac semimetal Cd3As2.

Cadmium arsenide (Cd3As2) is known for its inverted band structure and ultra-high electron mobility. It has been theoretically predicted and also confirmed by ARPES experiments to exhibit a 3D Dirac semimetal phase containing degenerate Weyl nodes. From magneto-transport measurements in high quality single crystals of Cd3As2, a small effective mass m(*) ≈ 0.05 me is determined from the Shubnikov-de Haas (SdH) oscillations. In certain field orientations, we find a splitting of the SdH oscillation frequency in the FFT spectrum suggesting a possible lifting of the double degeneracy in accord with the helical spin texture at outer and inner Fermi surfaces with opposite chirality predicted by our ab initio calculations. Strikingly, a large antisymmetric magnetoresistance with respect to the applied magnetic fields is uncovered over a wide temperature range in needle crystal of Cd3As2 with its long axis along [112] crystal direction. It reveals a possible contribution of intrinsic anomalous velocity term in the transport equation resulting from a unique 3D Rashba-like spin splitted bands that can be obtained from band calculations with the inclusion of Cd antisite defects.

Geometry- and Length Scale-Dependent Deformation and Recovery on Micro- and Nanopatterned Shape Memory Polymer Surfaces.

Micro- and nanoscale surface textures, when optimally designed, present a unique approach to improve surface functionalities. Coupling surface texture with shape memory polymers may generate reversibly tuneable surface properties. A shape memory polyetherurethane is used to prepare various surface textures including 2 µm- and 200 nm-gratings, 250 nm-pillars and 200 nm-holes. The mechanical deformation via stretching and recovery of the surface texture are investigated as a function of length scales and shapes. Results show the 200 nm-grating exhibiting more deformation than 2 µm-grating. Grating imparts anisotropic and surface area-to-volume effects, causing different degree of deformation between gratings and pillars under the same applied macroscopic strain. Full distribution of stress within the film causes the holes to deform more substantially than the pillars. In the recovery study, unlike a nearly complete recovery for the gratings after 10 transformation cycles, the high contribution of surface energy impedes the recovery of holes and pillars. The surface textures are shown to perform a switchable wetting function. This study provides insights into how geometric features of shape memory surface patterns can be designed to modulate the shape programming and recovery, and how the control of reversibly deformable surface textures can be applied to transfer microdroplets.

Thermoelectric Power in Bilayer Graphene Device with Ionic Liquid Gating.

The quest for materials showing large thermoelectric power has long been one of the important subjects in material science and technology. Such materials have great potential for thermoelectric cooling and also high figure of merit ZT thermoelectric applications. We have fabricated bilayer graphene devices with ionic-liquid gating in order to tune its band gap via application of a perpendicular electric field on a bilayer graphene. By keeping the Fermi level at charge neutral point during the cool-down, we found that the charge puddles effect can be greatly reduced and thus largely improve the transport properties at low T in graphene-based devices using ionic liquid gating. At (Vig, Vbg) = (-1 V, +23 V), a band gap of about 36.6 ± 3 meV forms, and a nearly 40% enhancement of thermoelectric power at T = 120 K is clearly observed. Our works demonstrate the feasibility of band gap tuning in a bilayer graphene using ionic liquid gating. We also remark on the significant influence of the charge puddles effect in ionic-liquid-based devices.