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Background: To avoid complete elimination of hen eggs (HE) from diet, we introduced a very-low-dose (VLD) oral food challenge (OFC) in patients with severe HE allergy in 2019. Herein, we investigated the efficacy of VLD HE OFC for achieving the full dose OFC. Methods: Patients with an overt allergic reaction to LD (1/32 HE [≤100 mg]) or less, egg white (EW) protein within 6 months were included. In the VLD group, patients not achieving full-dose OFC (1/2 HE: 1600 mg EW protein) within 2 years were excluded. We retrospectively compared the rate of passing a full-dose OFC between patients who underwent a LD OFC before 2019 (LD group) and those who underwent a VLD OFC (1/100 HE: 32 mg EW protein) after 2019 (VLD group). The period for passing the full-dose OFC was evaluated using Kaplan–Meier survival analysis. Results: We enrolled 411 and 111 patients in the LD and VLD groups, respectively. The median age at OFC initiation was 2.2 [1.5–3.6] and 2.1 [1.4–3.2] years in the LD and VLD groups, respectively. EW- and ovomucoid-specific IgE levels were 38.3 (12.5–72.9) and 21.0 (8.3–46.2) kUA/L in the LD group and 49.8 [18.8–83.9] and 32.1 [15.6–67.8] kUA/L in the VLD group, respectively. Over 4 years, the LD and VLD groups passed the full-dose OFC at rates of 70 and 95%, respectively, with significant differences (log-rank test, P

Background: There are no reports on the relationship between food protein–induced enterocolitis syndrome (FPIES) diagnosis and procalcitonin levels. Objective: Our study sought to demonstrate a correlation between the presence or absence and severity of FPIES symptoms and postemetic procalcitonin levels. Methods: The subjects were 53 patients with FPIES (44 with hen’s egg allergy, 4 with milk allergy, 4 with wheat allergy, and 3 with soy allergy), who collectively underwent a total of 75 oral food challenges (OFCs). Procalcitonin levels at 5 hours after antigen ingestion were compared between patients with a positive OFC result and those with a negative OFC result and between patients who experienced mild or moderate events and those who experienced severe events. Results: At 5 hours after ingestion of the causative food, the median procalcitonin levels in patients with a negative OFC result, patients who experienced a mild or moderate event, and patients who experienced a severe event were 0.02, 0.03, and 0.16 ng/mL, respectively. The procalcitonin level was significantly higher in the groups with a positive OFC result than in the groups with a negative OFC result (P < .001), and it was significantly higher in those who experienced severe events than in those who experienced mild or moderate events (P = .012). Conclusion: Measurement of procalcitonin levels has the potential to provide a quantitative and objective assessment of FPIES diagnosis and severity.

Abstract Microplastic (MP) pollution is a major concern in aquatic environments. Many studies have detected MPs in fishes; however, little is known about differences of microplastic uptake by fish in freshwater (FW) and those in seawater (SW), although physiological conditions of fish differ significantly in the two media. In this study, we exposed larvae (21 days post-hatching) of Oryzias javanicus (euryhaline SW) and Oryzias latipes (euryhaline FW), to 1-µm polystyrene microspheres in SW and FW for 1, 3, or 7 days, after which, microscopic observation was conducted. MPs were detected in the gastrointestinal tracts in both FW and SW groups, and MP numbers were higher in the SW group in both species. Vertical distribution of MPs in the water, and body sizes of both species exhibited no significant difference between SW and FW. Detection of water containing a fluorescent dye revealed that O. javanicus larvae swallowed more water in SW than in FW, as has also been reported for O. latipes. Therefore, MPs are thought to be ingested with water for osmoregulation. These results imply that SW fish ingest more MPs than FW fish when exposed to the same concentration of MPs.

A novel experiment device was employed to investigate the tensile strength and fracture mechanism of single abaca fibers. Twenty specimens of untreated single fibers with a gauge length of 30 mm were subjected to tensile force with a loading rate of 0.46 N/s. Results show that the tensile strength of the fiber ranges from 417 MPa to 1548 MPa. The tensile strength was calculated using the measured value of cross-sectional area of each fiber, evaluated by using a three-dimensional microscopic observation. The observation conducted for all specimens reveals the fracture mechanism of the single fiber classified into three types, i.e. shear, tension, and combined of shear and tension. The considerably high tensile strength of the single fiber and fracture mechanism of the single fiber provide a possibility for designing high strength abaca fiber reinforced composite for various engineering applications.

ABSTRACT Scleractinian corals form symbiotic relationships with a variety of microorganisms, including endosymbiotic dinoflagellates of the family Symbiodiniaceae, and with bacteria, which are collectively termed coral holobionts. Interactions between hosts and their symbionts are critical to the physiological status of corals. Coral-microorganism interactions have been studied extensively, but dinoflagellate-bacterial interactions remain largely unexplored. Here, we developed a microbiome manipulation method employing KAS-antibiotic treatment (kanamycin, ampicillin, and streptomycin) to favor pigmented bacteria residing on cultured Cladocopium and Durusdinium, major endosymbionts of corals, and isolated several carotenoid-producing bacteria from cell surfaces of the microalgae. Following KAS-antibiotic treatment of Cladocopium sp. strain NIES-4077, pigmented bacteria increased 8-fold based on colony-forming assays from the parental strain, and 100% of bacterial sequences retrieved through 16S rRNA amplicon sequencing were affiliated with the genus Maribacter. Microbiome manipulation enabled host microalgae to maintain higher maximum quantum yield of photosystem II (variable fluorescence divided by maximum fluorescence [Fv/Fm]) under light-stress conditions, compared to the parental strain. Furthermore, by combining culture-dependent and -independent techniques, we demonstrated that species of the family Symbiodiniaceae and pigmented bacteria form strong interactions. Dinoflagellates protected bacteria from antibiotics, while pigmented bacteria protected microalgal cells from light stress via carotenoid production. Here, we describe for the first time a symbiotic relationship in which dinoflagellates and bacteria mutually reduce environmental stress. Investigations of microalgal-bacterial interactions further document bacterial contributions to coral holobionts and may facilitate development of novel techniques for microbiome-mediated coral reef conservation. IMPORTANCE Coral reefs cover less than 0.1% of the ocean floor, but about 25% of all marine species depend on coral reefs at some point in their life cycles. However, rising ocean temperatures associated with global climate change are a serious threat to coral reefs, causing dysfunction of the photosynthetic apparatus of endosymbiotic microalgae of corals, and overproducing reactive oxygen species harmful to corals. We manipulated the microbiome using an antibiotic treatment to favor pigmented bacteria, enabling their symbiotic microalgal partners to maintain higher photosynthetic function under insolation stress. Furthermore, we investigated mechanisms underlying microalgal-bacterial interactions, describing for the first time a symbiotic relationship in which the two symbionts mutually reduce environmental stress. Our findings extend current insights about microalgal-bacterial interactions, enabling better understanding of bacterial contributions to coral holobionts under stressful conditions and offering hope of reducing the adverse impacts of global warming on coral reefs.

Mieko Sassa et al. report a novel divalent metal transporter protein (DMTRP) in the crown-of-thorns starfish genome and determine that all organisms with a DMTRP gene are located in marine habitats. They also show in a functional yeast system that DMTRP can prevent uptake of certain metals, bringing insight into the evolution of metal regulation for marine organisms.

Abstract Magnetic Barkhausen Noise (MBN) method is known as an effective nondestructive evaluation (NDE) method for evaluation of residual stress in ferromagnetic materials. Some studies on the feasibility of the MBN method for NDE of residual strains were also conducted and found applicable. However, these studies are mainly focused on the state of residual strains which were introduced through a one-cycle-loading process. In practice, however, structures may suffer from an unpredictable and complicated loading history, i.e., the final state of plastic strain may be induced by several times of large loads. Whether the loading history has influences on MBN signals or not is of great importance for the practical application of the MBN method. In this paper, several ferromagnetic specimens with the same final state of residual strain but of different loading history were fabricated and inspected by using a MBN testing system. The experimental results reveal that the loading history has a significant influence on the detected MBN signals especially for a residual strain in range less than 1%, which doubts the feasibility to apply the MBN method simply in the practical environment. In addition, micro-observations on the magnetic domain structures of the plastic damaged specimens were also carried out to clarify the influence mechanism of loading history on the MBN signals.

Achieving low-friction and robust tribosystems is an open and challenging question to tribologists. In this study, we are considering the diamond films as candidates. Quantification of friction is obtained here using an original technique, so called the oscillating relaxation tribometry. It is based on the study of the oscillating motion of a free-damped 1-DOF mechanical oscillator, the sliding contact acting as a main source of mechanical dissipation (“relaxation”). Therefore, it is possible to determine friction value and its sliding speed dependency, i.e. a kind of “Stribeck curve“ under non-stationary conditions. The interest of such “relaxation tribometer“ is to characterize low friction with an unequalled sensitivity, and to directly obtain the “friction law“ thanks to a robust and rapid experimental test. Polycrystalline diamond films are deposited by the Hot Filament CVD method on SiC substrate, which were partly polished and finished to gradient surface roughness with random-textured asperities. Stainless steel balls of 6.0 mm diameter are used as the rubbing counterface. The normal force is varied between 50 and 300 mN, leading respectively to a maximum Hertzian contact pressure of 0.30 and 0.71 GPa, respectively. Taking into account the experimental setup, the sliding speed is decaying as a damped pseudo-sine motion, the maximum sliding value being set to 0.16 m/s, progressively decaying to 0 when mechanical equilibrium is reached, within a typical duration of 5 s. First results are reported here, using this innovative friction characterization technique. The different contributions to friction of the surface roughness are analyzed and discussed. These results show the major interest of the use of this method to characterize the low-friction behavior of textured diamond films. These results are discussed and the high potential of such textured films in actual tribosystems is presented here.

Inside living organisms, concentration gradients dynamically change over time as biological processes progress. Therefore, methods to construct dynamic microscale concentration gradients in a spatially controlled manner are needed to provide more realistic research environments. Here, we report a novel method for the construction of dynamic microscale concentration gradients in a stepwise manner around cells in micropatterned hydrogel. In our method, cells are encapsulated in a photodegradable hydrogel formed inside a microfluidic perfusion culture device, and perfusion microchannels are then fabricated in the hydrogel by micropatterned photodegradation. The cells in the micropatterned hydrogel can then be cultured by perfusing culture medium through the fabricated microchannels. By using this method, we demonstrate the simultaneous construction of two dynamic concentration gradients, which allowed us to expose the cells encapsulated in the hydrogel to a dynamic microenvironment.

ABSTRACT Reef-building corals form a complex consortium with photosynthetic algae in the family Symbiodiniaceae and bacteria, collectively termed the coral holobiont. These bacteria are hypothesized to be involved in the stress resistance of the coral holobiont, but their functional roles remain largely elusive. Here, we show that cultured Symbiodiniaceae algae isolated from the reef-building coral Galaxea fascicularis are associated with novel bacteria affiliated with the family Flavobacteriaceae. Antibiotic treatment eliminated the bacteria from cultured Symbiodiniaceae, resulting in a decreased maximum quantum yield of PSII (variable fluorescence divided by maximum fluorescence [Fv/Fm]) and an increased production of reactive oxygen species (ROS) under thermal and light stresses. We then isolated this bacterial strain, named GF1. GF1 inoculation in the antibiotic-treated Symbiodiniaceae cultures restored the Fv/Fm and reduced the ROS production. Furthermore, we found that GF1 produces the carotenoid zeaxanthin, which possesses potent antioxidant activity. Zeaxanthin supplementation to cultured Symbiodiniaceae ameliorated the Fv/Fm and ROS production, suggesting that GF1 mitigates thermal and light stresses in cultured Symbiodiniaceae via zeaxanthin production. These findings could advance our understanding of the roles of bacteria in Symbiodiniaceae and the coral holobiont, thereby contributing to the development of novel approaches toward coral protection through the use of symbiotic bacteria and their metabolites. IMPORTANCE Occupying less than 1% of the seas, coral reefs are estimated to harbor ∼25% of all marine species. However, the destruction of coral reefs has intensified in the face of global climate changes, such as rising seawater temperatures, which induce the overproduction of reactive oxygen species harmful to corals. Although reef-building corals form complex consortia with bacteria and photosynthetic endosymbiotic algae of the family Symbiodiniaceae, the functional roles of coral-associated bacteria remain largely elusive. By manipulating the Symbiodiniaceae bacterial community, we demonstrated that a bacterium that produces an antioxidant carotenoid could mitigate thermal and light stresses in cultured Symbiodiniaceae isolated from a reef-building coral. Therefore, this study illuminates the unexplored roles of coral-associated bacteria under stressful conditions.

Unidirectional friction experiments on uniaxially compressed pure Cu powder were performed to clarify how the solid-phase interparticle bonding proceeds during a powder molding method by applying biaxial force, termed as a compression shearing method at room temperature. Relations among the applied normal load, number of sliding cycles, and microstructural changes of the powder particles were investigated by morphological and cross-sectional observations of the samples after the friction experiments. The structural observations revealed some layered regions with different microstructures within the sample cross-section. All regions increased in size at a higher applied normal load, but their size did not change as the number of the sliding cycles increased. This phenomenon was quantitatively explained by Hamilton and Goodman’s model, which showed that the applied normal load correlated with the stress distribution applied to the sample. Tensile stress applied to the powder particles along the sliding direction appeared to be most effective for interparticle bonding. In addition, it was suggested that the bonding process of the powder particles proceeded through the steps: (1) plastic deformation; (2) initially crystal grain refinement to micrometer size; (3) bonding by local sliding between powder particles; and (4) crystal grain refinement to sub-micrometer size.

We use a Cu/MoS2 composite to provide a new approach to control the consolidation of materials by compression–shearing at room temperature. Cu/MoS2 samples were formed under several shearing distances and the resulting microstructures were observed and compared with pure Cu samples. The microstructural change related to the decrease in applied shearing force is discussed. The structural observations indicate that the reason for the decrease in shearing force appears to be the slip of the sample on the lower plate because of MoS2 lubrication. The internal structure of the Cu/MoS2 samples appears to be interrupted midway through the consolidation process by dissipating the applied shearing force. In contrast, particle bonding and grain refinement occurred only on the sample surface, as for the friction process, and extended gradually to the inside of the sample when the shearing distance increased. We controlled the metal consolidation by compression shearing at room temperature by dispersing MoS2 into a Cu matrix. The shearing force appears to be more effective in metal consolidation by compression shearing at room temperature than the shearing distance.

Cadmium telluride (CdTe) is used as an X-ray image detector for dental applications. However, it is difficult to fabricate the large CdTe chips for such applications. Therefore, it is necessary to increase the detection area by tiling. In this study, to minimize the dead space caused by bonding CdTe and application-specific integrated circuits (ASICs), the detector was three-dimensionally stacked by flip-chip bonding. Furthermore, to achieve a high spatial resolution, a diode-type detector that can apply a high electric field was used. However, in flipchip bonding, layers were stacked while applying pressure and heat; therefore, Schottky-type detectors, which are diode-type detectors, were expected to have a low breakdown voltage because the Schottky junction was located at the interface between the CdTe layer and the electrode. However, the p-n junction was expected to have a high voltage resistance because it was located inside the CdTe layer. Therefore, we performed pressure tests on Schottky-type and p-n junction CdTe detectors, and the I-V and gamma-ray spectral characteristics before and after the tests were evaluated. As expected, the Schottky-type detector stopped exhibiting diode characteristics after pressurization, the reverse current increased, and gamma rays could hardly be detected; however, the p-n junction detector maintained its diode characteristics even after pressurization, and the I-V characteristics indicated a high voltage resistance with almost no change in both the I-V and the gamma-ray spectral characteristics. [ABSTRACT FROM AUTHOR]

Polarization poses a significant challenge in cadmium telluride (CdTe) detectors, preventing the simultaneous achievement of high energy resolution and long-term stability at room temperature. The mechanism driving bias-induced polarization is presumed to involve an increase in the number of ionized acceptors resulting from hole detrapping. Simultaneously, the accumulation of negative charges is suppressed as the hole density in the bulk increases. Consequently, polarization effects occur in diode-type detectors with low current densities but not in ohmic detectors with high current densities. In this study, we fabricated a diode-type detector with a high current density, which is between those of the ohmic and diode types, and evaluated its long-term stability. The detector had dimensions of 3 × 3 × 0.75 mm³, comprising a central electrode of 0.5 × 0.5 mm² surrounded by a guard-ring electrode. By finely patterning the anode, we increased the current density, achieving a current density comparable to that of the ohmic type while enabling the application of a higher bias voltage. [ABSTRACT FROM AUTHOR]

The significance of X-ray spectral information is steadily growing. However, pile-up is becoming a pertinent problem at high dosage levels. Additionally, attempts to mitigate pile-up by reducing the surface area of the detector result in charge sharing, making accurate spectrum determination complicated. When materials such as cadmium telluride are employed as detectors, a significant disparity in the mobility of electrons and holes can lead to pulses in the opposite direction across multiple electrodes. We propose to identify charge-sharing events by detecting these opposing pulses. We found that eliminating events associated with negative pulses from the spectrum reduced the full width at half maximum of the peak from 15.9 to 14.4 keV. The proposed method improves the accuracy of spectral measurements under high flux to reduce the effect of charge sharing in single-point spectral measurements. [ABSTRACT FROM AUTHOR]

Cu/MoS2 composite material was formed by a novel powder-molding technique, which is termed the compression shearing method at room temperature (COSME-RT). Cu/MoS2 sample mechanical and tribological properties and microstructures were investigated. Samples were prepared using five different MoS2 concentrations between 0 to 20 vol.%. No unwanted compounds were generated by the Cu and MoS2 because a high temperature is unnecessary in COSME-RT. Scanning electron microscopy observations confirmed that the MoS2 particles were dispersed homogeneously in the Cu host matrix. The indentation hardness of Cu/MoS2 with 0, 1.0 and 5.0 vol.% MoS2 was higher than 1.6 GPa, and is higher than that formed by conventional powder metallurgy methods and a pure Cu plate. The indentation hardness of the Cu/MoS2 decreased with increasing MoS2 concentration. In contrast, the lubricating performance of MoS2 became more pronounced at 5.0 vol.% or above. The coefficient of friction of Cu/MoS2 with 5.0, 10 and 20 vol.% MoS2 was ~0.20, and is the same as for MoS2 in air. The sample coefficient of friction was maintained because of lubrication by forming a transferred film of wear debris that contained MoS2. Cu/MoS2 had a low coefficient of friction, but maintained its material strength at 5.0 vol.% MoS2.

Engineered blood vessels generally recapitulate vascular function in vitro and can be utilized in drug discovery as a novel microphysiological system. Recently, various methods to fabricate vascular models in hydrogels have been reported to study the blood vessel functions in vitro; however, in general, it is difficult to fabricate hollow structures with a designed size and structure with a tens of micrometers scale for blood vessel tissue engineering. This study reports a method to fabricate the hollow structures in photodegradable hydrogels prepared in a microfluidic device. An infrared femtosecond pulsed laser, employed to induce photodegradation via multi-photon excitation, was scanned in the hydrogel in a program-controlled manner for fabricating the designed hollow structures. The photodegradable hydrogel was prepared by a crosslinking reaction between an azide-modified gelatin solution and a dibenzocyclooctyl-terminated photocleavable tetra-arm polyethylene glycol crosslinker solution. After assessing the composition of the photodegradable hydrogel in terms of swelling and cell adhesion, the hydrogel prepared in the microfluidic device was processed by laser scanning to fabricate linear and branched hollow structures present in it. We introduced a microsphere suspension into the fabricated structure in photodegradable hydrogels, and confirmed the fabrication of perfusable hollow structures of designed patterns via the multi-photon excitation process.

Formation processes of metal-rich tribofilm on the counterface during sliding against metal/diamondlike-carbon nanocomposite coatings have been investigate. The hybridization between DLC matrix and Cu or Ag provides good electric conductivity to solid lubricant films. Metal-rich tribofilms are formed on the counterface of both Cu-DLC and Ag-DLC during sliding, which is important factor to obtain excellent tribological performance as well as good electric conductivity. Such tribofilms are almost pure Cu and Ag. The origin of the tribofilm is the metal clusters in the Me-DLC, and the adhered Cu and Ag clusters on the counterfaces are possibly sintered and refined during iterative plastic deformation in the frictional interface which generates high pressure and high shear rate.

To accurately measure crack lengths, we developed a real-time surface imaging method (SAW PA) combining an ultrasonic phased array (PA) with a surface acoustic wave (SAW). SAW PA using a Rayleigh wave with a high sensitivity to surface defects was implemented for contact testing using a wedge with the third critical angle that allows the Rayleigh wave to be generated. Here, to realize high sensitivity imaging, SAW PA was optimized in terms of the wedge and the imaging area. The improved SAW PA was experimentally demonstrated using a fatigue crack specimen made of an aluminum alloy. For further verification in more realistic specimens, SAW PA was applied to stainless-steel specimens with a fatigue crack and stress corrosion cracks (SCCs). The fatigue crack was visualized with a high signal-to-noise ratio (SNR) and its length was measured with a high accuracy of better than 1 mm. The SCCs generated in the heat-affected zones (HAZs) of a weld were successfully visualized with a satisfactory SNR, although responses at coarse grains appeared throughout the imaging area. The SCC lengths were accurately measured. The imaging results also precisely showed complicated distributions of SCCs, which were in excellent agreement with the optically observed distributions.

Understanding tumor heterogeneity is an urgent and unmet need in cancer research. In this study, we used a morphology-based optical cell separation process to classify a heterogeneous cancer cell population into characteristic subpopulations. To classify the cell subpopulations, we assessed their morphology in hydrogel, a three-dimensional culture environment that induces morphological changes according to the characteristics of the cells (i.e., growth, migration, and invasion). We encapsulated the murine breast cancer cell line 4T1E, as a heterogeneous population that includes highly metastatic cells, in click-crosslinkable and photodegradable gelatin hydrogels, which we developed previously. We observed morphological changes within 3 days of encapsulating the cells in the hydrogel. We separated the 4T1E cell population into colony- and granular-type cells by optical separation, in which local UV-induced degradation of the photodegradable hydrogel around the target cells enabled us to collect those cells. The obtained colony- and granular-type cells were evaluated in vitro by using a spheroid assay and in vivo by means of a tumor growth and metastasis assay. The spheroid assay showed that the colony-type cells formed compact spheroids in 2 days, whereas the granular-type cells did not form spheroids. The tumor growth assay in mice revealed that the granular-type cells exhibited lower tumor growth and a different metastasis behavior compared with the colony-type cells. These results suggest that morphology-based optical cell separation is a useful technique to classify a heterogeneous cancer cell population according to its cellular characteristics.

Electrically conductive tribo-coatings (i.e. Ir-DLCs) were developed using a hybrid deposition process, combining RF-PECVD with DC magnetron sputtering of Ir. Pin-on-plate tribotests in reciprocating motion were performed in air on Ir, DLC and Ir-DLC coated plates against bearing steel pins under 0.5 N load. The electrical contact resistance was measured during the tribotests, and for Ir-DLC it was below 30 Ω. Neither the pure DLC layer nor the pure Ir layer reached friction coefficients lower than 0.2, while the Ir-DLC went down to 0.05. For Ir-DLCs, however, relatively high and unstable friction was occasionally observed. Possible causes of the instability are discussed by focusing on the characteristics of the tribofilm and the formation of wear debris.

To promote the functional restoration of the nervous system following injury, it is necessary to provide optimal extracellular signals that can induce neuronal regenerative activities, particularly neurite formation. This study aimed to examine the regulation of neuritogenesis by temperature-controlled repeated thermal stimulation (TRTS) in rat PC12 pheochromocytoma cells, which can be induced by neurotrophic factors to differentiate into neuron-like cells with elongated neurites. A heating plate was used to apply thermal stimulation, and the correlation of culture medium temperature with varying surface temperature of the heating plate was monitored. Plated PC12 cells were exposed to TRTS at two different temperatures via heating plate (preset surface temperature of the heating plate, 39.5°C or 42°C) in growth or differentiating medium for up to 18 h per day. We then measured the extent of growth, neuritogenesis, or acetylcholine esterase (AChE) activity (a neuronal marker). To analyze the mechanisms underlying the effects of TRTS on these cells, we examined changes in intracellular signaling using the following: tropomyosin-related kinase A inhibitor GW441756; p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580; and MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126 with its inactive analog, U0124, as a control. While a TRTS of 39.5°C did not decrease the growth rate of cells in the cell growth assay, it did increase the number of neurite-bearing PC12 cells and AChE activity without the addition of other neuritogenesis inducers. Furthermore, U0126, and SB203580, but not U0124 and GW441756, considerably inhibited TRTS-induced neuritogenesis. These results suggest that TRTS can induce neuritogenesis and that participation of both the ERK1/2 and p38 MAPK signaling pathways is required for TRTS-dependent neuritogenesis in PC12 cells. Thus, TRTS may be an effective technique for regenerative neuromedicine.