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Sensorimotor information processing underlies normal cognitive and behavioral traits and has classically been evaluated through prepulse inhibition (PPI) of a startle reflex. PPI is a behavioral dimension deregulated in several neurological and psychiatric disorders, yet the mechanisms underlying the cross-diagnostic nature of PPI deficits across these conditions remain to be understood. To identify circuitry mechanisms for PPI, we performed circuitry recording over the prefrontal cortex and striatum, two brain regions previously implicated in PPI, using wild-type (WT) mice compared to Disc1-locus-impairment (LI) mice, a model representing neuropsychiatric conditions. We demonstrated that the corticostriatal projection regulates neurophysiological responses during the PPI testing in WT, whereas these circuitry responses were disrupted in Disc1-LI mice. Because our biochemical analyses revealed attenuated brain-derived neurotrophic factor (Bdnf) transport along the corticostriatal circuit in Disc1-LI mice, we investigated the potential role of Bdnf in this circuitry for regulation of PPI. Virus-mediated delivery of Bdnf into the striatum rescued PPI deficits in Disc1-LI mice. Pharmacologically augmenting Bdnf transport by chronic lithium administration, partly via phosphorylation of Huntingtin (Htt) serine-421 and its integration into the motor machinery, restored striatal Bdnf levels and rescued PPI deficits in Disc1-LI mice. Furthermore, reducing the cortical Bdnf expression negated this rescuing effect of lithium, confirming the key role of Bdnf in lithium-mediated PPI rescuing. Collectively, the data suggest that striatal Bdnf supply, collaboratively regulated by Htt and Disc1 along the corticostriatal circuit, is involved in sensorimotor gating, highlighting the utility of dimensional approach in investigating pathophysiological mechanisms across neuropsychiatric disorders.

Lymphoepithelial carcinoma is an extremely rare malignant tumor, especially those localized at the head and neck region. The histological prototype of lymphoepithelial carcinoma is undifferentiated nasopharyngeal carcinoma. Herein, we report a case of a tumor localized in the left submandibular gland in a 20-year-old male. The tumor mass was surgically excised with the submandibular gland, and the specimen was pathologically confirmed to be lymphoepithelial carcinoma.

Conjugated polymer-based energy-harvesting devices hold distinctive advantages in terms of low toxicity, high flexibility, and capability of large-area integration at low cost for sustainable development. An organic thermoelectric (OTE) device has been considered one of the promising energy-harvesting candidates in recent years because it can efficiently convert low-temperature waste heat into electricity over its inorganic counterparts. However, a cruel irony is that environmentally toxic solvents and acids are utilized for fabrication and performance improvement of the OTE devices, retarding the development and use of genuinely green energy-harvesting. Here, we present eco-friendly, non-toxic strategies for a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)-based high-performance OTE device by incorporating a nature-abundant material, vitamin C (VC), as an additive. We found that the intrinsic polar nature and reducing ability of VC induce synergy effects of microstructure alignment with PSS removal and dedoping of PEDOT, leading to simultaneous enhancement of the electrical conductivity (400 S cm

The all-hydrogel gripper was composed of three temperature-responsive hydrogels that mimicked the human bone, cartilage, and flexor tendon. With tough adhesion via split-brushing adhesion, our all-hydrogel gripper showed a high load capacity.

Deficits in social cognition consistently underlie functional disabilities in a wide range of psychiatric disorders. Neuroimaging studies have suggested that the anterior insula is a "common core" brain region that is impaired across neurological and psychiatric disorders, which include social cognition deficits. Nevertheless, neurobiological mechanisms of the anterior insula for social cognition remain elusive. This study aims to fill this knowledge gap.To determine the role of the anterior insula in social cognition, the authors manipulated expression of Cyp26B1, an anterior insula-enriched molecule that is crucial for retinoic acid degradation and is involved in the pathology of neuropsychiatric conditions. Social cognition was mainly assayed using the three-chamber social interaction test. Multimodal analyses were conducted at the molecular, cellular, circuitry, and behavioral levels.At the molecular and cellular level, anterior insula-mediated social novelty recognition is maintained by proper activity of the layer 5 pyramidal neurons, for which retinoic acid-mediated gene transcription can play a role. The authors also demonstrate that oxytocin influences the anterior insula-mediated social novelty recognition, although not by direct projection of oxytocin neurons, nor by direct diffusion of oxytocin to the anterior insula, which contrasts with the modes of oxytocin regulation onto the posterior insula. Instead, oxytocin affects oxytocin receptor-expressing neurons in the dorsal raphe nucleus, where serotonergic neurons are projected to the anterior insula. Furthermore, the authors show that serotonin 5-HTThe anterior insula plays a pivotal role in social novelty recognition that is partly regulated by a local retinoic acid cascade but also remotely regulated by oxytocin via a long-range circuit mechanism.

Minoxidil is the most widely used treatment for hair growth, but has been associated with several side effects. In this study, we investigated the effects of heat-killed Enterococcus faecalis EF-2001 on hair loss prevention and regrowth using human dermal papilla cells and male C57BL/6 mice. To examine the effects of EF-2001, we used minoxidil as the positive control. In the in vitro experiments, EF-2001 treatment (75–500 μg/mL) led to the proliferation of human dermal papilla cells in a concentration-dependent manner. In the in vivo experiment, the topical application of 200 µL EF-2001 on the dorsal surface of C57BL/6 male mice led to hair growth. Changes in hair regrowth were examined by visual comparison and hematoxylin and eosin staining of skin sections. We also determined the expression levels of marker genes (Wnt) and growth factors (fibroblast growth factor, insulin growth factor 1, and vascular endothelial growth factor) in the skin tissues of the back of each mouse using a quantitative polymerase chain reaction. EF-2001 accelerated the progression of hair regrowth in mice and promoted hair-follicle conversion from telogen to anagen, likely by increasing the expression levels of growth factors and marker genes.

Objectives. Although osteotomy is an important part of rhinoplasty, it is known to be closely related to postoperative eyelid edema and ecchymosis. We aimed to evaluate the effects of periosteal elevation prior to osteotomy on eyelid edema and ecchymosis.Methods. Two authors reviewed studies in the Medline, Scopus, and Cochrane databases published through May 2019. Randomized controlled trials comparing periosteal elevation (subperiosteal tunneling) with periosteal preservation that reported eyelid edema or ecchymosis or subconjunctival hemorrhage as outcomes of interest were included. From each study, the baseline characteristics of the study subjects, the quality of the study, the number of patients in the treatment and control groups, and outcomes were extracted.Results. Data for meta-analysis were identified in six studies with a total of 208 patients. Eyelid ecchymosis and edema within 3 days postoperatively were significantly more common in the periosteal elevation group than in the preservation group, although such an association was not found for edema on postoperative day 7 (standardized mean difference [SMD], 0.21; 95% confidence interval [CI], –0.09 to 0.50; I2 =0%). There was no significant difference in subconjunctival hemorrhage on day 1 (SMD, 0.31; 95% CI, –0.09 to 0.72; I2 =0%).Conclusion. Periosteal preservation during lateral osteotomy may reduce eyelid edema and ecchymosis compared to periosteal elevation. Further studies with rigorous research methods should be carried out to determine the effectiveness of different techniques in lateral osteotomy.

High stability, stretchable speed insensitive properties, high stretchability, and electrical conductivity are key characteristics for the realisation of wearable devices. However, conventional research is mainly focused on achieving only high stretchability and electrical conductivity. Studies on the stability and stretching speed insensitive properties generally require complex fabrication processes, which are in need of further improvement. In this study, we propose a facile formation of a conductive bridge in composites by using surface damage and the viscoelastic property of the polymer. Surface cracks due to repeated stretching cycles formed conductive bridges via stress relaxation of the viscoelastic polymer matrix. The conductive bridge resulted in the conductor having highly stable resistance values at target strains and stretching speed insensitive resistance, even at stretching speeds that were 20 times faster than the minimum.

Objectives Although lateral osteotomy is an important part of rhinoplasty, it is known to be closely associated with postoperative eyelid edema and ecchymosis after rhinoplasty. There is no consensus on which osteotomy methods are effective in reducing morbidity from rhinoplasty. This study compared the effects of different osteotomy methods on edema and ecchymosis after lateral osteotomy using a meta-analysis. Study design A literature search using MEDLINE, SCOPUS, and Cochrane databases. Methods Two authors independently reviewed the databases published until May 2019. Randomized controlled trials that compared lateral osteotomy methods (external approach) with different methods (internal approach), for which the outcomes of interest were mucosal injury, edema, and ecchymosis on postoperative days, were included. Sufficient data for meta-analysis was found in six studies with a total of 224 patients. Results In a comparison of the external approach with the internal approach, mucosal injury was significantly lower in the external approach (odds ratio = 0.41; 95% confidence interval = [0.11; 0.99], I2 = 29%). There were significant differences between the external and internal approach in eyelid ecchymosis and edema, except for eyelid ecchymosis at 7 days postoperatively. However, all significant results showed a small effect size with a standardized mean difference near 0.2. Conclusions The external approach during lateral osteotomy had no significant advantage in edema and ecchymosis compared to the internal approach. Further studies with good research methodology should be carried out to determine the effect on the postoperative complications of different lateral osteotomy methods. Laryngoscope, 131:54-58, 2021.

Minoxidil is the most widely used treatment for hair growth, but has been associated with several side effects. In this study, we investigated the effects of heat-killed

Increasing consumption of food with high caloric density and a sedentary lifestyle have influenced the increasing obesity prevalence worldwide. The recent pandemic has contributed to this problem. Obesity refers to a state in which lipid accumulates excessively in adipocytes and adipose tissues. Dried heat-killed Enterococcus faecalis (EF-2001) prevents allergic mechanisms, inflammation, and tumor progression. In the present study, we investigated the effects of EF-2001 on high fat diet (HFD)-induced obese rats. The degree of obesity in experimental rats was reduced after 6 weeks of oral administration of 3 mg/kg or 30 mg/kg dosages of EF-2001, indicating regulating effects in rats with HFD-induced obesity. We found that EF-2001 decreased the amounts of total cholesterol, triglyceride, and non-high density lipoprotein (HDL) in HFD-induced obese rats. The effects of EF-2001 on 3T3-L1 adipocytes stained with Oil red O stain are shown in reductions of lipid accumulation, respectively. In addition, we examined the relationships between EF-2001 treatment and mechanisms for the insulin signaling of adipogenesis in 3T3-L1 cells. EF-2001 induced down-regulation in phosphorylation of Erk, JNK, and Akt through the inhibition of insulin receptor phosphorylation. EF-2001 inhibits the expressions of C/EBP-α and PPAR-γ, a lipid metabolism-related transcription factor through confocal microscope observation and Western blot on 3T3-L1 adipocytes and HFD-induced obese rats. Based on our results, intake of EF-2001 significantly prevented HFD-induced obesity in rats through inhibition of C/EBP-α and PPAR-γ in the insulin signaling pathway on lipid accumulation.

Increasing consumption of food with high caloric density and a sedentary lifestyle have influenced the increasing obesity prevalence worldwide. The recent pandemic has contributed to this problem. Obesity refers to a state in which lipid accumulates excessively in adipocytes and adipose tissues. Dried heat-killed

Background: The lateral septum (LS) is a critical social behavior node. The LS is activated by social novelty, and perturbing LS activity impairs social recognition. However, the neural circuits and cell signaling pathways that converge on the LS to mediate this behavior aren9t known. We identify brain-derived neurotrophic factor (BDNF) in projection neurons from the basolateral amgydala (BLA) to the LS, and tropomyosin kinase B receptor (TrkB) signaling in LS neurons, as required for social novelty recognition. Methods: We used single-molecule fluorescent in-situ hybridization to quantify Ntrk2 expression in LS. Viral transgenesis was used to induce cre-recombinase mediated TrkB knockdown in LS to evaluate impact on social recognition behavior, and social novelty-induced c-Fos expression in the LS. We used viral approaches for projection-specific ablation and BDNF-depletion in BLA-LS projection neurons to assess the role of this circuit in social recognition behavior. Results: The majority of GABAergic neurons in LS express TrkB. TrkB knockdown in LS abolishes social novelty recognition, and decreases LS activation in response to social novelty. Selectively ablating BLA-LS projection neurons abolishes social novelty recognition behavior, an effect that is phenocopied by depleting BDNF in this circuit. Conclusions: BLA-LS projection neurons depend on BDNF expression to regulate social recognition in the mouse. Within the LS, neurons require intact TrkB receptor signaling to mediate this behavior.

A monolithic integration of high-performance soft electronic modules into various fabric materials has enabled a paradigm shift in wearable textile electronics. However, the current textile electronics have struggled against fatigue under repetitive deformation due to the absence of materials and structural design strategies for imparting electrical and mechanical robustness to individual fibers. Here, we report a mechanically and electrically durable, stretchable electronic textile (MED-ET) enabled by a precisely controlled diffusion of tough self-healing stretchable inks into fibers and an adoption of the kirigami-inspired design. Remarkably, the conductive percolative pathways in the fabric of MED-ET even under a harshly deformed environment were stably maintained due to an electrical recovery phenomenon which originates from the spontaneous rearrangement of Ag flakes in the self-healing polymer matrix. Specifically, such a unique property enabled damage-resistant performance when repetitive deformation and scratch were applied. In addition, the kirigami-inspired design was capable of efficiently dissipating the accumulated stress in the conductive fabric during stretching, thereby providing high stretchability (a tensile strain of 300%) without any mechanical fracture or electrical malfunction. Finally, we successfully demonstrate various electronic textile applications such as stretchable micro-light-emitting diodes (Micro-LED), electromyogram (EMG) monitoring and all-fabric thermoelectric devices (F-TEG).

BackgroundDeficits in social cognition consistently underlie functional disabilities in a wide range of psychiatric disorders. Neuroimaging studies have suggested that the anterior insula is a ‘common core’ brain region that is impaired across neurological and psychiatric disorders, which include social cognition deficits. Nevertheless, neurobiological mechanisms of the anterior insula for social cognition remain elusive.MethodsTo determine the role of anterior insula in social cognition, we manipulated expression of Cyp26B1, an anterior insula-enriched molecule that is crucial for retinoic acid degradation and involved in the pathology of neuropsychiatric conditions. Social cognition was mainly assayed using the three-chamber social interaction test. We conducted multimodal analyses at the molecular, cellular, circuitry, and behavioral levels.ResultsAt the molecular/cellular level, anterior insula-mediated social novelty recognition is maintained by proper activity of the layer 5 pyramidal neurons, for which retinoic acid-mediated gene transcription can play a role. We also demonstrate that oxytocin influences the anterior insula-mediated social novelty recognition, not by direct projection of oxytocin neurons, nor by direct diffusion of oxytocin to the anterior insula, which contrasts the modes of oxytocin regulation onto the posterior insula. Instead, oxytocin affects oxytocin receptor-expressing neurons in the dorsal raphe nucleus where serotonergic neurons are projected to the anterior insula. Furthermore, we show that serotonin 5HT2C receptor expressed in the anterior insula influences social novelty recognition.ConclusionsAnterior insula plays a pivotal role in social novelty recognition that is partly regulated by a local retinoic acid cascade, but also remotely regulated by oxytocin via a non-classic mechanism.

Conventional stretchable electronics entailing the adoption of a wavy design, a neutral mechanical plane, and a conformal contact between abiotic and biotic interfaces have shown diverse skin-interfaced applications. Despite such remarkable progress, there have been challenged to be evolved to intelligent skin prosthetics due to the absence of the monolithic integration of neuromorphic constituents into individual sensing and actuating components. Herein, we demonstrate a golden tortoise beetle-inspired stretchable sensory-neuromorphic system comprising an artificial mechanoreceptor, an artificial synapse, and an epidermal photonic actuator as three biomimetic functionalities that correspond to a stretchable capacitive pressure sensor, a resistive random-access memory, and a quantum dot light-emitting diode, respectively. This system features a rigid-island structure interconnected with a sinter-free printable conductor (stretchability ~ 160%, conductivity ~ 18,550 S/cm), which allows one to improve both areal density and structural reliability while avoiding the thermal degradation of heat-sensitive stretchable electronic components. Moreover, even in the skin deformation range, the system accurately recognizes various patterned stimuli via an artificial neural network with training/inferencing functions. Our new bioinspired system is therefore expected to be an important step toward the implementation of intelligent wearable electronics.

Sodium butyrate (NaBu) is an efficient supplement for increasing recombinant protein production in Chinese hamster ovary (CHO) cell culture. To elucidate the effects of NaBu on miRNA expression profile in recombinant CHO (rCHO) cells, differentially expressed miRNAs in NaBu-treated rCHO cells were assessed by NanoString nCounter analysis. This result showed that eight mature mouse miRNAs (let-7b, let-7d, miR-15b, miR-25, miR-27a, miR-99a, miR-125a-5p, and miR-125b-5p) were differentially expressed. Furthermore, quantitative real-time RT-PCR analysis of eight mature CHO miRNAs, annotated using a miRBase database, confirmed the transcriptomic findings. Among the potential corresponding target mRNAs for the selected mature miRNAs, seven cell growth-related target genes (e2f2, akt2, mtor, bcl-2, bim, p38α, and bmf) and five N-glycosylation-related target genes (neu1, b4galt3, gale, man1b1 and mgat4a) were selected by considering the effectiveness of NaBu on rCHO cell culture. The altered expression patterns of the 12 target mRNAs were inversely correlated with those of the selected mature miRNAs. Altogether, NanoString nCounter analysis may be useful for identifying differentially expressed miRNAs in rCHO cells.

Despite the relatively low transfection efficiency and low specific foreign protein productivity (qp) of Chinese hamster ovary (CHO) cell-based transient gene expression (TGE) systems, TGE-based recombinant protein production technology predominantly employs CHO cells for pre-clinical research and development purposes. To improve TGE in CHO cells, Epstein-Barr virus nuclear antigen-1 (EBNA-1)/polyoma virus large T antigen (PyLT)-co-amplified recombinant CHO (rCHO) cells stably expressing EBNA-1 and PyLT were established using dihydrofolate reductase/methotrexate-mediated gene amplification. The level of transiently expressed Fc-fusion protein was significantly higher in the EBNA-1/PyLT-co-amplified pools compared to control cultures. Increased Fc-fusion protein production by EBNA-1/PyLT-co-amplification resulted from a higher qp attributable to EBNA-1 but not PyLT expression. The qp for TGE-based production with EBNA-1/PyLT-co-amplified rCHO cells (EP-amp-20) was approximately 22.9-fold that of the control culture with CHO-DG44 cells. Rather than improved transfection efficiency, this cell line demonstrated increased levels of mRNA expression and replicated DNA, contributing to an increased qp. Furthermore, there was no significant difference in N-glycan profiles in Fc-fusion proteins produced in the TGE system. Taken together, these results showed that the use of rCHO cells with co-amplified expression of the viral elements EBNA-1 and PyLT improves TGE-based therapeutic protein production dramatically. Therefore, EBNA-1/PyLT-co-amplified rCHO cells will likely be useful as host cells in CHO cell-based TGE systems.

Conventional stretchable electronics that adopt a wavy design, a neutral mechanical plane, and conformal contact between abiotic and biotic interfaces have exhibited diverse skin-interfaced applications. Despite such remarkable progress, the evolution of intelligent skin prosthetics is challenged by the absence of the monolithic integration of neuromorphic constituents into individual sensing and actuating components. Herein, a bioinspired stretchable sensory-neuromorphic system, comprising an artificial mechanoreceptor, artificial synapse, and epidermal photonic actuator is demonstrated; these three biomimetic functionalities correspond to a stretchable capacitive pressure sensor, a resistive random-access memory, and a quantum dot light-emitting diode, respectively. This system features a rigid-island structure interconnected with a sinter-free printable conductor, which is optimized by controlling the evaporation rate of solvent (≈160% stretchability and ≈18 550 S cm-1 conductivity). Devised design improves both areal density and structural reliability while avoiding the thermal degradation of heat-sensitive stretchable electronic components. Moreover, even in the skin deformation range, the system accurately recognizes various patterned stimuli via an artificial neural network with training/inferencing functions. Therefore, the new bioinspired system is expected to be an important step toward implementing intelligent wearable electronics.

We purified as-received CNT fibers (CNTFs) with four different methods and systematically examined effects of various purifications on the morphology, structure, and electrical conductivity of the resultant CNTFs, respectively. The purified CNTFs were characterized by an optical microscope, transmission electron microscope (TEM) coupled with an energy dispersive X-ray spectrometer (EDS), Raman spectroscopy, and multiple source meters. Optical images showed that morphology of CNTFs did not largely change after purification. TEM images and EDS results showed that the Fe impurities, 21.9 wt%, in CNTFs were decreased to 0.17-1.20 wt% and were nearly eliminated by acid and alkali purifications, respectively. Raman results identified the ID/IG ratio of CNTFs was 0.71, while those of HCl treatment after steam with heat (HSCNTFs-HCl), NaOCl treatment after steam with heat (HSCNTFs-NaOCl), and NaOH treatment with heat without steam (NaOH-HCNTFs) were 0.45, 0.49, and 0.57, respectively, which means that purification methods of CNTFs performed in this study are thought to be satisfactory for manufacturing high-purity CNTFs. Electrical conductivity (1.4×104 S/m) of NaOH-HCNTFs (one-step procedure) was twice as high as that (7.3×103 S/m) of CNTFs, but lower than those (2.1-2.3×104 S/m) of HSCNTFs-HCl and HSCNTFs-NaOCl (two-step processes), which demonstrates that two-step processes rather than one-step procedure would have a positive effect on the electrical conductivity of the resultant CNTFs.

Butanol is a promising alternative to ethanol and is desirable for use in transportation fuels and additives to gasoline and diesel fuels. Microbial production of butanol is challenging primarily because of its toxicity and low titer of production. Herein, we compared the transcriptome and phenome of wild-type Escherichia coli and its butanol-tolerant evolved strain to understand the global cellular physiology and metabolism responsible for butanol tolerance. When the ancestral butanol-sensitive E. coli was exposed to butanol, gene activities involved in respiratory mechanisms and oxidative stress were highly perturbed. Intriguingly, the evolved butanol-tolerant strain behaved similarly in both the absence and presence of butanol. Among the mutations occurring in the evolved strain, cis-regulatory mutations may be the cause of butanol tolerance. This study provides a foundation for the rational design of the metabolic and regulatory pathways for enhanced biofuel production.

Background Nasal obstruction is a common cause of breathing problems with lateral wall insufficiency (LWI) a key anatomic contributor. Recently, a bioabsorbable nasal implant was introduced to correct LWI and treat nasal obstruction. The goal of this study was to perform a systematic review with meta-analysis to determine the efficacy of the bioabsorbable nasal implant for treating nasal obstruction caused by LWI. Methods Five databases (PubMed, SCOPUS, EMBASE, Web of Science, and the Cochrane Database) were independently reviewed by 2 researchers, starting at the earliest time point recorded in the database to September 2019. Studies that scored endoscopic lateral wall movement and nasal obstruction related to quality of life (QOL) postoperatively before and after bioabsorbable nasal implants and those that compared the outcomes of nasal implants (treatment group) with outcomes of sham surgery (control group) were included in the analysis. Results Five studies (396 patients) met the inclusion criteria. Bioabsorbable nasal implants significantly reduced endoscopic lateral wall motion compared to pretreatment values and also improved QOL at 12 months postoperatively. Most adverse effects following the nasal implant, such as skin or mucosal reaction, infection, or implant retrieval, were reported with a 5% incidence rate. All adverse outcomes were resolved without significant sequelae. Compared with sham surgery, bioabsorbable nasal implants significantly improved disease-specific QOL. Conclusion Bioabsorbable nasal implants may reduce nasal wall movement and subjective symptom scores compared to preoperative status. More randomized clinical trials must be conducted to further verify the effectiveness of bioabsorbable nasal implants.

Both self-healable conductors and stretchable conductors have been previously reported. However, it is still difficult to simultaneously achieve high stretchability, high conductivity, and self-healability. Here, we observed an intriguing phenomenon, termed “electrical self-boosting”, which enables reconstructing of electrically percolative pathways in an ultrastretchable and self-healable nanocomposite conductor (over 1700% strain). The autonomously reconstructed percolative pathways were directly verified by using microcomputed tomography and in situ scanning electron microscopy. The encapsulated nanocomposite conductor shows exceptional conductivity (average value: 2578 S cm–1; highest value: 3086 S cm–1) at 3500% tensile strain by virtue of efficient strain energy dissipation of the self-healing polymer and self-alignment and rearrangement of silver flakes surrounded by spontaneously formed silver nanoparticles and their self-assembly in the strained self-healing polymer matrix. In addition, the condu...

Soft neuroprosthetics that monitor signals from sensory neurons and deliver motor information can potentially replace damaged nerves. However, achieving long-term stability of devices interfacing peripheral nerves is challenging, since dynamic mechanical deformations in peripheral nerves cause material degradation in devices. Here, a durable and fatigue-resistant soft neuroprosthetic device is reported for bidirectional signaling on peripheral nerves. The neuroprosthetic device is made of a nanocomposite of gold nanoshell (AuNS)-coated silver (Ag) flakes dispersed in a tough, stretchable, and self-healing polymer (SHP). The dynamic self-healing property of the nanocomposite allows the percolation network of AuNS-coated flakes to rebuild after degradation. Therefore, its degraded electrical and mechanical performance by repetitive, irregular, and intense deformations at the device-nerve interface can be spontaneously self-recovered. When the device is implanted on a rat sciatic nerve, stable bidirectional signaling is obtained for over 5 weeks. Neural signals collected from a live walking rat using these neuroprosthetics are analyzed by a deep neural network to predict the joint position precisely. This result demonstrates that durable soft neuroprosthetics can facilitate collection and analysis of large-sized in vivo data for solving challenges in neurological disorders.

Stretchable conductors have recently attracted much attention because of rapid developments in wearable and deformable electronics. Conductors are one of the essential components of electronic devices. A photonic sintering process with intense pulsed light from a xenon lamp is used for sintering printed ink to fabricate conductors, without damaging the substrate. However, it is difficult to achieve the most desired properties such as high conductivity and mechanical stretchability in stretchable conductors fabricated by photonic sintering. Here, highly stretchable conductors are developed by the selective sintering of conductive materials embedded in silicone elastomers, overcoming this drawback. The conductors are composed of conductive Ag flakes and elastomeric Ecoflex. Photonic sintering generates conductive paths without damaging the transparent elastomer. As a result, a stretchability of 500% is achieved without the need for any structural designs. Furthermore, a wireless power transfer circuit incorporating the conductors was successfully applied to operate a light emitting diode wirelessly. This approach opens up the possibility of developing new types of stretchable and deformable electronics for future applications.

Sensorimotor information processing that underlies normal cognitive and behavioral traits is dysregulated across a subset of neurological and psychiatric disorders. The cross-disease deficit in sensorimotor gating poses a unique opportunity to integrate hierarchical findings at molecular, cellular, through circuitry levels to obtain an in-depth mechanistic understanding of this process that contributes to brain physiology and pathophysiology beyond categorical segmentation of brain disorders. Based on circuitry recording with wild-type mice, we demonstrated that the cortico-striatal projection mediates sensorimotor gating responses during prepulse inhibition (PPI) task. We also found that these circuitry responses were disrupted in Disc1 locus-impairment (LI) mice, a model representing neuropsychiatric conditions. Thus, we hypothesized that Disc1-mediated molecular and cellular machinery along the cortico-striatal circuit may regulate sensorimotor gating. Anatomical and biochemical analyses of Disc1-LI mice revealed attenuated Bdnf transport along the cortico-striatal circuit. Pharmacologically augmenting Bdnf transport by chronic lithium administration, in part via Ser-421 phosphorylation of Huntingtin (Htt) and its integration into the motor machinery, restored the striatal Bdnf levels and PPI deficits in Disc1-LI mice, suggesting that the Bdnf transport attenuation mechanistically underlies the circuitry and behavioral deficits. These results also shed light on a novel mechanism and utility of lithium that is currently used as a major mood stabilizer in clinical settings. Collectively, the present study illustrates integrative biological mechanisms for sensorimotor gating, underscoring the cross-disease nature of this behavioral dimension and translational utility of the findings under the era of precision medicine in brain disorders.

Electrochromic devices (ECDs) are emerging as a novel technology for various applications like commercialized smart window glasses, and auto-dimming rear-view mirrors. Recently, the development of low-power, lightweight, flexible, and stretchable devices has been accelerated to meet the growing demand in the new wearable devices market. Silver nanowires (AgNWs) can become new primary transparent conducting electrode (TCE) materials to replace indium tin oxide (ITO) for ECDs. However, issues such as substrate adhesion, delamination, and higher resistance still exist with AgNWs. Herein, we report a high-performance stretchable flash-induced AgNW-network-based TCE on surface-treated polydimethylsiloxane (PDMS) substrates. A Xe flash light method was used to create nanowelded networks of AgNWs. Surface silane treatments increased the adhesion and durability of the films as well. Finally, ECDs were fabricated under the optimal conditions and examined under strained conditions to demonstrate the resistance and mechanical behaviours of the devices. Results showed a flexible and durable film maintaining a high level of conductivity and reversible resistance behaviour, beyond those currently achievable with standard ITO/PET flexible TCEs.

The prefrontal cortex (PFC) and its connections with other brain areas are crucial for cognitive function. Cognitive impairments are one of the core symptoms associated with schizophrenia, and manifest even before the onset of the disorder. Altered neural networks involving PFC contribute to cognitive impairments in schizophrenia. Both genetic and environmental risk factors affect the development of the local circuitry within PFC as well as development of broader brain networks, and make the system vulnerable to further insults during adolescence, leading to the onset of the disorder in young adulthood. Since spared cognitive functions correlate with functional outcome and prognosis, a better understanding of the mechanisms underlying cognitive impairments will have important implications for novel therapeutics for schizophrenia focusing on cognitive functions. Multidisciplinary approaches, from basic neuroscience to clinical studies, are required to link molecules, circuitry, networks, and behavioral phenotypes. Close interactions among such fields by sharing a common language on connectomes, behavioral readouts, and other concepts are crucial for this goal.

Printing technology can be used for manufacturing stretchable electrodes, which represent essential parts of wearable devices requiring relatively high degrees of stretchability and conductivity. In this work, a strategy for fabricating printable and highly stretchable conductors are proposed by transferring printed Ag ink onto stretchable substrates comprising Ecoflex elastomer and tough hydrogel layers using a water-soluble tape. The elastic modulus of the produced hybrid film is close to that of the hydrogel layer, since the thickness of Ecoflex elastomer film coated on hydrogel is very thin (30 µm). Moreover, the fabricated conductor on hybrid film is stretched up to 1780% strain. The described transfer method is simpler than other techniques utilizing elastomer stamps or sacrificial layers and enables application of printable electronics to the substrates with low elastic moduli (such as hydrogels). The integration of printed electronics with skin-like low-modulus substrates can be applied to make wearable devices more comfortable for human skin.

Butanol is a promising alternative to ethanol and is desirable for use in transportation fuels and additives to gasoline and diesel fuels. Microbial production of butanol is challenging primarily because of its toxicity and low titer of production. Herein, we compared the transcriptome and phenome of wild-type

Huntington's disease (HD) is a polyglutamine (polyQ) disease caused by aberrant expansion of the polyQ tract in Huntingtin (HTT). While motor impairment mediated by polyQ-expanded HTT has been intensively studied, molecular mechanisms for nonmotor symptoms in HD, such as psychiatric manifestations, remain elusive. Here we have demonstrated that HTT forms a ternary protein complex with the scaffolding protein DiSC1 and cAMP-degrading phosphodiesterase 4 (PDE4) to regulate PDE4 activity. We observed pathological cross-seeding between DiSC1 and mutant HTT aggregates in the brains of HD patients as well as in a murine model that recapitulates the polyQ pathology of HD (R6/2 mice). In R6/2 mice, consequent reductions in soluble DiSC1 led to dysregulation of DiSC1-PDE4 complexes, aberrantly increasing the activity of PDE4. Importantly, exogenous expression of a modified DiSC1, which binds to PDE4 but not mutant HTT, normalized PDE4 activity and ameliorated anhedonia in the R6/2 mice. We propose that cross-seeding of mutant HTT and DiSC1 and the resultant changes in PDE4 activity may underlie the pathology of a specific subset of mental manifestations of HD, which may provide an insight into molecular signaling in mental illness in general.

A series of anionic copolyester/dodecylbenzenesulfonate (DBS) blend films were prepared by a melt-com-pounding method and then annealed under a range of conditions. To eliminate possible experimental errors in measur-ing the alkaline reduction rate of the samples, the crystallinity should be uniform. We used Fourier transform infrared(FT-IR) spectroscopy to measure and control the relative crystallinity of the annealed samples. The relationshipbetween the crystallinity and reduction rate, as well as the annealing conditions of the annealed blend samples, wasderived. FT-IR analysis showed that the crystallization rate of copolyester/DBS blend films is lower than that of purecopolyester. However, the alkaline weight reduction rate of the blend films, which have similar crystallinities, increasesdramatically with increasing DBS content, even at a low DBS content of 1 to 3 wt%, although the effect of the DBSbecomes negligible above 5 wt%. However, unlike the result for annealed films, the alkaline weight reduction rate foramorphous films exhibited a linear relationship between the alkaline reduction rate and the DBS content for all of theexamined DBS content, demonstrating that the effects of the DBS on the alkaline weight reduction of the copolysestercould be affected by processing conditions such as post-drawing and annealing. Keywords: anionic copolyesters, DBS, annealing, alkaline weight reduction, FT-IR

Supported by recent human neuroimaging studies, the insula is re-emerging as an important brain area not only in the physiological understanding of the brain, but also in pathological contexts in clinical research. In this opinion article, we briefly introduce the anatomical and histological features of the human insula. We then summarize the physiological functions of the insula and underscore its pathological roles in psychiatric and neurological disorders that have long been underestimated. We finally propose possible strategies through which the role of the insula may be further understood for both basic and clinical neuroscience.

Neuronal nitric oxide synthase is involved in diverse signaling cascades that regulate neuronal development and functions via S-Nitrosylation-mediated mechanism or the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway activated by nitric oxide. Although it has been studied extensively in vitro and in invertebrate animals, effects on mammalian brain development and underlying mechanisms remain poorly understood. Here we report that genetic deletion of “Nos1” disrupts dendritic development, whereas pharmacological inhibition of the sGC/cGMP pathway does not alter dendritic growth during cerebral cortex development. Instead, nuclear distribution element-like (NDEL1), a protein that regulates dendritic development, is specifically S-nitrosylated at cysteine 203, thereby accelerating dendritic arborization. This post-translational modification is enhanced by N-methyl-D-aspartate receptor-mediated neuronal activity, the main regulator of dendritic formation. Notably, we found that disruption of S-Nitrosylation of NDEL1 mediates impaired dendritic maturation caused by developmental alcohol exposure, a model of developmental brain abnormalities resulting from maternal alcohol use. These results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure.

p53 has been implicated in the pathophysiology of Huntington's disease (HD). Nonetheless, the molecular mechanism of how p53 may play a unique role in the pathology remains elusive. To address this question at the molecular and cellular biology levels, we initially screened differentially expressed molecules specifically dependent on p53 in a HD animal model. Among the candidate molecules, wild-type p53-induced gene 1 (Wig1) is markedly upregulated in the cerebral cortex of HD patients. Wig1 preferentially upregulates the level of mutant Huntingtin (Htt) compared with wild-type Htt. This allele-specific characteristic of Wig1 is likely to be explained by higher affinity binding to mutant Htt transcripts than normal counterpart for the stabilization. Knockdown of Wig1 level significantly ameliorates mutant Htt-elicited cytotoxicity and aggregate formation. Together, we propose that Wig1, a key p53 downstream molecule in HD condition, play an important role in stabilizing mutant Htt mRNA and thereby accelerating HD pathology in the mHtt-p53-Wig1 positive feedback manner.

While a rational approach based on genomic data has become the preferred method for microbial strain development, radiation-induced random mutagenesis is still a robust method for organisms such as plants whose genome or target gene information is unavailable. We previously reported on a combined approach that consists of proton irradiation and a long-term experimental evolution to enhance 1-butanol tolerance of the E. coli C strain so that it can be used as a basal strain for the production of 1-butanol, a potential biofuel along with ethanol. Genome sequencing of one randomly chosen clone (PKH5000) from the endpoint population revealed eleven mutations occurring in the coding regions, and we found that a mutation (F74C) in fabF gene encoding β-ketoacyl-ACP synthases II is associated with a twofold increase in the major unsaturated fatty acid, cis-vaccenic acid. The increase of cis-vaccenic acid by wild-type FabF, which is more active at low temperatures or in the presence of organic compounds, is considered to be a protective mechanism against cold stress. A structural analysis of the FabF protein suggests that the F74C mutation may affect the enzyme activity through a change in flexibility around the catalytic site. The expression of a plasmid that harbors mutant fabF gene in the fabF knockout strain enhanced growth in a medium containing butanol with a concomitant elevation of the cis-vaccenic acid level. Among the eight available Keio knockout strains for genes that have amino acid substitution in the PKH5000 strain, the fabF mutant showed the slowest growth in the presence of 0.7% butanol. We propose that fabF, as probably the gene most responsible for butanol tolerance in wild-type form, contributes further when converted into a F74C missense mutation, which is beneficial as it increases the level of cis-vaccenic acid.

Neuronal nitric oxide synthase (nNOS) forms nitric oxide (NO), which functions as a signaling molecule via S-nitrosylation of various proteins and regulation of soluble guanylate cyclase (cGC)/cyclic guanosine monophosphate (cGMP) pathway in the central nervous system. nNOS signaling regulates diverse cellular processes during brain development and molecular mechanisms required for higher brain function. Human genetics have identified nNOS and several downstream effectors of nNOS as risk genes for schizophrenia. Besides the disease itself, nNOS has also been associated with prefrontal cortical functioning, including cognition, of which disturbances are a core feature of schizophrenia. Although mice with genetic deletion of nNOS display various behavioral deficits, no studies have investigated prefrontal cortex-associated behaviors. Here, we report that nNOS knockout (KO) mice exhibit hyperactivity and impairments in contextual fear conditioning, results consistent with previous reports. nNOS KO mice also display mild impairments in object recognition memory. Most importantly, we report for the first time working memory deficits, potential impairments in prefrontal cortex mediated cognitive function in nNOS KO mice. Furthermore, we demonstrate Disrupted-in-Schizophrenia 1 (DISC1), another genetic risk factor for schizophrenia that plays roles for cortical development and prefrontal cortex functioning, including working memory, is a novel protein binding partner of nNOS in the developing cerebral cortex. Of note, genetic deletion of nNOS appears to increase the binding of DISC1 to NDEL1, regulating neurite outgrowth as previously reported. These results suggest that nNOS KO mice are useful tools in studying the role of nNOS signaling in cortical development and prefrontal cortical functioning.

Experimental and clinical studies on the accuracy of the intramedullary alignment method have produced different results, and few have addressed accuracy in the sagittal plane. Reported deviations are not only attributable to the alignment method but also to radiological errors. The purpose of this study was to evaluate the accuracy of the intramedullary alignment method in the sagittal plane using computed tomography (CT) and 3-dimensional imaging software. Thirty-one TKAs were performed using an intramedullary alignment method involving the insertion of a long 8-mm diameter rod into the medullary canal to the distal metaphysis of the tibia. All alignment instruments were set to achieve an ideal varus/valgus angle of 0° in the coronal plane and a tibial slope of 0° in the sagittal plane. The accuracy of the intramedullary alignment system was assessed by measuring the coronal tibial component angle and sagittal tibial slope angles, i.e., angles between the tibial anatomical axis and the tangent to the medial and lateral tibial plateau or the cut-surface. The mean coronal tibial component angle was 88.5° ± 1.2° and the mean tibial component slope in the sagittal plane was 1.6° ± 1.2° without anterior slope. Our intramedullary tibial alignment method, which involves passing an 8-mm diameter long rod through the tibial shaft isthmus, showed good accuracy (less than 3 degrees of variation and no anterior slope) in the sagittal plane in neutral or varus knees.