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Intrinsically stretchable organic photovoltaics have emerged as a prominent candidate for the next-generation wearable power generators regarding their structural design flexibility, omnidirectional stretchability, and in-plane deformability. However, formulating strategies to fabricate intrinsically stretchable organic photovoltaics that exhibit mechanical robustness under both repetitive strain cycles and high tensile strains remains challenging. Herein, we demonstrate high-performance intrinsically stretchable organic photovoltaics with an initial power conversion efficiency of 14.2%, exceptional stretchability (80% of the initial power conversion efficiency maintained at 52% tensile strain), and cyclic mechanical durability (95% of the initial power conversion efficiency retained after 100 strain cycles at 10%). The stretchability is primarily realised by delocalising and redistributing the strain in the active layer to a highly stretchable PEDOT:PSS electrode developed with a straightforward incorporation of ION E, which simultaneously enhances the stretchability of PEDOT:PSS itself and meanwhile reinforces the interfacial adhesion with the polyurethane substrate. Both enhancements are pivotal factors ensuring the excellent mechanical durability of the PEDOT:PSS electrode, which further effectively delays the crack initiation and propagation in the top active layer, and enables the limited performance degradation under high tensile strains and repetitive strain cycles., (© 2024. The Author(s).)

Olfaction feedback systems could be utilized to stimulate human emotion, increase alertness, provide clinical therapy, and establish immersive virtual environments. Currently, the reported olfaction feedback technologies still face a host of formidable challenges, including human perceivable delay in odor manipulation, unwieldy dimensions, and limited number of odor supplies. Herein, we report a general strategy to solve these problems, which associates with a wearable, high-performance olfactory interface based on miniaturized odor generators (OGs) with advanced artificial intelligence (AI) algorithms. The OGs serve as the core technology of the intelligent olfactory interface, which exhibit milestone advances in millisecond-level response time, milliwatt-scale power consumption, and the miniaturized size. Empowered by robust AI algorithms, the olfactory interface shows its great potentials in latency-free mixed reality (MR) and fast olfaction enhancement, thereby establishing a bridge between electronics and users for broad applications ranging from entertainment, to education, to medical treatment, and to human machine interfaces., (© 2024. The Author(s).)

The current challenge of wearable/implantable personal dosimeters for medical diagnosis and radiotherapy applications is lack of suitable detector materials possessing both excellent detection performance and biocompatibility. Here, we report a solution-grown biocompatible organic single crystalline semiconductor (OSCS), 4-Hydroxyphenylacetic acid (4HPA), achieving real-time spectral detection of charged particles with single-particle sensitivity. Along in-plane direction, two-dimensional anisotropic 4HPA exhibits a large electron drift velocity of 5 × 10 5  cm s -1 at "radiation-mode" while maintaining a high resistivity of (1.28 ± 0.003) × 10 12 Ω·cm at "dark-mode" due to influence of dense π-π overlaps and high-energy L1 level. Therefore, 4HPA detectors exhibit the record spectra detection of charged particles among their organic counterparts, with energy resolution of 36%, (μt) e of (4.91 ± 0.07) × 10 -5  cm 2  V -1 , and detection time down to 3 ms. These detectors also show high X-ray detection sensitivity of 16,612 μC Gy abs -1  cm -3 , detection of limit of 20 nGy air s -1 , and long-term stability after 690 Gy air irradiation., (© 2024. The Author(s).)

Ultraflexible organic photovoltaics have emerged as a potential power source for wearable electronics owing to their stretchability and lightweight nature. However, waterproofing ultraflexible organic photovoltaics without compromising mechanical flexibility and conformability remains challenging. Here, we demonstrate waterproof and ultraflexible organic photovoltaics through the in-situ growth of a hole-transporting layer to strengthen interface adhesion between the active layer and anode. Specifically, a silver electrode is deposited directly on top of the active layers, followed by thermal annealing treatment. Compared with conventional sequentially-deposited hole-transporting layers, the in-situ grown hole-transporting layer exhibits higher thermodynamic adhesion between the active layers, resulting in better waterproofness. The fabricated 3 μm-thick organic photovoltaics retain 89% and 96% of their pristine performance after immersion in water for 4 h and 300 stretching/releasing cycles at 30% strain under water, respectively. Moreover, the ultraflexible devices withstand a machine-washing test with such a thin encapsulation layer, which has never been reported. Finally, we demonstrate the universality of the strategy for achieving waterproof solar cells., (© 2024. The Author(s).)

SARS-CoV-2 Omicron subvariants have evolved to evade receptor-binding site (RBS) antibodies that exist in diverse individuals as public antibody clones. We rationally selected RBS antibodies resilient to mutations in emerging Omicron subvariants. Y489 was identified as a site of virus vulnerability and a common footprint of broadly neutralizing antibodies against the subvariants. Multiple Y489-binding antibodies were encoded by public clonotypes and additionally recognized F486, potentially accounting for the emergence of Omicron subvariants harboring the F486V mutation. However, a subclass of antibodies broadly neutralized BA.4/BA.5 variants via hydrophobic binding sites of rare clonotypes along with high mutation-resilience under escape mutation screening. A computationally designed antibody based on one of the Y489-binding antibodies, NIV-10/FD03, was able to bind XBB with any 486 mutation and neutralized XBB.1.5. The structural basis for the mutation-resilience of this Y489-binding antibody group may provide important insights into the design of therapeutics resistant to viral escape., (© 2023. The Author(s).)

Although several long noncoding RNAs (lncRNAs) have recently been shown to encode small polypeptides, those in testis remain largely uncharacterized. Here we identify two sperm-specific polypeptides, Kastor and Polluks, encoded by a single mouse locus (Gm9999) previously annotated as encoding a lncRNA. Both Kastor and Polluks are inserted in the outer mitochondrial membrane and directly interact with voltage-dependent anion channel (VDAC), despite their different amino acid sequences. Male VDAC3-deficient mice are infertile as a result of reduced sperm motility due to an abnormal mitochondrial sheath in spermatozoa, and deficiency of both Kastor and Polluks also severely impaired male fertility in association with formation of a similarly abnormal mitochondrial sheath. Spermatozoa lacking either Kastor or Polluks partially recapitulate the phenotype of those lacking both. Cooperative function of Kastor and Polluks in regulation of VDAC3 may thus be essential for mitochondrial sheath formation in spermatozoa and for male fertility., (© 2022. The Author(s).)

Solution processability of polymer semiconductors becomes an unfavorable factor during the fabrication of pixelated films since the underlying layer is vulnerable to subsequent solvent exposure. A foundry-compatible patterning process must meet requirements including high-throughput and high-resolution patternability, broad generality, ambient processability, environmentally benign solvents, and, minimal device performance degradation. However, known methodologies can only meet very few of these requirements. Here, a facile photolithographic approach is demonstrated for foundry-compatible high-resolution patterning of known p- and n-type semiconducting polymers. This process involves crosslinking a vertically phase-separated blend of the semiconducting polymer and a UV photocurable additive, and enables ambient processable photopatterning at resolutions as high as 0.5 μm in only three steps with environmentally benign solvents. The patterned semiconducting films can be integrated into thin-film transistors having excellent transport characteristics, low off-currents, and high thermal (up to 175 °C) and chemical (24 h immersion in chloroform) stability. Moreover, these patterned organic structures can also be integrated on 1.5 μm-thick parylene substrates to yield highly flexible (1 mm radius) and mechanically robust (5,000 bending cycles) thin-film transistors., (© 2021. The Author(s).)

Ultraflexible optical devices have been used extensively in next-generation wearable electronics owing to their excellent conformability to human skins. Long-term health monitoring also requires the integration of ultraflexible optical devices with an energy-harvesting power source; to make devices self-powered. However, system-level integration of ultraflexible optical sensors with power sources is challenging because of insufficient air operational stability of ultraflexible polymer light-emitting diodes. Here we develop an ultraflexible self-powered organic optical system for photoplethysmogram monitoring by combining air-operation-stable polymer light-emitting diodes, organic solar cells, and organic photodetectors. Adopting an inverted structure and a doped polyethylenimine ethoxylated layer, ultraflexible polymer light-emitting diodes retain 70% of the initial luminance even after 11.3 h of operation under air. Also, integrated optical sensors exhibit a high linearity with the light intensity exponent of 0.98 by polymer light-emitting diode. Such self-powered, ultraflexible photoplethysmogram sensors perform monitoring of blood pulse signals as 77 beats per minute.

Dysregulation of epigenetic processes involving histone methylation induces neurodevelopmental impairments and has been implicated in schizophrenia (SCZ) and autism spectrum disorder (ASD). Variants in the gene encoding lysine demethylase 4C (KDM4C) have been suggested to confer a risk for such disorders. However, rare genetic variants in KDM4C have not been fully evaluated, and the functional impact of the variants has not been studied using patient-derived cells. In this study, we conducted copy number variant (CNV) analysis in a Japanese sample set (2605 SCZ and 1141 ASD cases, and 2310 controls). We found evidence for significant associations between CNVs in KDM4C and SCZ (p = 0.003) and ASD (p = 0.04). We also observed a significant association between deletions in KDM4C and SCZ (corrected p = 0.04). Next, to explore the contribution of single nucleotide variants in KDM4C, we sequenced the coding exons in a second sample set (370 SCZ and 192 ASD cases) and detected 18 rare missense variants, including p.D160N within the JmjC domain of KDM4C. We, then, performed association analysis for p.D160N in a third sample set (1751 SCZ and 377 ASD cases, and 2276 controls), but did not find a statistical association with these disorders. Immunoblotting analysis using lymphoblastoid cell lines from a case with KDM4C deletion revealed reduced KDM4C protein expression and altered histone methylation patterns. In conclusion, this study strengthens the evidence for associations between KDM4C CNVs and these two disorders and for their potential functional effect on histone methylation patterns.

Achieving high power conversion efficiency and good mechanical robustness is still challenging for the ultraflexible organic solar cells. Interlayers simultaneously having good mechanical robustness and good chemical compatibility with the active layer are highly desirable. In this work, we present an interlayer of Zn 2+ -chelated polyethylenimine (denoted as PEI-Zn), which can endure a maximum bending strain over twice as high as that of ZnO and is chemically compatible with the recently emerging efficient nonfullerene active layers. On 1.3 μm polyethylene naphthalate substrates, ultraflexible nonfullerene solar cells with the PEI-Zn interlayer display a power conversion efficiency of 12.3% on PEDOT:PSS electrodes and 15.0% on AgNWs electrodes. Furthermore, the ultraflexible cells show nearly unchanged power conversion efficiency during 100 continuous compression-flat deformation cycles with a compression ratio of 45%. At the end, the ultraflexible cell is demonstrated to be attached onto the finger joint and displays reversible current output during the finger bending-spreading.

Clozapine is an antipsychotic agent prescribed to psychotic patients exhibiting tolerance and/or resistance to the conventional antipsychotic medications that mainly drive monoamine antagonism. As the pharmacological fundamentals of its unique antipsychotic profile have been unrevealed, here, we attempted to obtain hints at this question. Here, we found that clozapine directly acts on ErbB kinases to downregulate epidermal growth factor (EGF)/neuregulin signaling. In cultured cell lines and cortical neurons, EGF-triggered ErbB1 phosphorylation was diminished by 30 μM clozapine, but not haloperidol, risperidone, or olanzapine. The neuregulin-1-triggered ErbB4 phosphorylation was attenuated by 10 μM clozapine and 30 μM haloperidol. We assumed that clozapine may directly interact with the ErbB tyrosine kinases and affect their enzyme activity. To test this assumption, we performed in vitro kinase assays using recombinant truncated ErbB kinases. Clozapine (3-30 μM) significantly decreased the enzyme activity of the truncated ErbB1, B2, and B4 kinases. Acute in vivo administration of clozapine (20 mg/kg) to adult rats significantly suppressed the basal phosphorylation levels of ErbB4 in the brain, although we failed to detect effects on basal ErbB1 phosphorylation. Altogether with the previous findings that quinazoline inhibitors for ErbB kinases harbor antipsychotic potential in animal models for schizophrenia, our present observations suggest the possibility that the micromolar concentrations of clozapine can attenuate the activity of ErbB receptor kinases, which might illustrate a part of its unique antipsychotic psychopharmacology.

In biointegrated electronics, the facile control of mechanical properties such as softness and stretchability in electronic devices is necessary to minimize the perturbation of motions inherent in biological systems 1-5 . For in vitro studies, multielectrode-embedded dishes 6-8 and other rigid devices 9-12 have been widely used. Soft or flexible electronics on plastic or elastomeric substrates 13-15 offer promising new advantages such as decreasing physical stress 16-18 and/or applying mechanical stimuli 19,20 . Recently, owing to the introduction of macroporous plastic substrates with nanofibre scaffolds 21,22 , three-dimensional electrophysiological mapping of cardiomyocytes has been demonstrated. However, quantitatively monitoring cells that exhibit significant dynamical motions via electric probes over a long period without affecting their natural motion remains a challenge. Here, we present ultrasoft electronics with nanomeshes that monitor the field potential of human induced pluripotent stem cell-derived cardiomyocytes on a hydrogel, while enabling them to move dynamically without interference. Owing to the extraordinary softness of the nanomeshes, nanomesh-attached cardiomyocytes exhibit contraction and relaxation motions comparable to that of cardiomyocytes without attached nanomeshes. Our multilayered nanomesh devices maintain reliable operations in a liquid environment, enabling the recording of field potentials of the cardiomyocytes over a period of 96 h without significant degradation of the nanomesh devices or damage of the cardiomyocytes.

The conversion of light into electrical signal in a photodetector is a crucial process for a wide range of technological applications. Here we report a new device concept of dual-gate phototransistor that combines the operation of photodiodes and phototransistors to simultaneously enable high-gain and linear photoresponse without requiring external circuitry. In an oppositely biased, dual-gate transistor based on a solution-processed organic heterojunction layer, we find that the presence of both n- and p-type channels enables both photogenerated electrons and holes to efficiently separate and transport in the same semiconducting layer. This operation enables effective control of trap carrier density that leads to linear photoresponse with high photoconductive gain and a significant reduction of electrical noise. As we demonstrate using a large-area, 8 × 8 imaging array of dual-gate phototransistors, this device concept is promising for high-performance and scalable photodetectors with tunable dynamic range.

Using light to manipulate materials into desired states is one of the goals in condensed matter physics, since light control can provide ultrafast and environmentally friendly photonics devices. However, it is generally difficult to realise a photo-induced phase which is not merely a higher entropy phase corresponding to a high-temperature phase at equilibrium. Here, we report realisation of photo-induced insulator-to-metal transitions in Ta 2 Ni(Se 1-x S x ) 5 including the excitonic insulator phase using time- and angle-resolved photoemission spectroscopy. From the dynamic properties of the system, we determine that screening of excitonic correlations plays a key role in the timescale of the transition to the metallic phase, which supports the existence of an excitonic insulator phase at equilibrium. The non-equilibrium metallic state observed unexpectedly in the direct-gap excitonic insulator opens up a new avenue to optical band engineering in electron-hole coupled systems.

In organic electronics the functionalization of dielectric substrates with self-assembled monolayers is regarded as an effective surface modification strategy that may significantly improve the resulting device performance. However, this technique is not suitable for polymer substrates typically used in flexible electronics. Here, we report organic modifiers based on a paraffinic tripodal triptycene, which self-assembles into a completely oriented two-dimensional hexagonal triptycene array and one-dimensional layer stacking structure on polymer surfaces. Such few-layer films are analogous to conventional self-assembled monolayers on inorganic substrates in that they neutralize the polymer surface. Furthermore, the triptycene films significantly improve the crystallinity of an organic semiconductor and the overall performance of organic thin-film transistors, therefore enabling the fabrication of high-performance organic complementary circuits on polymer substrates with high oscillation speeds and low operation voltage.

In schizophrenia (SCZ) and autism spectrum disorder (ASD), the dysregulation of glutamate transmission through N-methyl-D-aspartate receptors (NMDARs) has been implicated as a potential etiological mechanism. Previous studies have accumulated evidence supporting NMDAR-encoding genes' role in etiology of SCZ and ASD. We performed a screening study for exonic regions of GRIN1, GRIN2A, GRIN2C, GRIN2D, GRIN3A, and GRIN3B, which encode NMDAR subunits, in 562 participates (370 SCZ and 192 ASD). Forty rare variants were identified including 38 missense, 1 frameshift mutation in GRIN2C and 1 splice site mutation in GRIN2D. We conducted in silico analysis for all variants and detected seven missense variants with deleterious prediction. De novo analysis was conducted if pedigree samples were available. The splice site mutation in GRIN2D is predicted to result in intron retention by minigene assay. Furthermore, the frameshift mutation in GRIN2C and splice site mutation in GRIN2D were genotyped in an independent sample set comprising 1877 SCZ cases, 382 ASD cases, and 2040 controls. Both of them were revealed to be singleton. Our study gives evidence in support of the view that ultra-rare variants with loss of function (frameshift, nonsense or splice site) in NMDARs genes may contribute to possible risk of SCZ.

Thin-film electronic devices can be integrated with skin for health monitoring and/or for interfacing with machines. Minimal invasiveness is highly desirable when applying wearable electronics directly onto human skin. However, manufacturing such on-skin electronics on planar substrates results in limited gas permeability. Therefore, it is necessary to systematically investigate their long-term physiological and psychological effects. As a demonstration of substrate-free electronics, here we show the successful fabrication of inflammation-free, highly gas-permeable, ultrathin, lightweight and stretchable sensors that can be directly laminated onto human skin for long periods of time, realized with a conductive nanomesh structure. A one-week skin patch test revealed that the risk of inflammation caused by on-skin sensors can be significantly suppressed by using the nanomesh sensors. Furthermore, a wireless system that can detect touch, temperature and pressure is successfully demonstrated using a nanomesh with excellent mechanical durability. In addition, electromyogram recordings were successfully taken with minimal discomfort to the user.

CX3CR1, a G protein-coupled receptor solely expressed by microglia in the brain, has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in transcriptomic and animal studies but not in genetic studies. To address the impacts of variants in CX3CR1 on neurodevelopmental disorders, we conducted coding exon-targeted resequencing of CX3CR1 in 370 Japanese SCZ and 192 ASD patients using next-generation sequencing technology, followed by a genetic association study in a sample comprising 7054 unrelated individuals (2653 SCZ, 574 ASD and 3827 controls). We then performed in silico three-dimensional (3D) structural modeling and in vivo disruption of Akt phosphorylation to determine the impact of the detected variant on CX3CR1-dependent signal transduction. We detected a statistically significant association between the variant Ala55Thr in CX3CR1 with SCZ and ASD phenotypes (odds ratio=8.3, P=0.020). A 3D structural model indicated that Ala55Thr could destabilize the conformation of the CX3CR1 helix 8 and affect its interaction with a heterotrimeric G protein. In vitro functional analysis showed that the CX3CR1-Ala55Thr mutation inhibited cell signaling induced by fractalkine, the ligand for CX3CR1. The combined data suggested that the variant Ala55Thr in CX3CR1 might result in the disruption of CX3CR1 signaling. Our results strengthen the association between microglia-specific genes and neurodevelopmental disorders.

Printable elastic conductors promise large-area stretchable sensor/actuator networks for healthcare, wearables and robotics. Elastomers with metal nanoparticles are one of the best approaches to achieve high performance, but large-area utilization is limited by difficulties in their processability. Here we report a printable elastic conductor containing Ag nanoparticles that are formed in situ, solely by mixing micrometre-sized Ag flakes, fluorine rubbers, and surfactant. Our printable elastic composites exhibit conductivity higher than 4,000 S cm -1 (highest value: 6,168 S cm -1 ) at 0% strain, and 935 S cm -1 when stretched up to 400%. Ag nanoparticle formation is influenced by the surfactant, heating processes, and elastomer molecular weight, resulting in a drastic improvement of conductivity. Fully printed sensor networks for stretchable robots are demonstrated, sensing pressure and temperature accurately, even when stretched over 250%.

Measuring small normal pressures is essential to accurately evaluate external stimuli in curvilinear and dynamic surfaces such as natural tissues. Usually, sensitive and spatially accurate pressure sensors are achieved through conformal contact with the surface; however, this also makes them sensitive to mechanical deformation (bending). Indeed, when a soft object is pressed by another soft object, the normal pressure cannot be measured independently from the mechanical stress. Here, we show a pressure sensor that measures only the normal pressure, even under extreme bending conditions. To reduce the bending sensitivity, we use composite nanofibres of carbon nanotubes and graphene. Our simulations show that these fibres change their relative alignment to accommodate bending deformation, thus reducing the strain in individual fibres. Pressure sensitivity is maintained down to a bending radius of 80 μm. To test the suitability of our sensor for soft robotics and medical applications, we fabricated an integrated sensor matrix that is only 2 μm thick. We show real-time (response time of ∼20 ms), large-area, normal pressure monitoring under different, complex bending conditions.

In vivo electronic monitoring systems are promising technology to obtain biosignals with high spatiotemporal resolution and sensitivity. Here we demonstrate the fabrication of a biocompatible highly conductive gel composite comprising multi-walled carbon nanotube-dispersed sheet with an aqueous hydrogel. This gel composite exhibits admittance of 100 mS cm(-2) and maintains high admittance even in a low-frequency range. On implantation into a living hypodermal tissue for 4 weeks, it showed a small foreign-body reaction compared with widely used metal electrodes. Capitalizing on the multi-functional gel composite, we fabricated an ultrathin and mechanically flexible organic active matrix amplifier on a 1.2-μm-thick polyethylene-naphthalate film to amplify (amplification factor: ∼200) weak biosignals. The composite was integrated to the amplifier to realize a direct lead epicardial electrocardiography that is easily spread over an uneven heart tissue.

The development of advanced flexible large-area electronics such as flexible displays and sensors will thrive on engineered functional ink formulations for printed electronics where the spontaneous arrangement of molecules aids the printing processes. Here we report a printable elastic conductor with a high initial conductivity of 738 S cm(-1) and a record high conductivity of 182 S cm(-1) when stretched to 215% strain. The elastic conductor ink is comprised of Ag flakes, a fluorine rubber and a fluorine surfactant. The fluorine surfactant constitutes a key component which directs the formation of surface-localized conductive networks in the printed elastic conductor, leading to a high conductivity and stretchability. We demonstrate the feasibility of our inks by fabricating a stretchable organic transistor active matrix on a rubbery stretchability-gradient substrate with unimpaired functionality when stretched to 110%, and a wearable electromyogram sensor printed onto a textile garment.

Future electronic skin aims to mimic nature's original both in functionality and appearance. Although some of the multifaceted properties of human skin may remain exclusive to the biological system, electronics opens a unique path that leads beyond imitation and could equip us with unfamiliar senses. Here we demonstrate giant magnetoresistive sensor foils with high sensitivity, unmatched flexibility and mechanical endurance. They are <2 μm thick, extremely flexible (bending radii <3 μm), lightweight (≈3 g m(-2)) and wearable as imperceptible magneto-sensitive skin that enables proximity detection, navigation and touchless control. On elastomeric supports, they can be stretched uniaxially or biaxially, reaching strains of >270% and endure over 1,000 cycles without fatigue. These ultrathin magnetic field sensors readily conform to ubiquitous objects including human skin and offer a new sense for soft robotics, safety and healthcare monitoring, consumer electronics and electronic skin devices.

To measure electrophysiological signals from the human body, it is essential to establish stable, gentle and nonallergic contacts between the targeted biological tissue and the electrical probes. However, it is difficult to form a stable interface between the two for long periods, especially when the surface of the biological tissue is wet and/or the tissue exhibits motion. Here we resolve this difficulty by designing and fabricating smart, stress-absorbing electronic devices that can adhere to wet and complex tissue surfaces and allow for reliable, long-term measurements of vital signals. We demonstrate a multielectrode array, which can be attached to the surface of a rat heart, resulting in good conformal contact for more than 3 h. Furthermore, we demonstrate arrays of highly sensitive, stretchable strain sensors using a similar design. Ultra-flexible electronics with enhanced adhesion to tissue could enable future applications in chronic in vivo monitoring of biological signals.

Risperidone (RIS) is a frequently used efficacious psychotropic drug. However, it prolongs the QTc interval and may cause fatal arrhythmia. Little is known on the determinants of this RIS side effect. RIS is metabolized by CYP2D6, and is subject to drug efflux by P-glycoprotein (P-gp) encoded by the ATP-binding cassette subfamily B member 1 (ABCB1) gene. P-gp removes both RIS and its metabolite 9-OH-RIS from cardiac tissue. To investigate the effect of RIS metabolism and ABCB1 gene polymorphisms on QTc, steady-state plasma RIS and 9-OH-RIS levels, and QTc were measured. CYP2D6, ABCB1 C3435T and G2677T/A genotypes were determined in 66 schizophrenia patients on RIS. QTc was significantly longer in patients with ABCB1 3435CT+3435 TT than in those with 3435CC (P=0.006). ABCB1 G2677T/A genotype did not affect QTc. Multiple regression analysis showed that C/T or T/T genotypes at the ABCB1 C3435T locus, lower weight, and older age prolonged QTc. In summary, the T allele of the ABCB1 C3435T genotype should be considered in future diagnostic development efforts for RIS-associated QT.

We implemented a two-step approach to detect potential predictor gene variants for neuroleptic-induced tardive dyskinesia (TD) in schizophrenic subjects. First, we screened associations by using a genome-wide (Illumina HumanHapCNV370) SNP array in 61 Japanese schizophrenia patients with treatment-resistant TD and 61 Japanese schizophrenia patients without TD. Next, we performed a replication analysis in 36 treatment-resistant TD and 138 non-TD subjects. An association of an SNP in the DPP6 (dipeptidyl peptidase-like protein-6) gene, rs6977820, the most promising association identified by the screen, was significant in the replication sample (allelic P=0.008 in the replication sample, allelic P=4.6 × 10(-6), odds ratio 2.32 in the combined sample). The SNP is located in intron-1 of the DPP6 gene and the risk allele was associated with decreased DPP6 gene expression in the human postmortem prefrontal cortex. Chronic administration of haloperidol increased Dpp6 expression in mouse brains. DPP6 is an auxiliary subunit of Kv4 and regulates the properties of Kv4, which regulates the activity of dopaminergic neurons. The findings of this study indicate that an altered response of Kv4/DPP6 to long-term neuroleptic administration is involved in neuroleptic-induced TD.

Several studies have shown increased rates of hyperglycemia and diabetes in schizophrenic patients treated with olanzapine. However, the underlying mechanism is poorly understood. Glucose-dependent insulinotropic polypeptide (GIP) is known to affect insulin secretion by pancreatic β cells. Recently, a meta-analysis study reported an association between a GIP receptor (GIPR) gene polymorphism (rs10423928) and insulin secretion measured by an oral glucose tolerance test (OGTT). We assessed the influence of this GIPR gene polymorphism on glucose metabolism in 60 schizophrenic patients treated with olanzapine and 103 healthy controls. The GIPR gene polymorphism was determined using TaqMan methods. We performed repeated-measures analysis of variance (ANOVA) and one-way ANOVA for the glucose and insulin levels during OGTTs in four groups divided by the GIPR gene polymorphism and cohort (schizophrenia or control). We found significant effects of the GIPR gene and cohort on the insulin levels at 30 min. Our findings suggest that schizophrenic patients with the A allele of GIPR rs10423928 are at risk of developing hyperinsulinemia when treated with antipsychotics.

Panic disorder (PD) is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Due to the lack of power in previous association studies, genes that are truly associated with PD might not be detected. In this study, we conducted a genome-wide association study (GWAS) in two independent data sets using the Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0. We obtained imputed genotypes for each GWAS and performed a meta-analysis of two GWAS data sets (718 cases and 1717 controls). For follow-up, 12 single-nucleotide polymorphisms (SNPs) were tested in 329 cases and 861 controls. Gene ontology enrichment and candidate gene analyses were conducted using the GWAS or meta-analysis results. We also applied the polygenic score analysis to our two GWAS samples to test the hypothesis of polygenic components contributing to PD. Although genome-wide significant SNPs were not detected in either of the GWAS nor the meta-analysis, suggestive associations were observed in several loci such as BDKRB2 (P=1.3 × 10(-5), odds ratio=1.31). Among previous candidate genes, supportive evidence for association of NPY5R with PD was obtained (gene-wise corrected P=6.4 × 10(-4)). Polygenic scores calculated from weakly associated SNPs (P<0.3 and 0.4) in the discovery sample were significantly associated with PD status in the target sample in both directions (sample I to sample II and vice versa) (P<0.05). Our findings suggest that large sets of common variants of small effects collectively account for risk of PD.

Application-specific requirements for future lighting, displays and photovoltaics will include large-area, low-weight and mechanical resilience for dual-purpose uses such as electronic skin, textiles and surface conforming foils. Here we demonstrate polymer-based photovoltaic devices on plastic foil substrates less than 2 μm thick, with equal power conversion efficiency to their glass-based counterparts. They can reversibly withstand extreme mechanical deformation and have unprecedented solar cell-specific weight. Instead of a single bend, we form a random network of folds within the device area. The processing methods are standard, so the same weight and flexibility should be achievable in light emitting diodes, capacitors and transistors to fully realize ultrathin organic electronics. These ultrathin organic solar cells are over ten times thinner, lighter and more flexible than any other solar cell of any technology to date.

The excellent mechanical flexibility of organic electronic devices is expected to open up a range of new application opportunities in electronics, such as flexible displays, robotic sensors, and biological and medical electronic applications. However, one of the major remaining issues for organic devices is their instability, especially their thermal instability, because low melting temperatures and large thermal expansion coefficients of organic materials cause thermal degradation. Here we demonstrate the fabrication of flexible thin-film transistors with excellent thermal stability and their viability for biomedical sterilization processes. The organic thin-film transistors comprise a high-mobility organic semiconductor, dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene, and thin gate dielectrics comprising a 2-nm-thick self-assembled monolayer and a 4-nm-thick aluminium oxide layer. The transistors exhibit a mobility of 1.2 cm(2) V(-1)s(-1) within a 2 V operation and are stable even after exposure to conditions typically used for medical sterilization.

Flexible electronic circuits are an essential prerequisite for the development of rollable displays, conformable sensors, biodegradable electronics and other applications with unconventional form factors. The smallest radius into which a circuit can be bent is typically several millimetres, limited by strain-induced damage to the active circuit elements. Bending-induced damage can be avoided by placing the circuit elements on rigid islands connected by stretchable wires, but the presence of rigid areas within the substrate plane limits the bending radius. Here we demonstrate organic transistors and complementary circuits that continue to operate without degradation while being folded into a radius of 100 μm. This enormous flexibility and bending stability is enabled by a very thin plastic substrate (12.5 μm), an atomically smooth planarization coating and a hybrid encapsulation stack that places the transistors in the neutral strain position. We demonstrate a potential application as a catheter with a sheet of transistors and sensors wrapped around it that enables the spatially resolved measurement of physical or chemical properties inside long, narrow tubes.

Many gene variants are involved in the susceptibility to schizophrenia and some of them are expected to be associated with other human characters. Recently reported meta-analysis of genetic associations revealed nucleotide variants in synaptic vesicular transport/Golgi apparatus genes with schizophrenia. In this study, we selected the dymeclin gene (DYM) as a candidate gene for schizophrenia. The DYM gene encodes dymeclin that has been identified to be associated with the Golgi apparatus and with transitional vesicles of the reticulum-Golgi interface. A three-step case-control study of total of 2105 Japanese cases of schizophrenia and 2087 Japanese control subjects was carried out for tag single-nucleotide polymorphisms (SNPs) in the DYM gene and an association between an SNP, rs833497, and schizophrenia was identified (allelic P=2 × 10(-5), in the total sample). DYM is the causal gene for Dyggve-Melchior-Clausen syndrome and this study shows the second neuropsychiatric disorder in which the DYM gene is involved. The present data support the involvement of Golgi function and vesicular transport in the presynapse in schizophrenia.

Calcineurin (CN) is a calcium/calmodulin-dependent serine/threonine protein phosphatase and regulates neuronal structure, neurotransmission and activity-dependent gene expression. Several studies have indicated that CN signaling is likely to be involved in the pathogenesis of schizophrenia. The gene encoding CN-binding protein 1 (CABIN1) is located on 22q11.23, one of the common susceptibility loci for schizophrenia. Therefore, CABIN1 is a promising functional and positional candidate gene for schizophrenia. To assess whether CABIN1 is implicated in vulnerability to schizophrenia, we conducted a case-control association study between CABIN1 and schizophrenia. The results showed no evidence of an association between CABIN1 and schizophrenia using 11 tagging single nucleotide polymorphisms in 1193 Japanese subjects. Our results suggest that CABIN1 may not confer increased susceptibility for schizophrenia in the Japanese population.

Peptidylarginine deiminases (PADIs), five isoforms of which have been identified, catalyze the conversion of arginine residues to citrulline residues in proteins. Recent studies have revealed that abnormal activation of PADI2, the gene for which is expressed throughout the nervous system, is likely to be related to the pathogenesis of neuropsychiatric diseases with neurodegenerative processes, such as Alzheimer's disease and multiple sclerosis. Such a progressive neurodegenerative process could be involved in the etiology and/or course of schizophrenia, and PADI2 may be a candidate gene for schizophrenia. To assess whether PADI2 has a role in vulnerability to schizophrenia, we conducted a two-stage case-control association study in Japanese individuals. In a screening population of 534 patients and 559 control individuals, we examined eight single-nucleotide polymorphisms (SNPs) including four haplotype tag SNPs and four coding SNPs in PADI2. There was a potential association of a synonymous SNP in exon 7 with schizophrenia. However, we could not replicate this association in a confirmatory population of 2126 patients and 2228 control individuals. The results of this study suggest that PADI2 does not contribute to genetic susceptibility to schizophrenia.

Stretchability will significantly expand the applications scope of electronics, particularly for large-area electronic displays, sensors and actuators. Unlike for conventional devices, stretchable electronics can cover arbitrary surfaces and movable parts. However, a large hurdle is the manufacture of large-area highly stretchable electrical wirings with high conductivity. Here, we describe the manufacture of printable elastic conductors comprising single-walled carbon nanotubes (SWNTs) uniformly dispersed in a fluorinated rubber. Using an ionic liquid and jet-milling, we produce long and fine SWNT bundles that can form well-developed conducting networks in the rubber. Conductivity of more than 100 S cm(-1) and stretchability of more than 100% are obtained. Making full use of this extraordinary conductivity, we constructed a rubber-like stretchable active-matrix display comprising integrated printed elastic conductors, organic transistors and organic light-emitting diodes. The display could be stretched by 30-50% and spread over a hemisphere without any mechanical or electrical damage.

There is strong evidence for a negative association between schizophrenia and rheumatoid arthritis (RA). However, the mechanism for this association is unknown. We hypothesize that these two diseases share susceptibility genes. Recently, extensive studies have identified some RA susceptibility genes, including NFKBIL1, SLC22A4, RUNX1, FCRL3 and PADI4, in the Japanese population. To assess whether polymorphisms in these RA susceptibility genes are implicated in vulnerability to schizophrenia, we conducted a two-stage case-control association study in Japanese subjects. In a screening population of 534 patients and 559 control subjects, we examined eight polymorphisms in RA susceptibility genes and found a potential association of padi4&#95;94 in PADI4 with schizophrenia. However, we could not replicate this association in a confirmatory population of 2126 patients and 2228 control subjects. The results of this study suggest that these polymorphisms in RA susceptibility genes do not contribute to genetic susceptibility to schizophrenia.

The electronics fields face serious problems associated with electric power; these include the development of ecologically friendly power-generation systems and ultralow-power-consuming circuits. Moreover, there is a demand for developing new power-transmission methods in the imminent era of ambient electronics, in which a multitude of electronic devices such as sensor networks will be used in our daily life to enhance security, safety and convenience. We constructed a sheet-type wireless power-transmission system by using state-of-the-art printing technologies using advanced electronic functional inks. This became possible owing to recent progress in organic semiconductor technologies; the diversity of chemical syntheses and processes on organic materials has led to a new class of organic semiconductors, dielectric layers and metals with excellent electronic functionalities. The new system directly drives electronic devices by transmitting power of the order of tens of watts without connectors, thereby providing an easy-to-use and reliable power source. As all of the components are manufactured on plastic films, it is easy to place the wireless power-transmission sheet over desks, floors, walls and any other location imaginable.

We investigated the effect of 5-hydroxytryptamine 3A and 3B receptor (HTR3A and HTR3B) gene polymorphisms on nausea induced by paroxetine in Japanese psychiatric patients. Blood samples were collected from 78 individuals after at least 2 weeks treatment with the same daily dose of paroxetine. The patients visited every 2 weeks and the paroxetine dose was changed in response to their clinical symptoms. Nausea was assessed at each visit. The Tyr129Ser polymorphism of the HTR3B gene had a significant effect on the incidence of nausea (P=0.038). Logistic regression analysis also showed that patients with the Tyr/Tyr genotype had a 3.95-fold (P=0.048) higher risk of developing nausea than patients with the Ser allele. HTR3A gene polymorphisms and the CYP2D6 gene polymorphisms had no significant effect on the incidence of nausea. The mean score of nausea severity was corrected by the Bonferroni test. HTR3B gene polymorphisms are significant predictors of paroxetine-induced nausea.

We investigated the effects of a 5-hydroxytryptamine (5-HT) 1A receptor gene polymorphism on the clinical response to fluvoxamine (FLV) in 65 depressed outpatients who gave written consent to participate in the study. Patients visited every 2 weeks after the first examination until the week 12 end point and were evaluated by the 17-item Hamilton Rating Scale for Depression (HAM-D-17) at each visit. FLV dose was changed in response to their clinical symptoms. The Gly272Asp polymorphism of the 5-HT1A receptor gene was identified by a PCR method. The subjects with the Asp allele had a significantly higher % reduction in the HAM-D-17 score than those with the Gly/Gly genotype at week 2 (P=0.009), week 6 (P=0.036), and week 12 (P=0.031). There was a significant difference in the genotype distribution between the responders and nonresponders. These results suggest that the Gly272Asp polymorphism of the 5-HT1A receptor gene may predict the response to FLV.