A GLP-1/GLP-2 receptor dual agonist to treat NASH: Targeting the gut-liver axis and microbiome.

BACKGROUND AND AIMS: Currently there is no Food and Drug Administration-approved drug to treat NAFLD and NASH, the rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut-liver axis in their pathogenesis, we investigated the therapeutic effect of a long-acting dual agonist of glucagon-like peptide (GLP)-1 and GLP-2 receptors in mice with NAFLD/NASH. APPROACH AND RESULTS: C57BL/6J mice were fed a choline-deficient high-fat diet/high fructose and sucrose solution. After 16 weeks, mice were randomly allocated to receive vehicle, GLP1-Fc, GLP2-Fc, or GLP1/2-Fc fusion (GLP1/2-Fc) subcutaneously every 2 days for 4 weeks. Body weight was monitored, insulin/glucose tolerance tests were performed, feces were collected, and microbiome profiles were analyzed. Immobilized cell systems were used to evaluate direct peptide effect. Immunohistochemistry, quantitative PCR, immunoblot analysis, tunnel assay, and biochemical assays were performed to assess drug effects on inflammation, hepatic fibrosis, cell death, and intestinal structures. The mice had well-developed NASH phenotypes. GLP1/2-Fc reduced body weight, glucose levels, hepatic triglyceride levels, and cellular apoptosis. It improved liver fibrosis, insulin sensitivity, and intestinal tight junctions, and increased microvillus height, crypt depth, and goblet cells of intestine compared with a vehicle group. Similar effects of GLP1/2-Fc were found in in vitro cell systems. GLP1/2-Fc also changed microbiome profiles. We applied fecal microbiota transplantation (FMT) gain further insight into the mechanism of GLP1/2-Fc-mediated protection. We confirmed that FMT exerted an additive effect on GLP1-Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation, and hepatic fibrosis. CONCLUSIONS: A long-acting dual agonist of GLP-1 and GLP-2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.

Live isolation of naïve ESCs via distinct glucose metabolism and stored glycogen.

Naïve and primed pluripotent stem cells recapitulate the peri- and post-implantation development, respectively. Thus, investigation of distinct traits between each pluripotent stem cell type would shed light on early embryonic processes. Herein, by screening a fluorescent probe library, we found that intracellular glycogen led to specific reactivity to CDg4, a glycogen fluorescence sensor, in both human and mouse naïve embryonic stem cells (ESCs). The requirement of constant inhibition of Gsk3ß as well as high oxidative phosphorylation (OxPHOS) in naïve compared to primed ESCs was closely associated to high level of intracellular glycogen in naïve ESCs. Both capacity of OxPHOS and stored glycogen, rescued naïve ESCs by transient inhibition of glycolysis, which selectively eliminated primed ESCs. Additionally, naïve ESCs with active OxPHOS were enriched from a mixture with primed ESCs by high reactivity to ATP-Red1, a mitochondrial ATP fluorescence probe. These results indicate the active OxPHOS and high intracellular glycogen as a novel "biomarker" delineating metabolic remodeling during the transition of naïve pluripotency.

Correction of an adult Class III malocclusion through regaining of orthodontic space and an implant restoration.

This case report describes the interdisciplinary treatment of a 23-year-old female with Class III malocclusion and a missing maxillary left second premolar. Treatment alternatives were discussed, and the selected treatment plan was presented to illustrate a way to gain space for the premolar implant restoration and correct Class III relationship through maxillary molar retraction followed by maxillary total arch protraction with a palatal temporary skeletal anchorage device. Esthetic anterior alignment and functional occlusal rehabilitation was achieved, and facial balance was maintained at the end of treatment. CLINICAL SIGNIFICANCE: Implant restoration in conjunction with regaining orthodontic space by a team of multidisciplinary dental specialists presents an effective treatment solution to permanent tooth agenesis. Class III malocclusion can be treated with a combination of maxillary protraction and mandibular retraction using temporary skeletal anchorage devices. The versatility of modified palatal C-plates presents greater clinical application when related side effects are controlled with solid understanding of their biomechanics.

Microbiota changes with fermented kimchi contributed to either the amelioration or rejuvenation of Helicobacter pylori-associated chronic atrophic gastritis.

Korean fermented kimchi is probiotic food preventing Helicobacter pylori (H. pylori)-associated atrophic gastritis in both animal and human trial. In order to reveal the effect of fermented kimchi against H. pylori infection, we performed clinical trial to document the changes of fecal microbiota in 32 volunteers (H. pylori (-) chronic superficial gastritis (CSG), H. pylori (+) CSG, and H. pylori (+) chronic atrophic gastritis (CAG) with 10 weeks kimchi. Each amplicon is sequenced on MiSeq of Illumina and the sequence reads were clustered into operational taxonomic units using VSEARCH and the Chao, Simpson, and Shannon Indices. Though significant difference in α- or ß-diversity was not seen in three groups, kimchi intake led to significant diversity of fecal microbiome. As results, Klebsiella, Enterococcus, Ruminococcaceae, Streptococcus, Roseburia, and Clostirdiumsensu were significantly increased in H. pylori (+) CAG, while Akkermansia, Citrobacter, and Lactobacillus were significantly decreased in H. pylori (+) CAG. With 10 weeks of kimchi administration, Bifidobacterium, Lactobacillus, and Ruminococcus were significantly increased in H. pylori (+) CAG, whereas Bacteroides, Subdoligranulum, and Eubacterium coprostanolines were significantly decreased in H. pylori (-) CAG. 10 weeks of kimchi intake significantly improved pepsinogen I/II ratio (p<0.01) with significant decreases in interleukin-1ß. Conclusively, fermented kimchi significantly changed fecal microbiota to mitigate H. pylori-associated atrophic gastritis.

Fermented kimchi rejuvenated precancerous atrophic gastritis via mitigating Helicobacter pylori-associated endoplasmic reticulum and oxidative stress.

Dietary intervention to prevent Helicobacter pylori (H. pylori)-gastric cancer might be ideal by long-term intervention, rejuvenating action, and no risk of bacterial resistance. Stimulated with finding that kimchi prevented H. pylori-gastric cancer, we compared the efficacy of cancer preventive kimchi (cpkimchi) and standard recipe kimchi (skimchi) and the efficacy between fermented kimchi and non-fermented kimchi (kimuchi) in H. pylori-initiated gastric cancer model and explored novel mechanisms hinted from RNAseq transcriptome analysis. Animal models assessing gastric pathology on 24 and 36 weeks after H. pylori initiated, salt diet-promoted gastric mutagenesis model showed fermented cpkimchi afforded the best outcome of either rejuvenating atrophic gastritis or inhibiting tumorigenesis compared to skimchi and kimuchi. Highest inhibition of atrophic gastritis was achieved with cpkimchi, while significantly lower in kimuchi. Transcriptomic analysis showed ameliorated-endoplasmic reticulum (ER) stress, -oxidative stress, and -apoptosis as major rejuvenating action of cpkimchi. Homogenates from animal model showed that elevated expressions of p-PERK, IRE, ATF6, p-elf, and XBP1 in control group, while significantly decreased with dietary intake of only cpkimchi. Significantly increased expressions of HO-1 and γ-GCS were only noted with cpkimchi. Conclusively, long-term dietary intervention of fermented cpkimchi can be potential way preventing H. pylori-associated carcinogenesis via rejuvenation of atrophic gastritis.

Transcriptome profiling implicated in beneficiary actions of kimchi extracts against Helicobacter pylori infection.

Dietary intervention to prevent Helicobacter pylori (H. pylori)-gastric cancer might be ideal because of no risk of bacterial resistance, safety, and rejuvenating action of atrophic gastritis. We have published data about the potential of fermented kimchi as nutritional approach for H. pylori. Hence recent advances in RNAseq analysis lead us to investigate the transcriptome analysis to explain these beneficiary actions of kimchi. gastric cells were infected with either H. pylori or H. pylori plus kimchi. 943 genes were identified as significantly increased or decreased genes according to H. pylori infection and 68 genes as significantly changed between H. pylori infection and H. pylori plus kimchi (p<0.05). Gene classification and Medline database showed DLL4, FGF18, PTPRN, SLC7A11, CHAC1, FGF21, ASAN, CTH, and CREBRF were identified as significantly increased after H. pylori, but significantly decreased with kimchi and NEO1, CLDN8, KLRG1, and IGFBP1 were identified as significantly decreased after H. pylori, but increased with kimchi. After KEGG and STRING-GO analysis, oxidative stress, ER stress, cell adhesion, and apoptosis genes were up-regulated with H. pylori infection but down-regulated with kimchi, whereas tissue regeneration, cellular anti-oxidative response, and anti-inflammation genes were reversely regulated with kimchi (p<0.01). Conclusively, transcriptomes of H. pylori plus kimchi showed significant biological actions.

Fecal microbiota changes with fermented kimchi intake regulated either formation or advancement of colon adenoma.

Gut bacteria might contribute in early stage of colorectal cancer through the development and advancement of colon adenoma, by which exploring either beneficial bacteria, which are decreased in formation or advancement of colon adenoma and harmful bacteria, which are increased in advancement of colon adenoma may result in implementation of dietary interventions or probiotic therapies to functional means for prevention. Korean fermented kimchi is one of representative probiotic food providing beneficiary microbiota and exerting significant inhibitory outcomes in both APC/Min+ polyposis model and colitis-associated cancer. Based on these backgrounds, we performed clinical trial to document the changes of fecal microbiota in 32 volunteers with normal colon, simple adenoma, and advanced colon adenoma with 10 weeks of fermented kimchi intake. Each amplicon is sequenced on MiSeq of Illumina and the sequence reads were clustered into Operational Taxonomic Units using VSEARCH and the Chao Indices, an estimator of richness of taxa per individual, were estimated to measure the diversity of each sample. Though significant difference in α or ß diversity was not seen between three groups, kimchi intake significantly led to significant diversity of fecal microbiome. After genus analysis, Acinobacteria, Cyanobacteria, Clostridium sensu, Turicibacter, Gastronaeophillales, H. pittma were proven to be increased in patients with advanced colon adenoma, whereas Enterococcua Roseburia, Coryobacteriaceau, Bifidobacterium spp., and Akkermansia were proven to be significantly decreased in feces from patients with advanced colon adenoma after kimchi intake. Conclusively, fermented kimchi plentiful of beneficiary microbiota can afford significant inhibition of either formation or advancement of colon adenoma.

Dietary intake of probiotic kimchi ameliorated IL-6-driven cancer cachexia.

Cancer cachexia is a syndrome accompanying weight loss, skeletal muscle atrophy, and loss of adipose tissue in patients with advanced cancer. Since interleukin-6 (IL-6) is one of core mediators causing cancer cachexia and kimchi can modulate IL-6 response, we hypothesized dietary intake of kimchi can ameliorate cancer cachexia. In this study, we studied preemptive administration of kimchi can ameliorate mouse colon carcinoma cells colon (C26) adenocarcinoma-induced cancer cachexia and explored anti-cachexic mechanisms of kimchi focused on the changes of muscle atrophy, cachexic inflammation, and catabolic catastrophe. As results, dietary intake of kimchi significantly attenuated the development of cancer cachexia, presented with lesser weight loss, higher muscle preservation as well as higher survival from cancer cachexia in mice. Starting from significant inhibition of IL-6 and its signaling, kimchi afforded significant inhibition of muscle specific ubiquitin-proteasome system including inhibition of atrogin-1 and muscle ring finger protein-1 (MuRF-1) with other muscle related genes including mitofusin-2 (Mfn-2) and PGC-1α. Significant inhibition of lipolysis gene such as adipose triglyceride lipase (ATGL) and hormone-sensitive ligase (HSL) accompanied with significant induction of fatty acid synthase (FAS) and sterol response element binding protein 1 (SREBP1) was achieved with kimchi. As gene regulation, IL-6 and their receptor as well as Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were significantly attenuated with kimchi. In conclusion, dietary intake of cancer preventive kimchi can be an anticipating option to ameliorate cancer cachexia via suppressive action of IL-6 accompanied with decreased muscle atrophy and lipolysis.

High Glucose-Induced Reactive Oxygen Species Stimulates Human Mesenchymal Stem Cell Migration Through Snail and EZH2-Dependent E-Cadherin Repression.

BACKGROUND/AIMS: Glucose plays an important role in stem cell fate determination and behaviors. However, it is still not known how glucose contributes to the precise molecular mechanisms responsible for stem cell migration. Thus, we investigate the effect of glucose on the regulation of the human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) migration, and analyze the mechanism accompanied by this effect. METHODS: Western blot analysis, wound healing migration assays, immunoprecipitation, and chromatin immunoprecipitation assay were performed to investigate the effect of high glucose on hUCB-MSC migration. Additionally, hUCB-MSC transplantation was performed in the mouse excisional wound splinting model. RESULTS: High concentration glucose (25 mM) elicits hUCB-MSC migration compared to normal glucose and high glucose-pretreated hUCB-MSC transplantation into the wound sites in mice also accelerates skin wound repair. We therefore elucidated the detailed mechanisms how high glucose induces hUCB-MSC migration. We showed that high glucose regulates E-cadherin repression through increased Snail and EZH2 expressions. And, we found high glucose-induced reactive oxygen species (ROS) promotes two signaling; JNK which regulates γ-secretase leading to the cleavage of Notch proteins and PI3K/Akt signaling which enhances GSK-3ß phosphorylation. High glucose-mediated JNK/Notch pathway regulates the expression of EZH2, and PI3K/Akt/GSK-3ß pathway stimulates Snail stabilization, respectively. High glucose enhances the formation of EZH2/Snail/HDAC1 complex in the nucleus, which in turn causes E-cadherin repression. CONCLUSION: This study reveals that high glucose-induced ROS stimulates the migration of hUCB-MSC through E-cadherin repression via Snail and EZH2 signaling pathways.

Benefit of adding digital breast tomosynthesis to digital mammography for breast cancer screening focused on cancer characteristics: a meta-analysis.

PURPOSE: We evaluated the benefit of adding digital breast tomosynthesis (DBT) to full-field digital mammography (FFDM) compared to FFDM alone for breast cancer detection, focusing on cancer characteristics. METHODS: We searched electronic databases and relevant references for published studies comparing DBT plus FFDM to FFDM alone for breast cancer screening. Pooled risk ratios (RRs) for various pathologic findings were determined using random effects models. RESULTS: Eleven eligible studies were included. Pooled RRs showed a greater cancer detection for DBT plus FFDM than for FFDM alone for invasive cancer (1.327; 95% CI, 1.168-1.508), stage T1 (1.388; 95% CI, 1.137-1.695), nodal-negative (1.451; 95% CI, 1.209-1.742), all histologic grades (grade I, 1.812; grade II/III, 1.403), and histologic types of invasive cancer (ductal, 1.437; lobular, 1.901). However, adding DBT did not increase for detection of carcinoma in situ (1.198; 95% CI, 0.942-1.524), stage ≥T2 (1.391; 95% CI, 0.895-2.163), or nodal-positive cancer (1.336; 95% CI, 0.921-1.938). Heterogeneity among studies was not significant in any subset analysis. CONCLUSIONS: Adding DBT to FFDM enabled detection of early invasive breast cancer that might have been missed with FFDM alone. Knowing which cancer characteristic DBT detects may allow it to play a complementary role in predicting long-term patient outcomes and facilitate treatment planning.

Relationship Between ß-Amyloid and Mitochondrial Dynamics.

Mitochondria as dynamic organelles undergo morphological changes through the processes of fission and fusion which are major factors regulating their functions. A disruption in the balance of mitochondrial dynamics induces functional disorders in mitochondria such as failed energy production and the generation of reactive oxygen species, which are closely related to pathophysiological changes associated with Alzheimer's disease (AD). Recent studies have demonstrated a relationship between abnormalities in mitochondrial dynamics and impaired mitochondrial function, clarifying the effects of morphofunctional aberrations which promote neuronal cell death in AD. Several possible signaling pathways have been suggested for a better understanding of the mechanism behind the key molecules regulating mitochondrial morphologies. However, the exact machinery involved in mitochondrial dynamics still has yet to be elucidated. This paper reviews the current knowledge on signaling mechanisms involved in mitochondrial dynamics and the significance of mitochondrial dynamics in controlling associated functions in neurodegenerative diseases, particularly in AD.

Comparison of Low- and Standard-Dose CT for the Diagnosis of Acute Appendicitis: A Meta-Analysis.

OBJECTIVE: A meta-analysis was performed to compare low-dose CT and standard-dose CT in the diagnosis of acute appendicitis with an emphasis on diagnostic value. MATERIALS AND METHODS: A systematic literature search for articles published through June 2016 was performed to identify studies that compared low-dose CT with standard-dose CT for the evaluation of patients suspected of having acute appendicitis. Summary estimates of sensitivity and specificity with 95% CIs were calculated using a bivariate random-effects model. Meta-regression was used to perform statistical comparisons of low-dose CT and standard-dose CT. RESULTS: Of 154 studies, nine studies investigating a total of 2957 patients were included in this meta-analysis. The pooled sensitivity and specificity of low-dose CT were 96.25% (95% CI, 91.88-98.31%) and 93.22% (95% CI, 88.75-96.00%), respectively. The pooled sensitivity and specificity of standard-dose CT were 96.40% (95% CI, 93.55-98.02%) and 92.17% (95% CI, 88.24-94.86%), respectively. In a joint model estimation of meta-regression, lowand standard-dose CT did not show a statistically significant difference (p = 0.71). Both lowand standard-dose CT seem to be characterized by high positive and negative predictive values across a broad spectrum of pretest probabilities for acute appendicitis. CONCLUSION: Low-dose CT is highly effective for the diagnosis of suspected appendicitis and can be considered a valid alternative first-line imaging test that reduces the potential risk of exposure to ionizing radiation.

Oxide Semiconductor-Based Flexible Organic/Inorganic Hybrid Thin-Film Transistors Fabricated on Polydimethylsiloxane Elastomer.

We demonstrate flexible organic/inorganic hybrid thin-film transistors (TFTs) on a polydimethysilox- ane (PDMS) elastomer substrate. The active channel and gate insulator of the hybrid TFT are composed of In-Ga-Zn-O (IGZO) and blends of poly(vinylidene fluoride-trifluoroethylene) [P(VDF- TrFE)] with poly(methyl methacrylate) (PMMA), respectively. It has been confirmed that the fabri- cated TFT display excellent characteristics: the recorded field-effect mobility, sub-threshold voltage swing, and I(on)/I(off) ratio were approximately 0.35 cm2 V(-1) s(-1), 1.5 V/decade, and 10(4), respectively. These characteristics did not experience any degradation at a bending radius of 15 mm. These results correspond to the first demonstration of a hybrid-type TFT using an organic gate insulator/oxide semiconducting active channel structure fabricated on PDMS elastomer, and demonstrate the feasibility of a promising device in a flexible electronic system.

Gamma Knife radiosurgery for cystic brain metastases.

OBJECTIVE: The goal of this study was to investigate the treatment results of Gamma Knife radiosurgery (GKRS) for cystic brain metastases and relevant factors associated with local tumor control. MATERIALS AND METHODS: We retrospectively reviewed the clinical, radiological, and dosimetry data of 37 cystic brain metastases of 28 patients who were treated with GKRS. Cyst drainage was performed in 8 large lesions before GKRS to decrease the target volume. The mean target volume was 4.8 (range, 0.3-15.8) cc at the time of GKRS, and the mean prescription dose was 16.6 (range, 13-22) Gy. RESULTS: The actuarial median survival time was 17.7 ± 10.2 months, and the primary tumor status was a significant prognostic factor for survival. The actuarial local tumor control rate at 6 and 12 months was 93.1 and 82.3%, respectively. Among the various factors, only prescription dose (>15 Gy) was a significant factor related to local tumor control after multivariate analysis (p = 0.049). Cyst volume or cyst/total tumor volume ratio did not influence local control after GKRS, when the target volume was reduced to about 15 cc after cyst drainage. CONCLUSION: According to our results, we suggest that stereotactic radiosurgery should be considered as one of the treatment options for cystic brain metastases, when large tumor volume can be reduced by surgical drainage before radiosurgery, especially for patients with a controlled primary tumor.

Electrical properties of solution-deposited ZnO thin-film transistors by low-temperature annealing.

Flexible oxide thin-film transistors (Oxide-TFTs) have emerged as next generation transistors because of their applicability in electronic device. In particular, the major driving force behind solution-processed zinc oxide film research is its prospective use in printing for electronics. A low-temperature process to improve the performance of solution-processed n-channel ZnO thin-film transistors (TFTs) fabricated via spin-coating and inkjet-printing is introduced here. ZnO nanoparticles were synthesized using a facile sonochemical method that was slightly modified based on a previously reported method. The influence of the annealing atmosphere on both nanoparticle-based TFT devices fabricated via spin-coating and those created via inkjet printing was investigated. For the inkjet-printed TFTs, the characteristics were improved significantly at an annealing temperature of 150 degrees C. The field effect mobility, V(th), and the on/off current ratios were 3.03 cm2/Vs, -3.3 V, and 10(4), respectively. These results indicate that annealing at 150 degrees C 1 h is sufficient to obtain a mobility (µ(sat)) as high as 3.03 cm2/Vs. Also, the active layer of the solution-based ZnO nanoparticles allowed the production of high-performance TFTs for low-cost, large-area electronics and flexible devices.

DUSP6 is a memory retention feedback regulator of ERK signaling for cellular resilience of human pluripotent stem cells in response to dissociation.

Cultured human pluripotent stem cells (hPSCs) grow as colonies that require breakdown into small clumps for further propagation. Although cell death mechanism by single-cell dissociation of hPSCs has been well defined, how hPSCs respond to the deadly stimulus and recover the original status remains unclear. Here we show that dissociation of hPSCs immediately activates ERK, which subsequently activates RSK and induces DUSP6, an ERK-specific phosphatase. Although the activation is transient, DUSP6 expression persists days after passaging. DUSP6 depletion using the CRISPR/Cas9 system reveals that DUSP6 suppresses the ERK activity over the long term. Elevated ERK activity by DUSP6 depletion increases both viability of hPSCs after single-cell dissociation and differentiation propensity towards mesoderm and endoderm lineages. These findings provide new insights into how hPSCs respond to dissociation in order to maintain pluripotency.

Partial in vivo reprogramming enables injury-free intestinal regeneration via autonomous Ptgs1 induction.

Tissue regeneration after injury involves the dedifferentiation of somatic cells, a natural adaptive reprogramming that leads to the emergence of injury-responsive cells with fetal-like characteristics. However, there is no direct evidence that adaptive reprogramming involves a shared molecular mechanism with direct cellular reprogramming. Here, we induced dedifferentiation of intestinal epithelial cells using OSKM (Oct4, Sox2, Klf4, and c-Myc) in vivo. The OSKM-induced forced dedifferentiation showed similar molecular features of intestinal regeneration, including a transition from homeostatic cell types to injury-responsive-like cell types. These injury-responsive-like cells, sharing gene signatures of revival stem cells and atrophy-induced villus epithelial cells, actively assisted tissue regeneration following damage. In contrast to normal intestinal regeneration involving Ptgs2 induction, the OSKM promotes autonomous production of prostaglandin E2 via epithelial Ptgs1 expression. These results indicate prostaglandin synthesis is a common mechanism for intestinal regeneration but involves a different enzyme when partial reprogramming is applied to the intestinal epithelium.

Generation of integration-free induced pluripotent stem cell line (KSCBi012-A) from urinary epithelial cells of a healthy male individual.

A human induced pluripotent cell (hiPSC) line, KSCBi012-A, was generated from a 40-year-old male individual using non-integrating episomal vectors expressing reprogramming factors. The generated hiPSCs were integration-free, expressed pluripotency markers, exhibited the potential for differentiation into three germ layers in vivo, and maintained the normal karyotype. This cell line can be used as a control for a disease model and is available from Korea National Stem Cell Bank.

High density integration of stretchable inorganic thin film transistors with excellent performance and reliability.

Transistors with inorganic semiconductors have superior performance and reliability compared to organic transistors. However, they are unfavorable for building stretchable electronic products due to their brittle nature. Because of this drawback, they have mostly been placed on non-stretchable parts to avoid mechanical strain, burdening the deformable interconnects, which link these rigid parts, with the strain of the entire system. Integration density must therefore be sacrificed when stretchability is the first priority because the portion of stretchable wirings should be raised. In this study, we show high density integration of oxide thin film transistors having excellent performance and reliability by directly embedding the devices into stretchable serpentine strings to defeat such trade-off. The embedded transistors do not hide from deformation and endure strain up to 100% by themselves; thus, integration density can be enhanced without sacrificing the stretchability. We expect that our approach can create more compact stretchable electronics with high-end functionality than before.

Dual-Functional Self-Attachable and Stretchable Interface for Universal Three-Dimensional Modular Electronics.

Stretchable electronics have become essential for custom-built electronics, self-assembling robotics, and wearable devices. Although many stretchable electronics contain integrated systems, they still limit bulky connection systems. We introduce a new dual-functioned self-attachable and stretchable interface (SASI), allowing a direct and instant interconnection between rigid and soft electronics. The SASI consists of a sticky and stretchable substrate and surface-embedded serpentine conductors with the single-sided polyimide fabricated using the embedded transfer process. The adhesion property of the SASI is controlled by the mixed elastomer ratio. The resulting sticky and conductive SASI can instantly adhere to a metal surface and create conductive paths. The SASI serpentine conductors exhibit high stretchability (∼290%) and provide self-attachable, re-attachable, and low-resistant electrical contacts (0.85 ohms in 0.25 mm2) between interfaces without pressure, heat, or extra solder. In addition, three-dimensional curved and modular electronics can be formed with the SASI by compiling functional blocks. SASI provides a novel strategy for assembling functional chips or modules for stretchable electronics, opening a path to onboard integrated electronics that are customizable by users for real-world stretchable electronics.