Materials-Driven Soft Wearable Bioelectronics for Connected Healthcare.

In the era of Internet-of-things, many things can stay connected; however, biological systems, including those necessary for human health, remain unable to stay connected to the global Internet due to the lack of soft conformal biosensors. The fundamental challenge lies in the fact that electronics and biology are distinct and incompatible, as they are based on different materials via different functioning principles. In particular, the human body is soft and curvilinear, yet electronics are typically rigid and planar. Recent advances in materials and materials design have generated tremendous opportunities to design soft wearable bioelectronics, which may bridge the gap, enabling the ultimate dream of connected healthcare for anyone, anytime, and anywhere. We begin with a review of the historical development of healthcare, indicating the significant trend of connected healthcare. This is followed by the focal point of discussion about new materials and materials design, particularly low-dimensional nanomaterials. We summarize material types and their attributes for designing soft bioelectronic sensors; we also cover their synthesis and fabrication methods, including top-down, bottom-up, and their combined approaches. Next, we discuss the wearable energy challenges and progress made to date. In addition to front-end wearable devices, we also describe back-end machine learning algorithms, artificial intelligence, telecommunication, and software. Afterward, we describe the integration of soft wearable bioelectronic systems which have been applied in various testbeds in real-world settings, including laboratories that are preclinical and clinical environments. Finally, we narrate the remaining challenges and opportunities in conjunction with our perspectives.

Deciphering the regulatory role of PheSnRK genes in Moso bamboo: insights into hormonal, energy, and stress responses.

The SnRK (sucrose non-fermentation-related protein kinase) plays an important role in regulating various signals in plants. However, as an important bamboo shoot and wood species, the response mechanism of PheSnRK in Phyllostachys edulis to hormones, low energy and stress remains unclear. In this paper, we focused on the structure, expression, and response of SnRK to hormones and sugars. In this study, we identified 75 PheSnRK genes from the Moso bamboo genome, which can be divided into three groups according to the evolutionary relationship. Cis-element analysis has shown that the PheSnRK gene can respond to various hormones, light, and stress. The PheSnRK2.9 proteins were localized in the nucleus and cytoplasm. Transgenic experiments showed that overexpression of PheSnRK2.9 inhibited root development, the plants were salt-tolerant and exhibited slowed starch consumption in Arabidopsis in the dark. The results of yeast one-hybrid and dual luciferase assay showed that PheIAAs and PheNACs can regulate PheSnRK2.9 gene expression by binding to the promoter of PheSnRK2.9. This study provided a comprehensive understanding of PheSnRK genes of Moso bamboo, which provides valuable information for further research on energy regulation mechanism and stress response during the growth and development of Moso bamboo.

PheGRF4e initiated auxin signaling during moso bamboo shoot development.

BACKGROUND: As a ubiquitous acid-regulating protein family in eukaryotes, general regulatory factors (GRFs) are active in various life activities of plants. However, detailed investigations of the GRFs gene family in moso bamboo are scarce. METHODS AND RESULTS: Genome-wide characteristics of the GRF gene family in moso bamboo were analyzed using the moso bamboo genome. GRF phylogeny, gene structure, conserved domains, cis-element promoters, and gene expression were systematically analyzed. A total of 20 GRF gene family members were identified in the moso bamboo genome. These genes were divided into ε and non-ε groups. qRT-PCR (real-time quantitative reverse transcription polymerase chain reaction) showed that PheGRF genes responded to auxin and gibberellin treatment. To further study PheGRF gene functions, a yeast two-hybrid experiment was performed and verified by a bimolecular fluorescence complementation experiment. The results showed that PheGRF4e could interact with PheIAA30 (auxin/indole-3-acetic acid, an Aux/IAA family gene), and both were found to act mainly on the root tip meristem and vascular bundle cells of developing shoots by in situ hybridization assay. CONCLUSIONS: This study revealed that PheGRF genes were involved in hormone response during moso bamboo shoot development, and the possible regulatory functions of PheGRF genes were enriched by the fact that PheGRF4e initiated auxin signaling by binding to PheIAA30.

Orientation-Dependent Soft Plasmonics of Gold Nanobipyramid Plasmene Nanosheets.

In parallel to the burgeoning field of soft electronics, soft plasmonics focuses on the design and fabrication of plasmonic structures supported on elastomers and to understand how their properties respond to mechanical deformations. Here, we report on a partial ligand-stripping strategy to fabricate elastomer-supported gold nanobipyramid (NBP) plasmene nanosheets. Unlike spherelike building blocks, NBP-building blocks display complex orientation-dependent plasmonic responses to external strains. By collecting polarized plasmonic resonance spectra in conjunction with electrostatic eigenmode modeling, we reveal simultaneous changes in interparticle spacing and spatial orientations of NBP building blocks under mechanical strains. Such changes are directly related to initial NBP packing orders. Further analysis of strain sensitivities for various NBP plasmenes indicated that plasmonic spectra of ∼45° oriented samples are mostly susceptible to strain at acute polarized angles. The results presented may enable novel applications in future soft optoelectronic devices in sensing, encryption, and data storage.

Vertically Aligned Gold Nanowires as Stretchable and Wearable Epidermal Ion-Selective Electrode for Noninvasive Multiplexed Sweat Analysis.

The noninvasive continuous analysis of human sweat is of great significance for improved healthcare diagnostics and treatment in the future, for which a wearable potentiometry-based ion-selective electrode (ISE) has attracted increasing attention, particularly involving ion detection. Note that traditional solid-state ISE electrodes are rigid ion-to-electron transducers that are not conformal to soft human skin and cannot function under stretched states. Here, we demonstrated that vertically aligned mushroom-like gold nanowires (v-AuNW) could serve as stretchable and wearable ion-to-electron transducers for multiplexed, in situ potentiometric analysis of pH, Na+, and K+ in sweat. By modifying v-AuNW electrodes with polyaniline, Na ionophore X, and a valinomycin-based selective membrane, we could specifically detect pH, Na+, and K+, respectively, with high selectivity, reproducibility, and stability. Importantly, the electrochemical performance could be maintained even under 30% strain and during stretch-release cycles without the need of extrinsic structural design. Furthermore, our stretchable v-AuNW ISEs could be seamlessly integrated with a flexible printed circuit board, enabling wireless on-body detection of pH, Na+, and K+ with fast response and negligible cross-talk, indicating considerable promise for noninvasive wearable sweat analysis.

Skin-Like Stretchable Fuel Cell Based on Gold-Nanowire-Impregnated Porous Polymer Scaffolds.

Skin-like energy devices can be conformally attached to the human body, which are highly desirable to power soft wearable electronics in the future. Here, a skin-like stretchable fuel cell based on ultrathin gold nanowires (AuNWs) and polymerized high internal phase emulsions (polyHIPEs) scaffolds is demonstrated. The polyHIPEs can offer a high porosity of 80% yet with an overall thickness comparable to human skin. Upon impregnation with electronic inks containing ultrathin (2 nm in diameter) and ultrahigh aspect-ratio (>10 000) gold nanowires, skin-like strain-insensitive stretchable electrodes are successfully fabricated. With such designed strain-insensitive electrodes, a stretchable fuel cell is fabricated by using AuNWs@polyHIPEs, platinum (Pt)-modified AuNWs@polyHIPEs, and ethanol as the anode, cathode, and fuel, respectively. The resulting epidermal fuel cell can be patterned and transferred onto skin as "tattoos" yet can offer a high power density of 280 µW cm-2 and a high durability (>90% performance retention under stretching, compression, and twisting). The results presented here demonstrate that this skin-thin, porous, yet stretchable electrode is essentially multifunctional, simultaneously serving as a current collector, an electrocatalyst, and a fuel host, indicating potential applications to power future soft wearable 2.0 electronics for remote healthcare and soft robotics.

Drug-Eluting Balloon Versus Plain Balloon Angioplasty For The Treatment of Failing Hemodialysis Access: A Systematic Review and Meta-analysis.

BACKGROUND: Hemodialysis access dysfunction is the major cause of hospitalization for patients undergoing hemodialysis due to stenosis at the anastomotic site. Our purpose is to perform a meta-analysis comparing target lesion primary patency rates at 6 months and one year, and major procedure-associated complications between drug-eluting balloon (DEB) and plain balloon angioplasty (PBA) for the treatment of arteriovenous fistula (AVF) or synthetic arteriovenous graft (AVG) stenosis. METHODS: PubMed, Embase, and MEDLINE databases were screened up to December 2018 to compare target lesion primary patency and complications between DEB and PBA. Two independent reviewers identified studies fulfilling our inclusion/exclusion criteria, extracted relevant data, and assessed quality. Fixed- or random-effects models were used to calculate overall effect estimates. RESULTS: Our literature search identified 10 articles eligible for inclusion in the review and analysis. DEB provided significantly higher target lesion primary patency rates for failing hemodialysis access than did PBA at 6 months [70% vs. 54%; odds ratio (OR), 2.71, 95% confidence interval (CI), 1.51 to 4.85; P < 0.01] and one year (59% vs. 37%; OR, 3.12, 95% CI, 2.14 to 4.55; P < 0.01). No major procedure-associated complications were observed in the 2 groups. CONCLUSIONS: DEB is an effective and safe technology that can significantly prolong 6-month and one-year target lesion primary patency for failing hemodialysis access when compared to PBA.

Softening gold for elastronics.

Gold, one of the noble metals, has played a significant role in human society throughout history. Gold's excellent electrical, optical and chemical properties make the element indispensable in maintaining a prosperous modern electronics industry. In the emerging field of stretchable electronics (elastronics), the main challenge is how to utilize these excellent material properties under various mechanical deformations. This review covers the recent progress in developing "softening" gold chemistry for various applications in elastronics. We systematically present material synthesis and design principles, applications, and challenges and opportunities ahead.

Electronic Skin Wearable Sensors for Detecting Lumbar-Pelvic Movements.

BACKGROUND: A nanomaterial-based electronic-skin (E-Skin) wearable sensor has been successfully used for detecting and measuring body movements such as finger movement and foot pressure. The ultrathin and highly sensitive characteristics of E-Skin sensor make it a suitable alternative for continuously out-of-hospital lumbar-pelvic movement (LPM) monitoring. Monitoring these movements can help medical experts better understand individuals' low back pain experience. However, there is a lack of prior studies in this research area. Therefore, this paper explores the potential of E-Skin sensors to detect and measure the anatomical angles of lumbar-pelvic movements by building a linear relationship model to compare its performance to clinically validated inertial measurement unit (IMU)-based sensing system (ViMove). METHODS: The paper first presents a review and classification of existing wireless sensing technologies for monitoring of body movements, and then it describes a series of experiments performed with E-Skin sensors for detecting five standard LPMs including flexion, extension, pelvic tilt, lateral flexion, and rotation, and measure their anatomical angles. The outputs of both E-Skin and ViMove sensors were recorded during each experiment and further analysed to build the comparative models to evaluate the performance of detecting and measuring LPMs. RESULTS: E-Skin sensor outputs showed a persistently repeating pattern for each movement. Due to the ability to sense minor skin deformation by E-skin sensor, its reaction time in detecting lumbar-pelvic movement is quicker than ViMove by ~1 s. CONCLUSIONS: E-Skin sensors offer new capabilities for detecting and measuring lumbar-pelvic movements. They have lower cost compared to commercially available IMU-based systems and their non-invasive highly stretchable characteristic makes them more comfortable for long-term use. These features make them a suitable sensing technology for developing continuous, out-of-hospital real-time monitoring and management systems for individuals with low back pain.

Highly Stretchable and Strain-Insensitive Fiber-Based Wearable Electrochemical Biosensor to Monitor Glucose in the Sweat.

Development of high-performance fiber-shaped wearable sensors is of great significance for next-generation smart textiles for real-time and out-of-clinic health monitoring. The previous focus has been mainly on monitoring physical parameters such as pressure and strains associated with human activities. Development of an enzyme-based non-invasive wearable electrochemical sensor to monitor biochemical vital signs of health such as the glucose level in sweat has attracted increasing attention recently, due to the unmet clinical needs for the diabetic patients. To achieve this, the key challenge lies in the design of a highly stretchable fiber with high conductivity, facile enzyme immobilization, and strain-insensitive properties. Herein, we demonstrate an elastic gold fiber-based three-electrode electrochemical platform that can meet the aforementioned criteria toward wearable textile glucose biosensing. The gold fiber could be functionalized with Prussian blue and glucose oxidase to obtain the working electrode and modified by Ag/AgCl to serve as the reference electrode; and the nonmodified gold fiber could serve as the counter electrode. The as-fabricated textile glucose biosensors achieved a linear range of 0-500 µM and a sensitivity of 11.7 µA mM-1 cm-2. Importantly, such sensing performance could be maintained even under a large strain of 200%, indicating the potential applications in real-world wearable biochemical diagnostics from human sweat.

Real-Time and In-Situ Monitoring of H2O2 Release from Living Cells by a Stretchable Electrochemical Biosensor Based on Vertically Aligned Gold Nanowires.

Traditional electrochemical biosensing electrodes (e.g., gold disk, glassy carbon electrode, etc.) can undergo sophisticated design to detect chemicals/biologicals from cells. However, such electrodes are typically rigid and nonstretchable, rendering it challenging to detect cellular activities in real-time and in situ when cells are in mechanically deformed states. Here, we report a new stretchable electrochemical cell-sensing platform based on vertically aligned gold nanowires embedded in PDMS (v-AuNWs/PDMS). Using H2O2 as a model analyte, we show that the v-AuNWs/PDMS electrode can display an excellent sensing performance with a wide linear range, from 40 µM to 15 mM, and a high sensitivity of 250 mA/cm2/M at a potential of -0.3 V. Moreover, living cells can grow directly on our stretchable high-surface area electrodes with strong adhesion, demonstrating their excellent biocompatibility. Further cell stimulation by adding chemicals induced H2O2 generation, which can be detected in real-time and in situ using our v-AuNWs/PDMS platform for both natural and stretched states of cells. Our results indicate the v-AuNWs/PDMS electrochemical biosensor may serve as a general cell-sensing platform for living organisms under deformed states.

Embedding Pinhole Vertical Gold Nanowire Electronic Skins for Braille Recognition.

Electronic skins (e-skins) have the potential to be conformally integrated with human body to revolutionize wearable electronics for a myriad of technical applications including healthcare, soft robotics, and the internet of things, to name a few. One of the challenges preventing the current proof of concept translating to real-world applications is the device durability, in which the strong adhesion between active materials and elastomeric substrate or human skin is required. Here, a new strategy is reported to embed vertically aligned standing gold nanowires (v-AuNWs) into polydimethylsiloxane, leading to a robust e-skin sensor. It is found that v-AuNWs with pinholes can have an adhesion energy 18-fold greater than that for pinhole-free v-AuNWs. Finite element modeling results show that this is due to friction force from interfacial embedment. Furthermore, it is demonstrated that the robust e-skin sensor can be used for braille recognition.

Machine learning based temperature prediction of poly(N-isopropylacrylamide)-capped plasmonic nanoparticle solutions.

The temperature-dependent optical properties of gold nanoparticles that are capped with the thermo-sensitive polymer: 'poly(N-isopropylacrylamide)' (PNIPAM), have been studied extensively for several years. Also, their suitability to function as nanoscopic thermometers for bio-sensing applications has been suggested numerous times. In an attempt to establish this, many have studied the temperature-dependent optical resonance characteristics of these particles; however, developing a simple mathematical relationship between the optical measurements and the solution temperature remains an open challenge. In this paper, we attempt to systematically address this problem using machine learning techniques to quickly and accurately predict the solution-temperature, based on spectroscopic data. Our emphasis is on establishing a simple and practically useful solution to this problem. Our dataset comprises spectroscopic absorption data from both nanorods and nanobipyramids capped with PNIPAM, measured at discretely varied and pre-set temperature states. Specific regions of the spectroscopic data are selected as features for prediction using random forest (RF), gradient boosting (GB) and adaptive boosting (AB) regression techniques. Our prediction results indicate that RF and GB techniques can be used successfully to predict solution temperatures instantly to within 1 °C of accuracy.

Fractal Gold Nanoframework for Highly Stretchable Transparent Strain-Insensitive Conductors.

Percolation networks of one-dimensional (1D) building blocks (e.g., metallic nanowires or carbon nanotubes) represent the mainstream strategy to fabricate stretchable conductors. One of the inherent limitations is the control over junction resistance between 1D building blocks in natural and strained states of conductors. Herein, we report highly stretchable transparent strain-insensitive conductors using fractal gold (F-Au) nanoframework based on a one-pot templateless wet chemistry synthesis method. The monolayered F-Au nanoframework (∼20 nm in thickness) can be obtained from the one-pot synthesis without any purification steps involved and can be transferred directly to arbitrary substrates like polyethylene terephthalate, food-wrap, polydimethylsiloxane (PDMS), and ecoflex. The F-Au thin film with no capping agents leads to a highly conductive thin film without any post-treatment and can be stretched up to 110% strain without significantly losing conductivity yet with the optical transparency of 70% at 550 nm. Remarkably, the F-Au thin film shows the strain-insensitive behavior up to 20% stretching strain. This originates from the unique fractal nanomesh-like structure which can absorb external mechanical forces, thus maintaining electron pathways throughout the nanoframework. In addition, a semitransparent bilayered F-Au film on 100% prestrained PDMS could achieve to a high stretchability of 420% strain with negligible resistance changes under low-level strains.

A Facile Ion-Doping Strategy To Regulate Tumor Microenvironments for Enhanced Multimodal Tumor Theranostics.

Integration of multiple therapeutic/diagnostic modalities into a single system holds great promise to improve theranostic efficiency for tumors, but still remains a technical challenge. Herein, we report a new multimodal theranostic nanoconstruct based on Fe-doped polydiaminopyridine nanofusiforms, built easily and on a large scale, which can dual-regulate intracellular oxygen and glutathione levels, transport iron ions, and simultaneously be used for thermal imaging and magnetic resonance imaging. Co-loading of dihydroartemisinin and methylene blue generates a superior multifunctional theranostic agent with enhanced photochemotherapy efficiency and biodegradability, leading to almost complete destruction of tumors with near-infrared light irradiation. This represents an attractive route to develop multimodal anticancer theranostics.

Quercetin protects against chronic prostatitis in rat model through NF-κB and MAPK signaling pathways.

BACKGROUND: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a common disease of urology, of which the pathogenesis and therapy remain to be further elucidated. Quercetin has been reported to improve the symptoms of CP/CPPS patients. We aimed to verify the therapeutic effect of quercetin on CP/CPPS and identify the mechanism responsible for it. METHODS: A novel CP/CPPS model induced with Complete Freund Adjuvant in Sprague Dawley rats was established and the prostates and blood specimens were harvested for further measurement after oral administration of quercetin for 4 weeks. RESULTS: Increased prostate index and infiltration of lymphocytes, up-regulated expression of IL-1ß, IL-2, IL-6, IL-17A, MCP1, and TNFα, decreased T-SOD, CAT, GSH-PX, and increased MDA, enhanced phosphorylation of NF-κB, P38, ERK1/2, and SAPK/JNK were detected in CP/CPPS rat model. Quercetin was identified to ameliorate the histo-pathologic changes, decrease the expression of pro-inflammatory cytokines IL-1ß, IL-2, IL-6, IL-17A, MCP1, and TNFα, improve anti-oxidant capacity, and suppress the phosphorylation of NF-κB and MAPKs. CONCLUSIONS: Quercetin has specific protective effect on CP/CPPS, which is mediated by anti-inflammation, anti-oxidation, and at least partly through NF-κB and MAPK signaling pathways.

Vertical Gold Nanowires Stretchable Electrochemical Electrodes.

Conventional electrodes produced from gold or glassy carbon are outstanding electrochemical platforms for biosensing applications due to their chemical inertness and wide electrochemical window, but are intrinsically rigid and planar in nature. Hence, it is challenging to seamlessly integrate them with soft and curvilinear biological tissues for real-time wearable or implantable electronics. In this work, we demonstrate that vertically gold nanowires (v-AuNWs) possess an enokitake-like structure, with the nanoparticle (head) on one side and nanowires (tail) on the opposite side of the structure, and can serve as intrinsically stretchable, electrochemical electrodes due to the stronger nanowire-elastomer bonding forces preventing from interfacial delamination under strains. The exposed head side of the electrode comprising v-AuNWs can achieve a detection limit for H2O2 of 80 µM, with a linear range of 0.2-10.4 mM at 20% strain, with a reasonably high sensitivity using chronoamperometry. This excellent electrochemical performance in the elongated state, in conjunction with low-cost wet-chemistry fabrication, demonstrates that v-AuNWs electrodes may become a next-generation sensing platform for conformally integrated, in vivo biodiagnostics.

Influence of Contralateral Carotid Occlusion on Outcomes After Carotid Endarterectomy: A Meta-Analysis.

BACKGROUND: There is a controversy about whether the contralateral carotid occlusion (CO) in patients undergoing carotid endarterectomy (CEA) is associated with worse early and long-term outcomes. The aim of this systematic review and meta-analysis was to investigate the impact of CO on outcomes after CEA. METHODS: PubMed, Embase, and MEDLINE databases were searched until January 2018 for studies comparing early and long-term outcomes of CEA in patients with CO and with patent contralateral carotid (CP). Two independent reviewers identified studies meeting our inclusion/exclusion criteria, extracted relevant data and assessed quality. Fixed- or random-effects models were used to calculate the overall effect estimates. RESULTS: Our literature search identified 35 articles eligible for inclusion in the review and analysis. Patients with CO had higher rate of preoperative symptoms (Stroke + transient ischemic attack [TIA]) (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.11-1.31) and had increased risk of perioperative neurological complications (Stroke + TIA) (OR = 1.63, 95% CI: 1.36-1.94) compared with those with CP. No significant difference in the perioperative mortality rate (OR = 1.40, 95% CI: .99-1.98) and the stroke-free survival rate at 5 years (OR = 1.06, 95% CI: .79-1.40) between 2 groups was identified. CONCLUSIONS: The presence of CO results in higher rate of preoperative symptoms and increases perioperative risk of neurological complications in CEA, but do not have a significant impact on the perioperative mortality rate and the stroke-free survival rate at 5 years. Careful consideration should be given in perioperative care in these patients.

mTOR activation is critical for betulin treatment in renal cell carcinoma cells.

Betulin, a natural product isolated from the bark of the birch trees, exhibits multiple anticancer effects. Activation of mTOR signaling pathway has been found in numerous cancers, including renal cell carcinoma (RCC). Here, we attempted to study whether mTOR signaling was essential for betulin to treat RCC. Based on cell survival and colony formation assays, we found that mTOR hyperactive RCC cell line 786-O cells were more sensitive to betulin treatment compared with mTOR-inactive Caki-2 cells. Knockdown of TSC2 in Caki-2 cells had similar results to 786-O cells, and mTOR silencing in 786-O cells rescued the inhibitory effect of betulin, indicating that betulin inhibited RCC cell proliferation in an mTOR-dependent manner. Furthermore, betulin treatment decreases the levels of glucose consumption and lactate production in 786-O cells, while minimal effects were observed in Caki-2 cells. In addition, betulin significantly inhibited the expression of PKM2 and HK2 in 786-O cells. Finally, knockdown of PKM2 or HK2 in 786-O reversed the anti-proliferative effects of betulin, and overexpression of PKM2 or HK2 in Caki-2 cells enhanced the sensitivity to betulin treatment. Taken together, these findings demonstrated the critical role of mTOR activation in RCC cells to betulin treatment, suggesting that betulin might be valuable for targeted therapies in RCC patients with mTOR activation.

Non-Convex Sparse and Low-Rank Based Robust Subspace Segmentation for Data Mining.

Parsimony, including sparsity and low-rank, has shown great importance for data mining in social networks, particularly in tasks such as segmentation and recognition. Traditionally, such modeling approaches rely on an iterative algorithm that minimizes an objective function with convex l1-norm or nuclear norm constraints. However, the obtained results by convex optimization are usually suboptimal to solutions of original sparse or low-rank problems. In this paper, a novel robust subspace segmentation algorithm has been proposed by integrating lp-norm and Schatten p-norm constraints. Our so-obtained affinity graph can better capture local geometrical structure and the global information of the data. As a consequence, our algorithm is more generative, discriminative and robust. An efficient linearized alternating direction method is derived to realize our model. Extensive segmentation experiments are conducted on public datasets. The proposed algorithm is revealed to be more effective and robust compared to five existing algorithms.