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The properties of self-healing polymers are traditionally identified through destructive testing. This means that the mechanics are explored in hindsight with either theoretical derivations and/or simulations. Here, a self-healing property evolution using energy functional dynamical (SPEED) model is proposed to predict and understand the mechanics of self-healing of polymers using images of cuts dynamically healing over time. Using machine learning, an energy functional minimization (EFM) model extracted an effective underlying dynamical system from a time series of two-dimensional cut images on a self-healing polymer of constant thickness. This model can be used to capture the physics behind the self-healing dynamics in terms of potential and interface energies. When combined with a static property prediction model, the SPEED model can predict the macroscopic evolution of material properties after training only on a small set of experimental measurements. Such temporal evolutions are usually inaccessible from pure experiments or computational modeling due to the need for destructive testing. As an example, we validate this approach on toughness measurements of an intrinsic self-healing conductive polymer by capturing over 100 000 image frames of cuts to build the machine learning (ML) model. The results show that the SPEED model can be applied to predict the temporal evolution of macroscopic properties using few measurements as training data.

To investigate the therapeutic effect of Jingfang Granules on carbon tetrachloride(CCl_4)-induced liver fibrosis in mice and its mechanism. Forty-nine 8-week-old male C57 BL/6 J mice were randomly divided into a blank group, a CCl_4 group, a silybin group(positive control, 100 mg·kg~(-1))+CCl_4, a Jingfang high-dose(16 g·kg~(-1)) group, a Jingfang high-dose(16 g·kg~(-1))+CCl_4 group, a Jingfang medium-dose(8 g·kg~(-1))+CCl_4 group, and a Jingfang low-dose(4 g·kg~(-1))+CCl_4 group, with 7 mice in each group. The mice in the blank group and Jingfang high-dose group were intraperitoneally injected olive oil solution, and mice in other groups were intraperitoneally injected with 10% CCl_4 olive oil solution(5 mL·kg~(-1)) to induce liver fibrosis, twice a week with an interval of 3 d, for 8 weeks. At the same time, except for the blank group and CCl_4 group, which were given deionized water, the mice in other groups were given the corresponding dose of drugs by gavage once daily for 8 weeks with the gavage volume of 10 mL·kg~(-1). All mice were fasted and freely drank for 12 h after the last administration, and then the eyeballs were removed for blood collection. The liver and spleen were collected, and the organ index was calculated. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bile acid(TBA), and triglyceride(TG) in the serum of mice were detected by an automated analyzer. Tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-1β(IL-1β) levels were detected by enzyme-linked immunosorbent assay(ELISA). Kits were used to detect the contents of superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the liver tissue. Pathological changes in the liver tissue were observed by hematoxylin-eosin(HE), Masson, and Sirius red staining. Western blot was used to detect protein expressions of transforming growth factor-β(TGF-β), α-smooth muscle actin(α-SMA) and Smad4 in the liver tissue. The results indicated that Jingfang Granules significantly reduced the organ index, levels of ALT, AST, TBA,TG, TNF-α, IL-6, and IL-1β in the serum, and the content of MDA in the liver tissue of mice with CCl_4-induced liver fibrosis. Jingfang Granules also significantly increased the content of SOD and GSH in the liver tissue. Meanwhile, Jingfang Granules down-regulated the protein levels of TGF-β, α-SMA, and Smad4. Furthermore, Jingfang Granules had no significant effect on the liver tissue morphology and the above indexes in the normal mice. In conclusion, Jingfang Granules has obvious therapeutic effect on CCl_4-induced liver fibrosis, and its mechanism may be related to reducing the expression of pro-inflammatory factors, anti-oxidation, and regulating TGF-β/Smad4 signaling pathway.

Electronic skins are essential for real-time health monitoring and tactile perception in robots. Although the use of soft elastomers and microstructures have improved the sensitivity and pressure-sensing range of tactile sensors, the intrinsic viscoelasticity of soft polymeric materials remains a long-standing challenge resulting in cyclic hysteresis. This causes sensor data variations between contact events that negatively impact the accuracy and reliability. Here, we introduce the Tactile Resistive Annularly Cracked E-Skin (TRACE) sensor to address the inherent trade-off between sensitivity and hysteresis in tactile sensors when using soft materials. We discovered that piezoresistive sensors made using an array of three-dimensional (3D) metallic annular cracks on polymeric microstructures possess high sensitivities (> 10(7) Ω ⋅ kPa(−1)), low hysteresis (2.99 ± 1.37%) over a wide pressure range (0–20 kPa), and fast response (400 Hz). We demonstrate that TRACE sensors can accurately detect and measure the pulse wave velocity (PWV) when skin mounted. Moreover, we show that these tactile sensors when arrayed enabled fast reliable one-touch surface texture classification with neuromorphic encoding and deep learning algorithms.

Poly(dimethylsiloxane) (PDMS) as one of the electron-drawing materials has been widely used in triboelectric nanogenerators (TENG), which is expected to generate electron through friction and required to endure dynamic loads. However, the nature of the siloxane bond and the low interchain interaction between the methyl side groups result in low fracture energy in PDMS elastomers. Here, a strategy that combined the advantages of the dynamic of hierarchical hydrogen bonding and phase-separation-like structure was adopted to improve the toughness of PDMS elastomers. By varying both stronger and weaker hydrogen bonding within the PDMS network, a series of super tough (up to 24,000 J/m2), notch-insensitive, transparent, and autonomous self-healable elastomers were achieved. In addition, a hydrophilic polymeric material (PDMAS-U10) was synthesized as the conductive layer. A transparent TENG was fabricated by sandwiching the PDMAS-U10 between two pieces of the PDMS elastomer. Despite its hydrophilic nature, PDMAS-U10 exhibit strong adhesion interaction with hydrophobic PDMS elastomers. As such, a tough (16,500 J/m2), self-healable (efficiency ∼97%), and transparent triboelectric nanogenerator was constructed. A self-powered system employing the TENG is also demonstrated in this work.

Shen-Qi-Jiang-Tang granule (SQJTG), a classic traditional Chinese medicine (TCM) prescription, has been widely used in clinical for diabetes, especially type Ⅱ diabetes. Previous anti-diabetic studies stumbled across that SQJTG has a potential kidney protective effect on diabetic nephropathy (DN). However, the protective mechanism of SQJTG on DN still needs to be explored.The purpose of the present study was to explore the therapeutic effect of SQJTG on DN through both bioinformatics analysis and in vivo experiments.The TCMIP database was used for screening potential compounds and targets of SQJTG, and the GeneCards, OMIM, DrugBank, and TTD databases were used for collecting DN-related genes. Then protein-protein interaction analysis for the common targets of SQJTG and DN was performed by the STRING database. Meanwhile, KEGG and GO were carried out using the Metascape and DAVID databases. In vivo experiments, to testify the potential kidney protective effects of SQJTG, STZ-induced DN mice with different dosages of SQJTG treatment were collected and the renal tissues were detected by HE, PAS, Masson and TUNEL staining. Immunohistochemistry and immunoblotting were used to assess the proteins' expressions. Flow cytometry and ELISA assay were used to detect the levels of pro-inflammatory cytokines.Among the 338 compounds ascertained by SQJTG, there were 789 related targets as well. Moreover, 1,221 DN-related targets were predicted and 20 core targets were screened by the PPI analyses. According to GO and KEGG pathway analysis, SQJTG may affect DN via the TNF pathway. For the in vivo experiments, renal histomorphological examinations demonstrated that SQJTG treatment significantly ameliorated STZ-induced kidney damage and had a dosage dependence. Meanwhile, mice with DN were found to have dramatic increases in IL-1, TNF-α, IL-6, and IL-12, but markedly decreased after administration of SQJTG. In addition, the protein levels of TNF signaling molecules, like p-P65, p-JNK, and p-p38, showed significantly elevated in kidney tissues of DN mice and attenuated after SQJTG treatment.SQJTG exerts a kidney protective effect in DN mice via modulating TNF signaling pathways, and it has promising applications for the treatment of DN.

Adsorption and coagulation were commonly used to alleviate reverse osmosis (RO) membrane fouling caused by dissolved organic matters (DOM), but the effects of changed composition and structure of DOM in dyeing wastewater after adsorption and coagulation on RO membrane fouling have seldom been studied. This study aimed at resolving the mechanism how the RO membrane fouling during dyeing wastewater treatment was alleviated by using adsorption and coagulation. The dyeing wastewater caused serious RO membrane fouling. Pretreatment with granular activated carbon (GAC), polyferric sulfate (PFS) and polyaluminum chloride (PACl) were conducted. It was shown that GAC could remove most of the DOM (95%) and preferred to adsorb protein, hydrophobic neutrals and fluorescent compounds. Both coagulants of PFS and PACl preferred to remove polysaccharides (the removal rate was 9-19% higher than that of DOM), high-MW compounds and these compounds with high fouling potential. Afterwards, the RO membrane fouling potential of the dyeing wastewater was tested. The GAC and PFS performed well to alleviate fouling. After GAC treatment, the decline rate of RO flux was similar to that of raw wastewater after 6-fold dilution. With pretreatment by PFS or PACl, the fouling potential of dyeing wastewater was much lower than that of raw wastewater after diluted to the same DOM content. Changes in polysaccharides content in the DOM had more effects on RO membrane fouling than that of proteins after these pretreatment. Although the DOM changed significantly after pretreatment, the fouling type was still intermediate blocking.

Wireless networks of sensors, displays and smart devices that can be placed on a person’s body could have applications in health monitoring, medical interventions and human–machine interfaces. Such wireless body networks are, however, typically energy-inefficient and vulnerable to eavesdropping because they rely on radio-wave communications. Here, we report energy-efficient and secure wireless body sensor networks that are interconnected through radio surface plasmons propagating on metamaterial textiles. The approach uses clothing made from conductive fabrics that can support surface-plasmon-like modes at radio communication frequencies. Our body sensor networks enhance transmission efficiencies by three orders of magnitude compared to conventional radiative networks without the metamaterial textile, and confine wireless communication to within 10 cm of the body. We also show that the approach can offer wireless power transfer that is robust to motion and textile-based wireless touch sensing. Energy-efficient and secure wireless body sensor networks can be created by using conductive fabrics that support surface-plasmon-like modes at radio communication frequencies.

Purpose: There is an urgent need to develop effective anti-pneumonia drugs. Phillygenin (PHI) is derived from Forsythia suspense and possesses anti-inflammation, anti-oxidant bioactivities. In the present study, we aimed to evaluate the therapeutic potential of phillygenin (PHI) on lipopolysaccharide (LPS)-induced acute pneumonia.Methods: The molecular target of PHI was predicted by bioinformatic analysis. Hollow fiber-based ligand fishing (HFLF) strategy and luciferase reporter assay were further used to identify the target of PHI. LPS-induced acute pneumonia rat model and A549 cells model were used to evaluate PHI function. TNF-α pathway and apoptosis associated proteins were detected by Western Blot, immunofluorescence and immunohistochemistry. Cell cycle and cytokines were determined by flow cytometry.Results: The bioinformatic analysis and luciferase reporter assay identified that the target protein of PHI was pregnane X receptor (PXR) PHI could directly bind to PXR protein and inhibit NF-κB P65 activity. PHI significantly decreased the expression of phosphorylated JNK, P38, Erk, P65 in acute pneumonia rat model. PHI also declined the expression of Bax, Caspase-3 and Caspase-9 and repressed lung epithelial cell apoptosis induced by LPS in vivo and in vitro. In addition, PHI inhibited inflammation cytokines production including TNF-α, IFN-γ, IL-6, IL-1β and IL-18.Conclusions: PHI significantly alleviated LPS-induced lung injury in vivo by exerting anti-inflammatory effects. This is the first study to demonstrate that PHI, a small molecule natural product, significantly alleviates LPS-induced acute pneumonia by binding to PXR. Thus, PHI can be a novel therapeutic agent for pneumonia.

Power sources with good mechanical compliance are essential for various flexible and stretchable electronics. However, most of the current energy storage devices comprise of hazardous materials that may cause environmental pollution when improperly disposed. We show the first example of a stretchable, yet fully degradable battery made from nontoxic and environmentally friendly materials such as fruit‐based gel electrolytes and cellulose paper electrodes. The battery exhibits an areal capacity of 2.9 μAh cm−2 at 40 μA cm−2, corresponding to a maximum energy density around 4.0 μW h cm−2 at 56 μW cm−2 power density. The biomaterials constituted battery shows good mechanical tolerance to twisting, bending, and stretching while powering various electronic devices when combined with kirigami. Importantly, the entire battery disintegrates readily in phosphate buffered saline/cellulase solution. We integrate the “green” battery with various sensors in wearable healthcare devices for pulsation sensing and low‐noise surface electromyography applications.

Human skin is a self-healing mechanosensory system that detects various mechanical contact forces efficiently through three-dimensional innervations. Here, we propose a biomimetic artificially innervated foam by embedding three-dimensional electrodes within a new low-modulus self-healing foam material. The foam material is synthesized from a one-step self-foaming process. By tuning the concentration of conductive metal particles in the foam at near-percolation, we demonstrate that it can operate as a piezo-impedance sensor in both piezoresistive and piezocapacitive sensing modes without the need for an encapsulation layer. The sensor is sensitive to an object’s contact force directions as well as to human proximity. Moreover, the foam material self-heals autonomously with immediate function restoration despite mechanical damage. It further recovers from mechanical bifurcations with gentle heating (70 °C). We anticipate that this material will be useful as damage robust human-machine interfaces., Designing mechanosensory system that detects mechanical contact forces like human skin remains a challenge. Here, the authors present artificially innervated self-healing foams by embedding 3D electrodes for piezo-impedance sensors that can operate in both piezoresistive and piezocapacitive sensing modes to address various proximity and mechanical interactions efficiently.

Robots are increasingly assisting humans in performing various tasks. Like special agents with elite skills, they can venture to distant locations and adverse environments, such as the deep sea and outer space. Micro/nanobots can also act as intrabody agents for healthcare applications. Self-healing materials that can autonomously perform repair functions are useful to address the unpredictability of the environment and the increasing drive toward the autonomous operation. Having self-healable robotic materials can potentially reduce costs, electronic wastes, and improve a robot endowed with such materials longevity. This review aims to serve as a roadmap driven by past advances and inspire future cross-disciplinary research in robotic materials and electronics. By first charting the history of self-healing materials, new avenues are provided to classify the various self-healing materials proposed over several decades. The materials and strategies for self-healing in robotics and stretchable electronics are also reviewed and discussed. It is believed that this article encourages further innovation in this exciting and emerging branch in robotics interfacing with material science and electronics.

Gelatinous underwater invertebrates such as jellyfish have organs that are transparent, stretchable, touch-sensitive and self-healing, which allow the creatures to navigate, camouflage themselves and, indeed, survive in aquatic environments. Artificial skins that emulate such functionality could be used to develop applications such as aquatic soft robots and water-resistant human–machine interfaces. Here we report a bio-inspired skin-like material that is transparent, electrically conductive and can autonomously self-heal in both dry and wet conditions. The material, which is composed of a fluorocarbon elastomer and a fluorine-rich ionic liquid, has an ionic conductivity that can be tuned to as high as 10−3 S cm−1 and can withstand strains as high as 2,000%. Owing to ion–dipole interactions, it offers fast and repeatable electro-mechanical self-healing in wet, acidic and alkali environments. To illustrate the potential applications of the approach, we used our electronic skins to create touch, pressure and strain sensors. We also show that the material can be printed into soft and pliable ionic circuit boards. A transparent electronic skin, composed of an elastomer and an ionic liquid, can autonomously self-heal in both dry and wet conditions due to ion–dipole interactions.

A promising approach for improving the interfacial bonding of a three-dimensionally (3D) printed multilayered structure has been investigated by taking advantage of the electrostatic interactions between two hydrogels with oppositely charges. Here, two hydrogels namely gelatin and κ-carrageenan, which are the cationic and anionic hydrogels respectively, are used. It is found that the interfacial bonding strength between these two oppositely charged hydrogels is significantly higher than that of a bilayered gelatin or a bilayered κ-carrageenan. The bioprinted multilayered κ-carrageenan-gelatin hydrogel construct demonstrates a very good biocompatibility and a good structure integrity at 37 °C. Our strategy also overcomes the limitation of using gelatin for bio-fabrication at 37 °C, without further post crosslinking. MOE (Min. of Education, S’pore)

Objective To investigate the protective effects of icaritin (ICT), one of the active ingredients in Epimedii Folium , on mouse model of cerebral ischemia-reperfusion (I/R) in vivo . Methods ICR mice were subjected to an 1 h transient middle cerebral artery occlusion (MCAO) and followed by 24 h of reperfusion. Neurological deficits, infarct volume, brain edema and survive rate were measured, respectively. The levels of brain IL-1β, TNF-α, ROS and DNA-binding activity of NF-κB p65 were measured by ELISA kits. The levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) were detected by spectrophotometry, and the release of nitric oxide (NO) were detected by Griess kit. Results ICT markedly reduced the neurological deficit scores, brain edema, infarct volume and increased the survival rate of the cerebral I/R mice. The expression of IL-1β, TNF-α, NO, MDA and DNA-binding activity of NF-κB p65 were significantly inhibited by ICT, while the activity of SOD were up-regulated at the same time. Conclusion ICT possessed significant neuroprotective effects in cerebral I/R mice, which might be related to prevent neuroinflammatory and oxidative damage.

Fouling of reverse osmosis (RO) membranes is a severe problem for desalination of dyeing wastewater with high chemical oxygen demand (COD). In this paper, fouled RO membranes in a pilot-scale desalination system of biologically treated dyeing wastewater containing high COD (143–228 mg/L) with or without injection of non-oxidizing biocides were analyzed. The two non-oxidizing biocides used are K5030 (a kind of isothiazoline biocide) and FR110 (an inorganic base type of combined chlorine agent), respectively. For the RO membrane from the system without non-oxidizing biocide injection to the influent, a typical biofilm occurred on the RO membrane in a short operation time of 19 days. The injection of non-oxidizing biocides caused a decline of nearly 99.0% in active biomass on the RO membrane. Burkholderiales ruled mature biofilm on the RO membrane without injection of non-oxidizing biocide. Pseudoxanthomonas exhibited a certain resistance to non-oxidizing biocides and ruled the bacterial community on the RO membrane with injection of non-oxidizing biocides. Fe, P and Al were major inorganic elements on RO membranes, decreasing with injection of non-oxidizing biocides. Hydrophobic neutral (HON) fraction was the most major organic component of dissolved organic matter (DOM) on RO membranes, decreasing notably with injection of non-oxidizing biocides.

Metallic cellular scaffold is one of the best choices for orthopaedic implants as a replacement of human body parts, which could improve life quality and increase longevity for the people needed. Unlike conventional methods of making cellular scaffolds, three-dimensional (3D) printing or additive manufacturing opens up new possibilities to fabricate those customisable intricate designs with highly interconnected pores. In the past decade, metallic powder-bed based 3D printing methods emerged and the techniques are becoming increasingly mature recently, where selective laser melting (SLM) and selective electron beam melting (SEBM) are the two representatives. Due to the advantages of good dimensional accuracy, high build resolution, clean build environment, saving materials, high customisability, etc., SLM and SEBM show huge potential in direct customisable manufacturing of metallic cellular scaffolds for orthopaedic implants. Ti-6Al-4V to date is still considered to be the optimal materials for producing orthopaedic implants due to its best combination of biocompatibility, corrosion resistance and mechanical properties. This paper presents a state-of-the-art overview mainly on manufacturing, topological design, mechanical properties and biocompatibility of cellular Ti-6Al-4V scaffolds via SLM and SEBM methods. Current manufacturing limitations, topological shortcomings, uncertainty of biocompatible test were sufficiently discussed herein. Future perspectives and recommendations were given at the end.

Background As an inodilator, milrinone is commonly used for patients who undergo coronary artery bypass graft (CABG) surgery because of its effectiveness in decreasing the cardiac index and mitral regurgitation. The aim of this study was to perform a systematic review and meta-analysis of existing studies from the past 20 years to evaluate the impact of milrinone on mortality in patients who undergo CABG surgery. Methods We performed a systematic literature search on the application of milrinone in patients who underwent CABG surgery in studies published between 1997 and 2017 in BioMed Central, PubMed, EMBASE, and the Cochrane Central Register. The included studies evaluated milrinone groups compared to groups receiving either placebo or standard treatment and further compared the systemic administration. Results The network meta-analysis included 723 patients from 16 randomized clinical trials. Overall, there was no significant difference in mortality between the milrinone group and the placebo/standard care group when patients underwent CABG surgery. In addition, 9 trials (with 440 randomized patients), 4 trials (with 212 randomized patients), and 10 trials (with 470 randomized patients) reported that the occurrence of myocardial infarction (MI), myocardial ischemia, and arrhythmia was lower in the milrinone group than in the placebo/standard care group. Between the milrinone treatment and placebo/standard care groups, the occurrence of myocardial infarction, myocardial ischemia, and arrhythmia was significantly different. However, the occurrence of stroke and renal failure, the duration of inotropic support (h), the need for an intra-aortic balloon pump (IABP), and mechanical ventilation (h) between these two groups showed no differences. Conclusions Based on the current results, compared with placebo, milrinone might be unable to decrease mortality in adult CABG surgical patients but can significantly ameliorate the occurrence of MI, myocardial ischemia, and arrhythmia. These results provide evidence for the further clinical application of milrinone and of therapeutic strategies for CABG surgery. However, along with milrinone application in clinical use, sufficient data from randomized clinical trials need to be collected, and the potential benefits and adverse effects should be analyzed and reevaluated.

Background: As an inodilator, milrinone is commonly used for patients underwent coronary artery bypass graft surgery (CABG) because of its effectiveness in decreasing cardiac index and mitral regurgitation. This study was to perform a systematic meta-analysis of existing studies in the past 20 years to evaluate the impact of milrinone on mortality in patients underwent CABG surgery. Methods: We performed a systematic literature search on the application of milrinone in patients underwent CABG surgery, which published between 1997 and 2017 in BioMed Central, PubMed, EMBASE, and the Cochrane Central Register. The included literatures should be set as milrinone compared to a group receiving either placebo or standard treatment, and further compare to systemic administration. Results: The network meta-analysis included 723 patients from 16 randomized clinical trials. Overall, there was no significant difference in mortality between the milrinone group and the placebo/standard care group when patients underwent CABG surgery. Besides that, 9 trials (with 440 randomized patients), 4 trials (with 212 randomized patients), and 10 trials (with 470 randomized patients) reported that the occurrence of myocardial infarction (MI), myocardial ischemia, and arrhythmias in the milrinone group were decreased comparing with the placebo/standard care group, respectively. Between the milrinone treatment and placebo/standard care groups, the occurrence of myocardial infarction, myocardial ischemia, arrhythmias was all significantly different. However, the occurrence of stroke and renal failure, duration of inotropic support (h), need for intra-aortic balloon pump (IABP), and mechanical ventilation (h) between these two groups showed no differences. Conclusions: Based on the current results, milrinone might be unable to decrease the mortality in adult CABG surgical patients, but can significantly ameliorate the occurrence of MI, myocardial ischemia, and arrhythmias compared with placebo-treated patients. These results provide evidence for further clinical application of milrinone and therapy strategies for CABG surgery. However, along with milrinone application in clinical use, sufficient randomized clinical trials need to be collected, and the potential benefit and adverse effects should be analyzed and reevaluated.

The extrusion-based bioprinting of hydrogels such as gelatin methacrylate (GelMA) into structures with complex shape suffers from poor printability due to their low viscosity. The present study deals with hydrogel materials by using the mixture of cell-laden photopolymerizable GelMA as a main printing material and the mixture of alginate and methylcellulose (Alg/MC) as a support material because of its high viscosity and good thixotropic property. One extrusion-based approach is developed by printing the two mixtures into structures in an alternating layer-by-layer manner, with the electrostatic interactions between polycationic GelMA and polyanionic Alg/MC contributing to the integrity of the structures. The final printed structures are exposed to ultraviolet (UV) light to form crosslinks in GelMA through photopolymerization for further structural strengthening. The one-time UV exposure minimizes cell damage in cell-GelMA, demonstrating an advantage over those in previously reported studies that required repeated UV exposures upon the printing of each layer of a structure. The other approach is developed by submerging the extrusion nozzle into a bath of Alg/MC to print cell-laden GelMA structures, which, upon printing completion, are also subject to one-time UV exposure before the removal of the support material Alg/MC. A flower with living cells is printed to demonstrate the capability of the second approach of fabricating structures with geometric complexity. The structures printed using both approaches demonstrate a well-maintained shape fidelity, structural integrity and cell viability of over 93% up to five culturing days. The proposed two printing approaches based on the cell-GelMA and Alg/MC pair will be beneficial for exploring new opportunities in bioprinting. National Research Foundation (NRF) Accepted version This research is supported by the National Research Foundation, Prime Minister’s Office, Singapore under its Medium-Sized Centre funding scheme through the Marine and Offshore Program.

Acute myocardial infarction (AMI) is an acute heart disease. Cycloastragenol, as a natural product, inhibits inflammation and protects cardiomyocytes. Cycloastragenol (Y006) modulates inflammation in AMI is not known. To explore the function of Cycloastragenol in AMI, this study investigated the effect of Y006 and its mechanisms both in vitro and in vivo. Y006 influences the concentration of 11 proteins, as shown by a proteomics analysis, immunohistochemistry and western blotting. Among these 11 proteins, Erk1/2, PLCG1, IKBKG, and ZEB1 are related to inflammatory regulation. BAX, COX2, and GSK3β are involved in modulating cardiomyocyte apoptosis, and RhoA and DSC2 are directly associated with myocardial function. However, the functions of ARHGAP17 and Rit2 in heart are less well established. Additionally, Y006 suppressed TNF-α, IFN-γ and IL-17 production in PBMCs (peripheral blood monocytes) from patients with acute myocardial infarction and enhanced IL-10 and IL-4 expression. Similar results were obtained in a rat model of AMI by flow cytometry detection and ELISA. Our findings indicate that Y006 protects rats from AMI through direct or indirect inhibition of inflammation and cardiomyocyte apoptosis. However, the specific mechanism of Y006's protective function requires further study. Nonetheless, this research revealed a novel aspect for the treatment of myocardial infarction. SIGNIFICANCE: In the present study, we undertook the first proteomic evaluation of Cycloastragenol (Y006) function in acute myocardial infarction (AMI). Y006 significantly improved myocardial function in vivo by regulating multiple molecular expressions. Hypoxia is a direct reason for AMI. And our data support a role of Y006 in gene expression, cell apoptosis under hypoxia. The conclusions of this research assist to explain the potential molecular mechanism in Cycloastragenol treating AMI and supply a new method for ameliorating AMI.

OBJECTIVE: Milrinone is commonly used for patients performed coronary artery bypass graft surgery (CABG) because of its effectiveness in decreasing cardiac index and mitral regurgitation. This study was to perform a systematic meta-analysis of existing studies in the past 20 years to evaluate the impact of milrinone on mortality in patients undergoing CABG surgery. EASUREMENTS AND MAIN RESULTS: The network meta-analysis included 723 patients from 16 randomized clinical trials. Overall, there was no significantly difference in mortality between the milrinone group and the placebo/standard care group [11/352 (3.13%) vs. 9/346 (2.60%), risk ratio = 1.18 (0.53–2.62), p for effect = 0.69, I 2 = 0 %] when patients underwent CABG surgery. Besides that, 9 trials (with 440 randomized patients), 4 trials (with 212 randomized patients), and 10 trials (with 470 randomized patients) reported that the occurrence of myocardial infarction (MI), myocardial ischemia, and arrhythmias in the milrinone group were decreased in comparsion with the placebo/standard care group, respectively. Between the milrinone treatment and placebo/standard care groups, the occurrence of myocardial infarction was [5/219 (2.28 %) vs. 25/212 (17.79 %), odds ratio(OR) = 0.19 (0.08–0.49), p value = 0.0005, I 2 = 5%], the occurrence of myocardial ischemia was [12/106 (11.32 %) vs. 41/106 (36.68 %), OR = 0.20 (0.10–0.42), p value

Stretchable electronics have advanced rapidly and many applications require high repeatability and robustness under various mechanical deformations. It has been described here that how a highly stretchable and reliable conductor composite made from helical copper wires and a soft elastomer, named eHelix, can provide mechanically robust and strain-insensitive electronic conductivity for wearable devices. The reversibility of the mechanical behavior of the metal-elastomer system has been studied using finite element modeling methods. Optimal design parameters of such helical metal-elastomer structures are found. The scaling of multiple copper wires into such helical shapes to form a Multi-eHelix system is further shown. With the same elastomer volume, Multi-eHelix has more conductive paths and a higher current density than the single-eHelix. Integrations of these eHelix stretchable conductors with fabrics showed wearable displays that can survive machine-washes and hundreds of mechanical loading cycles. The integration of the eHelix developed by us with a wearable optical heart rate sensor enabled a wearable health monitoring system that can display measured heart rates on clothing. Furthermore, Multi-eHelix conductors are used to connect flexible printed circuit boards and piezoresistive sensors on a tactile sensing glove for the emerging sensorized prosthetics.

Stretchable optoelectronic materials are essential for applications in wearable electronics, human-machine interfaces and soft robots. However, intrinsically stretchable optoelectronic devices such as light-emitting capacitors usually require high driving alternating voltages and excitation frequencies to achieve sufficient luminance in ambient lighting conditions. Here, we present a healable, low-field illuminating optoelectronic stretchable (HELIOS) device by introducing a transparent, high permittivity polymeric dielectric material. The HELIOS device turns on at an alternating voltage of 23 V and a frequency below 1 kHz, safe operating conditions for human-machine interactions. We achieved a brightness of 1,460 cd m

The reverse osmosis (RO) process is of great significance for the desalination and reclamation of dyeing wastewater. However, fouling of RO membranes has been a severe problem and key limiting factor in the widespread application of the RO process. The operating characteristics and fouling characteristics of a RO membrane system for desalination of dyeing wastewater were investigated in an industrial park in Guangdong Province. The results showed that the COD and turbidity of RO influent after ozone oxidation-sand filtration-ultrafiltration (UF) processes were 12.4 mg ·L

Background and purpose Acute kidney injury (AKI) is a rapid renal dysfunctional disease, for which no effective drugs or therapies are available to improve prognosis. Loganetin is a natural product with unknown bioactivities. Here, we identified a new protective effect and mechanism of Loganetin in a mouse model of AKI induced by rhabdomyolysis. Experimental approach AKI was induced using glycerol by i.m. injection in mice models. Thirty minutes and 24 and 48 hr after injection of glycerol, the mice received 2 and 18 mg·kg-1 of Loganetin i.p. respectively. Then mice blood and kidney were collected for various biochemical and histopathological studies. Mechanistic studies on modulation of AKI by Loganetin were performed using HK-2 cells and Toll-like receptor 4 (TLR4) knockout mice. Key results In the Loganetin treated group, kidney damage and mortality rate were declined, and blood urea nitrogen and serum creatinine were much lower. Loganetin prevented damage to the tubular structures induced by glycerol and decreased apoptotic cells at the corticomedullary junction. In HK-2 cells, Loganetin could inhibit NF-κB pathway and pro-apoptotic genes expression. However, TLR4 was silenced by a specific shRNA, and the inhibitory effect of Loganetin in HK-2 cells vanished. Loganetin also down-regulated the expression of inflammation factors by suppressing TLR4 activity. Conclusion and implications All the results suggested that TLR4 plays a critical role in AKI development, and Loganetin ameliorates AKI by inhibiting TLR4 activity and blocking the JNK/p38 pathway, which provides a new strategy for AKI treatment.

A highly aligned microfibrous tubular scaffold was developed for esophageal tissue engineering, aiming to fabricate a biomechanically compatible esophageal scaffold. The tubular scaffold was fabricated by melt-drawing of poly( l -lactide-co-ɛ-caprolactone) (PLC). Different melt-drawing speeds were evaluated in order to obtain an optimal microfiber dimension for the scaffold. Preliminary tensile results show that these scaffolds have comparable tensile properties with the native esophagus. All the scaffolds were found to promote cell adhesion and proliferation based on the in vitro results. It suggests that the melt-drawn PLC tubular scaffold with an autologous cell-seeding could be a good candidate for the esophageal tissue engineering.

Electron beam melting (EBM®)-built Ti–6Al–4V has increasingly shown great potential for orthopedic implant and aerospace applications in recent years. The microstructure and mechanical properties of EBM-built Ti–6Al–4V have been systematically investigated in this work. Its microstructure consists of columnar prior β grains delineated by wavy grain boundary α and transformed α/β structures with both cellular colony and basket-weave morphology as well as numerous singular α bulges within the prior β grains. The β phase is found to form as discrete flat rods embedded in continuous α phase and its volume fraction is determined to be ∼3.6%. Moreover, α′ martensite was not observed as it has decomposed into α and β phases. In particular, the α/β interface was studied in detail combined transmission electron microscopy with atom probe tomography. Of note is that graded Ti–6Al–4V microstructure i.e. both prior β grain width and β phase interspacing continuously increase with the build height, was observed, which mainly arises from the decreasing cooling rate. Furthermore, an increasingly pronounced strain hardening effect was also observed as the previously built layers undergo a longer annealing compared to the subsequent layers. As a result, graded mechanical properties of Ti–6Al–4V with degraded microhardness and tensile properties were found. A good agreement with the Hall–Petch relation indicates that the graded property takes place mainly due to the graded microstructure. In addition, this graded microstructure and mechanical properties were discussed based on a quantitative characterization.

The precipitation of B2 s-NiAl/C14-Laves eutectics with a volume fraction of ∼0.5% in the interdendritic γ/γ′ eutectic regions of a 3 wt% Ru-containing single crystal Ni-based superalloy has been characterized. It is found that the eutectic reaction Liquid→s+Laves (C14) takes place at the end of solidification process. Transmission electron microscopy image shows that numerous fine “butterfly-like” Laves precipitates with a size of ∼30 nm are embedded in the coarse blocky s-NiAl, suggesting a coherent or semi-coherent interface between these two phases. The crystallography relationship of $(0001)_{Laves} //(\bar 110)_\beta $ and $[11\bar 20]_{Laves} //[111]_\beta $ between Laves and s-NiAl phase was obtained in terms of selected area electron diffraction patterns. Electron probe microanalysis results reveal that 3 wt% Ru addition makes more Al, Ta and other refractory elements segregate to the interdendritic regions, which is believed to be the main reason for this undesirable eutectic reaction. In addition, the formation of these eutectics is found to be strongly affected by solidification conditions.

Tissue engineering (TE) offers an important alternative for surgical replacement of diseased or traumatized esophagus. The TE replacement can replicate the native esophagus in shape and performance. This dissertation describes the fabrication and characterization of two key components in esophageal TE, i.e. the muscle and the epithelium. Two different additive fabrication techniques are investigated due to the inherent diversity in structure of an esophagus. Customizations of dimension and mechanical properties are made possible by the additive fabrication, which are vital factors for implantation across ages and genders. Tubular poly(L-lactide-co-e-caprolactone) (PLC) scaffold is fabricated by a melt-drawing method to mimic the structure of circular muscles. The microfibrous solid scaffold serves as exterior of the TE replacement, which is strong and elastic circumferentially to accommodate bolus. Moreover, it consists of highly aligned microfibers in the circumferential direction with a uniform distribution of fiber diameters, which allows the muscle cells to grow along the fiber alignment direction. The crystallinity of PLC fibers increases with an increasing melt-drawing speed due to the strain-induced crystallization. The modulus and the strength are increased with an increase in crystallinity of the PLC scaffold. Tensile properties of the tubular scaffold are comparable to those of the human esophagus in the circumferential direction, which also can be finetuned by adjusting the melt-drawing fabrication parameters. Furthermore, tubular scaffolds with varying diameters and lengths are fabricated. In addition, 3D bioprinting is employed to regenerate a layer of cell-laden, folded epithelium in a lumen of esophagus. A new bioink using cell-laden microspheres (CLMs) with a thin encapsulation of agarose-collagen blend hydrogel (AC blend hydrogel) is introduced. Highly porous microspheres provide high specific surface areas for anchorage-dependent cells to attach, infiltrate and proliferate before printing. AC blend hydrogel allows a good printability of CLMs, with immediate gelation of the construct upon printing on the chilled build platform. Tightly packed construct is bioprinted with high stacking ability using a micropipette extrusionbased method. The mechanical strength of the bioprinted construct is considerably enhanced when compared to that with just AC blend hydrogel. The bioprinted cells proliferate and maintain high viability for up to 2 weeks. In vitro performance of individual components of a hybrid esophageal TE construct is successfully illustrated. The hybrid bioengineering of muscle cell-seeded exterior tubular scaffold and 3D bioprinted interior folded epithelium in the lumen have taken a great step towards functional esophageal TE. Doctor of Philosophy (MAE)

Aims TGF-β-induced alveolar epithelial cells apoptosis were involved in idiopathic pulmonary fibrosis (IPF). This study aimed to explore potential targets and mechanisms of IPF. Main methods mRNA and microRNA arrays were used to analyze differentially expressed genes and miRNAs. Several essential targets of TGF-β-SMADs and TGF-β-PI3K-AKT pathways were detected. Key findings miR-31 and miR-184 expression levels were positively correlated with smad6 and smad2/akt expression levels in IPF patients. TGF-β could induce miR-31 and suppress miR-184 levels in A549 cells. miR-31 was confirmed to bind to the smad6-3′UTR and functionally suppress its expression. Down-regulated SMAD6 enhanced SMAD2/SMAD4 dimer formation and translocation due to its failure to prevent SMAD2 phosphorylation. In contrast, anti-fibrotic functions of miR-184 were abolished due to TGF-β directly suppressing miR-184 levels in A549 cells. When A549 was stimulated by TGF-β combined with or without miR-31 inhibitor/miR-184 mimic, it was showed that depleted miR-31 and/or increased miR-184 significantly ameliorated TGF-β-induced viability of A549 cells, as well as inhibited the expression of profibrotic factors, MMP7 and RUNX2. Significance Inhibiting miR-31 and/or promoting miR-184 protect against TGF-β-induced fibrogenesis by respectively repressing the TGF-β-SMAD2 and TGF-β-PI3K-AKT signaling pathways, implying that miR-31/184 are potential targets and suggesting a new management strategy for IPF.

Gelatin methacryloyl (GelMA) is a versatile biomaterial that has been shown to possess many advantages such as good biocompatibility, support for cell growth, tunable mechanical properties, photocurable capability, and low material cost. Due to these superior properties, much research has been carried out to develop GelMA as a bioink for bioprinting. However, there are still many challenges, and one major challenge is the control of its rheological properties to yield good printability. Herein, this study presents a strategy to control the rheology of GelMA through partial enzymatic crosslinking. Unlike other enzymatic crosslinking strategies where the rheological properties could not be controlled once reaction takes place, we could, to a large extent, keep the rheological properties stable by introducing a deactivation step after obtaining the optimized rheological properties. Ca2+-independent microbial transglutaminase (MTGase) was introduced to partially catalyze covalent bond formation between chains of GelMA. The enzyme was then deactivated to prevent further uncontrolled crosslinking that would render the hydrogel not printable. After printing, a secondary post-printing crosslinking step (photo crosslinking) was then introduced to ensure long-term stability of the printed structure for subsequent cell studies. Biocompatibility studies carried out using cells encapsulated in the printed structure showed excellent cell viability for at least 7 d. This strategy for better control of rheological properties of GelMA could more significantly enhance the usability of this material as bioink for bioprinting of cell-laden structures for soft tissue engineering. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) Published version

Stretchable conductors are critical building blocks for enabling new forms of wearable and curvilinear electronics. In this paper, we introduce a new method using the interfacial design to enable stretchable conductors with ultra-high conductivity and robustness to strain using three-dimensional helical copper micro-interconnects embedded in an elastic rubber substrate (eHelix-Cu). We studied the interfacial mechanics of the metal-elastomer to achieve highly reversible conductivities with strains. The stretchable eHelix-Cu interconnect has an ultra-high conductivity (∼105 S cm−1) that remains almost invariant when stretched to 170%, which is significantly higher than in other approaches using nanomaterials. The stretchable conductors can withstand strains of 100% for thousands of cycles, demonstrating remarkable durability for exciting potential wearable electronic applications.

Minute pH changes impact all living organisms, and thus facile pH monitoring in environment and onthe cellular level is important. A low cost and flexible carbon nanotube based pH sensor is fabricated inthis work using Aerosol jet printing technique. The chemiresistive pH sensor is fabricated with a CNT-based miniaturized serpentine sensing element printed on top of the silver electrodes. The trace width ofthe serpentine sensing element is accurately controlled to about the same size as the gaps between thetraces. Aerosol jet parameters are optimized to achieve high resolution printing of 20 m. The fabricatedpH sensor shows good sensitivity (up to 59 k /pH) and repeatability (coefficient of variance

A hybrid 3D bioprinting approach using porous microscaffolds and extrusion-based printing method is presented. Bioink constitutes of cell-laden poly(D,L-lactic-co-glycolic acid) (PLGA) porous microspheres with thin encapsulation of agarose-collagen composite hydrogel (AC hydrogel). Highly porous microspheres enable cells to adhere and proliferate before printing. Meanwhile, AC hydrogel allows a smooth delivery of cell-laden microspheres (CLMs), with immediate gelation of construct upon printing on cold build platform. Collagen fibrils were formed in the AC hydrogel during culture at body temperature, improving the cell affinity and spreading compared to pure agarose hydrogel. Cells were proven to proliferate in the bioink and the bioprinted construct. High cell viability up to 14 days was observed. The compressive strength of the bioink is more than 100 times superior to those of pure AC hydrogel. A potential alternative in tissue engineering of tissue replacements and biological models is made possible by combining the advantages of the conventional solid scaffolds with the new 3D bioprinting technology.

As an important metal three-dimensional printing technology, electron beam melting (EBM) is gaining increasing attention due to its huge potential applications in aerospace and biomedical fields. EBM processing of Ti-6Al-4V as well as its microstructure and mechanical properties were extensively investigated. However, it is still lack of quantitative studies regarding its microstructural evolution, indicative of EBM thermal process. Here, we report α′ martensitic transformation and α/β interface evolution in varied printing thicknesses of EBM-printed Ti-6Al-4V block samples by means of atom probe tomography. Quantitative chemical composition analysis suggests a general phase transformation sequence. By increasing in-fill hatched thickness, elemental partitioning ratios arise and β volume fraction is increased. Furthermore, we observe kinetic vanadium segregation and aluminum depletion at interface front and the resultant α/β interface widening phenomenon. It may give rise to an increased α/β lattice mismatch and weakened α/β interfaces, which could account for the degraded strength as printing thickness increases. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version

A solvent-free melt-drawing of aligned poly(L-lactide-co-ε-caprolactone) copolymer (PLC) microfibers into the tubular scaffold with the endocircular and exolongitudinal patterns has been investigated for the esophageal tissue engineering. The PLC microfibrous tubular scaffold was melt-drawn onto the 3D printed grooved mandrel. The experimental results show that the parallel grooves normal to the microfiber direction formed on the inner surface of the tubular scaffold. The surface topography of the tubular scaffold will mimic the endocircular and exolongitudinal muscle layers of the esophagus when the scaffold is turned inside out. It is proposed that this surface architecture may induce the cells orientation and cells attachment during its interaction with the individual smooth muscle cell. A large shrinkage of scaffold in dimension is observed along the fiber direction after the removal of scaffold from mandrel, which indicates that the PLC scaffold has a high elasticity. Therefore, the PLC scaffold will be mechanically compatible with the esophagus. Furthermore, it is suggested that the melt-drawing could be combined with the bioprinting technologies to print the tubular organs efficiently. Published version

Polymeric fibrous scaffolds for guiding cell growth are designed to be potentially used for the tissue engineering (TE) of tubular organs including esophagi, blood vessels, tracheas, etc. Tubular scaffolds were fabricated via melt-drawing of highly elastic poly(l-lactide-co-ε-caprolactone) (PLC) fibers layer-by-layer on a cylindrical mandrel. The diameter and length of the scaffolds are customizable via 3D printing of the mandrel. Thickness of the scaffolds was varied by changing the number of layers of the melt-drawing process. The morphology and tensile properties of the PLC fibers were investigated. The fibers were highly aligned with a uniform diameter. Their diameters and tensile properties were tunable by varying the melt-drawing speeds. These tailorable topographies and tensile properties show that the additive-based scaffold fabrication technique is customizable at the micro- and macro-scale for different tubular tissues. The merits of these scaffolds in TE were further shown by the finding that myoblast and fibroblast cells seeded onto the scaffolds in vitro showed appropriate cell proliferation and distribution. Human mesenchymal stem cells (hMSCs) differentiated to smooth muscle lineage on the microfibrous scaffolds in the absence of soluble induction factors, showing cellular shape modulation and scaffold elasticity may encourage the myogenic differentiation of stem cells.