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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.

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.

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.

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.

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.

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.

Our previous studies have investigated the systematic pharmacokinetic characteristics, biological activities, and toxicity of arctigenin. In this research, the potential toxicities of arctigenin in beagle dogs were investigated via repeated 28-day subcutaneous injections. Beagle dogs were randomly divided into control, vehicle [polyethylene glycol (PEG)], and arctigenin 6, 20, 60 mg/kg treated groups. The whole experimental period lasted 77 days, including adaptive period (35 days), drug exposure period (animals were treated with saline, PEG, or arctigenin for 28 consecutive days), and recovery period (14 days). Arctigenin injection (60 mg/kg) affected the lymphatic hematopoietic, digestive, urinary, and cardiovascular systems, and all the impact on these tissues resulted in death in five dogs (three female and two male dogs); 20 mg/kg arctigenin injection resulted in toxic reactions of the lymphatic hematopoietic and digestive systems; and 6 mg/kg arctigenin and PEG injection did not lead to significant toxic reactions. Meanwhile, there were no sexual differences of drug exposure and accumulation when dogs underwent different dosages. As stated previously, the toxic target organs of arctigenin administration include lymphatic hematopoietic, digestive (liver and gallbladder), urinary (kidney), and cardiovascular (heart) systems, and the no observed adverse effect level (NOAEL) of arctigenin is less than 6 mg/kg.

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

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.

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.

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.

Arctium lappa (burdock) is the most popular daily edible vegetable in China and Japan because of its general health tonic effects. Previous studies focused on the beneficial role of Arctigenin but neglected its potential side-effects and toxicities. In the present study, the sub-chronic toxicity profile of Arctigenin following 28 days of consecutive exposure was investigated in rats. The results showed that during the drug exposure period, Arctigenin-12 mg/kg administration resulted in focal necrosis and lymphocytes infiltration of heart ventricular septal muscle cells. In the kidney cortical zone, the renal tubular epithelial cells were swollen, mineralized, and lymphocyte infiltrated. In the liver, the partial hepatocyte cytoplasm showed vacuolation and fatty changes, focal necrosis, and interstitial lymphocyte infiltration. In the rats that underwent 36 mg/kg/day administration, there was bilateral testis and epididymis atrophy. In the lung and primary bronchus, erythrocytes and edema fluid were observed. Changes of proestrus or estrus were observed in the uterus, cervix, and vagina intimal epithelial cells. Lymphocytic focal infiltration occurred in the prostate mesenchyme. The high dosage of Arctigenin only decreased the body weight at day 4. At the end of the recovery period, histopathological changes were irreversible, even after withdrawal of the drug for 28 days. Focal necrosis still existed in the heart ventricular septal muscle cells and hepatocytes. Lymphocyte infiltrations were observed in the heart, renal cortex, hepatocyte, and pancreas exocrine gland. Meanwhile, atrophy occurred in the testicles and pancreas. In addition, in the Arctigenin-12 mg/kg group, creatinine (CREA) and brain weight were both significantly increased. The toxicokinetical study demonstrated that Arctigenin accumulated in the organs of rats. The food consumption, hematological, and biochemical parameters were not associated with the above results. These contradictory results might result from the lesions induced by Arctigenin, which were not sufficiently serious to change the parameters. These results suggest that Arctium lappa should be consumed daily with caution because of the potential toxicity induced by Arctigenin. According to all results, the lowest observed adverse effect level (LOAEL) was induced by 12 mg/kg daily exposure to Arctigenin, and the No-observed-adverse-effect-level (NOAEL) should be lower than 12 mg/kg.

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.

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

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