Liquid Metal-Doped Conductive Hydrogel for Construction of Multifunctional Sensors.

Interest in wearable and stretchable multifunctional sensors has grown rapidly in recent years. The sensing elements must accurately detect external stimuli to expand their applicability as sensors. However, the sensor's self-healing and adhesion to a target object have been major challenges in developing such practical and versatile devices. In this study, we prepared a hydrogel (LM-SA-PAA) composed of liquid metal (LM), sodium alginate (SA), and poly(acrylic acid) (PAA) with ultrastretchable, excellent self-healing, self-adhesive, and high-sensitivity sensing capabilities that enable the conformal contact between the sensor and skin even during dynamic movements. The excellent self-healing performance of the hydrogel stems from its double cross-linked networks, including physical and chemical cross-linked networks. The physical cross-link formed by the ionic interaction between the carboxyl groups of PAA and gallium ions provide the hydrogel with reversible autonomous repair properties, whereas the covalent bond provides the hydrogel with a stable and strong chemical network. Alginate forms a microgel shell around LM nanoparticles via the coordination of its carboxyl groups with Ga ions. In addition to offering exceptional colloidal stability, the alginate shell has sufficient polar groups, ensuring that the hydrogel adheres to diverse substrates. Based on the efficient electrical pathway provided by the LM, the hydrogel exhibited strain sensitivity and enabled the detection of various human motions and electrocardiographic monitoring. The preparation method is simple and versatile and can be used for the low-cost fabrication of multifunctional sensors, which have broad application prospects in human-machine interface compatibility and medical monitoring.

Contributions of Cathepsin A and Carboxylesterase 1 to the Hydrolysis of Tenofovir Alafenamide in the Human Liver, and the Effect of CES1 Genetic Variation on Tenofovir Alafenamide Hydrolysis.

The prodrug tenofovir alafenamide (TAF) is a first-line antiviral agent for the treatment of chronic hepatitis B infection. TAF activation involves multiple steps, and the first step is an ester hydrolysis reaction catalyzed by hydrolases. This study was to determine the contributions of carboxylesterase 1 (CES1) and cathepsin A (CatA) to TAF hydrolysis in the human liver. Our in vitro incubation studies showed that both CatA and CES1 catalyzed TAF hydrolysis in a pH-dependent manner. At their physiologic pH environment, the activity of CatA (pH 5.2) was approximately 1,000-fold higher than that of CES1 (pH 7.2). Given that the hepatic protein expression of CatA was approximately 200-fold lower than that of CES1, the contribution of CatA to TAF hydrolysis in the human liver was estimated to be much greater than that of CES1, which is contrary to the previous perception that CES1 is the primary hepatic enzyme hydrolyzing TAF. The findings were further supported by a TAF incubation study with the CatA inhibitor telaprevir and the CES1 inhibitor bis-(p-nitrophenyl) phosphate. Moreover, an in vitro study revealed that the CES1 variant G143E (rs71647871) is a loss-of-function variant for CES1-mediated TAF hydrolysis. In summary, our results suggest that CatA may play a more important role in the hepatic activation of TAF than CES1. Additionally, TAF activation in the liver could be affected by CES1 genetic variation, but the magnitude of impact appears to be limited due to the major contribution of CatA to hepatic TAF activation. SIGNIFICANCE STATEMENT: Contrary to the general perception that carboxylesterase 1 (CES1) is the major enzyme responsible for tenofovir alafenamide (TAF) hydrolysis in the human liver, the present study demonstrated that cathepsin A may play a more significant role in TAF hepatic hydrolysis. Furthermore, the CES1 variant G143E (rs71647871) was found to be a loss-of-function variant for CES1-mediated TAF hydrolysis.

FRACPRED-2D-PRM: A Fraction Prediction Algorithm-Assisted 2D Liquid Chromatography-Based Parallel Reaction Monitoring-Mass Spectrometry Approach for Measuring Low-Abundance Proteins in Human Plasma.

Multidimensional fractionation-based enrichment methods improve the sensitivity of proteomic analysis for low-abundance proteins. However, a major limitation of conventional multidimensional proteomics is the extensive labor and instrument time required for analyzing many fractions obtained from the first dimension separation. Here, a fraction prediction algorithm-assisted 2D LC-based parallel reaction monitoring-mass spectrometry (FRACPRED-2D-PRM) approach for measuring low-abundance proteins in human plasma is presented. Plasma digests are separated by the first dimension high-pH RP-LC with data-dependent acquisition (DDA). The FRACPRED algorithm is then usedto predict the retention times of undetectable target peptides according to those of other abundant plasma peptides during the first dimension separation. Fractions predicted to contain target peptides are analyzed by the second dimension low-pH nano RP-LC PRM. The accuracy and robustness of fraction prediction with the FRACPRED algorithm are demonstrated by measuring two low-abundance proteins, aldolase B and carboxylesterase 1, in human plasma. The FRACPRED-2D-PRM proteomics approach demonstrates markedly improved efficiency and sensitivity over conventional 2D-LC proteomics assays. It is expected that this approach will be widely used in the study of low-abundance proteins in plasma and other complex biological samples.

Acetaminophen-Induced Liver Injury Alters Expression and Activities of Cytochrome P450 Enzymes in an Age-Dependent Manner in Mouse Liver.

Drug-induced liver injury (DILI) is a global medical problem. The risk of DILI is often related to expression and activities of drug-metabolizing enzymes, especially cytochrome P450s (P450s). However, changes on expression and activities of P450s after DILI have not been determined. The aim of this study is to fill this knowledge gap. Acetaminophen (APAP) was used as a model drug to induce DILI in C57BL/6J mice at different ages of days 10 (infant), 22 (child), and 60 (adult). DILI was assessed by levels of alanine aminotransferase and aspartate aminotransferase in plasma with a confirmation by H&E staining on liver tissue sections. The expression of selected P450s at mRNA and protein levels was measured by real-time polymerase chain reaction and liquid chromatography-tandem mass spectrometry, respectively. The activities of these P450s were determined by the formation of metabolites from probe drugs for each P450 using ultraperformance liquid chromatography-quadrupole time of flight mass spectrometry. DILI was induced at mild to severe levels in a dose-dependent manner in 200, 300, and 400 mg/kg APAP-treated groups at child and adult ages, but not at the infant age. Significantly decreased expression at mRNA and protein levels as well as enzymatic activities of CYP2E1, 3A11, 1A2, and 2C29 were found at child and adult ages. Adult male mice were more susceptible to APAP-induced liver injury than female mice with more decreased expression of P450s. These results suggest that altered levels of P450s in livers severely injured by drugs may affect the therapeutic efficacy of drugs, which are metabolized by P450s, more particularly for males. SIGNIFICANCE STATEMENT: The current study in an animal model demonstrates that acetaminophen-induced liver injury results in decreased expression and enzyme activities of several examined drug-metabolizing cytochrome P450s (P450s). The extent of such decreases is correlated to the degree of liver injury severity. The generated data may be translated to human health for patients who have drug-induced liver injury with decreased capability to metabolize drugs by certain P450s.

Low Cerebral Exposure Cannot Hinder the Neuroprotective Effects of Panax Notoginsenosides.

A bidirectional route of communication between the gastrointestinal tract and the central nervous system, termed the "gut-brain axis," is becoming increasingly relevant to treatment of cerebral damage. Panax Notoginsenoside extract (PNE) is popular for prevention and treatment of cardio-cerebrovascular ischemic diseases although plasma and cerebral exposure levels are extremely low. To date, the mechanisms underlying the neuroprotective effects of PNE remain largely unknown. In the present study, the neuroprotective effects of PNE were systematically studied via investigation of the regulation by PNE of the gastrointestinal microbial community and γ aminobutyric acid (GABA) receptors. The results demonstrated that pretreatment with PNE exerted a remarkable neuroprotective effect on focal cerebral ischemia/reperfusion (I/R) injury in rats, and the efficiency was attenuated in germ-free rats. Pretreatment with PNE could significantly prevent downregulation of Bifidobacterium longum (B.L) caused by I/R surgery, and colonization by B.L could also exert neuroprotective effects. More importantly, both PNE and B.L could upregulate the expression of GABA receptors in the hippocampus of I/R rats, and coadministration of a GABA-B receptor antagonist could significantly attenuate the neuroprotective effects of PNE and B.L. The study above suggests that the neuroprotective effects of PNE may be largely attributable to its regulation of intestinal flora, and oral treatment with B.L was also useful in therapy of ischemia/reperfusion injury (I/R) by upregulating GABA-B receptors.

Bioanalytical assay development and validation for simultaneous quantification of five schisandra lignans in rat primary hepatocytes based on LC-MS/MS: application to a real-time uptake study for Schisandra Lignan Extract.

Schisandra lignans, mainly including schizandrol A, schizandrol B, schisantherin A, schizandrin A, schizandrin B, etc., are the major active ingredients of Schisandra chinensis. In the present study, a robust liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous quantification of schisandra lignans in rat primary hepatocytes. Lovastatin was used as an internal standard, and chromatographic separation was achieved on a Shimadzu C18 column with a gradient elution at the flow rate of 0.2 mL/min. All of the analytes were detected in multiple reaction monitoring mode with positive electrospray ionization since the sodium adduct ion [M + Na]+ was observed as the most intensive peak in the MS spectrum. For schizandrol A, schisantherin A and schizandrin A, the dynamic range was within 2-1000 ng/mg protein, and the linear range of schizandrol B and schizandrin B was from 5 to 1000 ng/mg protein. The intra- and inter-day precision was <15% and the accuracy (relative error) ranged from -15 to 15%. No significant variation was observed in the stability tests. The validated method was then successfully applied to the time-dependent uptake study for the Schisandra Lignan Extract in rat primary hepatocytes.

Development and validation of a quantification method for ziyuglycoside I and II in rat plasma: Application to their pharmacokinetic studies.

This study provided a novel and generally applicable method to determine ziyuglycoside I and ziyuglycoside II in rat plasma based on liquid chromatography with tandem mass spectrometry. A single step of liquid-liquid extraction with n-butanol was utilized, and ginsenoside Rg3 was chosen as internal standard. Final extracts were analyzed based on liquid chromatography with tandem mass spectrometry. Chromatographic separation was achieved using a Thermo Golden C18 column, and the applied gradient elution program allowed for the simultaneous determination of two ziyuglycosides in a one-step chromatographic separation with a total run time of 10 min. The fully validated methodology for both analytes demonstrated high sensitivity (the lower limit of quantitation was 2.0 ng/mL), good accuracy (% RE ≤ ± 15) and precision (% RSD ≤ 15). The average recoveries of both ziyuglycosides and internal standard were all above 75% and no obvious matrix effect was found. This method was then successfully applied to the preclinical pharmacokinetic studies of ziyuglycoside I and ziyuglycoside II. The presently developed methodology would be useful for the preclinical and clinical pharmacokinetic studies for ziyuglycoside I and ziyuglycoside II.

Differential Bioactivation Profiles of Different GS-441524 Prodrugs in Cell and Mouse Models: ProTide Prodrugs with High Cell Permeability and Susceptibility to Cathepsin A Are More Efficient in Delivering Antiviral Active Metabolites to the Lung.

We assessed factors that determine the tissue-specific bioactivation of ProTide prodrugs by comparing the disposition and activation of remdesivir (RDV), its methylpropyl and isopropyl ester analogues (MeRDV and IsoRDV, respectively), the oral prodrug GS-621763, and the parent nucleotide GS-441524 (Nuc). RDV and MeRDV yielded more active metabolite remdesivir-triphosphate (RDV-TP) than IsoRDV, GS-621763, and Nuc in human lung cell models due to superior cell permeability and higher susceptivity to cathepsin A. Intravenous administration to mice showed that RDV and MeRDV delivered significantly more RDV-TP to the lung than other compounds. Nevertheless, all four ester prodrugs exhibited very low oral bioavailability (<2%), with Nuc being the predominant metabolite in blood. In conclusion, ProTides prodrugs, such as RDV and MeRDV, are more efficient in delivering active metabolites to the lung than Nuc, driven by high cell permeability and susceptivity to cathepsin A. Optimizing ProTides' ester structures is an effective strategy for enhancing prodrug activation in the lung.

Clarity improvement of the discoloration boundary and detection of Hg2+ ions by using a polystyrene nanoparticle-modified paper-based microdevice.

Distance-based microfluidic paper-based analytical devices (µPADs) can be used to calculate the analyte content by reading the length of the discolored area in the channel. A blurred discoloration boundary is difficult to distinguish, resulting in reading errors. In this study, we constructed a µPAD modified with carboxyl-containing polystyrene nanoparticles (PS-µPAD) to improve the discoloration-boundary clarity. The filling of the pores of the fibers with the deposited polystyrene nanoparticles (PS NPs) caused a decrease in the paper porosity, resulting in a flow delay. Meanwhile, the carboxyl groups carried by PS NPs were able to form hydrogen bonds with hydroxyl-containing compounds FLPI, a Hg2+ probe, and the two factors acted synergistically to fix the FLPI to react in situ, raising the discoloration-boundary clarity. Compared with the unmodified µPAD, the detection of Hg2+ ions using the PS-µPAD still had a good linear relationship. Importantly, the color-depth difference inside and outside the discoloration boundary improved by about four times and showed excellent reproducibility in different populations. The method was simple and easy to expand, thereby providing an idea for more widespread application of distance-based µPADs.

Physiologically-Based Pharmacokinetic Modeling to Predict Methylphenidate Exposure Affected by Interplay Among Carboxylesterase 1 Pharmacogenetics, Drug-Drug Interactions, and Sex.

BACKGROUND AND OBJECTIVE: The pharmacokinetics (PK) of methylphenidate (MPH) differ significantly among individuals. Carboxylesterase 1 (CES1) is the primary enzyme metabolizing MPH, and its function is affected by genetic variants, drug-drug interaction (DDI), and sex. The object of this study is to evaluate CES1 pharmacogenetics as related to MPH metabolism using human liver samples and develop a physiologically-based pharmacokinetic (PBPK) modeling approach to investigate the influence of CES1 genotypes and other factors on MPH PK. METHODS: The effect of the CES1 variant G143E (rs71647871) on MPH metabolism was studied utilizing 102 individual human liver S9 (HLS9) fraction samples. PBPK models were developed using the population-based PBPK software PK-Sim® by incorporating the HLS9 incubation data. The established models were applied to simulate MPH PK profiles under various clinical scenarios, including different genotypes, drug-alcohol interactions, and the difference between males and females. RESULTS: The HLS9 incubation study showed that subjects heterozygous for the CES1 variant G143E metabolized MPH at a rate of approximately 50% of that in non-carriers. The developed PBPK models successfully predicted the exposure alteration of MPH from the G143E genetic variant, ethanol-MPH DDI, and sex. Importantly, the study suggests that male G143E carriers who are alcohol consumers are at a higher risk of MPH overexposure. CONCLUSION: PBPK modeling provides a means for better understanding the mechanisms underlying interindividual variability in MPH PK and PD and could be utilized to develop a safer and more effective MPH pharmacotherapy regimen.

The aero body righting of frog Rana rugulosus via hindleg swings.

Frogs can keep an excellent aerial balance for landing and achieve consecutive jumps reliably. A safe landing requires an accurate body righting in the air. However, there is no systematic study on how the frogs adjust the aerial postures and body attitudes after jumping. The stretched long hindlegs swung quickly in the aerial phase, which revealed a clear relationship with the body attitudes. This study aimed to verify the function of frogs' hindlegs on aero body righting in the air. We captured the motions of both hindlegs and found the hindlegs adopted two movement modes, the bilateral parallel, and separated swings. The hindleg-induced torques by the two movements were negatively correlated with the body's angular accelerations on pitch and roll, respectively. Moreover, an analytical model was derived based on the conservation of angular momentum and verified by the dynamic simulations. Thus, we confirmed that the hindlegs are the dominant mechanism in aerial pitch and roll controls. We anticipate our achievements to inspire the design of air-righting tools.

Plasma Carboxylesterase 1 Predicts Methylphenidate Exposure: A Proof-of-Concept Study Using Plasma Protein Biomarker for Hepatic Drug Metabolism.

Hepatic drug-metabolizing enzymes (DMEs) play critical roles in determining the pharmacokinetics and pharmacodynamics of numerous therapeutic agents. As such, noninvasive biomarkers capable of predicting DME expression in the liver have the potential to be used to personalize pharmacotherapy and improve drug treatment outcomes. In the present study, we quantified carboxylesterase 1 (CES1) protein concentrations in plasma samples collected during a methylphenidate pharmacokinetics study. CES1 is a prominent hepatic enzyme responsible for the metabolism of many medications containing small ester moieties, including methylphenidate. The results revealed a significant inverse correlation between plasma CES1 protein concentrations and the area under the concentration-time curves (AUCs) of plasma d-methylphenidate (P = 0.014, r = -0.617). In addition, when plasma CES1 protein levels were normalized to the plasma concentrations of 24 liver-enriched proteins to account for potential interindividual differences in hepatic protein release rate, the correlation was further improved (P = 0.003, r = -0.703), suggesting that plasma CES1 protein could explain ~ 50% of the variability in d-methylphenidate AUCs in the study participants. A physiologically-based pharmacokinetic modeling simulation revealed that the CES1-based individualized dosing strategy might significantly reduce d-methylphenidate exposure variability in pediatric patients relative to conventional trial and error fixed dosing regimens. This proof-of-concept study indicates that the plasma protein of a hepatic DME may serve as a biomarker for predicting its metabolic function and the pharmacokinetics of its substrate drugs.

On the kinematics of forelimb landing of frog Rana rugulosus.

A frog can jump several times higher than its own height and then land smoothly on the ground. During the buffering phase, both forelimbs touch the ground and compact quickly to absorb most of the impact energy. However, the adjustment of the joint angles of the forelimb and the induced cushioning effect during the landing process have not been thoroughly investigated. In this study, we statistically summarized the angular displacements of forelimb joints with respect to landing velocities by using a high-speed motion capture system. It is found many joint angles were linearly influenced by landing velocity at both ground touching moment and maximum compression moment. Moreover, the double-peak pattern of ground reactive force was measured, which attributes to the forelimb landing and the followed abdomen/hindlimb landing. Before the appearance of the first peak, the compression of the forelimb and the reactive force revealed a linear relationship regardless of velocity, implying that the forelimbs act as a constant stiffness spring in landing. Accordingly, a simple spring-mass model was proposed and verified by simulation for forelimb cushioning of the frog. We anticipate our achievements to inspire the design of future landing mechanisms.

Impact of carboxylesterase 1 genetic polymorphism on trandolapril activation in human liver and the pharmacokinetics and pharmacodynamics in healthy volunteers.

Trandolapril, an angiotensin-converting enzyme inhibitor prodrug, needs to be activated by carboxylesterase 1 (CES1) in the liver to exert its intended therapeutic effect. A previous in vitro study demonstrated that the CES1 genetic variant G143E (rs71647871) abolished CES1-mediated trandolapril activation in cells transfected with the variant. This study aimed to determine the effect of the G143E variant on trandolapril activation in human livers and the pharmacokinetics (PKs) and pharmacodynamics (PDs) in human subjects. We performed an in vitro incubation study to assess trandolapril activation in human livers (5 G143E heterozygotes and 97 noncarriers) and conducted a single-dose (1 mg) PK and PD study of trandolapril in healthy volunteers (8 G143E heterozygotes and 11 noncarriers). The incubation study revealed that the mean trandolapril activation rate in G143E heterozygous livers was 42% of those not carrying the variant (p = 0.0015). The clinical study showed that, relative to noncarriers, G143E carriers exhibited 20% and 15% decreases, respectively, in the peak concentration (Cmax ) and area under the curve from 0 to 72 h (AUC0-72 h ) of the active metabolite trandolaprilat, although the differences were not statistically significant. Additionally, the average maximum reductions of systolic blood pressure and diastolic blood pressure in carriers were ~ 22% and 23% less than in noncarriers, respectively, but the differences did not reach a statistically significant level. In summary, the CES1 G143E variant markedly impaired trandolapril activation in the human liver under the in vitro incubation conditions; however, this variant had only a modest impact on the PK and PD of trandolapril in healthy human subjects.

Developing a SWATH capillary LC-MS/MS method for simultaneous therapeutic drug monitoring and untargeted metabolomics analysis of neonatal plasma.

Most medications prescribed to neonatal patients are off-label uses. The pharmacokinetics and pharmacodynamics of drugs differ significantly between neonates and adults. Therefore, personalized pharmacotherapy guided by therapeutic drug monitoring (TDM) and drug response biomarkers are particularly beneficial to neonatal patients. Herein, we developed a capillary LC-MS/MS metabolomics method using a SWATH-based data-independent acquisition strategy for simultaneous targeted and untargeted metabolomics analysis of neonatal plasma samples. We applied the method to determine the global plasma metabolomics profiles and quantify the plasma concentrations of five drugs commonly used in neonatal intensive care units, including ampicillin, caffeine, fluconazole, vancomycin, and midazolam and its active metabolite α-hydroxymidazolam, in neonatal patients. The method was successfully validated and found to be suitable for the TDM of the drugs of interest. Moreover, the global metabolomics analysis revealed plasma metabolite features that could differentiate preterm and full-term neonates. This study demonstrated that the SWATH-based capillary LC-MS/MS metabolomics approach could be a powerful tool for simultaneous TDM and the discovery of neonatal plasma metabolite biomarkers.

Biliary Excretion-Mediated Food Effects and Prediction.

Many orally administered drugs with negative food effects (i.e., lower exposure under fed conditions) are often primarily or partially eliminated by biliary excretion. The aim of this study is to assess the potential correlation between a negative food effect and biliary excretion. Correlation analysis was conducted using a training dataset containing 27 drugs which met the following criteria: (1) immediate-release formulations, (2) shows a negative food effect, (3) > 10% biliary clearance, and (4) does not undergo extensive metabolism. A correlation between fed-state biliary clearance (CLb,fed) and fasted-state biliary clearance (CLb,fast) (y = 1.81*x, R2 = 0.68) was observed. The 1.8-fold increase in biliary clearance was then used as a correction factor to improve physiologically based pharmacokinetic (PBPK) prediction of food effects for 12 test drugs. The mean deviations of predicted fed/fasting AUC ratio and Cmax ratio from clinically observed values were reduced from 32.4 to 17.2% and from 63.3 to 54.3%, respectively. In contrast to the positive food effects on most biopharmaceutics classification system (BCS) class II drugs for which food-stimulated bile flow increases drug solubility and absorption, our results suggest that the elimination of biliary excreted drugs is increased by food-stimulated bile flow, resulting in negative food effects.

Au nanoparticle-based probe for selenol in living cells and selenium-rich tea and rice.

Selenocysteine (Sec) is a primary kind of reactive selenium species in cells, and its vital roles in physiological processes have been characterized. Therefore, the highly effective method for sensing Sec in metabolic processes and selenium-rich food must be developed. This study presents a new fluorescent probe, namely, GSH-NB@AuNPs, for highly selective detection of selenol based on the fluorescence quenching quality on the surface of gold nanoparticles (AuNPs). The probe consists of glutathione (GSH) and Nile blue (NB) moieties assembled on AuNPs. The probe exhibits excellent sensitivity and selectivity for Sec and is applied in imaging endogenous and exogenous Sec in living cells through confocal fluorescence microscopy. The proposed probe provides a promising and powerful method for detecting selenol in foodstuff (such as selenium-rich rice and tea) with the detection limit of 9.5 nM.

Lecithin doped electrospun poly(lactic acid)-thermoplastic polyurethane fibers for hepatocyte viability improvement.

The development of hepatocyte cultures in vitro holds great significance in the study of bioartificial liver support systems. Electrospun fiber cultures have received widespread attention as an effective method to culture hepatocytes in vitro. Polylactic acid (PLA) -a synthetic polymer with high biocompatibility and biodegradability- is widely used to fabricate electrospun fibers in the biomedical field. However, the use of PLA is limited in cell cultures due to its brittleness, strong hydrophobicity, and lack of biologically active functional groups. In this study, thermoplastic polyurethane (TPU) and lecithin (Lec) were used to modify PLA by spiking them into the PLA electrospun solution in attempt to establish a suitable fiber scaffold for hepatocyte culture in bioreactors. TPU and lecithin incorporation into PLA increases the flexibility, hydrophilicity, and biologically active groups of the fibers which further promotes the growth, proliferation, and viability of hepatocytes. The morphology, wettability, and biocompatibility of the as-prepared PLA-TPU-Lec fibers were carefully characterized. The results showed that the PLA-TPU-Lec fibers possessed favorable morphology and hydrophilicity, as well as high biocompatibility ability. HepG2 cells on the PLA-TPU-Lec fibers and tissue culture plates (TCP) were exposed to hepatotoxins for 24 h and we found that HepG2 cells on the PLA-TPU-Lec fibers had higher viability than cells on TCP. The PLA-TPU-Lec fibers are therefore expected to be used in vitro for hepatocyte culture to improve cellular activity in artificial liver bioreactors.

Preparation and study of the antibacterial ability of graphene oxide-catechol hybrid polylactic acid nanofiber mats.

The functionalization of electrospun mats with antimicrobial nanomaterials is an attractive strategy when developing functional graphene oxide coating materials to prevent bacterial colonization on surfaces. In this study, we demonstrated a simple approach to produce antimicrobial electrospun mats by dip-coating a polylactic acid (PLA) nanofiber into a graphene oxide-catechol derivative. PLA was first electrospun to yield narrow-diameter polymeric nanofibers. We then modified the graphene oxide (GO) with a catechol derivative - dopamine methacrylamide monomer (DMA) - to synthesize a GO-DMA nanocomposite material which exhibited robust antimicrobial properties. The catechol groups promote the immobilization of graphene oxide onto the PLA nanofibers and possess strong antimicrobial properties. We therefore selected this functional group to modify GO. We dipped the GO-DMA onto the PLA nanofiber to produce the final functionalized electrospun mats. The PLA mats which were functionalized using the GO-DMA nanocomposite (PLA-GO-DMA) displayed antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. Furthermore, we studied the biocompatibility of the mats by culturing the cell lines (HepG2, A549, and HUVEC-C) of PLA-GO-DMA among the nanofibers which exhibited excellent biocompatibility. These results collectively demonstrate the potential of PLA-GO-DMA nanofiber mats as antimicrobial biomaterials and provide fundamental information toward the establishment of future biomedical applications.

Development of a novel sectional multiple filtering scheme for rapid screening and classifying metabolites of ziyuglycoside II in rat liver and excreta specimen based on high-resolution mass spectrometry.

Ziyuglycoside II, one of the major effective ingredients of Sanguisorba officinalis L., had various pharmacological activities including anticancer, anti-inflammation and anti-oxidation, etc. Better understanding of the pharmacology and toxicology of ziyuglycoside II requires the detailed elucidation of its biologic fates in vivo. Herein, the metabolic fate of ziyuglycoside II in rats was investigated based on liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS). To accelerate and simplify the process of metabolite identification from complicated biological matrix, the sectional multiple filtering (SMF) scheme was designed according to the relationship among the molecular weight (MW), mass defect (MD) and retention time (tR) of the metabolites. SMF-I (MW: 700-850Da, MD: 0.40-0.45Da, tR: 4.0-10.0min), SMF-II (MW: 550-700Da, MD: 0.30-0.40Da, tR: 6.0-14.0min) and SMF-III (MW: 400-550Da, MD at 0.25-0.35Da, tR at 9.5-16.0min) were built and utilized to screen phase II conjugations and phase I redox metabolites and deglycosylated derivatives, respectively. As a result, dozens of metabolites, including glucuronic conjugates, hydroxylation, oxidization, dehydration and deglycosylation products, were rapidly discovered, classified and structural identified in rat urine and feces based on SMF scheme and accurate MS(1)/MS(2) information. Obviously, the SMF technique showed superior efficiency and selectivity in ziyuglycoside II metabolite identification. More importantly, SMF would find its extensive application in, but not limited to, the metabolic study for single drug or homologous compounds in traditional Chinese medicine.