Design and fabrication of an integrated 3D dynamic multicellular liver-on-a-chip and its application in hepatotoxicity screening.

Nowadays, major methods of in vitro hepatotoxicity research are still based on traditional static two- or three-dimensional cell culture, although these means could investigate some toxic chemicals induced hepatotoxicity, but most of these toxicities failed to reappear in human, at least not in similar or calculable dose level. These failures may cause by the monoculture of only hepatocytes, ignored the signal communication to other non-parenchymal cells in liver tissue, also other complex microenvironment such as endothelial barrier, shear stress and other factors which were really existed in vivo but absent here, final leading to a low reliability of experimental results. In this study, a three-dimensional dynamic multi-cellular liver-on-a-chip device (3D-DMLoC) was developed to reproduce the microenvironment of in vivo liver tissue, including the simulation of hepatic sinusoid, perisinusoidal space and continuous liquid perfusion, hepatocytes could gather to some 3D cell spheroids in this chip. The perfusion could bring a real-time exchange of chemicals, nutrients, metabolites, supply suitable oxygen and a weak shear stress. The pressure and oxygen distribution inner the chip were simulated and evaluated by COMSOL Multiphysics software. HepaRG were co-cultured with HUVEC for 7 days in this chip, expression of hepatic polarization protein ZO-1 and MRP2, liver function factors ALB, UREA and CYP450s were almost all higher than in traditional static culture. Several drugs and heavy metal ions induced hepatotoxicity were then investigated, LDH released from hepatocyte spheroids in mostly 3D-DMLoC groups were higher than same-dosed 2D group, indicated the spheroids were more sensibility to the toxins. The hepatoxicity might be induced by acute hepatocytes injury according to the ratios of secreted AST/ALT contents. In conclusion, a liver-on-a-chip device was successfully developed and verified for better reproducing the in vivo physiological microenvironment of liver. It could be applied for easily, efficiently, and accurately screening the potential hepatotoxic chemicals in future.

Recent progress of microfluidic technology for pharmaceutical analysis.

In recent years, the progress of microfluidic technology has provided new tools for pharmaceutical analysis and the proposal of pharm-lab-on-a-chip is appealing for its great potential to integrate pharmaceutical test and pharmacological test in a single chip system. Here, we summarize and highlight recent advances of chip-based principles, techniques and devices for pharmaceutical test and pharmacological/toxicological test focusing on the separation and analysis of drug molecules on a chip and the construction of pharmacological models on a chip as well as their demonstrative applications in quality control, drug screening and precision medicine. The trend and challenge of microfluidic technology for pharmaceutical analysis are also discussed and prospected. We hope this review would update the insight and development of pharm-lab-on-a-chip.

Metabonomics Study on the Infertility Treated With Zishen Yutai Pills Combined With In Vitro Fertilization-embryo Transfer.

Zishen Yutai Pills (ZYP) is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction, including prevention of miscarriage, increase of pregnancy rate during in vitro fertilization-embryo transfer (IVF-ET). The plasma of patients was collected from a clinical trial, namely, "Effect of Traditional Chinese Medicine vs placebo on live births among women undergoing in vitro fertilization, a multi-center randomized controlled trial." Plasma samples were analyzed with metabonomics method. UPLC-MS technology was used to establish the plasma metabolic fingerprint. Multivariate statistical analysis was applied for comparing the differences of plasma metabolites between ZYP group and placebo group, 44 potential metabolites were screen out and identified. Pathway analysis was conducted with database mining. Compared with placebo, chemicals were found to be significantly down-regulated on HCG trigger day and 14 days after embryo transplantation, including trihexosylceramide (d18:1/26:1), glucosylceramide(d18:1/26:0), TG(22:6/15:0/22:6), TG(22:4/20:4/18:4). Compared with placebo, some chemicals were found to be significantly up-regulated on HCG trigger day and 14 days after embryo transplantation, i.e., PIP3(16:0/16:1), PIP2(18:1/18:1), tauroursodeoxycholic acid, L-asparagine, L-glutamic acid, kynurenic acid, 11-deoxycorticosterone, melatonin glucuronide, hydroxytyrosol. These metabolites were highly enriched in pathways including sphingolipid metabolism, alanine, aspartic acid and glutamic acid metabolism, aminoacyl tRNA biosynthesis, taurine and hypotaurine metabolism. This study revealed metabolic differences between subjects administered with ZYP and placebo. Relating metabolites were identified and pathways were enriched, providing basis on the exploration on the underlying mechanisms of ZYP combined with IVF-ET in the treatment of infertility.

Improving the accuracy and efficacy of diagnosing polycystic ovary syndrome by integrating metabolomics with clinical characteristics: study protocol for a randomized controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine syndrome with poorly understood mechanisms. To provide patients with PCOS with individualized therapy, it is critical to precisely diagnose the phenotypes of the disease. However, the criteria for diagnosing the different phenotypes are mostly based on symptoms, physical examination and laboratory results. This study aims to compare the accuracy and efficacy of diagnosing PCOS by integrating metabolomic markers with common clinical characteristics. METHODS: This is a prospective, multicenter, analyst-blinded, randomized controlled trial. Participants will be grouped into (1) people without PCOS (healthy control group), (2) patients diagnosed with PCOS based on clinical indices (experimental group 1), and (3) patients diagnosed with PCOS based on metabolomic indices (experimental group 2). A total of 276 participants, including 60 healthy people and 216 patients with PCOS, will be recruited. The 216 patients with PCOS will be randomly assigned to the two experimental groups in a 1:1 ratio, and each group will receive a different 6-month treatment. The primary outcome for the experimental groups will be the effect of PCOS treatment. DISCUSSION: The results of this trial should help to determine whether using metabolomic indices is more accurate and effective than using clinical characteristics in diagnosing the phenotypes of PCOS. The results could provide a solid foundation for the accurate diagnosis of different PCOS subgroups and for future research on individualized PCOS therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-INR-1800016346. Registered 26 May 2018.

Efficacy evaluation of Qingyan formulation in a smoking environment and screening of anti-inflammatory compounds.

Qingyan formulation (QF) is a common preparation that is often used to control inflammation in the haze environment. However, the efficacy and effective constituents of QF are still uncertain and difficult to identify. This paper aims to evaluate the efficacy by simulating a haze environment and determine its anti-inflammatory compounds by UPLC/Q-TOF-MS/MS combing with bioactivity screening. The therapeutic effect of QF in the simulated haze environment was confirmed from the aspects of lung histomorphology and inflammatory factor expression levels. QF showed strong anti-inflammatory activity with the minimum effective concentration reaching 1.5 g/kg. Potential anti-inflammatory components were screened by the NF-κB activity assay system and simultaneously identified based on mass spectral data. Then, the potential active compounds were verified by molecular biological methods, the minimum effective concentration can reach 0.1 mg/L. Six structural types of NF-κB inhibitors (phenolic acid, scopolamine, hydroxycinnamic acid, flavonoid, dihydroflavone and steroid) were identified. Further cytokine assays confirmed their potential anti-inflammatory effects of NF-κB inhibitors. This strategy clearly demonstrates that QF has a significant therapeutic effect on respiratory diseases caused by haze, so it is necessary to promote its commercialization and wider application.

Metabonomic Analysis of the Therapeutic Effects of Chinese Medicine Sanqi Oral Solution on Rats With Exhaustive Exercise.

Exhaustive exercise has emerged as an important health issue nowadays. This study was designed to assess the metabolite abnormalities of rats after exhaustive exercise and the holistic efficacy of Chinese medicine Sanqi oral solution (SQ). Through exhaustive swimming, the exhaustive exercise model in rats was established. Thirty male Sprague-Dawley rats were randomly divided into control, model, and treatment groups. SQ (12 mL·kg-1·d-1) or 0.9% saline solution was administrated orally by gastric gavage. After 4 weeks, serum samples were collected for biochemical measurements and ultra performance liquid chromatography (UPLC)/quadrupole time-of-flight mass spectrometry (Q-TOF-MS)-based metabonomic study. It was found that rats with SQ intervention showed longer exhaustive swimming time (P < 0.05) than model rats, with an average of 1,160.36 ± 123.89 s in SQ group and 906.57 ± 172.11 s in model group. Among the biochemical indices, the levels of creatine kinase isoenzyme, lactate dehydrogenase, and glucose of exhaustive exercise rats increased, whereas levels of creatine kinase, urea, triglyceride, and total cholesterol decreased. These biochemical indices came normal after SQ administration, except for triglyceride. Twenty-seven potential biomarkers belonging to sphingolipids, phospholipids, fatty acids, amino acid, and other classes were identified in serum. This study indicated that SQ exerted protective effects on exhaustive exercise by significantly prolonging the swimming endurance time. The metabonomic-based findings of the metabolic state and analysis of potential biomarkers in serum well correlated with biochemical assessment, confirming that SQ had a definite efficacy. Moreover, the shifts in lipid-related metabolites and glycolytic pathway suggested that SQ may serve as a potential supplementation in sports nutrition for its pharmacological effect of regulating energy metabolism as well as improving signal transduction and muscle-cell physiological functions.

A 3D construct of the intestinal canal with wrinkle morphology on a centrifugation configuring microfluidic chip.

A new in vitro gut microfluidic chip that mimics in vivo intestinal canal morphology and stimulation is developed to contribute to research into tissue engineering, and intestinal development and function. This strategy utilizes centrifugation to configure spatial cells along the side wall of a vertical cylinder-like microfluidic chamber, by which a tubular intestinal epithelium cell sheet is formed. Diverse intestinal cell lines are inoculated to address this approach. Furthermore, to generate microenvironmental stimulation, low-level centrifugation introduces fluid flow to this microfluidic system perpendicularly acting on cell sheet cultivation for several days. Fluid flow engenders the sectional cell sheet to bend toward the cell chamber lumen, which manifests an intestinal epithelium vaulted and wrinkle morphology. This may mimic the fluid flow existing in in vivo material transportation and the absorption of the gut epithelium barrier. In addition, the same fluid flow stimulation was reproduced in another Transwell system, which also exhibited a wrinkle epithelium cell sheet. Under fluid flow stimulation, some of the villus specific genes' expression level increased in the microfluidics and Transwell insert. Thus, this new centrifugation configuring gut microfluidic chip may offer novel insights into the research of intestinal structure and function.

UPLC/Q­TOF­MS based plasma metabolomics and clinical characteristics of polycystic ovarian syndrome.

The present study aimed to develop novel diagnostic methods for polycystic ovarian syndrome (PCOS) by screening and identifying specific PCOS­associated metabolic markers using plasma metabolomics. Ultra­performance liquid chromatography/quadrapole­time of flight­mass spectrometry was adopted to establish the plasma metabolic fingerprint of 49 patients and 50 normal controls, in order to screen the potential metabolic markers. In addition, these markers were integrated with the clinical indexes, followed by focused analysis to obtain diagnostic markers. The present results demonstrated that not only was the concentration of palmitoyl sphingomyelin in plasma of patients with PCOS significantly increased; however, a statistically significant difference between the two PCOS subgroups was additionally demonstrated. At the same time, the concentrations of cyclic guanosine monophosphate (cGMP) and dehydroepiandrosterone sulphate in the plasma of patients of the subgroup 1 were significantly elevated. These markers were additionally integrated with the clinical index number of follicles in the left ovary and high­density lipoprotein (HDL­C), followed by receiver operating characteristic curve analysis, which demonstrated a diagnostic accuracy of ~90% in the control and the two subgroups. The integrated marker system consisting of palmitoyl sphingomyelin, cGMP and androsterone sulfate, as well as the number of left follicles and HDL­C may be used for the accurate diagnosis and classification of PCOS. These results confirmed that the abnormalities in hormone metabolism and lipid metabolism disorder were primarily involved in the onset of PCOS.

Identification of fukinolic acid from Cimicifuga heracleifolia and its derivatives as novel antiviral compounds against enterovirus A71 infection.

Human enterovirus 71 (EV-A71) infections cause a wide array of diseases ranging from diarrhoea and rashes to hand-foot-and-mouth disease and, in rare cases, severe neurological disorders. No specific antiviral drug therapy is currently available. Extracts from 75 Chinese medicinal plants selected for antiviral activity based on the Chinese pharmacopeia and advice from traditional Chinese medicine clinicians were tested for activity against EV-A71. The aqueous extract of the rhizome of Cimicifuga heracleifolia (Sheng Ma) and Arnebia euchroma (Zi Cao) showed potent antiviral activity. The active fractions were isolated by bioassay-guided purification, and identified by a combination of high-resolution mass spectrometry and nuclear magnetic resonance. Fukinolic acid and cimicifugic acid A and J, were identified as active anti-EV-A71 compounds for C. heracleifolia, whereas for A. euchroma, two caffeic acid derivatives were tentatively deduced. Commercially available fukinolic acid analogues such as L-chicoric acid and D-chicoric also showed in vitro micromolar activity against EV-A71 lab-strain and clinical isolates.

Renoprotective effect of Zhenwu decoction against renal fibrosis by regulation of oxidative damage and energy metabolism disorder.

Zhenwu decoction (ZWD) is a promising traditional Chinese prescription against renal fibrosis, while its underlying mechanism remains unclear. Rat model of renal fibrosis were established and divided into control group, model group, ZWD treatment group and enalapril maleate treatment group. Metabolic profiles on serum samples from each group were acquired by using ultra performance liquid chromatography coupled with quadrupole time-of-flight high-resolution mass spectrometry. Metabolomics combined with molecular biology were comparatively conducted on samples of various groups. Fifteen potential biomarkers were identified and these biomarkers are mainly phospholipids and fatty acids. The results showed renal fibrosis was associated with oxidative damage and energy metabolism disorder. The results of histopathology, biochemistry and metabolomics demonstrated that ZWD exhibited an efficient renoprotective effect by alleviating oxidative stress, increasing energy metabolism and regulating fibrotic cytokines. This study provided scientific support for the research and development of new drugs from traditional Chinese medicine.

Simultaneous Assay of Oxygen-Dependent Cytotoxicity and Genotoxicity of Anticancer Drugs on an Integrated Microchip.

Oxygen deprivation is a common feature in a variety of cancer tissues and associated with tumor progression, acquisition of antiapoptotic potential, and clinical therapeutic resistance. Thus, great interest has been aroused to develop new platforms or approaches of activity assays to impact on the hypoxic microenvironment and oxygen-dependent drug responses to improve the productivity of new drug discovery. In this study, an integrated microsystem is established to combine the cytotoxic and genotoxic tests together for continuous multiple measurements under mimicking hypoxic tumor microenvironment. We fabricated a double-layer chip device by combining a single-cell-arrayed agarose layer with a microfluidics-based oxygen gradient-generating layer using a PDMS membrane. Using tirapazamine (TPZ) and blemycin (BLM) as model anticancer drugs, we demonstrated its application and performance in single cell loading, cell cultivation, and subsequent drug treatment as well as in situ analysis of oxygen-dependent cytotoxicity and genotoxicity of anticancer drugs. The results demonstrated the opposite oxygen-dependent toxicity of TPZ and BLM, which also indicated that the formation of DNA breaks is related with cell apoptosis. Compared with the traditional assays, this device takes advantage of microfluidic phenomena to generate various oxygen concentrations while exhibiting the combinatorial diversities achieved by the single cell microarray, offering a powerful tool to study single cell behaviors and responses under different oxygen conditions with desired high-content and high-throughput capabilities.

Amorphous Flowerlike Goethite FeOOH Hierarchical Supraparticles: Superior Capability for Catalytic Hydrogenation of Nitroaromatics in Water.

Fabrication of anilines from the corresponding nitroaromatics is a hot topic both for academia and for industry; however, conducting this protocol in water over a noble-metal-free catalytic system is still a great challenge. Continuous efforts are being made on exploiting novel catalysts for this transformation. In this work, we developed a scalable method for synthesizing the uniform flowerlike amorphous α-FeOOH hierarchical supraparticles. The well-defined amorphous α-FeOOH was prepared through an environmentally benign method, which is hydrolysis of the self-assembled iron glycolate at room temperature. Compared with other iron-only catalysts, this flowerlike amorphous α-FeOOH hierarchical supraparticle catalyst exhibits the best performance in the catalytic reduction of nitroaromatics to corresponding anilines by using water as the reaction solvent (turn over frequency is 106 h-1 for 4-nitrophenol in water). The further results indicated that the amorphous structure, special nanostructures, and adsorption-desorption synergy offered excellent activity. The kinetics study shows that the reduction of 4-nitrophenol is first order for α-FeOOH, and the apparent active energy Ea is 75.9 kJ mol-1. Furthermore, this catalyst can be used for eight times without obvious catalytic activity loss. We believe that this novel flowerlike amorphous α-FeOOH hierarchical supraparticle catalyst is a milestone in the reduction of nitro compounds.

Design and fabrication of a liver-on-a-chip platform for convenient, highly efficient, and safe in situ perfusion culture of 3D hepatic spheroids.

Spheroid-based three-dimensional (3D) liver culture models, offering a desirable biomimetic microenvironment, are useful for recapitulating liver functions in vitro. However, a user-friendly, robust and specially optimized method has not been well developed for a convenient, highly efficient, and safe in situ perfusion culture of spheroid-based 3D liver models. Here, we have developed a biomimetic and reversibly assembled liver-on-a-chip (3D-LOC) platform and presented a proof of concept for long-term perfusion culture of 3D human HepG2/C3A spheroids for building a 3D liver spheroid model. On the basis of a fast and reversible seal of concave microwell-based PDMS-membrane-PDMS sandwich multilayer chips, it enables a high-throughput and parallel perfusion culture of 1080 cell spheroids in a high mass transfer and low fluid shear stress biomimetic microenvironment as well as allowing the convenient collection and analysis of the cell spheroids. In terms of reducing spheroid loss and maintaining cell morphology and viability in long-term perfusion culture, the cell spheroids in the 3D-LOC were more safe and efficient. Notably, the polarisation, liver-specific functions, and metabolic activity of the cell spheroids in 3D-LOC were also remarkably improved and exhibited better long-term maintenance over conventional perfusion methods. Additionally, a robust micromilling method that incorporates secondary PDMS coating techniques (SPCs) for fabricating V-shaped concave microwells was also developed. The V-shaped concave microwell arrays exhibited a higher distribution density and aperture ratio, making it easy to form large-scale and uniform-sized cell spheroids with minimum cell loss. In summary, the proposed 3D-LOC could provide a convenient and robust solution for the long-term safe perfusion culture of hepatic spheroids and be beneficial for a variety of potential applications including development of bio-artificial livers, disease modeling, and drug toxicity screening.

Necklace-Like Microfibers with Variable Knots and Perfusable Channels Fabricated by an Oil-Free Microfluidic Spinning Process.

Fiber materials with different structural features, which in many cases endow the fibers extraordinary functions, are drawing considerable attention from biomedical and material researchers. Here, perfusable necklace-like knotted microfibers are presented for the first time. Additionally, a novel microfluidic spinning method facilitates the production of variable knots and channels. Not only spindle-, but also hemisphere- and petal-knotted microfibers can be controllably fabricated. Generation and perfusion of both Janus channels and helical channel in the knotted microfibers are also shown. With no need of oil and surfactant, the spinning process is highly cytocompatible. The potential bioengineering and biomedical application of the knotted hollow microfiber is demonstrated by its cell-encapsulation feasibility and the unique liver acinus-like diffusion gradient in the knot. The merits of perfusability, cytocompatibility, and structural diversity of the microfibers may open more avenues for further material and biomedical investigation.

From quality markers to data mining and intelligence assessment: A smart quality-evaluation strategy for traditional Chinese medicine based on quality markers.

BACKGROUND: The quality of traditional Chinese medicine (TCM) forms the foundation of its clinical efficacy. The standardization of TCM is the most important task of TCM modernization. In recent years, there has been great progress in the quality control of TCM. However, there are still many issues related to the current quality standards, and it is difficult to objectively evaluate and effectively control the quality of TCM. PURPOSE: To face these challenge, we summarized the current quality marker (Q-marker) research based on its characteristics and benefits, and proposed a reasonable and intelligentized quality evaluation strategy for the development and application of Q-markers. METHODS: Ultra-performance liquid chromatography-quadrupole/time-of-flight with partial least squares-discriminant analysis was suggested to screen the chemical markers from Chinese medicinal materials (CMM), and a bioactive-guided evaluation method was used to select the Q-markers. Near-infrared spectroscopy (NIRS), based on the distinctive wavenumber zones or points from the Q-markers, was developed for its determination. Then, artificial intelligence algorithms were used to clarify the complex relationship between the Q-markers and their integral functions. Internet and mobile communication technology helped us to perform remote analysis and determine the information feedback of test samples. CHAPTERS: The quality control research, evaluation, standard establishment and quality control of TCM must be based on the systematic analysis of Q-markers to study and describe the material basis of TCM efficacy, define the chemical markers in the plant body, and understand the process of herb drug acquisition, change and transmission laws affecting metabolism and exposure. Based on the advantages of chemometrics, new sensor technologies, including infrared spectroscopy, hyperspectral imaging, chemical imaging, electronic nose and electronic tongue, have become increasingly important in the quality evaluation of CMM. Inspired by the concept of Q-marker, the quantitation can be achieved with the help of artificial intelligence, and these subtle differences can be discovered, allowing the quantitative analysis by NIRS and providing a quick and easy detection method for CMM quality evaluations. CONCLUSION: The concept of Q-markers focused on unique CMM differences, dynamic changes and their transmission and traceability to establish an overall quality control and traceability system. Based on the basic attributes, an integration model and artificial intelligence research path was proposed, with the hope of providing new ideas and perspectives for the TCM quality management.

[Effect of processed Polygonum multiflorum on mRNA expression level of five subtypes of CYP450 enzymes in rat liver].

To observe the effect of processed Polygonum multiflorum on mRNA expression levels of five subtypes of CYP450 enzymes in rat liver. SD rats were randomly divided into the normal control group, processed P. multiflorum high dose and low dose groups (5.40 g•kg⁻¹ and 1.08 g•kg⁻¹). The rats in administration groups were continuously given with processed P. mutiflorum for 7 days by ig administration, and the rats in normal control group were given with the same volume of distilled water. After successive administration of 7 days, the serum biochemical indications were detected, and Real-time quantitative PCR technology was used to detect the mRNA expression levels of five subtypes of CYP450 enzymes in rat liver. Experimental results showed that AST was decreased significantly in both low and high dose groups. ALT was significantly decreased in low dose group and significantly increased in high dose group. The mRNA expression levels of five subtypes of CYP450 enzymes in rat liver were decreased in high dose and low dose groups in a dose-dependent manner. Especially the high dose processed P. multiflorum could significantly inhibit CYP1A2 and CYP2E1 mRNA expression levels in rats. The study showed that high dose P. multiflorum water extract had hepatotoxicity, and the degree of liver damage was increased with the increase of dose. It shall be noted that 5.40 g•kg⁻¹ water extract of P. multiflorum could significantly inhibit CYP1A2 and CYP2E1 mRNA expression levels in the liver of rats.

Disease-syndrome combination modeling: metabolomic strategy for the pathogenesis of chronic kidney disease.

Conventional disease animal models have limitations on the conformity to the actual clinical situation. Disease-syndrome combination (DS) modeling may provide a more efficient strategy for biomedicine research. Disease model and DS model of renal fibrosis in chronic kidney disease were established by ligating the left ureter and by ligating unilateral ureteral combined with exhaustive swimming, respectively. Serum metabolomics was conducted to evaluate disease model and DS model by using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Potential endogenous biomarkers were identified by multivariate statistical analysis. There are no differences between two models regarding their clinical biochemistry and kidney histopathology, while metabolomics highlights their difference. It is found that abnormal sphingolipid metabolism is a common characteristic of both models, while arachidonic acid metabolism, linolenic acid metabolism and glycerophospholipid metabolism are highlighted in DS model. Metabolomics is a promising approach to evaluate experiment animal models. DS model are comparatively in more coincidence with clinical settings, and is superior to single disease model for the biomedicine research.

Bioinspired Microfibers with Embedded Perfusable Helical Channels.

Materials with microchannels have attracted increasing attention due to their promising perfusability and biomimetic geometry. However, the fabrication of microfibers with more geometrically complex channels in the micro- or nanoscale remains a big challenge. Here, a novel method for generating scalable microfibers with consecutive embedded helical channels is presented using an easily made coaxial microfluidic device. The characteristics of the helical channel can be accurately controlled by simply adjusting the flow rate ratio of the fluids. The mechanism of the helix formation process is theorized with newly proposed heterogenerated rope-coil effect, which enhances the tunability of helical patterns and promotes the comprehension of this abnormal phenomenon. Based on this effect, microfibers with embedded Janus channels and even double helical channels are generated in situ by changing the design of the device. The uniqueness and potential applications of these tubular microfibers are also demonstrated by biomimetic supercoiling structures as well as the perfusable and permeable spiral vessel.

A new method to evaluate the dose-effect relationship of a TCM formula Gegen Qinlian Decoction: "Focus" mode of integrated biomarkers.

It is difficult to accurately evaluate the efficacy of traditional Chinese medicine (TCM), which leads to the uncertainty and complexity of dose-effect analysis. In this study we established the "Focus" mode of biomarkers to characterize the dose-effect relationship of Gegen Qinlian Decoction (GQD), a TCM formula for treating type 2 diabetes mellitus (2-DM). A rat model of 2-DM was established through high fat diet feeding combined with low-dose STZ injection. Rats with 2-DM were administered high, middle or low doses (6.785, 4.071, 1.357 mg·kg-1·d-1, respectively) of GQD extract for 60 d. Metformin (300 mg·kg-1·d-1) was taken as the positive control. Blood samples were collected to assess serum biochemical indexes and metabolic profiling. After "Focus" analysis, the biochemical index triglycerides (TG) and insulin sensitivity (ISI) were identified as focused integrated biomarkers (FIBs), while arachidonic acid and docosatetraenoic acid were the metabolic FIBs. Dose-effect relationship curves of GQD were built based on these types of FIBs. Furthermore, the two dose-effect relationship curves showed similar trends with the middle dosage displaying the greatest efficacy, suggesting that insulin function and arachidonic acid metabolism played important roles in 2-DM and the responses to GQD. The metabolic FIB docosatetraenoic should be further explored for understanding its involvement in the process of 2-DM occurrence and the treatment. This "Focus" mode provides a novel strategy to evaluate the dose-effect relationship of a TCM. The system and concepts established here may also be applicable for assessing the dose-effect relationships of Western medicines.

Double-Network Hydrogel with Tunable Mechanical Performance and Biocompatibility for the Fabrication of Stem Cells-Encapsulated Fibers and 3D Assemble.

Fabrication of cell-encapsulated fibers could greatly contribute to tissue engineering and regenerative medicine. However, existing methods suffered from not only unavoidability of cell damaging conditions and/or sophisticated equipment, but also unavailability of proper materials to satisfy both mechanical and biological expectations. In this work, a simple method is proposed to prepare cell-encapsulated fibers with tunable mechanical strength and stretching behavior as well as diameter and microstructure. The hydrogel fibers are made from optimal combination of alginate and poly(N-iso-propylacrylamide)-poly(ethylene glycol), characteristics of double-network hydrogel, with enough stiffness and flexibility to create a variety of three dimensional structures like parallel helical and different knots without crack. Furthermore, such hydrogel fibers exhibit better compatibility as indicated by the viability, proliferation and expression of pluripotency markers of embryonic stem cells encapsulated after 4-day culture. The double-network hydrogel possesses specific quick responses to either of alginate lyase, EDTA or lower environmental temperature which facilitate the optional degradation of fibers or fibrous assemblies to release the cells encapsulated for subsequent assay or treatment.