Structural Design of Intelligent Reversible Two-Way Structural Color Films.

Structural color always shows a reversible switch between reflection and transmission states when viewed from different angles, attracting increasing attention in display applications. However, this switching between reflection and transmission states of structural color suffers from the inherent lack of autonomous regulation, which is unmanageable in the case of different application scenarios. Here, we design an intelligent two-way structural color film which can reversibly change its color when applied with an extra stimulation such as voltage, heat signal, or light. A special structural feature contains a traditional photonic crystal film of polystyrene (PS) microspheres assembled by smart windows. Remarkably, our structural color film shows a prominent polarization sensitivity, and the angle dependence of the structural color broadens the gamut of display color demonstrated by both finite element theoretical analysis and experimental observation. Prospectively, this hierarchically designed film provides a promising pathway toward next-generation multicolor displays and smart windows.

The Quantitative Profiling of Oxylipins from Arachidonic Acid by LC-MS/MS in Feces at Birth 3 Days and 21 Days of Piglets.

Oxylipins (also called eicosanoids) are enzymatically or nonenzymatically generated by oxidation of arachidonic acid (ARA) and are major mediators of ARA effects in the body. Previous studies demonstrated the importance of ARA in infant growth, brain development, immune response, and health. With the developments in lipidomic methodologies, it is important for exploring more ARA-deprived oxylipins to better understand the physiological functions of ARA. The concentrations of oxylipins in feces were determined from days 3 to 21 postnatally of suckling piglets in vivo. Feces were collected at two critical time points of the suckling piglets (3d and 21d after birth) and about 48 oxylipins were analyzed by using a target metabolomics approach based on Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Here, 21 oxylipins were derived from ARA, and 11 differential oxylipins (Log2|fold change| ≥ 1.0) at birth 3d and 21d were identified. Particularly, 12-HETE was more abundant in feces at birth 3 days rather than 21 days. Considering that 12-HETE was a racemic mixture of stereoisomers containing the S and R enantiomers, we further detected the concentrations of 12(S)-HETE and 12(R)-HETE between the two time points by chiral LC-MS/MS analysis. There was no significant difference in the concentrations of 12(S)-HETE and 12(R)-HETE. It was showed that ARA - derived oxylipins might be related to the physiological changes of piglets during growing. Our results provided new information for describing the physiological changes of the piglets over the suckling period.

Development of Enzyme-Free DNA Amplifier Based on Chain Reaction Principle.

Enzyme-free DNA amplifiers can amplify the signal of nucleic acid molecules. They can be applied to DNA molecular operation and nucleic acid detection. The reaction speed is the core index to evaluate DNA amplifiers. In this study, we designed a DNA amplifier based on an enzyme-free chain reaction. This DNA amplifier can release one more signal molecule in each round of reaction and trigger the next round, which significantly improved reaction speed. Moreover, because the amplifier used a stable DNA structure, the reaction can occur at room temperature. To integrate the amplifier into other DNA molecular operations, we performed the amplification reaction in a microfluidic chip module. The results showed that the amplifier can realize real-time signal feedback at a proper input molecule concentration and reach the endpoint in 40 s, even at a low relative concentration. To apply the amplifier for nucleic acid detection, we also used a conventional fluorescent polymerase chain reaction instrument for the reaction. The results showed that the amplifier specifically detected trace DNA single-stranded molecules. To solve the leakage problem of existing amplifiers, we designed a DNA molecule as the chain reaction's inhibitor, which was crucial in controlling the reaction speed and preventing leakage. STATEMENT OF SIGNIFICANCE: Traditional amplifier strategies of enzyme-free DNA amplifiers relied on a constant number of cycling molecules to catalyze the amplifier molecules' changing structure and release fluorescent signals, which lead low reaction speed. Based on an enzyme-free chain reaction, we designed a DNA amplifier which can release one more cycling molecule in each loop and trigger the next loop and significantly improve reaction speed in this study. Our analysis on microfluidic chip module and PCR instrument verifies high sensitivity and selectivity. And this strategy of DNA amplifier realizes the control of reaction and prevents leakage. We believe that this automated amplification strategy could have great applications in vivo signal detection, imaging, and signal molecule translation.

A sliver deposition signal-enhanced optical biomolecular detection device based on reduced graphene oxide.

The development of high-sensitive biomolecular detection system is of great significance for diseases early diagnosis. The novel optical sensor based on the polarization-sensitive absorption of graphene has a great potential in biological detection. However, the detection sensitivity of the device can hardly meet the needs of clinical analysis currently. This study applies sliver deposition signal amplification to the optical biomolecular detection device based on reduced graphene oxide for the sensitive immunoassay. In redox cycling enzymatic silver deposition reaction, the more alkaline phosphatase label bound on chip surface will cause a faster silver deposition rate. The specific antibody detection confirms that the sliver deposition can enhance the detection signal significantly. In cardiac biomarker Creatine Kinase-MB measurement, the minimum detection concentration is 0.1 ng/mL. To be more important, within the range from detection limit to 10 ng/mL, the signal intensity is highly correlated with target protein concentration, so the biomolecular detection device can meet clinical assay requirements. The signal-enhanced optical biomolecular detection device based on reduced graphene oxide shows excellent sensitivity and selectivity, and provides a new strategy for biomolecules detection, which can be applied in diseases accurate prediction and diagnosis.

A Specific Nucleic Acid Microfluidic Capture Device Based on Stable DNA Nanostructure.

Benefiting from superior programmability and good biocompatibility, DNA nanomaterials have received considerable attention with promising prospects in biological detection applications. However, their poor stability and operability severely impede further development of the applications of DNA nanomaterials. Here, a thermally stable DNA nanomesh structure is integrated into a microfluidic chip. The specificity of the nucleic acid microfluidic capture device could reach the single-base mismatch level while capturing the ssDNA sample. The microfluidic chip provides a closed environment for the DNA nanomesh, giving the device excellent storage stability. After 6 months of storage at room temperature, the device still has a specific capture function on ssDNA samples with low concentration. The specific nucleic acid microfluidic capture device can be applied to the enrichment of ctDNA in the future and contribute to the early diagnosis of cancer.

A spatial resolution evaluation method of endoscopic optical coherence tomography system using the annular phantom.

As an important biomedical imaging method, endoscopic optical coherence tomography (OCT) is necessary to check its performance regularly. The ordinary plane phantoms are only able to evaluate part of image tangent to the probe. In this research, a spatial resolution estimate method of the endoscope OCT system is proposed. The annular phantom, made by uniformly distributing golden scattered microparticles in polydimethylsiloxane (PDMS), can provide dynamic scanning imaging evaluation of endoscopic OCT system, closer to its actual working status. The point spread function analysis method is used to analyze the imaging results of the annular phantom with the endoscopic OCT system. And many scattered particles are statistically analyzed to determine the spatial resolution of the endoscope OCT system. The method is low in cost, simple and convenient. It is valuable for the development of test standards for endoscope OCT systems.

Role of arachidonic acid-derived eicosanoids in intestinal innate immunity.

Arachidonic acid (ARA), an n-6 essential fatty acid, plays an important role in human and animal growth and development. The ARA presents in the membrane phospholipids can be released by phospholipase A2. These free arachidonic acid molecules are then used to produce eicosanoids through three different pathways. Previous studies have demonstrated that eicosanoids have a wide range of physiological functions. Although they are generally considered to be pro-inflammatory molecules, recent advances have elucidated they have an effect on innate immunity via regulating the development, and differentiation of innate immune cells and the function of the intestinal epithelial barrier. Here, we review eicosanoids generation in intestine and their role in intestinal innate immunity, focusing on intestinal epithelial barrier, innate immune cell in lamina propria (LP) and their crosstalk.

Effect of Sows Gestational Methionine/Lysine Ratio on Maternal and Placental Hydrogen Sulfide Production.

The placenta is a unique bond between the mother and the fetus during pregnancy, and a proper placental angiogenesis is vital for fetal development. H2S is an endogenous stimulator of angiogenesis that is mainly produced by the methionine transsulfurationpathway. The goal of this study was to evaluate the effect of gestational dietary methionine on maternal and placental H2S production in sows. Multiparous sows (Large×White; third parity; n = 65) were randomly allocated into five groups, with feed diets comprisingstandardized ileal digestible methionine/lysine (Met/Lys) ratios of 0.27 (nutrient requirements of swine (NRC); 2012 level), 0.32, 0.37, 0.42, and 0.47, respectively. The litter size and weight at birth were measured and recorded. Maternal blood samples were obtained at embryonic day (E) E40 d, E90 d, and E114 d of gestation. The placental samples were collected at parturition. The results showed that maternal plasma H2S concentration was not affected at E40 d. However, the maternal plasma H2S concentration changed quadratically with the dietary Met/Lys ratio at E90 d (p < 0.01) and E114 d (p = 0.03). The maximum maternal plasma H2S concentration was at the dietary Met/Lys ratio of 0.37. Meanwhile, maternal plasma H2S concentration was positively correlated with piglets born alive (p < 0.01) and litter weight (p < 0.01). Consistent with the maternal plasma, the placental H2S concentration also changed quadratically with the dietary Met/Lys ratio (p = 0.03); the Met/Lys ratio of 0.37 showed the maximum H2S concentration. In conclusion, our findings revealed that the gestational dietary Met/Lys ratio could affect maternal and placental H2S concentrations, which may be an important molecular mechanism affecting placental angiogenesis and piglet development.

SUMOylation inhibitors synergize with FXR agonists in combating liver fibrosis.

Farnesoid X receptor (FXR) is a promising target for nonalcoholic steatohepatitis (NASH) and fibrosis. Although various FXR agonists have shown anti-fibrotic effects in diverse preclinical animal models, the response rate and efficacies in clinical trials were not optimum. Here we report that prophylactic but not therapeutic administration of obeticholic acid (OCA) prevents hepatic stellate cell (HSC) activation and fibrogenesis. Activated HSCs show limited response to OCA and other FXR agonists due to enhanced FXR SUMOylation. SUMOylation inhibitors rescue FXR signaling and thereby increasing the efficacy of OCA against HSC activation and fibrosis. FXR upregulates Perilipin-1, a direct target gene of FXR, to stabilize lipid droplets and thereby prevent HSC activation. Therapeutic coadministration of OCA and SUMOylation inhibitors drastically impedes liver fibrosis induced by CCl4, bile duct ligation, and more importantly NASH. In conclusion, we propose a promising therapeutic approach by combining SUMOylation inhibitors and FXR agonists for liver fibrosis.

Maternal Eicosapentaenoic Acid Feeding Decreases Placental Lipid Deposition and Improves the Homeostasis of Oxidative Stress Through a Sirtuin-1 (SIRT1) Independent Manner.

SCOPE: Maternal obesity has been associated with increased placental lipotoxicity and impaired mitochondrial function. Sirtuin-1 (SIRT1) is an important regulator of both lipid metabolism and mitochondrial biogenesis. The present study aims to determine whether supplementation of the maternal diet with eicosapentaenoic acid (EPA) can decrease placental lipid deposition and improve antioxidant ability, in a SIRT1-dependent manner. METHODS AND RESULTS: Pregnant SIRT1+/- mice (mated with male SIRT1+/- ) are fed a high-fat diet consisting of 60% of the kcal from fat, or an equienergy EPA diet for 18.5 d. Supplementation with EPA significantly changes maternal plasma, placental and fetal fatty acid composition, and decreases placental and fetal lipid content. In addition, placental antioxidant capacity and lipid peroxidation products are increased, placental uncoupling protein 1 (UCP1) and PPARγ coactivator-1 α (PGC1α) expression are activated, and mitochondrial swelling decreases. While SIRT1 deficiency has little effect on placental fatty acid composition and lipid content, decreased fetal lipid deposition is observed, placental PGC1α expression decreases, mitochondrial swelling increases, and placental total superoxide dismutase (T-SOD) activity increases. Both EPA and SIRT1 have no effect on BODIPY-FL-C16 uptake. Interestingly, there is no significant interaction between diet and genotype. CONCLUSION: Maternal EPA feeding decreases placental lipid deposition and improves placental oxidative stress homeostasis independent of SIRT1.

Combined obeticholic acid and apoptosis inhibitor treatment alleviates liver fibrosis.

Obeticholic acid (OCA), the first FXR-targeting drug, has been claimed effective in the therapy of liver fibrosis. However, recent clinical trials indicated that OCA might not be effective against liver fibrosis, possibly due to the lower dosage to reduce the incidence of the side-effect of pruritus. Here we propose a combinatory therapeutic strategy of OCA and apoptosis inhibitor for combating against liver fibrosis. CCl4-injured mice, d-galactosamine/LPS (GalN/LPS)-treated mice and cycloheximide/TNFα (CHX/TNFα)-treated HepG2 cells were employed to assess the effects of OCA, or together with IDN-6556, an apoptosis inhibitor. OCA treatment significantly inhibited hepatic stellate cell (HSC) activation/proliferation and prevented fibrosis. Elevated bile acid (BA) levels and hepatocyte apoptosis triggered the activation and proliferation of HSCs. OCA treatment reduced BA levels but could not inhibit hepatocellular apoptosis. An enhanced anti-fibrotic effect was observed when OCA was co-administrated with IDN-6556. Our study demonstrated that OCA inhibits HSCs activation/proliferation partially by regulating BA homeostasis and thereby inhibiting activation of HSCs. The findings in this study suggest that combined use of apoptosis inhibitor and OCA at lower dosage represents a novel therapeutic strategy for liver fibrosis.

Measurement of the refractive index of whole blood and its components for a continuous spectral region.

The refractive index of blood is a key biophysical parameter, which can reflect the physiological state. We measured the refractive index of whole blood and other components, such as serum, plasma, and hemoglobin, based on internal reflection by using a homemade apparatus in the spectral range of 400 to 750 nm. In addition to the hemoglobin solution, which has a Soret band about 420 nm and two Q-bands between 500 and 600 nm, the measurements of other samples are the normal dispersion curve. The results are approximated by the Cauchy equation and Sellmeier equation, and the correlation coefficients are more than 0.997.

Noncanonical farnesoid X receptor signaling inhibits apoptosis and impedes liver fibrosis.

BACKGROUND: Hepatocyte is particularly vulnerable to apoptosis, a hallmark of many liver diseases. Although pro-apoptotic mechanisms have been extensively explored, less is known about the hepatocyte-specific anti-apoptotic molecular events and it lacks effective approach to combat hepatocyte apoptosis. We investigated the anti-apoptotic effect and mechanism of farnesoid X receptor (FXR), and strategies of how to target FXR for inhibiting apoptosis implicated in liver fibrosis. METHODS: Sensitivity to apoptosis was compared between wild type and Fxr-/- mice and in cultured cells. Cell-based and cell-free assays were employed to identify the binding protein of FXR and to uncover the mechanism of its anti-apoptotic effect. Overexpression of FXR by adenovirus-FXR was employed to determine its anti-fibrotic effect in CCl4-treated mice. Specimens from fibrotic patients were collected to validate the relevance of FXR on apoptosis/fibrosis. FINDINGS: FXR deficiency sensitizes hepatocytes to death receptors (DRs)-engaged apoptosis. FXR overexpression, but not FXR ligands, inhibits apoptosis both in vitro and in vivo. Apoptotic stimuli lead to drastic reduction of FXR protein levels, a prerequisite for DRs-engaged apoptosis. Mechanistically, FXR interacts with caspase 8 (CASP8) in the cytoplasm, thus preventing the formation of death-inducing signaling complex (DISC) and activation of CASP8. Adenovirus-FXR transfection impedes liver fibrosis in CCl4-treated mice. Specimens from fibrotic patients are characterized with reduced FXR expression and compromised FXR/CASP8 colocalization. INTERPRETATION: FXR represents an intrinsic apoptosis inhibitor in hepatocytes and can be targeted via restoring its expression or strengthening FXR/CASP8 interaction for inhibiting hepatocytes apoptosis in liver fibrosis. FUND: National Natural Science Foundation of China.

Caprylic acid and nonanoic acid upregulate endogenous host defense peptides to enhance intestinal epithelial immunological barrier function via histone deacetylase inhibition.

The intestinal epithelial barrier plays a critical role in the etiopathogenesis of ulcerative colitis. This study aims to explore the potential effects and underlying mechanisms of medium chain fatty acids (caprylic acid and nonanoic acid) on intestinal epithelial barrier function. Using the porcine jejunal epithelial cell line IPEC-J2, a well-established model, challenged with Escherichia coli ATCC 43889 (O157:H7), we found that treatment with caprylic acid (C8) and nonanoic acid (C9) significantly reduced bacterial translocation, enhanced antibacterial activity, and remarkably increased the secretion of porcine ß-defensins 1 (pBD-1) and pBD-2. Mechanistically, like TSA (a histone deacetylase inhibitor), C8 and C9 attenuated the activity of the classical histone deacetylase pathway to facilitate the acetylation of histone 3 lysine 9 (H3K9) at the promoters pBD-1 and pBD-2, and consequently augmented the gene expression of pBD-1 and pBD-2. In conclusion, with their combined antibacterial and defense peptide-induced roles, the use of C8 and C9 may provide a novel method to protect the intestinal barrier of animals and humans from bacterial infection.

Complex Refractive Index Dispersion of Strong Absorbing Material Determined Using Internal Reflectance Spectra Measurement.

Complex refractive index dispersion (CRID) of offset inks is an important spectral property that affects the quality of printing. Due to the strong absorption of offset inks, great difficulty exists when measuring their CRID. In this study, a recently proposed apparatus that can detect the internal reflectance spectra was used to measure the CRID of three strong absorbing offset inks (magenta, yellow, and cyan). Both anomalous dispersion curve and extinction coefficient curve were well determined over the spectral range of 400-750 nm. This study experimentally proves that the apparatus and related method are feasible for the CRID measurement of strong absorbing materials and could serve as a powerful measuring tool for optical parameters.

Blend of organic acids and medium chain fatty acids prevents the inflammatory response and intestinal barrier dysfunction in mice challenged with enterohemorrhagic Escherichia coli O157:H7.

Impaired epithelial barrier function disrupts immune homeostasis and increases inflammation in intestines, leading to many intestinal diseases. The blend of organic acids (OAs) and medium chain fatty acids (MCFAs) has been shown to have synergistic bactericidal effect. In this study, we demonstrated that two blends of OAs and MCFAs (OM1 and OM2) could prevent the inflammatory response and intestinal barrier dysfunction in enterohemorrhagic Escherichia coli (EHEC)-infected mice. Treatments of OM1 and OM2 significantly reduced the body weight loss and production of IL-6 and TNF-α induced by EHEC. Mice treated with OM1 and OM2 showed decrease in serum D-lactic concentration, DAO activity and bacterial transfer to liver and spleen. Furthermore, OM1 and OM2 increased the expression of tight junction proteins occludin and ZO-1, mucus protein MUC-2, and host defense peptides mBD1, mBD2 and mBD3. Finally, OM1 and OM2 increased the population of Lactobacillus spp. and Bifidobacterium spp., but decreased that of E. coli in the cecum. These findings indicate that OM1 and OM2 may be used to develop a prophylactic agent for intestinal inflammation and injury in enteric pathogen infection.