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To study the effect of weaning age on the gut microbiota diversity in the lambs of Chongming white goats, fresh feces from the lambs weaned at 30, 45, and 60 days of age were collected 3 days after weaning at 33, 48, and 63 days of age, for microbial composition analysis by 16S rRNA sequencing. The serum concentrations of lipid metabolites were also investigated at the fecal collection dates. Serum and feces from the ewe-reared groups at 33, 48, and 63 days of age were used as controls. The alpha diversity increased significantly after weaning and with the aging of the lambs. Levels of Ruminococcaceae, Lachnospiraceae, and Ruminococcus varied significantly according to the weaning treatment in lambs (P < 0.05). Butyrate-producing gut bacteria such as Ruminococcaceae_UCG-010, Ruminococcaceae_UCG-013, Ruminococcaceae_UCG-014, Ruminococcaceae_UCG-005, Ruminococcaceae_UCG-002, Lachnospiraceae_AC2044_group, and Lachnospiraceae_NK4B4 were identified as significantly increased genera (P < 0.05) in the feces of weaned Chongming white lambs. Additionally, the abundance of fiber degradation-associated bacteria including Ruminococcaceae_UCG-005, Ruminococcus_1, and Ruminococcus_2 significantly increased with lamb weaning age (P < 0.05). Correlation analysis showed that Lachnospiraceae_AC2044_group, norank_f__Bacteroidales_S24-7_group, and Ruminococcaceae_UCG_005 were negatively correlated, and Lachnoclostridium was positively correlated with levels of cholesterol, while Blautia showed positive correlation with low-density lipoprotein cholesterol in serum samples from weaned lambs. This study helped to understand the maturing development of gut microbiota in Chongming white goats under weaning stress. KEY POINTS: • Effects of weaning age on the gut microbiota diversity in Chongming white goat lambs were studied. • Some butyrate-producing gut bacteria were significantly increased after weaned. • Correlations of gut microbiota and lipid metabolites were analyzed.

We present a numerical method specifically designed for simulating three-dimensional fluid--structure interaction (FSI) problems based on the reference map technique (RMT). The RMT is a fully Eulerian FSI numerical method that allows fluids and large-deformation elastic solids to be represented on a single fixed computational grid. This eliminates the need for meshing complex geometries typical in other FSI approaches, and greatly simplifies the coupling between fluid and solids. We develop the first three-dimensional implementation of the RMT, parallelized using the distributed memory paradigm, to simulate incompressible FSI with neo-Hookean solids. As part of our new method, we develop a new field extrapolation scheme that works efficiently in parallel. Through representative examples, we demonstrate the method's accuracy and convergence, as well as its suitability in investigating many-body and active systems. The examples include settling of a mixture of heavy and buoyant soft ellipsoids, lid-driven cavity flow containing a soft sphere, and swimmers actuated via active stress., Comment: 12 pages, 5 figures (+ Supplemental Information: 26 pages, 10 figures, 3 tables, 6 movies, 1 dataset)

Multidrug resistance (MDR) is still a major reason for therapeutic failure in cancers. The mechanisms underlying MDR are multifactorial and are not fully understood. miRNAs are evolutionarily conserved non-coding RNAs that function as key post-transcriptional regulators of gene expression. Emerging evidence indicates a vital role of miRNAs in the resistance to cancer treatments and suggests their potential for cancer therapy, as they can modulate multiple mechanisms link to the development of MDR. This review summarizes the recent findings on the role of miRNAs in MDR, and highlights the molecular targets and mechanisms of miRNA regulated pathways in MDR. Finally, the challenges and prospects of miRNA-targeted therapies for reversing drug resistance are reviewed.

Background: The leaves of Folium Syringae (FS) have been long used as a traditional Chinese folk medicine for their anti-inflammatory effect, utilized as an antibacterial and antiviral treatment. The purpose of this study was to investigate the potential hepatoprotective effects of FS on acetaminophen-induced hepatic injury in primary hepatocytes and mice. Methods: Hepatocytes obtained by the inverse perfusion method were divided randomly into five groups. Prior to acetaminophen exposure, 3 different doses of FS ethanol extracts were given to hepatocytes and mice, respectively. Thereafter, transaminases, glutathione S-transferase A1 (GSTA1) and some hepatic indices were determined. Results: FS ethanol extracts (200 μg/mL) pretreatment prevented all of the alterations, returning their levels to nearly those levels observed in the control group in vitro. Treatment with FS ethanol extracts (200 mg/kg) significantly reduced the toxicity induced by acetaminophen in vivo, which manifested as a decrease in transaminases, and the hepatoprotective effects of FS were similar to Silymarin (positive group). GSTA1 represented the same change trend as transaminases and hepatic indices, and at a dose of 100 μg/mL FS ethanol extracts in vitro and 100 mg/kg in vivo, GSTA1 content changed significantly (p 0.05). Conclusion: The results of our investigation suggested that FS ethanol extracts possess significant protective effects against hepatotoxicity induced by acetaminophen both in vitro and in vivo. In addition, GSTA1 could be used as an indicator assessing the extents of hepatic injury, which is more sensitive than transaminases.

Background: Solanum nigrum is a herbaceous perennial plant, which is widely used in traditional medicine systems for its antioxidant, antiulcerogenic, antitumorigenic, and anti-inflammatory characteristics. The purpose of this study was to investigate the protective effects of S. nigrum against alcoholic liver damage in primary hepatocytes and mice, using glutathione S-transferase alpha 1 (GSTA1) as an indicator. Methods: Primary hepatocytes were obtained by the inverse perfusion method improved on Seglen two-step perfusion in situ. Results: In the presence of S. nigrum aqueous extracts (100 μg/mL), no hepatocytic damage was observed in cells treated with ethanol, compared with the model group, and GSTA1 (p

Acta crystallographica / D 74(8), 727 - 738 (2018). doi:10.1107/S2059798318005004, Biological small-angle X-ray solution scattering (BioSAXS) is now widely used to gain information on biomolecules in the solution state. Often, however, it is not obvious in advance whether a particular sample will scatter strongly enough to give useful data to draw conclusions under practically achievable solution conditions. Conformational changes that appear to be large may not always produce scattering curves that are distinguishable from each other at realistic concentrations and exposure times. Emerging technologies such as time-resolved SAXS (TR-SAXS) pose additional challenges owing to small beams and short sample path lengths. Beamline optics vary in brilliance and degree of background scatter, and major upgrades and improvements to sources promise to expand the reach of these methods. Computations are developed to estimate BioSAXS sample intensity at a more detailed level than previous approaches, taking into account flux, energy, sample thickness, window material, instrumental background, detector efficiency, solution conditions and other parameters. The results are validated with calibrated experiments using standard proteins on four different beamlines with various fluxes, energies and configurations. The ability of BioSAXS to statistically distinguish a variety of conformational movements under continuous-flow time-resolved conditions is then computed on a set of matched structure pairs drawn from the Database of Macromolecular Motions (http://molmovdb.org). The feasibility of experiments is ranked according to sample consumption, a quantity that varies by over two orders of magnitude for the set of structures. In addition to photon flux, the calculations suggest that window scattering and choice of wavelength are also important factors given the short sample path lengths common in such setups., Published by Wiley-Blackwell, Oxford

Acetaminophen (APAP) overdose causes serious hepatocyte injury, and new markers are needed to predict APAP-induced hepatic injury. Glutathione S-transferase A1 (GSTA1) plays a significant role in the metabolism of APAP. Primary mouse hepatocytes were isolated by a two-step perfusion in situ. An APAP-induced hepatocyte injury model was used to characterize GSTA1 in APAP treated cells and determine whether GSTA1 could be a prognostic marker in vitro. A significant increase (p .05) in GSTA1 in cell culture supernatant was detected at 6 h after APAP treatment, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) showed marked differences (p .05) at 8 h after APAP exposure, 2 h later than GSTA1. Furthermore, GSTA1 increased in a dose-dependent manner with APAP treatment. GSTA1 increased significantly (p .05) at a concentration of 5.0 mmol/L APAP, while the marked changes in ALT, AST and other indexes were undetectable until the concentration of APAP reached 7.5 mmol/L. These results suggest that increased GSTA1 can be more sensitive than ALT and other indexes as a marker of APAP-induced hepatic injury, which provide novel diagnostic index for APAP-induced hepatic injury and supply valuable information to further understand the pathogenesis of liver damage.

According to the calculated results on the charge distribution of oxygenated heme and deoxygenated heme, and based on the theory of electron excitations in photo-acceptor molecules and the absorption spectra of hemoglobin, it is found that low-level laser within the waveband of about 800–1060 nm can promote the release of oxygen from oxyhemoglobin and improve the oxygen supply of capillaries to surrounding tissues. Furthermore, the reasons have been explained that why the low-level laser at a wavelength of 830 nm is better in the treatment on burn injury and stimulation of hair growth. We also explained why the near-infrared laser of 1064 nm is applied to the forehead to improve cerebral oxygenation in healthy humans. Finally, according to comparison of atomic charge distribution in heme before and after bound to small molecule of carbon monoxide or nitric oxide, it could be inferred that the low-level laser with an appropriate wavelength can promote the carbon monoxide hemoglobin and nitric oxide hemoglobin to dissociate the carbon monoxide molecules and the nitric oxide molecules. This may be used for adjuvant therapy of carbon monoxide poisoning or nitric oxide poisoning.

Three acute hepatic injury models (a CCl4-induced model, APAP-induced model and ethanol-induced model) in mice were used to study the importance of GSTA1 in acute hepatic injury by comparison with a standard enzyme marker, alanine aminotransferase (ALT). GSTA1 release was demonstrated to be an earlier and more sensitive indicator of hepatotoxicity than was ALT. Significant increases in GSTA1 were detected at 2 h after CCl4 exposure, while ALT was undetected at this time. GSTA1 was also a more sensitive indicator of hepatotoxicity than ALT after 6 h. In the APAP and ethanol models, GSTA1 was markedly increased earlier than ALT, at 2 h post exposure. The release of GSTA1 was significantly increased at a dose of 12.5 mg/kg (CCl4 model), 100 mg/kg (APAP model) and 10 ml/kg (ethanol model), the lowest exposure concentration for each model. In contrast, AST release was not statistically significant. These results suggest that GSTA1 can be detected at low concentrations during the early stages of acute hepatic injury and that GSTA1 is a more sensitive and more accurate indicator than ALT.

The structure, electrostatic properties, and Raman spectra of aflatoxin B1 (AFB1) and AFB1-Ag complex are studied by density functional theory with B3LYP/6-311G(d,p)/Lanl2dz basis set. The results show that the surface-enhanced Raman scattering (SERS) and pre-resonance Raman spectra of AFB1-Ag complex strongly depend on the adsorption site and the excitation wavelength of the incident light. The SERS factors are found to enhance 102−103 order compared to normal Raman spectrum of AFB1 molecule due to the larger static polarizabilities of the AFB1-Ag complex, which directly results in the stronger chemical enhancement in SERS spectra. The pre-resonance Raman spectra of AFB1-Ag complex are explored at 266, 482, 785, and 1064 nm incident light wavelength, in which the enhancement factors are about 102−104, mainly caused by the charge-transfer excitation resonance. The vibrational modes are analyzed to explain the relationship between the vibrational direction and the enhanced Raman intensities.

The adsorbed structures, Surface-enhanced Raman scattering (SERS) and pre-resonance Raman spectra of the U Ag and U〈 〉U Ag complexes are calculated using density-functional theory (DFT) method with B3LYP/6-311g (d, p) (C, H, O)/Lanl2dz (Ag) basis set. The uracil and uracil dimer prefer to a perpendicular orientation adsorbed on the Ag surface via atom O 8 site. The SERS of the U Ag and U〈 〉U Ag complexes are similar with the normal Raman spectra of the isolated uracil and uracil dimer but with an enhancement factor less than 10. The enhancement mechanism is ascribed to the ground state static chemical enhancement from the static polarizability changes. The pre-resonance Raman spectra of the complexes are obtained at 316 nm and 315 nm, in which the enhancement factors are up to 10 3 –10 4 . The greatest enhancement factor is observed for the C 2 O 8 stretching vibration, caused by the electron transfer from the molecules to Ag atom. The charge transfer resonant enhancement plays the major role in the molecule–metal system.

The single proton transfer at the different sites of the Watson-Crick (WC) guanine-cytosine (GC) DNA base pair are studied here using density functional methods. The conventional protonated structures, transition state (TS) and proton-transferred product (PT) structures of every relevant species are optimized. Each transition state and proton-transferred product structure has been compared with the corresponding conventional protonated structure to demonstrate the process of proton transfer and the change of geometrical structures. The relative energies of the protonated tautomers and the proton-transfer energy profiles in gas and solvent are analyzed. The proton-transferred product structure G(+H(+))-H(+)C(N3)(-H(+))(PT) has the lowest relative energy for which only two hydrogen bonds exist. Almost all 14 isomers of the protonated GC base pair involve hydrogen-bonded proton transfer following the three pathways, with the exception of structure G-H(+)C(O2). When the positive charge is primarily "located" on the guanine moiety (H(+)G-C, G-H(+)C(C4), and G-H(+)C(C6)), the H(1) proton transfers from the N(1) site of guanine to the N(3) site of cytosine. The structures G-H(+)C(C5) and G-H(+)C(C4) involve H(4a) proton transfer from the N(4) of cytosine to the O(6) site of guanine. H(2a) proton transfer from the N(2) site of guanine to the O(2) site of cytosine is found only for the structure G-H(+)C(C4). The structures to which a proton is added on the six-centered sites adjoining the hydrogen bonds are more prone to proton transfer in the gas phase, whereas a proton added on the minor groove and the sites adjoining the hydrogen bonds is favorable to the proton transfer in energy in the aqueous phase.

A normal melting process is endothermic and causes volume expansion. Exothermic melting or volume contraction is therefore abnormal, and has important effects in condensed-matter physics. In the present study, we investigated the mechanism of abnormal exothermic melting of amorphous sulfur. Analysis of Raman spectra obtained before and after exothermic melting showed that before melting the amorphous sulfur contains clusters in the form of polymeric chains. After melting, sulfur clusters in the form of S8 predominate, i.e., the polymeric chains are converted to S8 rings during melting, which affects the overall internal energy of the system. Density functional method calculations confirmed that the net effect in the chain-ring transition is exothermic. This abnormal exothermic melting in amorphous sulfur can be described as chain-ring transitions coupled with melting. The difference between the chain-ring transition reported in this work and that reported in crystallization relaxation of amorphous sulfur is also discussed.

In the present study, three models of acute liver injury in mice were induced via the administration of CCl4 (35 mg/kg, 24 h), acetyl-para-aminophenol (APAP; 200 mg/kg, 12 h) and ethanol (14 ml/kg, 8 h) to study the effect of glutathione S-transferase A1 (GSTA1) on acute liver injury. The serum levels of alanine transaminase, aspartate transaminase and liver homogenate indicators (superoxide dismutase, glutathione and glutathione peroxidase) were significantly lower in model groups compared with the control group (P

Our previous study demonstrated that 14-3-3γ overexpression was able to inhibit the production of lipopolysaccharide (LPS)-induced cytokines in dairy cow mammary epithelial cells (DCMECs) by inhibiting the activation of nuclear factor-κB (NF-κB) signaling pathways. However, the association between 14-3-3γ overexpression and milk fat synthesis in LPS-induced DCMECs remains unclear. Therefore, the present study investigated the effect of 14-3-3γ on cell viability and milk fat synthesis in LPS-induced DCMECs. The results of the MTT assay and lactate dehydrogenase activity assay demonstrated that 14-3-3γ overexpression was able to attenuate LPS-induced cytotoxicity in DCMECs, and increase the viability of the cells. In addition, the results of reverse transcription-quantitative polymerase chain reaction suggested that mRNA expression levels of genes associated with milk fat synthesis, including sterol regulatory element binding protein (SREBP1), peroxisome proliferator-activated receptor-γ (PPARG), cluster of differentiation 36, acetyl-coA carboxylase (ACC), fatty acid synthase (FAS) and fatty acid binding protein-3, were significantly upregulated in cells overexpressing the 14-3-3γ protein. In addition, as compared with the LPS-treated group, the activities of FAS and ACC were significantly increased. Furthermore, western blotting demonstrated that 14-3-3γ overexpression enhanced the protein expression levels of phosphorylated SREBP1 and PPARG. These results suggested that high levels of 14-3-3γ protein were able to attenuate LPS-induced cell damage and promote milk fat synthesis in LPS-induced DCMECs by increasing the cell viability and upregulating the expression levels of transcription factors associated with milk fat synthesis.

According to the absorption spectra of blood and hemoglobin, a photon-bond energy formula is established using physical methods and the effects on hemoglobin of low-level laser at different wavelengths are analyzed. The results show that lasers with the peak wavelengths of 200∼240, 275, and 342 nm in the whole blood absorption spectra curve are easy to destroy protein molecules and then lead to hemoglobin lose biological activity. While lasers with wavelengths longer than 800 nm will reduce the oxygen carrying capacity of blood, only lasers with wavelengths between 630 and 670 nm have the best efficacy.

Motivated by the recent exact solution of the {\it stationary-state} Kardar-Parisi-Zhang (KPZ) statistics by Imamura & Sasamoto (Phys. Rev. Lett. {\bf 108}, 190603 (2012)), as well as a precursor experimental signature unearthed by Takeuchi (Phys. Rev. Lett. {\bf 110}, 210604 (2013)), we establish here the universality of these phenomena, examining scaling behaviors of directed polymers in a random medium, the stochastic heat equation with multiplicative noise, and kinetically roughened KPZ growth models. We emphasize the value of cross KPZ-Class universalities, revealing crossover effects of experimental relevance. Finally, we illustrate the great utility of KPZ scaling theory by an optimized numerical analysis of the Ulam problem of random permutations., 5 pages, 3 figures, 1 table

A dose–response experiment was conducted to find the sensitive and consistent biomarker for the estimation of dietary manganese (Mn) requirement and establish the optimal Mn level for broilers fed a practical corn–soybean meal diet from 1 to 21 days of age post-hatching. A total of 480 1-day-old Arbor Acres male chicks were randomly allotted to one of eight treatments with five replicates of 12 birds each and fed diets supplemented with 0, 20, 40, 60, 80, 100, 120, or 140 mg Mn/kg from reagent grade Mn sulfate. Tissue Mn concentrations, manganese-containing superoxide dismutase (MnSOD) activity, and MnSOD mRNA concentration within heart tissue were analyzed at 7, 14, and 21 days of age. Tissue Mn concentrations and heart MnSOD activity showed significant quadratic responses, and heart MnSOD mRNA concentration showed an asymptotic response to dietary supplemental Mn level, respectively. The estimate of dietary Mn for chicks from 1 to 21 days of age was 122–128 for heart Mn concentration, 141–159 for pancreas Mn concentration, 127–138 for liver Mn concentration, and 135–156 mg/kg for heart MnSOD activity, respectively. Heart MnSOD mRNA concentration was a consistent index for the estimation of the Mn requirement of broilers. Based on this index, the estimate of dietary Mn requirement for broilers from 1 to 21 days of age post-hatching was about 130 mg/kg, which was a little more than two times of the current NRC (1994) requirement.

The neutral DNA trimers with the hydrogen atom added to the C8 site of the middle guanine-cytosine (GC) base pair, the DNA trimers protonated at the N7 site of the middle GC base pair, and the anionic species resulting from hydride addition to the C6 site of the middle GC base pair are investigated using theoretical methods. The canonical Watson-Crick structures (WC), transition state structures (TS) and proton-transferred structures (PT) of each relevant system are optimized in the gas phase and in aqueous solution, in order to understand the processes of proton transfer. The proton transfer reactions of the DNA trimers are compared with the corresponding isolated hydrogenated GC base pairs to explore the influence of the surrounding molecules and the base sequence. The proton transfer reactions of the neutral species, cations, and anions are compared, aiming to clarify the effects of the system's total charge. The results reveal that the surrounding molecules decrease the reaction energies of proton-transfer in aqueous solution. The structures with the dATGCAT and dGCGCGC sequences facilitate proton H4a transfer, but hinder proton H1 transfer. The structures with the dCGGCCG and dTAGCTA sequences facilitate proton H1 transfer. The net charge on the system plays an important role in determining the single and double proton-transfer patterns. Anions are more likely to experience proton-transfer reactions than neutral species and cations, and all the proton-transfer reactions of the anions are exothermic.