Dietary Supplementation with Rumen-Protected Arginine or N-Carbamylglutamate Enhances Fetal Liver Development in Nutrient-Restricted Pregnant Hu Ewes.

This study was conducted in nutrient-restricted pregnant Hu ewes to determine whether rumen-protected arginine (RP-Arg) or N-carbamylglutamate (NCG) supplementation affects fetal liver growth and development. From 35 d to 110 d of gestation, 32 Hu ewes were randomly divided into four groups: a control group (100% of the National Research Council (NRC) requirements), a nutrient-restricted group (50% of the NRC requirements), and two treatment groups (ARG and NCG, 50% of the NRC requirements, supplemented with 20 g/day RP-Arg or 5 g/day NCG, respectively). Fetal body weights, fetal liver growth performance, the capability of antioxidation, and the expression of the mRNA and proteins of apoptosis-related genes in the fetal liver were determined and analyzed at 110 d of gestation. The dry matter, water, fat, protein, and ash components of the fetal livers in the RG group were found to be lower than in the CG group, and these components were significantly higher in the NCG group than in the RG group (p < 0.05). A decrease in DNA, RNA, and protein concentrations and contents, as well as in protein/DNA ratios, was observed in the RG group in comparison to the CG group (p < 0.05). Compared with the RG group, the NCG group had higher concentrations of DNA, RNA, and protein, as well as higher protein/DNA ratios (p < 0.05). The RG group had lower concentrations of cholinesterase, nitric oxide, nitric oxide synthase, superoxide dismutase, alanine aminotransferase, and total protein than the CG group (p < 0.05). The RG group had higher levels of glutathione peroxidase, maleic dialdehyde, and aspartate aminotransferase than the CG group (p < 0.05). In the RG group, the mRNA and protein expression of p53 and Bax was significantly increased (p < 0.05) compared with the CG group, and the gene expression of FasL and Bcl-2, the ratio of Bcl-2 to Bax, and the protein expression of Bcl-2 in the RG group were lower (p < 0.05) than in the CG group. It appears that RP-Arg and NCG supplementation during pregnancy could influence fetal liver growth and development. A nutrition-based therapeutic intervention to alleviate reduced fetal growth can be developed based on this study, which has demonstrated that maternal undernutrition during pregnancy induces the maldevelopment of the fetal liver.

Comparative analysis the chloroplast genomes of Celastrus (Celastraceae) species: Provide insights into molecular evolution, species identification and phylogenetic relationships.

BACKGROUND: The genus Celastrus is an important medicinal plant resource. The similarity of morphology and the lack of complete chloroplast genome analysis have significantly impeded the exploration of species identification, molecular evolution and phylogeny of Celastrus. PURPOSE: In order to resolve the phylogenic controversy of Celastrus species, the chloroplast genome comparative analysis was performed to provide genetic evidence. METHODS: In this study, we collected and sequenced ten chloroplast genomes of Celastrus species from China and downloaded three chloroplast genomes from the databases. The chloroplast genomes were compared and analyzed to explore their characteristics and evolution. Furthermore, the phylogenetic relationships of Celastrus species were inferred based on the whole chloroplast genomes and protein-coding genes. RESULTS: All the 13 Celastrus species chloroplast genomes showed a typical quadripartite structure with genome sizes ranging from 155,113 to 157,366 bp. The intron loss of the rps16 gene occurred in all the 13 Celastrus species. The GC content, gene sequence, repeat types and codon bias pattern were highly conserved. Ten highly variation regions were identified, which can be used as potential DNA markers in molecular identification of Celastrus species. Eight genes, including accD, atp4, ndhB, rpoC1, rbcL, rpl2, rpl20 and ycf1, were detected to experience positive selection. Phylogenetic analysis showed that Celastrus was a monophyletic group and Tripterygium was the closest sister-group. Noteworthy, C. gemmatus Loes. and C. orbiculatus Thunb. can be discriminated using the chloroplast genome as a super barcode. The comparative and phylogenetic analysis results proposed that C. tonkinensis Pitard. was the synonym of C. hindsii Benth. CONCLUSION: The comparative analysis of the Celastrus chloroplast genomes can provide comprehensive genetic evidence for molecular evolution, species identification and phylogenetic relationships.

Transcriptomic and metabolomic dissection of skeletal muscle of crossbred Chongming white goats with different meat production performance.

BACKGROUND: The transcriptome and metabolome dissection of the skeletal muscle of high- and low- growing individuals from a crossbred population of the indigenous Chongming white goat and the Boer goat were performed to discover the potential functional differentially expressed genes (DEGs) and differential expression metabolites (DEMs). RESULTS: A total of 2812 DEGs were detected in 6 groups at three time stages (3,6,12 Month) in skeletal muscle using the RNA-seq method. A DEGs set containing seven muscle function related genes (TNNT1, TNNC1, TNNI1, MYBPC2, MYL2, MHY7, and CSRP3) was discovered, and their expression tended to increase as goat muscle development progressed. Seven DEGs (TNNT1, FABP3, TPM3, DES, PPP1R27, RCAN1, LMOD2) in the skeletal muscle of goats in the fast-growing and slow-growing groups was verified their expression difference by reverse transcription-quantitative polymerase chain reaction. Further, through the Liquid chromatography-mass spectrometry (LC-MS) approach, a total of 183 DEMs in various groups of the muscle samples and these DEMs such as Queuine and Keto-PGF1α, which demonstrated different abundance between the goat fast-growing group and slow-growing group. Through weighted correlation network analysis (WGCNA), the study correlated the DEGs with the DEMs and identified 4 DEGs modules associated with 18 metabolites. CONCLUSION: This study benefits to dissection candidate genes and regulatory networks related to goat meat production performance, and the joint analysis of transcriptomic and metabolomic data provided insights into the study of goat muscle development.

Symbiotic virus-bacteria interactions in biological treatment of coking wastewater manipulating bacterial physiological activities.

Biological treatment is commonly used in coking wastewater (CWW) treatment. Prokaryotic microbial communities in CWW treatment have been comprehensively studied. However, viruses, as the critical microorganisms affecting microbial processes and thus engineering parameters, still remain poorly understood in CWW treatment context. Employing viromics sequencing, the composition and function of the viral community in CWW treatment were discovered, revealing novel viral communities and key auxiliary metabolic functions. Caudovirales appeared to be the predominant viral order in the oxic-hydrolytic-oxic (OHO) CWW treatment combination, showing relative abundances of 62.47 %, 56.64 % and 92.20 % in bioreactors O1, H and O2, respectively. At the family level, Myoviridae, Podoviridae and Siphoviridae mainly prevailed in bioreactors O1 and H while Phycodnaviridae dominated in O2. A total of 56.23-92.24% of novel viral contigs defied family-level characterization in this distinct CWW habitat. The virus-host prediction results revealed most viruses infecting the specific functional taxa Pseudomonas, Acidovorax and Thauera in the entire OHO combination, demonstrating the viruses affecting bacterial physiology and pollutants removal from CWW. Viral auxiliary metabolic genes (AMGs) were screened, revealing their involvement in the metabolism of contaminants and toxicity tolerance. In the bioreactor O1, AMGs were enriched in detoxification and phosphorus ingestion, where glutathione S-transferase (GSTs) and beta-ketoadipyl CoA thiolase (fadA) participated in biodegradation of polycyclic aromatic hydrocarbons and phenols, respectively. In the bioreactors H and O2, the AMGs focused on cell division and epicyte formation of the hosts, where GDPmannose 4,6-dehydratase (gmd) related to lipopolysaccharides biosynthesis was considered to play an important role in the growth of nitrifiers. The diversities of viruses and AMGs decreased along the CWW treatment process, pointing to a reinforced virus-host adaptive strategy in stressful operation environments. In this study, the symbiotic virus-bacteria interaction patterns were proposed with a theoretical basis for promoting CWW biological treatment efficiency. The findings filled the gaps in the virus-bacteria interactions at the full-scale CWW treatment and provided great value for understanding the mechanism of biological toxicity and sludge activity in industrial wastewater treatment.

Characterization and Comparative Analysis of Whole-Transcriptome Sequencing in High- and Low-Fecundity Chongming White Goat Ovaries during the Estrus Phase.

Reproductive performance is one of the most important economic traits in the goat industry. Increasing the number of goats is an effective measure to improve production efficiency and reduce production costs. Ovaries are important reproductive organs in female mammals that directly affect the estrous cycle and reproductive abilities. Understanding the complex transcription network of non-coding RNAs (lncRNAs, circRNAs, and miRNAs) and messenger RNA (mRNA) could lead to significant insights into the ovarian regulation of the reproductive processes of animals. However, the whole-transcriptome analysis of the non-coding RNAs and mRNA of the ovaries in Chongming white goats between high-fecundity (HP) and low-fecundity (LP) groups is limited. In this study, a whole-transcriptome sequencing approach was used to identify lncRNA, circRNA, miRNA, and mRNA expression in the ovaries of Chongming white goats during the estrus phase using RNA-Seq technology. More than 20,000 messenger RNAs (mRNAs), 10,000 long non-coding RNAs (lncRNAs), 3500 circular RNAs (circRNAs), and 1000 micro RNAs (miRNAs) were identified. A total of 1024 differential transcripts (724 mRNAs, 112 lncRNAs, 178 circRNAs, and 10 miRNAs) existing between the HP and the LP groups were revealed through a bioinformatics analysis. They were enriched in the prolactin signaling pathway, the Jak-STAT signaling pathway, and the GnRH signaling pathway, as well as various metabolic pathways. Differentially expressed mRNAs (such as LYPD6, VEGFA, NOS3, TNXB, and EPHA2) and miRNAs (such as miR-10a-5p) play key roles in the regulation of goat ovaries during the estrus phase. The enrichment of pathways related to reproduction, such as the Hippo, Hedgehog, PI3K-AKT, and MAPK signaling pathways, suggests that they might be involved in the prolificacy of goat ovaries. Overall, we identified several gene modules associated with goat fecundity and provided a basis for a molecular mechanism in the ovaries of Chongming white goats.

[Characterization and phylogenetic analysis of complete chloroplast genome of cultivated Qinan agarwood].

"Tangjie" leaves of cultivated Qinan agarwood were used to obtain the complete chloroplast genome using high-throughput sequencing technology. Combined with 12 chloroplast genomes of Aquilaria species downloaded from NCBI, bioinformatics method was employed to determine the chloroplast genome characteristics and phylogenetic relationships. The results showed that the chloroplast genome sequence length of cultivated Qinan agarwood "Tangjie" leaves was 174 909 bp with a GC content of 36.7%. A total of 136 genes were annotated, including 90 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Sequence repeat analysis detected 80 simple sequence repeats(SSRs) and 124 long sequence repeats, with most SSRs composed of A and T bases. Codon preference analysis revealed that AUU was the most frequently used codon, and codons with A and U endings were preferred. Comparative analysis of Aquilaria chloroplast genomes showed relative conservation of the IR region boundaries and identified five highly variable regions: trnD-trnY, trnT-trnL, trnF-ndhJ, petA-cemA, and rpl32, which could serve as potential DNA barcodes specific to the Aquilaria genus. Selection pressure analysis indicated positive selection in the rbcL, rps11, and rpl32 genes. Phylogenetic analysis revealed that cultivated Qinan agarwood "Tangjie" and Aquilaria agallocha clustered together(100% support), supporting the Chinese origin of Qinan agarwood from Aquilaria agallocha. The chloroplast genome data obtained in this study provide a foundation for studying the genetic diversity of cultivated Qinan agarwood and molecular identification of the Aquilaria genus.

Fluid-structure interactions of bristled wings: the trade-off between weight and drag.

The smallest flying insects often have bristled wings resembling feathers or combs. We combined experiments and three-dimensional numerical simulations to investigate the trade-off between wing weight and drag generation. In experiments of bristled strips, a reduced physical model of the bristled wing, we found that the elasto-viscous number indicates when reconfiguration occurs in the bristles. Analysis of existing biological data suggested that bristled wings of miniature insects lie below the reconfiguration threshold, thus avoiding drag reduction. Numerical simulations of bristled strips showed that there exist optimal numbers of bristles that maximize the weighted drag when the additional volume due to the bristles is taken into account. We found a scaling relationship between the rescaled optimal numbers and the dimensionless bristle length. This result agrees qualitatively with and provides an upper bound for the bristled wing morphological data analysed in this study.

Unraveling the Major Differences between the Trinuclear Cyclopentadienylmetal Carbonyl Chemistry of Cobalt and That of Nickel-A Theoretical Study.

The geometries and energetics of the trinuclear cyclopentadienylmetal carbonyls Cp3M3(CO)n (Cp = η5-C5H5); M = Co, Ni; n = 3, 2, 1, 0) have been investigated by density functional theory. The cobalt and nickel systems are found to be rather different owing to the different electronic configurations of the metal atoms. For cobalt, the small calculated energy separation of 5.0 kcal/mol between the two lowest-energy singlet Cp3Co3(µ3-CO)(µ-CO)2 and Cp3Co3(µ-CO)3 tricarbonyl structures accounts for the experimental results of both isomers as stable species that can be isolated and structurally characterized by X-ray crystallography. The corresponding Cp3Ni3(CO)3 species in the nickel system are predicted not to be viable owing to exothermic CO dissociation to give the experimentally observed very stable Cp3Ni3(µ-CO)2, which is found to be the lowest-energy isomer by a substantial margin of ∼25 kcal/mol. In all of the low-energy Cp3M3(CO)n (n = 2, 1) structures, including that of the experimentally known triplet spin state Cp3Co3(µ3-CO)2, all of the carbonyl groups are face-bridging or face-semi-bridging µ3-CO groups bonded to all three metal atoms of the M3 triangle. In the lowest-energy carbonyl-free Cp3M3 (M = Co, Ni) structures, agostic C-H-M interactions are found using hydrogens of the Cp rings. In addition, the lowest-energy Cp3Ni3 is the only structure among all of the low-energy Cp3M3(CO)n (M = Co, Ni; n = 3, 2, 1, 0) structures in which each Cp ring is a bridging rather than terminal ligand.

A subcellular biochemical model for T6SS dynamics reveals winning competitive strategies.

The type VI secretion system (T6SS) is a broadly distributed interbacterial weapon that can be used to eliminate competing bacterial populations. Although unarmed target populations are typically used to study T6SS function in vitro, bacteria most likely encounter other T6SS-armed competitors in nature. However, the connection between subcellular details of the T6SS and the outcomes of such mutually lethal battles is not well understood. Here, we incorporate biological data derived from natural competitors of Vibrio fischeri light organ symbionts to build a biochemical model for T6SS at the single-cell level, which we then integrate into an agent-based model (ABM). Using the ABM, we isolate and experiment with strain-specific physiological differences between competitors in ways not possible with biological samples to identify winning strategies for T6SS-armed populations. Through in vitro experiments, we discover that strain-specific differences exist in T6SS activation speed. ABM simulations corroborate that faster activation is dominant in determining survival during competition. Once competitors are fully activated, the energy required for T6SS creates a tipping point where increased weapon building and firing becomes too costly to be advantageous. Through ABM simulations, we identify the threshold where this transition occurs in the T6SS parameter space. We also find that competitive outcomes depend on the geometry of the battlefield: unarmed target cells survive at the edges of a range expansion where unlimited territory can be claimed. Alternatively, competitions within a confined space, much like the light organ crypts where natural V. fischeri compete, result in the rapid elimination of the unarmed population.

Regulation of the swimming kinematics of lampreys Petromyzon marinus across changes in viscosity.

The bodies of most swimming fishes are very flexible and deform as result of both external fluid dynamic forces and internal musculoskeletal forces. If fluid forces change, the body motion will also change unless the fish senses the change and alters its muscle activity to compensate. Lampreys and other fishes have mechanosensory cells in their spinal cords that allow them to sense how their body is bending. We hypothesized that lampreys (Petromyzon marinus) actively regulate body curvature to maintain a fairly constant swimming waveform even as swimming speed and fluid dynamic forces change. To test this hypothesis, we measured the steady swimming kinematics of lampreys swimming in normal water, and water in which the viscosity was increased by 10 or 20 times by adding methylcellulose. Increasing the viscosity over this range increases the drag coefficient, potentially increasing fluid forces up to 40%. Previous computational results suggested that if lampreys did not compensate for these forces, the swimming speed would drop by about 52%, the amplitude would drop by 39%, and posterior body curvature would increase by about 31%, while tail beat frequency would remain the same. Five juvenile sea lampreys were filmed swimming through still water, and midlines were digitized using standard techniques. Although swimming speed dropped by 44% from 1× to 10× viscosity, amplitude only decreased by 4%, and curvature increased by 7%, a much smaller change than the amount we estimated if there was no compensation. To examine the waveform overall, we performed a complex orthogonal decomposition and found that the first mode of the swimming waveform (the primary swimming pattern) did not change substantially, even at 20× viscosity. Thus, it appears that lampreys are compensating, at least partially, for the changes in viscosity, which in turn suggests that sensory feedback is involved in regulating the body waveform.

Comparative and phylogenetic analysis of the complete chloroplast genomes of Uncaria (Rubiaceae) species.

The genus Uncaria is famous for its high medicinal value. However, the high morphological similarities and unclear interspecific genetic relationships have posed challenges to the classification and identification of Uncaria species. Here, we newly sequenced six chloroplast genomes of Uncaria species: U. hirsuta, U. rhynchophylla, U. rhynchophylloides, U. homomalla, U. sinensis, and U. lancifolia. Comparisons among the chloroplast genomes of Uncaria species showed their conservation in structure, gene content, and order. Ten highly variable loci could be potentially used as specific molecular markers in the identification of Uncaria species. The third position of codons tended to use A/U base, and natural selection contributed more to the formation of codon usage bias in comparison to mutation pressure. Four genes (rbcL, ndhF, rps8, and ycf2) were detected to be subjected to positive selection. Phylogenetic analysis showed that the genus Uncaria was a monophyletic group, belonging to the tribe Naucleeae. Moreover, U. sinensis was not a variant of U. rhynchophylla. U. rhynchophylloides and U. rhynchophylla were not the same species. The results of the comparative and phylogenetic analysis provide valuable references for further research studies of classification, identification, breeding improvement, and phylogenetic relationships in Uncaria species.

chi-miR-99b-3p Regulates the Proliferation of Goat Skeletal Muscle Satellite Cells In Vitro by Targeting Caspase-3 and NCOR1.

We previously found that chi-miR-99b-3p was highly expressed in the skeletal muscle of 7-month-old (rapid growth period) goats and speculated that it may be associated with muscle development. To further investigate the role of chi-miR-99b-3p in goats, we found that chi-miR-99b-3p acted as a myogenic miRNA in the regulation of skeletal muscle development. Dual-luciferase reporter assays, qRT-PCR, and Western blot results confirmed that Caspase-3 and nuclear receptor corepressor 1 were direct targets for chi-miR-99b-3p as their expression was inhibited by this miR. Cell proliferation and qRT-PCR assays showed that chi-miR-99b-3p promoted proliferation through relevant targets and intrinsic apoptosis-related genes in goat skeletal muscle satellite cells (SMSCs), whereas inhibition of chi-miR-99b-3p had the opposite effect. Furthermore, integrative transcriptomic analysis revealed that overexpression of chi-miR-99b-3p induced various differentially expressed (DE) genes mainly associated with the cell cycle, relaxin signaling pathway, DNA replication, and protein digestion and absorption. Notably, most of the cell-cycle-related genes were downregulated in SMSCs after miR-99b-3p upregulation, including the pro-apoptosis-related gene BCL2. In addition, 47 DE miRNAs (16 upregulated and 31 downregulated) were determined by Small RNA-sequencing in SMSCs after chi-miR-99b-3p overexpression. Based on the KEGG enrichment analysis, we found that these DE miRNAs were involved in the biological pathways associated with the DE genes. Our study demonstrated that chi-miR-99b-3p was an effective facilitator of goat SMSCs and provided new insights into the mechanisms by which miRNAs regulate skeletal muscle growth in goats.

Eulerian simulation of complex suspensions and biolocomotion in three dimensions.

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 a three-dimensional implementation of the RMT, parallelized using the distributed memory paradigm, to simulate incompressible FSI with neo-Hookean solids. As part of our method, we develop a field extrapolation scheme that works efficiently in parallel. Through representative examples, we demonstrate the method's suitability in investigating many-body and active systems, as well as its accuracy and convergence. 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.

Ages of weaning influence the gut microbiota diversity and function in Chongming white goats.

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.

Altered expression of miRNAs and mRNAs reveals the potential regulatory role of miRNAs in the developmental process of early weaned goats.

MicroRNAs (miRNAs) play pivotal roles in growth, development, and stress responses. However, the regulatory function of miRNAs in early weaned goats remains unclear. Deep sequencing comparison of mRNA and miRNA expression profiles showed that 18 miRNAs and 373 genes were differentially expressed in pre- and post-weaning Chongming white goats. Bioinformatics analysis indicated that these differentially expressed genes are involved in cellular processes, developmental processes, and growth in terms of biological process analysis. KEGG analysis showed that downregulated genes were enriched in salivary secretion, bile secretion, vascular smooth muscle contraction, and calcium signaling pathways. Additionally, a miRNA-mRNA co-expression network of the 18 dysregulated miRNAs and their 107 target mRNAs was constructed using a combination of Pearson's correlation analysis and prediction by miRanda software. Among the downregulated miRNAs, two (chi-miR-206 and chi-miR-133a/b) were muscle development-related and the others were cell proliferation associated. Further RT-qPCR analysis confirmed that downregulated miRNAs (chi-miR-99b-3p, chi-miR-224, and chi-miR-10b-5p) were highly expressed in muscle tissues (heart, spleen, or kidney) of the rapid growth period (7-month old) in Chongming white goats. The results of the present study suggested that weaning induced cell proliferation repression in post-weaning goats, providing new insight into the mechanism of muscle development of goats, although additional details remain to be elucidated in the future.

Effects of C2-Ceramide and Oltipraz on Hepatocyte Nuclear Factor-1 and Glutathione S-Transferase A1 in Acetaminophen-Mediated Acute Mice Liver Injury.

In this study, acetaminophen (APAP)-induced acute liver injury mice model was used to investigate the effects of C2-ceramide and oltipraz on hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase A1 (GSTA1). Notably, C2-ceramide caused alteration in mice serum transaminases and liver tissue indexes, and aggravated hepatic injury, while oltipraz alleviated hepatic injury. By screening, the optimal concentrations of C2-ceramide and oltipraz were confirmed to be 120 and 150 µmol/L, respectively. In histopathology, karyolysis and more necrotic cells and bleeding spots were appeared on administration of C2-ceramide, but only a small amount of inflammatory cells infiltration was seen after oltipraz treatment. In addition, RT-PCR and western blot results revealed that the mRNA and protein expression levels of HNF-1 and GSTA1 in liver were significantly decreased (p < 0.01) with the administration of 120 µmol/L C2-ceramide. Meanwhile, GSTA1 content in serum increased up to 1.27-fold. In contrast, 150 µmol/L oltipraz incorporation to APAP model mice resulted in obvious elevation (p < 0.01) in the mRNA and protein expression levels of HNF-1 and GSTA1 in liver, and serum GSTA1 content decreased up to 0.77-fold. In conclusion, C2-ceramide could down-regulate the expression of HNF-1 and GSTA1 which exacerbated hepatic injury, while oltipraz could up-regulate the expression of HNF-1 and GSTA1 which mitigated hepatic injury.

Molecular pathways involved in microRNA-mediated regulation of multidrug resistance.

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.

Predicting data quality in biological X-ray solution scattering.

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.

Study on mechanism of release oxygen by photo-excited hemoglobin in low-level laser therapy.

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.

Expression of glutathione S-transferase A1, a phase II drug-metabolizing enzyme in acute hepatic injury on mice.

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<0.01), whereas the liver homogenate indicator malondialdehyde was significantly increased (P<0.01). The expression of GSTA1 in liver was significantly decreased in the model groups compared with the control group (P<0.01). GSTA1 protein content was 3.8, 1.3 and 2.6 times lower in the CCl4, APAP and ethanol model groups, respectively. Furthermore, GSTA1 mRNA expression levels decreased by 4.9, 2.1 and 3.7 times in the CCl4, APAP and ethanol model groups, respectively. Among the three models, the injury induced by CCl4 was the most marked, followed by ethanol and finally APAP. These results suggest that GSTA1 may be released by the liver and serve as an antioxidant in the prevention of liver damage.