Novel factor Xa inhibitors based on a benzoic acid scaffold and incorporating a neutral P1 ligand

A series of novel, highly potent, achiral factor Xa inhibitors based on a benzoic acid scaffold and containing a chlorophenethyl moiety directed towards the protease S1 pocket is described. A number of structural features, such as the requirements of the P1, P4 and ester-binding pocket ligands were explored with respect to inhibition of factor Xa. Compound 46 was found to be the most potent compound in a series of antithrombotic secondary assays.     

Seroma formation after surgery for breast cancer

Background  

Seroma formation is the most frequent postoperative complication after breast cancer surgery. We carried out a study to investigate the effect of various demographic, clinical and therapeutic variables on seroma formation.     

Bringing order to the glutamate chaos in schizophrenia

Recent genetic linkage studies complement the existing evidence that implicates abnormalities in NMDA receptor-mediated neurotransmission in the pathophysiology of schizophrenia. At the same time, advances in our understanding of the complex mechanisms that modulate the function of NMDA receptors suggest several novel sites for pharmacological manipulation of these receptors. This presents exciting opportunities for rational rather than serendipitous discovery of therapeutics for schizophrenia.     

Kinetics of Cr(VI) Removal by Iron Filings in Some Soils

In this research, kinetics of Cr(VI) reduction by iron filings was investigated through a batch study in seven different soils. Chromate reduction experiments were carried out for initial Cr(VI) concentrations ranging from 20 to 100 mgkg^?1 and iron filings dosage of 0 to 5% w/w. The experimental data were analyzed using various kinetic models including zero-order, pseudo first-order, power function, Elovich, and diffusion parabolic. Results showed that the Cr(VI) reduction efficiency in the presence of all studied soils increased with increasing iron filings dosage and decreased with increasing the initial Cr(VI) concentration. The reaction rates considerably depended on pH and were higher in acidic soils. The diffusion parabolic model was the best kinetic model as evidenced by the highest determination coefficient (r²) and the lowest standard error of the estimate (SE). The rate-limiting step(s) may be transport of chromate anions across a liquid film at the interface of soil-liquid, transport in liquid-filled macropores of iron filings aggregates, or diffusion in micropores and along the particle's surface.     

DNA Methylation Modulates Nociceptive Sensitization after Incision

DNA methylation is a key epigenetic mechanism controlling DNA accessibility and gene expression. Blockade of DNA methylation can significantly affect pain behaviors implicated in neuropathic and inflammatory pain. However, the role of DNA methylation with regard to postoperative pain has not yet been explored. In this study we sought to investigate the role of DNA methylation in modulating incisional pain and identify possible targets under DNA methylation and contributing to incisional pain. DNA methyltranferase (DNMT) inhibitor 5-Aza-2′-deoxycytidine significantly reduced incision-induced mechanical allodynia and thermal sensitivity. Aza-2′-deoxycytidine also reduced hindpaw swelling after incision, suggesting an anti-inflammatory effect. Global DNA methylation and DNMT3b expression were increased in skin after incision, but none of DNMT1, DNMT3a or DNMT3b was altered in spinal cord or DRG. The expression of proopiomelanocortin Pomc encoding β-endorphin and Oprm1 encoding the mu-opioid receptor were upregulated peripherally after incision; moreover, Oprm1 expression was further increased under DNMT inhibitor treatment. Finally, local peripheral injection of the opioid receptor antagonist naloxone significantly exacerbated incision-induced mechanical hypersensitivity. These results suggest that DNA methylation is functionally relevant to incisional nociceptive sensitization, and that mu-opioid receptor signaling might be one methylation regulated pathway controlling sensitization after incision.     

Sperm status and DNA dose play key roles in sperm/ICSI‐mediated gene transfer in caprine

In relation to the growing recent interest in the establishment of sperm‐mediated gene transfer (SMGT) technology as a convenient and effective method for the simple production of transgenic animals, in this study the possibility of using SMGT to produce transgenic caprine embryos was investigated for the first time. Buck sperm were directly incubated with different concentrations (0–500 ng) of pcDNA/his/Lac‐Z plasmid and used for IVF or ICSI. Sperm used for ICSI were categorized into motile or live‐immotile group before being injected into oocytes. In a separate experiment, dead sperm prepared by repeated freezing/thawing were used for DNA‐incubation before ICSI. Sham injection was carried out by intracytoplasmic injection of approximately the same volume of media containing different doses of DNA using an ICSI needle. Transgene expression and transmission were detected by X‐Gal staining and PCR analysis of developed embryos, respectively. A reasonable blastocyst rate was observed in all the groups. Only embryos in the sham group were negative for transgene transmission. Transgene expression was completely dependent on the delivery technique and status of sperm, and was only observed in the live‐immotile and dead ICSI groups. The results of this study showed that the technique (IVF vs. ICSI vs. sham injection), sperm status (motile vs. live‐immotile vs. dead) and to some extent DNA concentration affect embryo development, transgene transmission and expression. Mol. Reprod. Dev. 77:868–875, 2010. © 2010 Wiley‐Liss, Inc.     

Shotgun strategy-based proteome profiling analysis on the head of silkworm Bombyx mori

Insect head is comprised of important sensory systems to communicate with internal and external environment and endocrine organs such as brain and corpus allatum to regulate insect growth and development. To comprehensively understand how all these components act and interact within the head, it is necessary to investigate their molecular basis at protein level. Here, the spectra of peptides digested from silkworm larval heads were obtained from liquid chromatography tandem mass spectrometry (LC–MS/MS) and were analyzed by bioinformatics methods. Totally, 539 proteins with a low false discovery rate (FDR) were identified by searching against an in-house database with SEQUEST and X!Tandem algorithms followed by trans-proteomic pipeline (TPP) validation. Forty-three proteins had the theoretical isoelectric point (pI) greater than 10 which were too difficult to separate by two-dimensional gel electrophoresis (2-DE). Four chemosensory proteins, one odorant-binding protein, two diapause-related proteins, and a lot of cuticle proteins, interestingly including pupal cuticle proteins were identified. The proteins involved in nervous system development, stress response, apoptosis and so forth were related to the physiological status of head. Pathway analysis revealed that many proteins were highly homologous with the human proteins which involved in human neurodegenerative disease pathways, probably implying a symptom of the forthcoming metamorphosis of silkworm. These data and the analysis methods were expected to be of benefit to the proteomics research of silkworm and other insects.     

Complex permittivity of sodium chloride solutions at microwave frequencies

The complex permittivity of aqueous solutions at 20 degrees C has been measured at concentrations between 0.001 and 5 mol/L and over a frequency range 0.13-20 GHz. The results were combined with literature values to derive empirical equations to predict the dielectric behavior of sodium chloride solutions between 0 and 5 mol/L and 5 degrees C-35 degrees C.     

Effects of Stress Modifier Biostimulants on Vegetative Growth,Nutrients, and Antioxidants Contents of Garden Thyme (Thymus vulgaris L.) Under Water Deficit Conditions

The aim of this study is to investigate the effect of stress modulators on vegetative growth, antioxidants, and nutrient content of Thymus vulgaris L. under water deficit stress conditions. A factorial experiment was performed in the form of a randomized complete block design with 10 treatments and 3 replications in the 2019–2020 growing season. The factors were stress modulators at 5 levels (ZN: zinc nano-fertilizer, AA: amino acid, SW: seaweed, HA: humic acid and C: control) and irrigation regime at 2 levels [FIrr: full irrigation (100% field capacity) and DIrr: deficit irrigation (50% field capacity)]. The highest plant height, number of branches, and total dry weight of the garden thyme plant were observed in the foliar application of HA and SW under full irrigation conditions. Relative water content, chlorophyll a and b, and uptake of nutrients (N, P, and K) were reduced under water deficit stress, but the foliar application of stress modulators increased relative water content, chlorophyll content, and nutrient uptake of the garden thyme plant significantly compared with control. The water deficit increased proline content, total flavonoid, and phenol content in the garden thyme plant. So, the highest total flavonoid and phenol content was obtained from plants treated with HA, whereas proline content was higher in the control plants. Soluble sugars and essential oil increased significantly under water deficit stress conditions. The foliar application of HA compared to the control plant increased soluble sugars and essential oil in garden thymes. The activities of catalase, superoxide dismutase, and ascorbate peroxidase enzymes were improved in stress modulator treatments such as HA and SW compared to control plants under water deficit stress conditions. The plants of garden thymes showed a good response to stress modulator treatments under water stress conditions, and HA and SW treatments were found to be more effective.