Novel imidazophenoxazine-4-sulfonamides: Their synthesis and evaluation as potential inhibitors of PDE4

A number of novel imidazophenoxazine-4-sulfonamides have been designed as potential inhibitors of PDE4. All these compounds were readily prepared via an elegant multi-step method involving the initial construction of 1-nitro-10H-phenoxazine ring and then fused imidazole ring as key steps. Some of these compounds showed promising PDE4B and D inhibition when tested in vitro and good interactions with these proteins in silico. Three of these compounds showed dose dependent inhibition of PDE4B with IC₅₀ value of 3.31 ± 0.62, 1.23 ± 0.18 and 0.53 ± 0.18 μM.     

Phytoremediation of lead-contaminated soil by Sinapis arvensis and Rapistrum rugosum

Nowadays, public concern relating to ecological deleterious effects of heavy metals is on the rise. To evaluate the potential of Rapistrum rugosum and Sinapis arvensis in lead- contaminate phytoremediate, a pot culture experiment was conducted. The pots were filled by soil treated with different rates of leadoxide (PbO) including 0 (control), 100, 200, 300, 400, and 500 mg Pb per 1 kg soil. Germinated seeds were sown. Surprisingly, with increasing concentration of Pb, dry weight of R. rugosum and S. arvensis did not decrease significantly. In both of species, the concentration of Pb was higher in roots than shoots. In general, S.arvensis was absorbed more Pb compared to R. rugosum. The results revealed high potential of R. rugosum and S. arvensis in withdrawing Pb from contaminated soil. For both species, a positive linear relation was observed between Pb concentration in soil and roots. However, linear relationship was not observed between Pb concentration in the soil and shoots. Although both species test had low ability in translocation Pb from roots to shoots but they showed high ability in uptake soil Pb by roots. Apparently, these plants are proper species for using in phytoremediation technology.     

Long term organ culture of rat liver rudiment in a synthetic medium: morphological and biochemical development.

Embryonic rat liver rudiments were grown and maintained in a chemically defined medium for up to 16 weeks. Liver explants grew and developed liver plates, bile canaliculi and ductules. Liver cells differentiated and, by the end of the second culture week, revealed cytological and ultrastructural features of adult rat liver cells. Glycogen synthetase activity appeared and reached a plateau within 2 weeks.Plasma proteins produced by the explants appeared sequentially in the culture medium. Their relative concentrations in the medium increased progressively to a plateau and they persisted throughout the culture period. Albumin was present in trace amounts during early days of culture. Its relative concentration increased and it became the major protein constituent of the medium by the second week.Transferrin, α₁M-globulin, haptoglobin, β₁c- and α₁B-globulin appeared in that order. The three fibrinogen subunits were identified during the first week of culture.Fetal proteins were identified during the early culture period, the most prominent being α-fetoprotein. The relative concentration of fetal proteins declined steadily as the culture progressed.     

Steering of Guided Light with Graphene Metasurface for Refractive Index Sensing with High Figure of Merits

The steering of guided light in surface plasmon resonance (SPR) sensing platforms introduced more than eight decades ago from the first proposed optical sensor in 1983. However, sensing the environmental variation considering transverse modes is still require the attention from the scientist. Here, for the first time, by considering steering of guided light a high-performance SPR sensor base on Otto structure is proposed. By incorporating the graphene and white graphene in to a prism-waveguide configuration, we calculated the excitation of both TE(TM) modes as refractive index is changed from 1 to 1.04. to analysis of the structure finite-difference time-domain (FDTD) is applied. To benchmark of the structure performance parameters including sensitivity, figure of merit, polarization extinction ratio (PER), and insertion loss (IL) are calculated. Numerical results show that maximum sensitivity and figure of merit are obtained for TM modes of 1226 and 27 respectively. In such a case, graphene monolayer is applied. By considering coupling condition, at the μc?=?0.4 eV, the maximum value of PER is 75 dB, and IL is 0.022 dB. Moreover, it is obtained that in all these conditions PER is higher than 8 dB, and IL is less than 0.04 dB.

     

Using prey availability to evaluate Lower Colorado River riparian restoration

The Lower Colorado River Multi‐species Conservation Program (MSCP) is charged with restoring habitat for 26 species such as the southwestern willow flycatcher (Empidonax traillii extimus) impacted by water development projects on the river. As of 2015, the MSCP had spent $200 million to create 1,200 ha of habitat at nine sites, but the benefits to these insectivorous birds and other target species have not been quantified. Many MSCP projects emphasized riparian plantings of willow (Salix exigua, Salix gooddingii) and cottonwood (Populus fremontii) on high terraces disconnected from the river. We documented prey availability for insectivores in constructed habitats as an indicator of restoration effectiveness. Using sticky traps as a proxy to estimate aerial insect flux, we found the number of aquatic insects, proportion of aquatic insects, total number of insects, and number of insect orders were all significantly lower in MSCP plantation sites than at the river's edge. Riparian restoration sites over 100 m from the river had only 4% of the aquatic insects, 20% of the total insects, and only half as many insect orders as sites adjacent to the river. Thus, food availability and overall habitat quality for insectivores are likely low in restoration sites that are distant from the river.     

Protocol for Birmingham Atrial Fibrillation Treatment of the Aged study (BAFTA): a randomised controlled trial of warfarin versus aspirin for stroke prevention in the management of atrial fibrillation in an elderly primary care population [ISRCTN89345269]

Background

Statins effectively lower blood cholesterol and the risk of cardiovascular death. Immunomodulatory actions, independent of their lipid-lowering effect, have also been ascribed to these compounds. Since macrophages participate in several vascular pathologies, we examined the effect of statin treatment on the survival and differentiation of primary human monocytes.

Methods

Peripheral blood mononuclear cells (PBMCs) from healthy individuals were cultured in the presence or absence of mevastatin. Apoptosis was monitored by annexin V / PI staining and flow cytometry. In parallel experiments, cultures were stimulated with LPS in the presence or absence of mevastatin and the release of IL-1β and IL-1Ra was measured by ELISA.

Results

Among PBMCs, mevastatin-treated monocytes were particularly susceptible to apoptosis, which occurred at doses >1 microM and was already maximal at 5 microM. However, even at the highest mevastatin dose used (10 microM), apoptosis occurred only after 24 h of culture, possibly reflecting a requirement for cell commitment to differentiation. After 72 h of treatment the vast majority (>50%) of monocytes were undergoing apoptosis. Stimulation with LPS revealed that mevastatin-treated monocytes retained the high IL-1β output characteristic of undifferentiated cells; conversely, IL-1Ra release was inhibited. Concurrent treatment with mevalonolactone prevented the induction of apoptosis and suppressed both IL-1β and IL-1Ra release in response to LPS, suggesting a rate-limiting role for HMG-CoA reductase in monocyte differentiation.

Conclusions

Our findings indicate that statins arrest the functional differentiation of monocytes into macrophages and steer these cells into apoptosis, suggesting a novel mechanism for the vasculoprotective properties of HMG-CoA reductase inhibitors.