Isoxazole-containing neonicotinoids: Design,synthesis, and insecticidal evaluation

A series of novel isoxazole-containing neonicotinoids were synthesized from nitromethylene analogues and aromatic aldehydes in the presence of l-proline/K₂CO₃. Bioassays indicated that several synthesized compounds showed 40–70% mortality against brown planthopper (Nilaparvata lugens) under the concentration of 4 mg L^?1, higher than that of imidacloprid (20%). Against cowpea aphid (Aphis craccivora), the best activity of title compounds reached 90% at the concentration of 20 mg L^?1.     

Leucoflavonine,a new bioactive racemic flavoalkaloid from the leaves of Leucosceptrum canum

A new flavoalkaloid racemate, leucoflavonine (1), together with its flavonoid precursor pectolinarigenin (2), was isolated from the leaves of Leucosceptrum canum collected from Tibet. Its structure was established by comprehensive spectroscopic analysis. Chrial separation of the enantiomers of 1 was achieved, and their absolute configurations were determined as S-(+)- and R-(?)-leucoflavonines ((+)-1a and (?)-1b) by comparison of their computational and experimental optical rotations. Biological assays indicated that both (+)-1a and (?)-1b exhibited inhibitory activity against acetylchlorinesterase (AChE) in vitro (IC₅₀?=?68.0?±?8.6 and 18.3?±?1.8?μM, respectively). Moreover, (?)-1b displayed cytotoxicity against human hepatoma cells HepG2 (IC₅₀?=?52.9?±?3.6?μM), and inhibited the production of interleukelin-2 (IL-2) in Jurkat cells (IC₅₀?=?16.5?±?0.9?μM), while (+)-1a showed no obvious activity in these assays.     

Parasitism capacity and searching efficiency of Diaeretiella rapae parasitizing Brevicoryne brassicae on susceptible and resistant canola cultivars

Different cultivars of aplant species can affect the foraging and efficiency of natural enemies, both directly through physical and biochemical properties or indirectly through the herbivore's diet. In this study, the parasitism capacity and functional response of Diaeretiella rapae McIntosh were determined on the cabbage aphid, Brevicoryne brassicae (L.) reared on susceptible (Opera) and resistant (Okapi) canola cultivars under laboratory conditions at 25?±?1?°C, 60?±?5% RH and a16:8?h L:D photoperiod. The parasitoid exhibited Type II and Type III functional responses on the resistant and susceptible cultivars, respectively. The estimated value of searching efficiency (a) was 0.1637?±?0.1095?h^?1 on the resistant cultivar whereas its value was dependent on host density on the susceptible cultivar. The handling times (T_h) on the susceptible and resistant canola cultivars were 0.108?±?0.040 and 0.320?±?0.048?h, respectively. The net parasitism rate (C₀) of the parasitoid wasp varied from 128.09 hosts per parasitoid lifetime on the susceptible to 71.01hosts on the resistant canola cultivar. The transformation rate from host population to parasitoid offspring (Qp) was equal to 1 on both cultivars (C₀?=?R₀). The finite parasitism rate (ω) on the susceptible cultivar (0.819 hosts per parasitoid per day) was significantly higher than that on the resistant one (0.578 hosts per parasitoid per day). In conclusion, canola cultivars affected the performance of D. rapae in controlled small-scale laboratory experiments and compared with the susceptible cultivar, the resistant one had anadverseeffect on the efficiency of the parasitoid.     

Km (CO2) values of ribulose-1,5-bisphosphate carboxylase in grasses of different C4 type

Statistical analysis of K_m (CO₂) values of ribulose-1,5-bisphosphate (RuBP) carboxylase from 35 C₄ grass species shows that the mean value for PEP-carboxykinase (PCK) type C₄ species (41.4±s.e. 2.2 μM CO₂) is significantly different from that of NAD-malic enzyme (NAD-ME) type species (55.3±3.1 μM CO₂) or NADP-malic enzyme (NADP-ME type species (52.5±s.e. 2.0μM CO₂). These C₄ type differences remain detectable within both the eu-panicoid and chloridoid grass subfamilies. By contrast, no between-subfamily differences were found within C₄ types. Variation in K_m (CO₂) values of RuBP carboxylase may be related to in vivo differences in CO₂ concentration at the enzyme site, mediated perhaps by differences in CO₂-leakiness of C₄ leaf ‘photosynthetic carbon reduction’ (PCR or ‘Kranz’) tissue.     

Inorganic carbon and pH effect on growth and lipid productivity of Tetraselmis suecica and Chlorella sp (Chlorophyta) grown outdoors in bag photobioreactors

There has been considerable interest in cultivation of green microalgae (Chlorophyta) as a source of lipid that can alternatively be converted to biodiesel. However, almost all mass cultures of algae are carbon-limited. Therefore, to reach a high biomass and oil productivities, the ideal selected microalgae will most likely need a source of inorganic carbon. Here, growth and lipid productivities of Tetraselmis suecica CS-187 and Chlorella sp were tested under various ranges of pH and different sources of inorganic carbon (untreated flue gas from coal-fired power plant, pure industrial CO₂, pH-adjusted using HCl and sodium bicarbonate). Biomass and lipid productivities were highest at pH 7.5 (320?±?29.9 mg biomass L^?1 day^?1and 92?±?13.1 mg lipid L^?1 day^?1) and pH 7 (407?±?5.5 mg biomass L^?1 day^?1 and 99?±?17.2 mg lipid L^?1 day^?1) for T. suecica CS-187 and Chlorella sp, respectively. In general, biomass and lipid productivities were pH 7.5?>?pH 7?>?pH 8?>?pH 6.5 and pH 7?>?pH 7.5?=?pH 8?>?pH 6.5?>?pH 6?>?pH 5.5 for T. suecica CS-187 and Chlorella sp, respectively. The effect of various inorganic carbon on growth and productivities of T. suecica (regulated at pH?=?7.5) and Chlorella sp (regulated at pH?=?7) grown in bag photobioreactors was also examined outdoor at the International Power Hazelwood, Gippsland, Victoria, Australia. The highest biomass and lipid productivities of T. suecica (51.45?±?2.67 mg biomass L^?1 day^?1 and 14.8?±?2.46 mg lipid L^?1 day^?1) and Chlorella sp (60.00?±?2.4 mg biomass L^?1 day^?1 and 13.70?±?1.35 mg lipid L^?1 day^?1) were achieved when grown using CO₂ as inorganic carbon source. No significant differences were found between CO₂ and flue gas biomass and lipid productivities. While grown using CO₂ and flue gas, biomass productivities were 10, 13 and 18 %, and 7, 14 and 19 % higher than NaHCO₃, HCl and unregulated pH for T. suecica and Chlorella sp, respectively. Addition of inorganic carbon increased specific growth rate and lipid content but reduced biomass yield and cell weight of T. suecica. Addition of inorganic carbon increased yield but did not change specific growth rate, cell weight or content of the cell weight of Chlorella sp. Both strains showed significantly higher maximum quantum yield (F_v/F_m) when grown under optimum pH.     

Ventilation and oxygen consumption in the hagfish, Myxine glutinosa L.

Ventilation was measured directly in the hagfish, Myxine glutinosa L., by means of an electro-magnetic blood flowmeter. Ventilatory flow and frequency increased from 0.86 ± 0.27 ml·min^?, and 18.2 ± 5.1·min^?, respectively, at 7°C to 1.70 ± 0.20 ml·min^?, and 70.1 ± 9.5·min^? at 15 ·C.Standard oxygen consumption,V?O₂, was measured in non-buried hagfish. V?O₂ was 0.57 ± 0.17μl O₂·g^?1·min^?1 at 7°C, and 0.85 ± 0.12μl O₂·g^?1·min^?1 at 15°C.     

Changes in bacterial CO2 fixation with depth in agricultural soils

Soils were incubated continuously in an atmosphere of ¹⁴CO₂ and the distribution of labeled C into soil organic carbon (¹⁴C-SOC) was determined at 0–1, 1–5, and 5–17 cm down the profile. Significant amounts of ¹⁴C-SOC were measured in paddy soils with a mean of 1,180.6?±?105.2 mg kg^–1 at 0–1 cm and 135.3?±?47.1 mg kg^?1 at 1–5 cm. This accounted for 5.9?±?0.7 % and 0.7?±?0.2 %, respectively, of the total soil organic carbon at these depths. In the upland soils, the mean ¹⁴C-SOC concentrations were 43 times (0–1 cm) and 11 times (1–5 cm) lower, respectively, than those in the paddy soils. The amounts of ¹⁴C incorporated into the microbial biomass (MBC) were also much lower in upland soils (5.0?±?3.6 % and 2.9?±?1.9 % at 0–1 and 1–5 cm, respectively) than in paddy soils (34.1?±?12.4 % and 10.2?±?2.1 % at 0–1 and 1–5 cm, respectively). Similarly, the amount of ¹⁴C incorporated into the dissolved organic carbon (DOC) was considerably higher in paddy soils (26.1?±?6.9 % and 6.9?±?1.3 % at 0–1 and 1–5 cm, respectively) than in upland soils (6.0?±?2.7 % and 4.3?±?2.2 %, respectively). The observation that the majority of the fixed ¹⁴C-SOC, RubisCO activity and cbbL gene abundance were concentrated at 0–1 cm depth and the fact that light is restricted to the top few millimeters of the soil profiles highlighted the importance of phototrophs in CO₂ fixation in surface soils. Phylogenetic analysis of the cbbL genes showed that the potential for CO₂ fixation was evident throughout the profile and distributed between both photoautotrophic and chemoautotrophic bacteria such as Rhodopseudomonas palustris, Bradyrhizobium japonicum, Rubrivivax gelatinosus and Ralstonia eutropha.     

Kinetics of some electron-transfer reactions in biological photosystems. I. Pulse radiolysis study of spinach ferredoxin reduction by the hydrated electron and CO−2 radical

The reduction of spinach ferredoxin by the CO^?₂ radical and the hydrated electron (e^?_aq) has been studied by pulse radiolysis in the pH range between 5.05 and 9.67. The reduction of oxidized spinach ferredoxin by both CO^?₂ and e^?_aq was found to be essentially quantitative. The CO^?₂ radical reduces spinach ferredoxin by a single second-order process at a rate k₅ = (6.2 ± 0.6) · 10⁷ M^?1 · s^?1. Reduction by e^?_aq follows a biphasic pathway. The first phase obeys second-order kinetics for the reduction of the cluster, k_app = (9.4 ± 0.3) · 10⁹ M^?1 · s^?1. The second phase follows an intramolecular first-order reaction k_B = (8.3 ± 1.7) · 10² s^?1 which is observed as a further reduction of the active site. Spectral changes accompanying the reduction of oxidized spinach ferredoxin in the ultraviolet and visible range are discussed.     

Antiplasmodial flavanones and a stilbene from Carpha glomerata

Bioassay-guided fractionation of an extract of Carpha glomerata (Cyperaceae) led to the isolation of seven compounds. Compounds 1 (carphorin A), 3 (carphorin C), 4 (carphorin D), and 5 (carphabene) are new compounds, and compound 2 (8-(3″-hydroxyisoamyl)-naringenin) was isolated for the first time as a natural product. All structures were elucidated based on analyses of their HR-ESIMS and 1D and 2D NMR data. Compounds 1, 2, and 6, which have prenyl or hydroxyprenyl side chains, exhibited antiplasmodial activities with IC₅₀ values of 5.2?±?0.6, 3.4?±?0.4, and 6.7?±?0.8?µM against the drug-resistant Dd2 strain of Plasmodium falciparum. In addition the prenylated stilbene 5 also showed good activity, with IC₅₀ 5.8?±?0.7?µM.     

Total phenolic and flavonoid contents and antioxidant activity of ginger (Zingiber officinale Rosc.) rhizome,callus and callus treated with some elicitors

The present study was aimed at determining total phenolic and flavonoid contents and studying the antioxidant activity of ginger (Zingiber officinale Rosc.) rhizome and callus, 6-gingerol and 6-shogaol and callus treated with elicitors. Petroleum ether (PE) and chloroform: methanol (1:1, v/v) (CM) extracts were prepared by maceration. Highest total phenolic content was obtained from the CM extract (60.34?±?0.43?mg gallic acid/g) of rhizome while callus showed lower content detected in the CM extract (33.6?±?0.07?mg gallic acid/g). Flavonoids were only detected in rhizome (CM extract 40.25?±?0.21?mg quercetin/g). Both rhizome extracts exhibited good antioxidant activity with higher activity recorded in PE extract (IC₅₀ value 8.29?±?1.73?μg/mL). Callus extracts revealed lower antioxidant activity (IC₅₀ value 1265.49?±?59.9?μg/mL obtained from CM extract). 6-gingerol and 6-shogaol displayed high antioxidant activity in both assays with IC₅₀ 4.85?+?0.58_DPPH and 5.35?±?0.33_ABTS μg/mL for the former and IC₅₀ 7.61?±?0.81_DPPH and IC₅₀ 7.05?±?0.23_ABTS μg/mL for the latter. Treatment of callus with elicitors showed significant (p?<?0.05) effects in enhancing phenolic content and related antioxidant activity. The highest significant increase in phenolic content (37% and 34%) and antioxidant activity in DPPH assay (34% and 30%) was observed in callus treated with 100?mg/L yeast extract and 50?mg/L salicylic acid respectively. Therefore, studying the effect of the elicitation of ginger cultured tissues in phenolic accumulation would be of immense importance for pharmacological, cosmetic and agronomic industries.     

Interspecific variation in thermoregulation among three sympatric bats inhabiting a hot, semi-arid environment

Bats in hot roosts experience some of the most thermally challenging environments of any endotherms, but little is known about how heat tolerance and evaporative cooling capacity vary among species. We investigated thermoregulation in three sympatric species (Nycteris thebaica, Taphozous mauritianus and Sauromys petrophilus) in a hot, semi-arid environment by measuring body temperature (T _b), metabolic rate and evaporative water loss (EWL) at air temperatures (T _a) of 10?C42?°C. S. petrophilus was highly heterothermic with no clear thermoneutral zone, and exhibited rapid increases in EWL at high T _a to a maximum of 23.7?±?7.4?mg?g^?1?h^?1 at T _a????42?°C, with a concomitant maximum T _b of 43.7?±?1.0?°C. T. mauritianus remained largely normothermic at T _as below thermoneutrality and increased EWL to 14.7?±?1.3?mg?g^?1?h^?1 at T _a????42?°C, with a maximum T _b of 42.9?±?1.6?°C. In N. thebaica, EWL began increasing at lower T _a than in either of the other species and reached a maximum of 18.6?±?2.1?mg?g^?1?h^?1 at T _a?=?39.4?°C, with comparatively high maximum T _b values of 45.0?±?0.9?°C. Under the conditions of our study, N. thebaica was considerably less heat tolerant than the other two species. Among seven species of bats for which data on T _b as well as roost temperatures in comparison to outside T _a are available, we found limited evidence for a correlation between overall heat tolerance and the extent to which roosts are buffered from high T _a.     

Interactions between CO2 enhancement and N addition on net primary productivity and water‐use efficiency in a mesocosm with multiple subtropical tree species

Carbon dioxide (CO₂) enhancement (eCO₂) and N addition (aN) have been shown to increase net primary production (NPP) and to affect water‐use efficiency (WUE) for many temperate ecosystems, but few studies have been made on subtropical tree species. This study compared the responses of NPP and WUE from a mesocosm composing five subtropical tree species to eCO₂ (700 ppm), aN (10 g N m^?2 yr^?1) and eCO₂ × aN using open‐top chambers. Our results showed that mean annual ecosystem NPP did not changed significantly under eCO₂, increased by 56% under aN and 64% under eCO₂ × aN. Ecosystem WUE increased by 14%, 55%, and 61% under eCO₂, aN and eCO₂ × aN, respectively. We found that the observed responses of ecosystem WUE were largely driven by the responses of ecosystem NPP. Statistical analysis showed that there was no significant interactions between eCO₂ and aN on ecosystem NPP (P = 0.731) or WUE (P = 0.442). Our results showed that increasing N deposition was likely to have much stronger effects on ecosystem NPP and WUE than increasing CO₂ concentration for the subtropical forests. However, different tree species responded quite differently. aN significantly increased annual NPP of the fast‐growing species (Schima superba). Nitrogen‐fixing species (Ormosia pinnata) grew significantly faster only under eCO₂ × aN. eCO₂ had no effects on annual NPP of those two species but significantly increased annual NPP of other two species (Castanopsis hystrix and Acmena acuminatissima). Differential responses of the NPP among different tree species to eCO₂ and aN will likely have significant implications on the species composition of subtropical forests under future global change.     

Rh and Ir dibenzo[a,e]cyclooctatetraene complexes: Chloro, hydroxo, and mixed Au oxo complexes

New and improved procedures are reported for the synthesis of [M(DBCOT)(μ-Cl)]₂ (M = Rh, Ir; DBCOT = dibenzo[a,e]cyclooctatetraene) from MCl₃(H₂O)_x or [M(COD)(μ-Cl)]₂ and DBCOT. Treatment of [M(DBCOT)(μ-Cl)]₂ with [(LAu)₃(μ-O)]BF₄(L = PPh₃, P^tBu₃) yields the mixed-metal oxo complexes [M(DBCOT)(μ⁴-O)(AuL)₂]₂(BF₄)₂. Dimeric [Rh(DBCOT)(μ-OH)]₂ is obtained from the reaction of [M(DBCOT)(μ-Cl)]₂ with KOH in EtOH/H₂O. All complexes except [Rh(DBCOT)(μ-Cl)]₂ have been structurally characterized by single crystal X-ray diffraction.     

pH effects on growth and lipid accumulation of the biofuel microalgae Nannochloropsis salina and invading organisms

Biofuels derived from non-crop sources, such as microalgae, offer their own advantages and limitations. Despite high growth rates and lipid accumulation, microalgae cultivation still requires more energy than it produces. Furthermore, invading organisms can lower efficiency of algae production. Simple environmental changes might be able to increase algae productivity while minimizing undesired organisms like competitive algae or predatory algae grazers. Microalgae are susceptible to pH changes. In many production systems, pH is kept below 8 by CO₂ addition. Here, we uncouple the effects of pH and CO₂ input, by using chemical pH buffers and investigate how pH influences Nannochloropsis salina growth and lipid accumulation as well as invading organisms. We used a wide range of pH levels (5, 6, 7, 8, 9, and 10). N. salina showed highest growth rates at pH 8 and 9 (0.19?±?0.008 and 0.19?±?0.011, respectively; mean ± SD). Maximum cell densities in these treatments were reached around 21 days into the experiment (95.6?×?10⁶?±?9?×?10⁶ cells mL^?1 for pH 8 and 92.8?×?10⁶?±?24?×?10⁶ cells mL^?1 for pH 9). Lipid accumulation of unbuffered controls were 21.8?±?5.8 % fatty acid methyl esters content by mass, and we were unable to trigger additional significant lipid accumulation by manipulating pH levels at the beginning of stationary phase. Ciliates (grazing predators) occurred in significant higher densities at pH 6 (56.9?±?39.6?×?10⁴ organisms mL^?1) than higher pH treatments (0.1–6.8?×?10⁴ organisms mL^?1). Furthermore, the addition of buffers themselves seemed to negatively impact diatoms (algal competitors). They were more abundant in an unbuffered control (12.7?±?5.1?×?10⁴ organisms mL^?1) than any of the pH treatments (3.6–4.7?×?10⁴ organisms mL^?1). In general, pH values of 8 to 9 might be most conducive to increasing algae production and minimizing invading organisms. CO₂ addition seems more valuable to algae as an inorganic carbon source and not as an essential mechanism to reduce pH.     

YhjA - An Escherichia coli trihemic enzyme with quinol peroxidase activity

The trihemic bacterial cytochrome c peroxidase from Escherichia coli, YhjA, is a membrane-anchored protein with a C-terminal domain homologous to the classical bacterial peroxidases and an additional N-terminal (NT) heme binding domain. Recombinant YhjA is a 50?kDa monomer in solution with three c-type hemes covalently bound. Here is reported the first biochemical and spectroscopic characterization of YhjA and of the NT domain demonstrating that NT heme is His63/Met125 coordinated. The reduction potentials of P (active site), NT and E hemes were established to be ?170?mV, +133?mV and +210?mV, respectively, at pH?7.5. YhjA has quinol peroxidase activity in vitro with optimum activity at pH?7.0 and millimolar range K_M values using hydroquinone and menadiol (a menaquinol analogue) as electron donors (K_M?=?0.6?±?0.2 and 1.8?±?0.5?mM H₂O₂, respectively), with similar turnover numbers (k_cat?=?19?±?2 and 13?±?2?s^?1, respectively). YhjA does not require reductive activation for maximum activity, in opposition to classical bacterial peroxidases, as P heme is always high-spin 6-coordinated with a water-derived molecule as distal axial ligand but shares the need for the presence of calcium ions in the kinetic assays. Formation of a ferryl Fe(IV)?=?O species was observed upon incubation of fully oxidized YhjA with H₂O₂. The data reported improve our understanding of the biochemical properties and catalytic mechanism of YhjA, a three-heme peroxidase that uses the quinol pool to defend the cells against hydrogen peroxide during transient exposure to oxygenated environments.     

Synthesis and in vitro anti-proliferative activity of some novel isatins conjugated with quinazoline/phthalazine hydrazines against triple-negative breast cancer MDA-MB-231 cells as apoptosis-inducing agents

Treatment of patients with triple-negative breast cancer (TNBC) is challenging due to the absence of well- defined molecular targets and the heterogeneity of such disease. In our endeavor to develop potent isatin-based anti-proliferative agents, we utilized the hybrid-pharmacophore approach to synthesize three series of novel isatin-based hybrids 5a–h, 10a–h and 13a–c, with the prime goal of developing potent anti-proliferative agents toward TNBC MDA-MB-231 cell line. In particular, compounds 5e and 10g were the most active hybrids against MDA-MB-231 cells (IC₅₀?=?12.35?±?0.12 and 12.00?±?0.13?μM), with 2.37- and 2.44-fold increased activity than 5-fluorouracil (5-FU) (IC₅₀?=?29.38?±?1.24?μM). Compounds 5e and 10g induced the intrinsic apoptotic mitochondrial pathway in MDA-MB-231; evidenced by the reduced expression of the anti-apoptotic protein Bcl-2, the enhanced expression of the pro-apoptotic protein Bax and the up-regulated active caspase-9 and caspase-3 levels. Furthermore, 10g showed significant increase in the percent of annexin V-FITC positive apoptotic cells from 3.88 to 31.21% (8.4 folds compared to control).     

Variations in leaf respiration across different seasons for Mediterranean evergreen species

Leaf respiration (R _L) of evergreen species co-occurring in the Mediterranean maquis developing along the Latium coast was analyzed. The results on the whole showed that the considered evergreen species had the same R _L trend during the year, with the lowest rates [0.83 ± 0.43 μmol(CO₂) m^?2 s^?1, mean value of the considered species] in winter, in response to low air temperatures. Higher R _L were reached in spring [2.44 ± 1.00 μmol(CO₂) m^?2 s^?1, mean value] during the favorable period, and in summer [3.17 ± 0.89 μmol(CO₂) m^?2 s^?1] during drought. The results of the regression analysis showed that 42% of R _L variations depended on mean air temperature and 13% on total monthly rainfall. Among the considered species, C. incanus, was characterized by the highest R _L in drought [4.93 ± 0.27 μmol(CO₂) m^?2 s^?1], low leaf water potential at predawn (Ψ_pd= ?1.08 ± 0.18 MPa) and midday (Ψ_md = ?2.75 ± 0.11 MPa) and low relative water content at predawn (RWC_pd = 80.5 ± 3.4%) and midday (RWC_md = 67.1 ± 4.6%). Compared to C. incanus, the sclerophyllous species (Q. ilex, P. latifolia, P. lentiscus, A. unedo) and the liana (S. aspera), had lower R _L [2.72 ± 0.66 μmol(CO₂) m^?2 s^?1, mean value of the considered species], higher RWC_pd (91.8 ± 1.8%), RWC_md (82.4 ± 3.2%), Ψ_pd (?0.65 ± 0.28 MPa) and Ψ_md (?2.85 ± 1.20 MPa) in drought. The narrow-leaved species (E. multiflora, R. officinalis, and E. arborea) were in the middle. The coefficients, proportional to the respiration increase for each 10°C rise (Q₁₀), ranging from 1.49 (E. arborea) to 1.98 (A. unedo) were indicative of the different sensitivities of the considered species to air temperature variation.     

Latent pulmonary hypertension in atrial septal defect: Dynamic stress echocardiography reveals unapparent pulmonary hypertension and confirms rapid normalisation after ASD closure

Objective

Closure of atrial septal defects (ASD) prevents pulmonary hypertension, right heart failure and thromboembolic stroke. The exact timing for ASD closure is controversial.

Methods

In a prospective study to address the question whether unapparent pulmonary hypertension can be revealed prior to right ventricular (RV) remodelling, patients were investigated before and 6, 12, and 24 months after ASD closure using exercise stress echocardiography (ESE) and ergospirometry (n?=?24).

Results

At rest, RV systolic pressure (RVSP) was normal in 58.8 %, slightly elevated in 26.5 %, and moderately elevated in 11.8 %. One patient showed severe pulmonary hypertension. During ESE, all patients with normal RVSP at rest exhibited an increase (25.7?±?1.2 mmHg vs. 45.3?±?2.3 mmHg, p?<?0.001). After closure the RVSP was lower, both at rest and ESE. RV diameters decreased too. Tricuspid annulus plane systolic excursion (TAPSE) at rest remained lower after closure (24.0?±?0.9 vs. 22.0?±?0.9 mm, p?<?0.05). TAPSE in ESE was elevated, and stayed stable after closure (30.1?±?1.8 mm vs. 29.3?±?1.6 mm). Before closure, RV systolic tissue velocities (s^a) at rest were normal and decreased after closure (14.0?±?1.0 cm/s vs. 11.5?±?0.7 (6 month) vs. 10.6?±?0.5 cm/s (12 month), p?<?0.05). During ESE, s^a velocity was similar before and after closure (23.0?±?1.3 cm/s vs. 23.3?±?1.9 cm/s). Maximal oxygen uptake (VO₂/kg) did not differ between baseline and follow-ups.

Conclusion

Latent pulmonary hypertension may become apparent in ESE. ASD closure leads to a significant reduction in this stress-induced pulmonary hypertension and to a decrease in the right heart diameters indicating reverse RV remodelling. RV functional parameters at rest did not improve. The VO₂/kg did not change after ASD closure.     

Discovery of 1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazoles as novel class of corticotropin releasing factor 1 receptor antagonists

A new class of corticotropin releasing factor 1 (CRF₁) receptor antagonists characterized by a tricyclic core ring was designed and synthesized. Novel tricyclic derivatives 2a–e were designed as CRF₁ receptor antagonists based on conformation analysis of our original 2-anilinobenzimidazole CRF₁ receptor antagonist. The synthesized tricyclic derivatives 2a–e showed CRF₁ receptor binding activity with IC₅₀ values of less than 400?nM, and the 1,2,3,4-tetrahydropyrimido-[1,2-a]benzimidazole derivative 2e was selected as a lead compound with potent in vitro CRF₁ receptor binding activity (IC₅₀?=?7.1?nM). To optimize the pharmacokinetic profiles of lead compound 2e, we explored suitable substituents on the 1-position and 6-position, leading to the identification of compound 42c-R, which exhibited potent CRF₁ receptor binding activity (IC₅₀?=?58?nM) with good oral bioavailability (F?=?68% in rats). Compound 42c-R exhibited dose-dependent inhibition of [¹²⁵I]-CRF binding in the frontal cortex (5 and 10?mg/kg, p.o.) as well as suppression of locomotor activation induced by intracerebroventricular administration of CRF in rats (10?mg/kg, p.o.). These results suggest that compound 42c-R successfully binds CRF₁ receptors in the brain and exhibits the potential to be further examined for clinical studies.     

The role of Gracilaria lemaneiformis in eliminating the dissolved inorganic carbon released from calcification and respiration process of Chlamys farreri

Respiration and calcification rate were estimated to quantify the effect of Zhikong scallop Chlamys farreri on marine CO₂ system in Sanggou Bay, China. The C. farreri population in Sanggou Bay sequestered 78.06?±?5.76 g C m^?2 y^?1 for shell formation, while the CO₂ fluxes due to calcification and respiration were 53.95?±?3.98 and 71.69?±?6.51 g C m^?2 y^?1, respectively. In order to eliminate the additional CO₂ released from calcification and respiration process of C. farreri, Gracilaria lemaneiformis were introduced into the integrated system and its role was validated by in situ mesocosm methods. Eight mesocosms (1,000 L) were deployed over 42-h period and consisted of four treatments: seaweed-only, scallop-only (SP), seaweed integrated with scallop (SS), and control (C). The aqueous CO₂ concentration and partial pressure of CO₂ in SP treatments were significantly higher than the other three treatments (p?<?0.01), while there were no difference between SS treatments and C treatments (p?>?0.05). Furthermore, compared with the SP treatments, the presence of the G. lemaneiformis can keep the seawater pH stable. These findings suggest that seaweed and shellfish integrated aquaculture practice cannot only reduce dissolved inorganic carbon but also can alleviate ocean acidification.