Design, synthesis, biological evaluation and molecular docking study of novel pleuromutilin derivatives containing substituted benzoxazole as antibacterial agents.

A series of pleuromutilin analogs containing substituted benzoxazole were designed, synthesised, and assessed for their antibacterial activity both in vivo and in vitro. The MIC of the synthesised derivatives was initially assessed using the broth dilution method against four strains of Staphylococcus aureus (MRSA ATCC 43300, S. aureus ATCC 29213, clinical isolation of S. aureus AD3 and S. aureus 144). Most of the synthesised derivatives displayed prominent in vitro activity (MIC ≤ 0.5 µg/mL). Compounds 50 and 57 exhibited the most effective antibacterial effect against MRSA (MIC = 0.125 µg/mL). Furthermore, the time-kill curves showed that compounds 50 and 57 had a certain inhibitory effect against MRSA in vitro. The in vivo antibacterial activity of compound 50 was evaluated further using a murine thigh model infected with MRSA (-1.24 log10CFU/mL). Compound 50 exhibited superior antibacterial efficacy to tiamulin. It was also found that compound 50 did not display significant inhibitory effect on the proliferation of RAW 264.7 cells. Molecular docking study revealed that compound 50 can effectively bind to the active site of the 50S ribosome (the binding free energy -7.50 kcal/mol).

Design, synthesis, and biological evaluation of novel pleuromutilin derivatives containing benzimidazoles as effective anti-MRSA agents.

A series of pleuromutilin derivatives containing benzimidazole were designed, synthesized, and evaluated for their antibacterial activities against Methicillin-resistant Staphylococcus aureus (MRSA) in this study. The in vitro antibacterial activities of the synthesized derivatives against four strains of S. aureus (MRSA ATCC 43300, S. aureus ATCC 29213, S. aureus 144, and S. aureus AD3) were determined by the broth dilution method. Among these derivatives, compound 58 exhibited superior in vitro antibacterial effect against MRSA (minimal inhibitory concentration [MIC] = 0.0625 µg/mL) than tiamulin (MIC = 0.5 µg/mL). Compound 58 possessed a faster bactericidal kinetic and a longer post-antibiotic effect time against MRSA than tiamulin. Meanwhile, at 8 µg/mL concentration, compound 58 did not display obviously cytotoxic effect on the RAW 264.7 cells. In addition, compound 58 (-2.04 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (-1.02 log10 CFU/mL) in reducing MRSA load in mice thigh infection model. In molecular docking study, compound 58 can successfully attach to the 50S ribosomal active site (the binding free energy is -8.11 kcal/mol). Therefore, compound 58 was a potential antibacterial candidate for combating MRSA infections.

Latitudinal patterns of terrestrial phosphorus limitation over the globe.

Phosphorus limitation on terrestrial plant growth is being incorporated into Earth system models. The global pattern of terrestrial phosphorus limitation, however, remains unstudied. Here, we examined the global-scale latitudinal pattern of terrestrial phosphorus limitation by analysing a total of 1068 observations of aboveground plant production response to phosphorus additions at 351 forest, grassland or tundra sites that are distributed globally. The observed phosphorus-addition effect varied greatly (either positive or negative), depending significantly upon fertilisation regime and production measure, but did not change significantly with latitude. In contrast, phosphorus-addition effect standardised by fertilisation regime and production measure was consistently positive and decreased significantly with latitude. Latitudinal gradient in the standardised phosphorus-addition effect was explained by several mechanisms involving substrate age, climate, vegetation type, edaphic properties and biochemical machinery. This study suggests that latitudinal pattern of terrestrial phosphorus limitation is jointly shaped by macro-scale driving forces and the fundamental structure of life.

A global dataset on phosphorus in agricultural soils.

Numerous drivers such as farming practices, erosion, land-use change, and soil biogeochemical background, determine the global spatial distribution of phosphorus (P) in agricultural soils. Here, we revised an approach published earlier (called here GPASOIL-v0), in which several global datasets describing these drivers were combined with a process model for soil P dynamics to reconstruct the past and current distribution of P in cropland and grassland soils. The objective of the present update, called GPASOIL-v1, is to incorporate recent advances in process understanding about soil inorganic P dynamics, in datasets to describe the different drivers, and in regional soil P measurements for benchmarking. We trace the impact of the update on the reconstructed soil P. After the update we estimate a global averaged inorganic labile P of 187 kgP ha-1 for cropland and 91 kgP ha-1 for grassland in 2018 for the top 0-0.3 m soil layer, but these values are sensitive to the mineralization rates chosen for the organic P pools. Uncertainty in the driver estimates lead to coefficients of variation of 0.22 and 0.54 for cropland and grassland, respectively. This work makes the methods for simulating the agricultural soil P maps more transparent and reproducible than previous estimates, and increases the confidence in the new estimates, while the evaluation against regional dataset still suggests rooms for further improvement.

Intraspecific variations of leaf hydraulic, economic, and anatomical traits in Cinnamomum camphora along an urban-rural gradient.

Urbanization brings numerous benefits to residents, but it also introduces complex, variable, and heterogeneous habitat conditions to urban plants, resulting in an arid and hot urban environment that decreases tree growth and the ecological service capacity of trees. In this study, we evaluated leaf hydraulic, economic, and anatomical traits and their covariations of Cinnamomum camphora along an urban-rural gradient in Hefei, Eastern China. We found that Cinnamomum camphora in urban adopted a conservative hydraulic strategy with low leaf turgor loss point (Tlp), leaf hydraulic conductance (Kleaf), and leaf water potential resulting in 50 % loss of hydraulic conductance (P50), as well as a quick investment-return economic strategy with low unit leaf dry matter content (LMA) and high leaf nitrogen content (Leaf N). P50, Kleaf and LMA were significantly positively correlated with the urban-rural gradient (PC1urban-rural gradient), while Leaf N exhibited a negative correlation with it. The results showed a trade-off between intraspecific safety and efficiency in leaf hydraulic traits along the urban-rural gradient and an intraspecific coordinated variation in leaf hydraulic and economic traits. In addition, based on the analysis of a trait coordination network, it was revealed that leaf mesophyll and stomata were key structures for trait adjustment and coordination. Furthermore, our findings offer a significant theoretical underpinning for the effective management of landscape trees and the strategic planning of urban tree species.

Fate of dissolved inorganic nitrogen in turbulent rivers: The critical role of dissolved oxygen levels.

Dissolved inorganic nitrogen (DIN) is considered the main factor that induces eutrophication in water, and is readily influenced by hydrodynamic activities. In this study, a 4-year field investigation of nitrogen dynamics in a turbulent river was conducted, and a laboratory study was performed in the approximately homogeneous turbulence simulation system to investigate potential mechanisms involved in DIN transformation under turbulence. The field investigation revealed that, contrary to NO-3 dynamics, the NH+4 concentrations in water were lower in flood seasons than in drought seasons. Further laboratory results demonstrated that limitation of dissolved oxygen (DO) caused inactive nitrification and active denitrification in static river sediment. In contrast, the increased DO levels in turbulent river intensified the mineralization of organic nitrogen in sediment; moreover, ammonification and nitrification were activated, while denitrification was first activated and then depressed. Turbulence therefore decreased NH+4 and NO-2 concentrations, but increased NO-3 and total DIN concentrations in the overlying water, causing the total DIN to increase from 0.4 mg/L to maximum of 1.0 and 1.7 mg/L at low and high turbulence, respectively. The DIN was maintained at 0.7 and 1.0 mg/L after the 30-day incubation under low and high turbulence intensities (ε) of 3.4 × 10-4 and 7.4 × 10-2 m2/s3, respectively. These results highlight the critical role of DO in DIN budgets under hydrodynamic turbulence, and provide new insights into the DIN transport and transformation mechanisms in turbulent rivers.

Altitudinal patterns and controls of plant and soil nutrient concentrations and stoichiometry in subtropical China.

Altitude is a determining factor of ecosystem properties and processes in mountains. This study investigated the changes in the concentrations of carbon (C), nitrogen (N), and phosphorus (P) and their ratios in four key ecosystem components (forest floor litter, fine roots, soil, and soil microorganisms) along an altitudinal gradient (from 50 m to 950 m a.s.l.) in subtropical China. The results showed that soil organic C and microbial biomass C concentrations increased linearly with increasing altitude. Similar trends were observed for concentrations of total soil N and microbial biomass N. In contrast, the N concentration of litter and fine roots decreased linearly with altitude. With increasing altitude, litter, fine roots, and soil C:N ratios increased linearly, while the C:N ratio of soil microbial biomass did not change significantly. Phosphorus concentration and C:P and N:P ratios of all ecosystem components generally had nonlinear relationships with altitude. Our results indicate that the altitudinal pattern of plant and soil nutrient status differs among ecosystem components and that the relative importance of P vs. N limitation for ecosystem functions and processes shifts along altitudinal gradients.