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Precipitation minus evaporation over continents is the freshwater flux which can be sustainably exploited by mankind. Over a catchment and longer time periods, this flux is also the amount of water which flows into the ocean. An essential question for semi-arid areas of the world is how well this freshwater flux can be estimated and predicted to evolve under climate change and human water use. Knowing this flux is thus an essential element in regional water resources management. Here we examine this question over the catchment of the Mediterranean Sea. Using a novel data assimilation methodology that incorporates observed discharges of rivers in a land surface model, new estimates of the freshwater flux to the Mediterranean Sea for the period 1980–2013 are proposed. We find that more freshwater (40–60%) flows into the sea than previously estimated. The hypothesis we advance is that previous estimates have underestimated the discharges of the large number of unmonitored coastal basins and neglected submarine ground water flows. The proposed error bars on the estimate indicate that the degrading river gauging station network limits our ability to monitor this branch of the water cycle reliably. Nevertheless, the uncertainty is small enough to allow the identification of regions in which non-climatic decreases in the freshwater flows exist over the period.

Steroid hormones are essential in stress response, immune system regulation, and reproduction in mammals. Steroids with 3-oxo-Δ 4 structure, such as testosterone or progesterone, are catalyzed by steroid 5α-reductases (SRD5As) to generate their corresponding 3-oxo-5α steroids, which are essential for multiple physiological and pathological processes. SRD5A2 is already a target of clinically relevant drugs. However, the detailed mechanism of SRD5A-mediated reduction remains elusive. Here we report the crystal structure of PbSRD5A from Proteobacteria bacterium , a homolog of both SRD5A1 and SRD5A2, in complex with the cofactor NADPH at 2.0 Å resolution. PbSRD5A exists as a monomer comprised of seven transmembrane segments (TMs). The TM1-4 enclose a hydrophobic substrate binding cavity, whereas TM5-7 coordinate cofactor NADPH through extensive hydrogen bonds network. Homology-based structural models of HsSRD5A1 and -2, together with biochemical characterization, define the substrate binding pocket of SRD5As, explain the properties of disease-related mutants and provide an important framework for further understanding of the mechanism of NADPH mediated steroids 3-oxo-Δ 4 reduction. Based on these analyses, the design of therapeutic molecules targeting SRD5As with improved specificity and therapeutic efficacy would be possible. Steroid 5α-reductase 2 (SRD5A2), a testosterone metabolism enzyme, is implicated in human disease. Structural and biochemical analyses of PbSRD5A, a bacterial homolog, reveal SRD5A2 substrate binding pocket and provide framework for the design of new drugs targeting this enzyme.

Cueing facilitates retention and transfer of multimedia learning. From the perspective of cognitive load theory (CLT), cueing has a positive effect on learning outcomes because of the reduction in total cognitive load and avoidance of cognitive overload. However, this has not been systematically evaluated. Moreover, what remains ambiguous is the direct relationship between the cue-related cognitive load and learning outcomes. A meta-analysis and two subsequent meta-regression analyses were conducted to explore these issues. Subjective total cognitive load (SCL) and scores on a retention test and transfer test were selected as dependent variables. Through a systematic literature search, 32 eligible articles encompassing 3,597 participants were included in the SCL-related meta-analysis. Among them, 25 articles containing 2,910 participants were included in the retention-related meta-analysis and the following retention-related meta-regression, while there were 29 articles containing 3,204 participants included in the transfer-related meta-analysis and the transfer-related meta-regression. The meta-analysis revealed a statistically significant cueing effect on subjective ratings of cognitive load (d = -0.11, 95% CI = [-0.19, -0.02], p < 0.05), retention performance (d = 0.27, 95% CI = [0.08, 0.46], p < 0.01), and transfer performance (d = 0.34, 95% CI = [0.12, 0.56], p < 0.01). The subsequent meta-regression analyses showed that dSCL for cueing significantly predicted dretention for cueing (β = -0.70, 95% CI = [-1.02, -0.38], p < 0.001), as well as dtransfer for cueing (β = -0.60, 95% CI = [-0.92, -0.28], p < 0.001). Thus in line with CLT, adding cues in multimedia materials can indeed reduce SCL and promote learning outcomes, and the more SCL is reduced by cues, the better retention and transfer of multimedia learning.

Convection-permitting climate models have shown superior performance in simulating important aspects of the precipitation climate including extremes and also to give partly different climate change signals compared to coarser-scale models. Here, we present the first long-term (1998–2018) simulation with a regional convection-permitting climate model for Fenno-Scandinavia. We use the HARMONIE-Climate (HCLIM) model on two nested grids; one covering Europe at 12 km resolution (HCLIM12) using parameterized convection, and one covering Fenno-Scandinavia with 3 km resolution (HCLIM3) with explicit deep convection. HCLIM12 uses lateral boundaries from ERA-Interim reanalysis. Model results are evaluated against reanalysis and various observational data sets, some at high resolutions. HCLIM3 strongly improves the representation of precipitation compared to HCLIM12, most evident through reduced “drizzle” and increased occurrence of higher intensity events as well as improved timing and amplitude of the diurnal cycle. This is the case even though the model exhibits a cold bias in near-surface temperature, particularly for daily maximum temperatures in summer. Simulated winter precipitation is biased high, primarily over complex terrain. Considerable undercatchment in observations may partly explain the wet bias. Examining instead the relative occurrence of snowfall versus rain, which is sensitive to variance in topographic heights it is shown that HCLIM3 provides added value compared to HCLIM12 also for winter precipitation. These results, indicating clear benefits of convection-permitting models, are encouraging motivating further exploration of added value in this region, and provide a valuable basis for impact studies.

Efficient mechanized separation of Corcyra cephalonica eggs from impurities (appendages, scales, and dust) remains a major bottleneck in the mass production of Trichogramma wasps for the biocontrol of pests such as Chilo suppressalis . Here, discrete element method (DEM) parameter calibration is integrated with vibratory screening optimization for egg–impurity mixtures. Multi-factor experiments were conducted to quantify the intrinsic properties of C. cephalonica eggs (density: 1.043 g·cm⁻ 3 , elastic modulus: 3.34 MPa) and to determine key pneumatic separation thresholds. Based on suspension velocities, a feasible air velocity window of 0.4–4.6 ms⁻ 1 was identified (eggs: 0.8–2.3 ms⁻ 1 , appendages: 2.4–4.6 ms⁻ 1 , scales: 0.4–0.8 ms⁻ 1 ). DEM contact parameters (egg–egg dynamic friction, egg–steel static friction, and surface energy) were calibrated using the angle of repose as the response variable, yielding good agreement between experiments and simulations (22.37° vs. 23.19°, relative error: 3.7%). To our knowledge, this parameter set constitutes the first DEM database tailored to C. cephalonica eggs. Using the calibrated model, EDEM simulations were performed to evaluate key vibratory screening factors. The screening rate exhibited a non-monotonic dependence on vibration frequency, with an optimum at 12 Hz (78%·s⁻ 1 ). It peaked at an amplitude of 1 mm (77%·s⁻ 1 ), and optimization of the cone pendulum angle (defined as the inclination angle of the conical pendulum) showed a maximum screening rate of 81%·s⁻ 1 at 1.2°. Moreover, ultrasonic assistance improved the screening rate by up to 15% (at 12 Hz and 1.5 mm), likely by reducing particle agglomeration. Overall, the calibrated DEM parameters and the identified operating windows (airflow velocity, vibration frequency/amplitude, and pendulum angle) provide quantitative guidance for the design of vibratory screens and pneumatic separators for host egg cleaning, thereby supporting the automation and scalability of Trichogramma -based biocontrol for stored-product pests.

Nicotinamide adenine dinucleotide (NAD) is an essential coenzyme that has emerged as a central hub linking redox equilibrium and signal transduction in living organisms. The homeostasis of NAD is required for plant growth, development, and adaption to environmental cues. In this study, we isolated a chilling hypersensitive Arabidopsis thaliana mutant named qs-2 and identified the causal mutation in the gene encoding quinolinate synthase (QS) critical for NAD biosynthesis. The qs-2 mutant is also hypersensitive to salt stress and abscisic acid (ABA) but resistant to drought stress. The qs-2 mutant accumulates a reduced level of NAD and over-accumulates reactive oxygen species (ROS). The ABA-hypersensitivity of qs-2 can be rescued by supplementation of NAD precursors and by mutations in the ABA signaling components SnRK2s or RBOHF. Furthermore, ABA-induced over-accumulation of ROS in the qs-2 mutant is dependent on the SnRK2s and RBOHF. The expression of QS gene is repressed directly by ABI4, a transcription factor in the ABA response pathway. Together, our findings reveal an unexpected interplay between NAD biosynthesis and ABA and stress signaling, which is critical for our understanding of the regulation of plant growth and stress responses.

The high-latitude regions of the Northern Hemisphere are a nexus for the interaction between land surface physical properties and their exchange of carbon and energy with the atmosphere. At these latitudes, two carbon pools of planetary significance – those of the permanently frozen soils (permafrost), and of the great expanse of boreal forest – are vulnerable to destabilization in the face of currently observed climatic warming, the speed and intensity of which are expected to increase with time. Improved projections of future Arctic and boreal ecosystem transformation require improved land surface models that integrate processes specific to these cold biomes. To this end, this study lays out relevant new parameterizations in the ORCHIDEE-MICT land surface model. These describe the interactions between soil carbon, soil temperature and hydrology, and their resulting feedbacks on water and CO2 fluxes, in addition to a recently developed fire module. Outputs from ORCHIDEE-MICT, when forced by two climate input datasets, are extensively evaluated against (i) temperature gradients between the atmosphere and deep soils, (ii) the hydrological components comprising the water balance of the largest high-latitude basins, and (iii) CO2 flux and carbon stock observations. The model performance is good with respect to empirical data, despite a simulated excessive plant water stress and a positive land surface temperature bias. In addition, acute model sensitivity to the choice of input forcing data suggests that the calibration of model parameters is strongly forcing-dependent. Overall, we suggest that this new model design is at the forefront of current efforts to reliably estimate future perturbations to the high-latitude terrestrial environment.

Phage-antibiotic synergy (PAS) has been recently proposed as a superior strategy for the treatment of multidrug-resistant pathogens to effectively reduce bacterial load and slow down both phage and antibiotic resistance. However, the underlying mechanisms of resistance suppression by PAS have been poorly and rarely been studied. In this study, we tried to understand how PAS suppresses the emergence of resistance using a hypervirulent Klebsiella pneumoniae (KP) strain and a novel phage H5 in combination with ceftazidime (CAZ) as a model. Our study reveals a novel mechanism by which PAS drives altered evolutionary trajectory of bacterial populations, leading to suppressed emergence of resistance. The findings advance our understanding of how PAS suppresses the emergence of resistance, and are imperative for optimizing the efficacy of phage-antibiotic therapy to further improve clinical outcomes.

Abscisic acid （ABA） is the most important hormone for plants to resist drought and other abiotic stresses. ABA binds directly to the PYR/PYL family of ABA receptors, resulting in inhibition of type 2C phosphatases （PP2C） and activation of downstream ABA signaling. It is envisioned that intervention of ABA signaling by small molecules could help plants to overcome abiotic stresses such as drought, cold and soil salinity. However, chemical instability and rapid catabolism by plant enzymes limit the practical application of ABA itself. Here we report the identification of a small molecule ABA mimic （AM1） that acts as a potent activator of multiple members of the family of ABA receptors. In Arabidopsis, AM1 activates a gene network that is highly similar to that induced by ABA. Treatments with AM1 inhibit seed germination, prevent leaf water loss, and promote drought resistance. We solved the crystal structure of AM1 in complex with the PYL2 ABA receptor and the HAB1 PP2C, which revealed that AM1 mediates a gate-latch- lock interacting network, a structural feature that is conserved in the ABA-bound receptor/PP2C complex. Together, these results demonstrate that a single small molecule ABA mimic can activate multiple ABA receptors and protect plants from water loss and drought stress. Moreover, the AM1 complex crystal structure provides a structural basis for designing the next generation of ABA-mimicking small molecules.