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Background: Drug–drug interactions (DDIs) may occur when two or more drugs are taken together, leading to undesired side effects or potential synergistic effects. Most clinical effects of drug combinations have not been assessed in clinical trials. Therefore, predicting DDIs can provide better patient management, avoid drug combinations that can negatively affect patient care, and exploit potential synergistic combinations to improve current therapies in women’s healthcare. Methods: A DDI prediction model was built to describe relevant drug combinations affecting reproductive treatments. Approved drug features (chemical structure of drugs, side effects, targets, enzymes, carriers and transporters, pathways, protein–protein interactions, and interaction profile fingerprints) were obtained. A unified predictive score revealed unknown DDIs between reproductive and commonly used drugs and their associated clinical effects on reproductive health. The performance of the prediction model was validated using known DDIs. Results: This prediction model accurately predicted known interactions (AUROC = 0.9876) and identified 2991 new DDIs between 192 drugs used in different female reproductive conditions and other drugs used to treat unrelated conditions. These DDIs included 836 between drugs used for in vitro fertilization. Most new DDIs involved estradiol, acetaminophen, bupivacaine, risperidone, and follitropin. Follitropin, bupivacaine, and gonadorelin had the highest discovery rate (42%, 32%, and 25%, respectively). Some were expected to improve current therapies (n = 23), while others would cause harmful effects (n = 11). We also predicted twelve DDIs between oral contraceptives and HIV drugs that could compromise their efficacy. Conclusions: These results show the importance of DDI studies aimed at identifying those that might compromise or improve their efficacy, which could lead to personalizing female reproductive therapies. Full article

Chemical fertilizers pose significant risks to both human health and the environment. To investigate the effect of substituting nitrogen fertilizer with vermicompost tea on wheat yield, shoot chemical constituents, and grain quality under clay-loam soil conditions, two field experiments were conducted at the Faculty of Agriculture, Cairo University, Egypt, during the winter seasons of 2021–2022 and 2022–2023. A split-plot design in randomized complete blocks with three replications was employed. Vermicompost tea was assigned to the main plots, while wheat cultivars were assigned to the subplots. The cultivars were evaluated under four treatments involving partial substitution of mineral nitrogen (recommended dose of nitrogen (RDN%, 190 kg N ha⁻¹): a control (90% of RDN + 25 kg vermicompost tea), 80% of RDN + 37.5 kg vermicompost tea, and 70% of RDN + 50 kg vermicompost tea. Nitrogen fertilizer (RDN%) was applied at rates of 190 (control), 170 (90%), 150 (80%), and 130 (70%) kg N ha⁻¹. The results indicated that partially substituting mineral nitrogen with vermicompost tea significantly increased grain weight/Ha, chlorophyll A, chlorophyll B, carotenoids, nitrogen, phosphorus (P), and potassium (K) content in shoots, as well as ash, crude protein, crude fiber, total sugar, and N, P, and K content in wheat grains. The grain weight/Ha of the Sakha-95, Giza-171, and Sads-14 cultivars increased by 38.6%, 33.5%, and 39.3%, respectively, when treated with 70% RDN + 50 kg vermicompost tea. The combination of the Sads-14 cultivar and 70% RDN + 50 kg vermicompost tea resulted in the highest values for grain weight/ha (9.43 tons ha⁻¹), chlorophyll A (1.39 mg/g), chlorophyll B (1.04 mg/g), N (5.08%), P (1.63%), and P (2.43%) content in shoots. The same combination also improved ash (2.89%), crude fiber (2.84%), and K (6.05%) content in grains. In conclusion, the application of vermicompost tea in conjunction with chemical fertilizers offers a viable alternative to using chemical fertilizers alone, promoting sustainable agricultural practices and improving wheat production. It is recommended that mineral nitrogen fertilizer be partially replaced with vermicompost tea to enhance both the productivity and grain quality of wheat while minimizing environmental pollution. Full article

In China’s Loess Plateau, sustainable agricultural end products are affected by an insufficiency of water resources. Rising crop water use efficiency (WUE) through field management pattern improvement is a crucial plan of action to address this issue. However, there is no agreement among researchers on the most appropriate field management practices regarding WUE, which requires further integrated quantitative analysis. We conducted a meta-analysis by quantifying the effect of agricultural practices surrounding nitrogen (N) fertilizer management. The two experimental cultivars were Yunhan–20410 and Yunhan–618. The subplots included nitrogen 0 kg·ha⁻¹ (N0), 90 kg·ha⁻¹ (N90), 180 kg·ha⁻¹ (N180), 210 kg·ha⁻¹ (N210), and 240 kg·ha⁻¹ (N240). Our results show that higher N rates (up to N210) enhanced water consumption during the node-flowering and flowering-maturity time periods. YH–618 showed higher water use during the sowing–greening and node-flowering periods but decreased use during the greening-node and flowering-maturity periods compared to YH–20410. The N210 treatment under YH–618 maximized water use efficiency (WUE). Increased N rates (N180–N210) decreased covering temperatures (T_max, T_min, T_aver) during flowering, increasing the level of grain filling. Spike numbers rose with N application, with an off-peak at N210 for strong-gluten wheat. The 1000-grain weight was at first enhanced but decreased at the far end of N180–N210. YH–618 with N210 achieved a harvest index (HI) similar to that of YH–20410 with N180, while excessive N (N240) or water reduced the HI. Dry matter accumulation increased up to N210, resulting in earlier stabilization. Soil water consumption from wintering to jointing was strongly correlated with pre-flowering dry matter biological process and yield, while jointing–flowering water use was linked to post-flowering dry matter and spike numbers. Post-flowering dry matter accumulation was critical for yield, whereas spike numbers positively impacted yield but negatively affected 1000-grain weight. In conclusion, our results provide evidence for determining suitable integrated agricultural establishment strategies to ensure efficient water use and sustainable production in the Loess Plateau region. Full article

Achieving food security for a growing population under a changing climate is a key concern in Senegal, where agriculture employs 77% of the workforce with a majority of small farmers who rely on the production of crops for their subsistence and for income generation. Moreover, due to the underproductive soils and variable rainfall, Senegal depends on imports to fulfil 70% of its food requirements. In this research, we considered four crops that are crucial for Senegalese agriculture: millet, sorghum, peanuts and rice. We used crop simulation models to explore existing yield gaps and optimal agronomic practices. Improving the N fertilizer management in sorghum and millet resulted in 40–100% increases in grain yields. Improved N symbiotic fixation in peanuts resulted in yield increases of 20–100% with highest impact in wetter locations. Optimizing irrigation management and N fertilizer use resulted in 20–40% gains. The best N fertilizer strategy for sorghum and millet included applying low rates at sowing and in early development stages and adjusting a third application, considering the expected rainfall. Peanut yields of the variety 73-33 were higher than Fleur-11 in all locations, and irrigation showed no clear economic advantage. The best N fertilizer management for rainfed rice included applying 30 kg N/ha at sowing, 25 days after sowing (DAS) and 45 DAS. The best combination of sowing dates for a possible double rice crop depended on irrigation costs, with a first crop planted in January or March and a second crop planted in July. Our work confirmed results obtained in field research experiments and identified management practices for increasing productivity and reducing yield variability. Those crop management practices can be implemented in pilot experiments to further validate the results and to disseminate best management practices for farmers in Senegal. Full article

Vaccinium oldhamii, a blueberry species native to Korea, is a deciduous shrub in the Ericaceae family. Its fruit possesses various pharmacological properties, including anti-inflammatory effects and potential for treating osteoporosis. This study evaluated the effects of five fertilization concentration levels using Multifeed 20 (N:P:K = 20:20:20) on the growth and physiological characteristics of one-year-old V. oldhamii container seedlings. Treatments included 0 g·L⁻¹ (control), 0.5, 1.0, 1.5, and 2.0 g·L⁻¹. Increases in stem thickness, root length, and total dry weight were observed in the control, 0.5, 1.0, and 1.5 g·L⁻¹ treatments, whereas growth declined at 2.0 g·L⁻¹. Mortality rates exceeded 15% at concentrations above 1.0 g·L⁻¹. Photosynthetic capacity and chlorophyll content increased with fertilization. However, while growth improved with increasing fertilizer up to a certain level, it declined at the highest concentration. A fertilization rate of 0.5 g·L⁻¹ proved to be the most economically and environmentally efficient for producing healthy seedlings. This study provides the first fertilization threshold for V. oldhamii, offering practical guidance for nursery production and forming a foundation for future domestication strategies. Full article

(1) Background: Polyploid fish are highly important in increasing fish production, improving fish quality, and breeding new varieties. The loach (Misgurnus anguillicaudatus), as a naturally polyploid fish, serves as an ideal biological model for investigating the mechanisms of chromosome doubling; (2) Methods: In this study, tetraploidization in diploid loach was induced by heat shock treatment, and, for the first time, the role of the key cell cycle gene cdk1 (cyclin-dependent kinase 1) in chromosome doubling was investigated; (3) Results: The experimental results show that when eggs are fertilized for 20 min and then subjected to a 4 min heat shock treatment at 39–40 °C, this represents the optimal induction condition, resulting in a tetraploid rate of 44%. Meanwhile, the results of the cdk1 knockout model (2n cdk1^−/−) constructed using CRISPR/Cas9 showed that the absence of cdk1 significantly increased the chromosome doubling efficiency of the loach. The qPCR analysis revealed that knockout of cdk1 significantly upregulated cyclin genes (ccnb3,ccnc, and ccne1), while inhibiting expression of the separase gene espl1 (p < 0.05); (4) Conclusions: During chromosome doubling in diploid loaches induced by heat shock, knocking out the cdk1 gene can increase the tetraploid induction rate. This effect may occur through downregulation of the espl1 gene. This study offers novel insights into optimizing the induced breeding technology of polyploid fish and deciphering its molecular mechanism, while highlighting the potential application of integrating gene editing with physical induction. Full article

The premature senescence of red raspberry leaves severely affects plant growth. In this study, the double-season red raspberry cultivar ‘Polka’ was used, with N₁₅₀ (0.10 g N·kg⁻¹) selected as the treatment group (T150) and N₀ (0 g N·kg⁻¹) set as the control (CK). This study systematically investigated the mechanism of premature senescence in red raspberry leaves under different nitrogen application levels by measuring physiological parameters and conducting a combined multi-omics analysis of transcriptomics and metabolomics. Results showed that T150 plants had 8.34 cm greater height and 1.45 cm greater ground diameter than CK. The chlorophyll, carotenoid, soluble protein, and sugar contents in all leaf parts of T150 were significantly higher than those in CK, whereas soluble starch contents were lower. Malondialdehyde (MDA) content and superoxide anion (O₂⁻) generation rate in the lower leaves of T150 were significantly lower than those in CK. Superoxide sismutase (SOD) and peroxidase (POD) activities in the middle and lower functional leaves of T150 were higher than in CK, while catalase (CAT) activity was lower. Transcriptomic analysis identified 4350 significantly differentially expressed genes, including 2062 upregulated and 2288 downregulated genes. Metabolomic analysis identified 135 differential metabolites, out of which 60 were upregulated and 75 were downregulated. Integrated transcriptomic and metabolomic analysis showed enrichment in the phenylpropanoid biosynthesis (ko00940) and flavonoid biosynthesis (ko00941) pathways, with the former acting as an upstream pathway of the latter. A premature senescence pathway was established, and two key metabolites were identified: chlorogenic acid content decreased, and naringenin chalcone content increased in early senescent leaves, suggesting their pivotal roles in the early senescence of red raspberry leaves. Modulating chlorogenic acid and naringenin chalcone levels could delay premature senescence. Optimizing fertilization strategies may thus reduce senescence risk and enhance the productivity, profitability, and sustainability of the red raspberry industry. Full article

Water scarcity and spatial variability in soil fertility are key constraints to stable grain production in the Huang-Huai-Hai Plain. However, the interaction mechanisms between regulated deficit irrigation and soil fertility influencing yield formation and water-nitrogen use efficiency in winter wheat remain unclear. In this study, a two-year field experiment (2022–2024) was conducted to investigate the effects of two irrigation regimes—regulated deficit irrigation during the heading to grain filling stage (D) and full irrigation (W)—under four soil fertility levels: F1 (N: P: K = 201.84: 97.65: 199.05 kg ha⁻¹), F2 (278.52: 135: 275.4 kg ha⁻¹), F3 (348.15: 168.75: 344.25 kg ha⁻¹), and CK (no fertilization). The results show that aboveground dry matter accumulation, total nitrogen content, pre-anthesis dry matter and nitrogen translocation, and post-anthesis accumulation significantly increased with fertility level (p < 0.05). Regulated deficit irrigation promoted the contribution of post-anthesis dry matter to grain yield under the CK and F1 treatments, but suppressed it under the F2 and F3 treatments. However, it consistently enhanced the contribution of post-anthesis nitrogen to grain yield (p < 0.05) across all fertility levels. Higher fertility levels prolonged the grain filling duration by 18.04% but reduced the mean grain filling rate by 15.05%, whereas regulated deficit irrigation shortened the grain filling duration by 3.28% and increased the mean grain filling rate by 12.83% (p < 0.05). Grain yield significantly increased with improved fertility level (p < 0.05), reaching a maximum of 9361.98 kg·ha⁻¹ under the F3 treatment. Regulated deficit irrigation increased yield under the CK and F1 treatments but reduced it under the F2 and F3 treatments. Additionally, water use efficiency exhibited a parabolic response to fertility level and was significantly enhanced by regulated deficit irrigation. Nitrogen partial factor productivity (NPFP) declined with increasing fertility level (p < 0.05); Regulated deficit irrigation improved NPFP under the F1 treatment but reduced it under the F2 and F3 treatments. The highest NPFP (41.63 kg·kg⁻¹) was achieved under the DF1 treatment, which was 54.81% higher than that under the F3 treatment. TOPSIS analysis showed that regulated deficit irrigation combined with the F1 fertility level provided the optimal balance among yield, WUE, and NPFP. Therefore, implementing regulated deficit irrigation during the heading–grain filling stage under moderate fertility (F1) is recommended as the most effective strategy for achieving high yield and efficient resource utilization in winter wheat production in this region. Full article

Soil salinization and selenium (Se) deficiency threaten global food security. This study developed a composite bioinoculant combining ACC deaminase-producing Serratia liquefaciens and biogenically synthesized nano-selenium (SeNPs) to alleviate saline–alkali stress and enhance Se nutrition in rice (Oryza sativa L.). A strain of S. liquefaciens with high ACC deaminase activity was isolated and used to biosynthesize SeNPs with stable physicochemical properties. Pot experiments showed that application of the composite inoculant (S3: S. liquefaciens + 40 mmol/L SeNPs) significantly improved seedling biomass (fresh weight +53.8%, dry weight +60.6%), plant height (+31.6%), and root activity under saline–alkali conditions. S3 treatment also enhanced panicle weight, seed-setting rate, and grain Se content (234.13 μg/kg), meeting national Se-enriched rice standards. Moreover, it increased rhizosphere soil N, P, and K availability and improved microbial α-diversity. This is the first comprehensive demonstration that a synergistic bioformulation of ACC deaminase PGPR and biogenic SeNPs effectively mitigates saline–alkali stress, enhances soil fertility, and enables safe Se biofortification in rice. Full article

This study investigated the impact of nitrogen (N) fertilization on the yield and grain filling (GF) characteristics of two conventional japonica rice varieties with distinct panicle types: Yangchan 3501 (large-panicle: spikelets per panicle $> 150$) and Nangeng 46 (medium-panicle: $100 <$ spikelets per panicle $< 150$). Field experiments were conducted over two growing seasons (2022–2023) with three N application rates (T1: 225 kg ha⁻¹, T2: 270 kg ha⁻¹, T3: 315 kg ha⁻¹). Key measurements included tiller dynamics, panicle composition, GF parameters modeled using the Richards equation, and enzyme activities related to nitrogen metabolism (Fd-GOGAT, NR) and carbohydrate transport (α-amylase, SPS). Results showed that the yield increased with higher N levels for both varieties, with Yangchan 3501 achieving higher yields primarily through increased grains per panicle (15.65% rise under T3 vs. T1), while Nangeng 46 relied on panicle number (8.83% increase under T3 vs. T1). Nitrogen application enhanced Fd-GOGAT and NR activities, prolonging photosynthesis and improving GF rates, particularly in the inferior grains of Yangchan 3501 during middle and late stages. However, a high N reduced seed-setting rates and 1000-grain weight, with larger panicle types exhibiting a greater sensitivity to N-induced changes in branch structure and assimilate allocation. This study highlights that optimizing N management can improve nitrogen-metabolism enzyme activity and GF efficiency, especially in large-panicle rice, while medium-panicle types require higher N inputs to maximize panicle number. These findings provide actionable insights for achieving high yields and efficient nutrient use in conventional rice cultivation. Full article

Developing precision models to describe agricultural growth is a necessary step to promote sustainable agriculture and increase resource circulation. In this study, the researchers hydroponically cultivated Bibb lettuce (Lactuca sativa) across a variety of nitrogen, phosphorus, and potassium (NPK)-limited treatments and developed robust data-driven kinetic models observing nutrient uptake, biomass growth, and tissue composition based on all three primary macronutrients. The resulting Dynamic μ model is the first to integrate plant maturity’s impact on growth rate, significantly improving model accuracy across limiting nutrients, treatments, and developmental stages. This reduced error supports this simple expansion as a practical and necessary inclusion for agricultural kinetic modeling. Furthermore, analysis of nutrient uptake refines the ideal hydroponic nutrient balance for Bibb lettuce to 132, 35, and 174 mg L⁻¹ (N, P, and K, respectively), while qualitative cell yield analysis identifies minimum nutrient thresholds at approximately 26.2–41.7 mg-N L⁻¹, 3.7–5.6 mg-P L⁻¹, and 17.4–31.5 mg-K L⁻¹ to produce compositionally healthy lettuce. These findings evaluate reclaimed wastewater’s ability to offset the fertilizer burden for lettuce by 23–45%, 14–57%, and 3–23% for N, P, and K and guide the required minimum amount of wastewater pre-processing or nutrient supplements needed to completely fulfill hydroponic nutrient demands. Full article

Excessive fertilization is a widespread issue in onion (Allium cepa L.) production in Southwest China. This practice not only leads to environmental pollution but also decreases the marketable yield and fertilizer productivity of onions. Identifying an optimal fertilization rate is crucial for promoting high-yield and highly efficient onion cultivation. The objective of this research is to determine the appropriate amount of fertilizer by investigating the effects of different fertilization rates on the growth characteristics and bulb yield of onion. The study was conducted over two consecutive growing seasons utilizing a randomized complete block design, which included six treatments: local routine fertilizer application (F1), a 20% reduction from F1 (F2), a 40% reduction from F1 (F3), a 60% reduction from F1 (F4), an 80% reduction from F1 (F5), and no fertilizer application (F0). The results show that, at the mature stage, aboveground dry matter quantity and its accumulation rate of onion under treatment F2 were found to be the highest among all other treatments across both growing seasons. Following the onset of bulbing, dry matter accumulation initially increased but subsequently decreased with reduced fertilizer supply; notably, it was greater under treatment F2 compared to other treatments. Compared with F1, the PFPN (partial factor productivity of nitrogen fertilizer) under treatment F2 increased by 35.2% and 32.0%, and the marketable bulb yield under treatment F2 increased by 8.4% and 5.8% during the 2022–2023 and 2023–2024 growing seasons, respectively. The marketable bulb yield demonstrated extremely significant positive correlations with aboveground dry matter and the dry matter accumulation rate throughout all growth periods in both growing seasons. Furthermore, marketable bulb yield exhibited extremely significant positive correlations with dry matter translocation before the onset of bulbing and dry matter accumulation following bulbing initiation. It was concluded that the appropriate fertilizer application (F2), characterized by a fertilization rate of 339-216-318 kg ha⁻¹ for N-P₂O₅-K₂O, enhanced onion bulb yield and nitrogen fertilizer productivity by promoting post-bulbing dry matter accumulation. This study emphasizes the significance of optimizing the fertilization rate as a crucial factor in achieving high-yield and highly efficient onion cultivation by enhancing dry matter accumulation. Full article

Investigating the factors influencing rice grain yield (GY) is critical for optimizing nitrogen (N) management and enhancing resource use efficiency in rice cultivation. However, few studies have comprehensively investigated the factors affecting rice GY, considering an entire influence chain encompassing rice N uptake, growth indicators, and GY components. In this study, field experiment with six different N fertilizer rates (0, 60, 120, 180, 225, and 300 kg N ha⁻¹, i.e., N0, N60, N120, N180, N225, and N300) was conducted in the Jianghan Plain in the Middle Reaches of the Yangtze River, China, to comprehensively elucidate the factors influencing rice GY from aspects of rice N uptake, growth indicators, and GY components and determine the optimal N fertilizer rate. The results showed that rice GY and N uptake initially increased and then either stabilized or declined with higher N fertilizer rate, while apparent N loss escalated with increased N fertilizer rate. The application of N fertilizer significantly promoted the increase in straw N uptake, which was significantly positively correlated with growth indicators (p < 0.05). Among all GY components, panicle number per hill was the most significant positive factor influencing rice GY, and it was significantly positively correlated with all rice growth indicators (p < 0.05). In addition, N180 was the optimal N fertilizer rate, ensuring more than 95% of maximum GY and reducing N loss by 74% and 39% compared to N300, respectively. Meanwhile, the average N balance for N180 remained below 60 kg N ha⁻¹. In conclusion, optimizing the N fertilizer application in paddy fields can effectively maintain stable rice GY and minimize environmental pollution. Full article

Nitrogen (N) availability often limits primary productivity in terrestrial ecosystems, and arbuscular mycorrhizal fungi (AMF) can enhance plant N acquisition. This study investigated the interactive effects of N fertilization and AMF inoculation on N uptake, plant performance and phenolic acid content in Hyssopus officinalis L., with the aim of promoting sustainable N management in H. officinalis cultivation. A factorial randomized complete block design was employed to evaluate four AMF inoculation strategies (no inoculation, root inoculation, soil inoculation and combined root–soil inoculation) across three N application rates (0, 0.5 and 1,1 g N pot⁻¹ (7 L)) in a controlled greenhouse environment. Combined root and soil AMF inoculation alongside moderate N fertilization (0.5 mg N pot⁻¹) optimized N use efficiency, maximizing plant biomass and bioactive compound production. Compared to non-inoculated controls, this treatment combination increased N uptake by 30%, phosphorus uptake by 24% and potassium uptake by 22%. AMF colonization increased chlorophyll content and total phenolic compounds under moderate N supply. However, excessive N application (1 g N pot⁻¹) reduced AMF effectiveness and secondary metabolite accumulation. Notably, AMF inoculation without N fertilization yielded the highest levels of anthocyanin and salicylic acid, indicating differential N-dependent regulation of specific biosynthetic pathways. The interaction between AMF and N demonstrated that moderate N fertilization (0.5 g N pot⁻¹) combined with dual inoculation strategies can reduce total N input requirements by 50%, while maintaining optimal plant performance. These findings provide practical insights for developing N-efficient cultivation protocols in medicinal plant production systems, contributing to sustainable agricultural practices that minimize environmental N losses. Full article

The reduced N fertilization rate and N supplied by pea (Pisum sativum L.) residue may sustain subsequent spring wheat (Triticum aestivum L.) growth, yield, and quality. We examined the response of spring wheat growth, yield, and quality to cropping systems and N fertilization rates from 2012 to 2019 in the US northern Great Plains. Cropping systems were conventional till spring wheat–fallow (CTWF), no-till spring wheat–fallow (NTWF), no-till spring wheat–pea (NTWP), and no-till continuous wheat (NTCW), and N fertilization rates to spring wheat were 0, 50, 100, and 150 kg N ha⁻¹. Wheat plant density and straw yield were 13–100% greater for CTWF and NTWF than NTWP and NTCW in most years. Wheat grain yield and protein concentration were also 15–115% greater for CTWF and NTWF than other cropping systems at most N fertilization rates and years. In contrast, wheat grain test weight was 1–2% lower for CTWF and NTWF at most N fertilization rates and years. Increasing N fertilization rate mostly increased grain yield and protein concentration but reduced grain test weight for most cropping systems and years. Although CTWF and NTWF with or without N fertilization increased wheat yield and quality, these practices are not sustainable due to reduced annualized yield, soil health, and environmental quality. Because of similar or greater grain yields and test weights among NTWP with 50 kg N ha⁻¹ and NTWP and NTCW with other N rates, NTWP with reduced N rates may sustain spring wheat yield and grain size but not grain protein in the northern Great Plains. Full article