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Background: Advancements in nanoscience have led to a profound paradigm shift in the therapeutic applications of medicinally important natural drugs. The goal of this research is to develop a nano-natural product for efficient cancer treatment. Methods and Results: For this purpose, mesoporous silica nanoparticles (MSNPs) were formulated, characterized, and loaded with caffeine to develop a targeted drug delivery system, i.e., caffeine-coated nanoparticles (CcNPs). In silico docking studies were conducted to examine the binding efficiency of the CcNPs with different apoptotic targets followed by in vitro and in vivo bioassays in respective animal models. Caffeine, administered both as a free drug and in nanomedicine form, along with doxorubicin, was delivered intravenously to a benzene-induced AML model. The anti-leukemic potential was assessed through hematological profiling, enzymatic biomarker analysis, and RT-PCR examination of genetic alterations in leukemia markers. Docking studies show strong inter-molecular interactions between CcNPs and apoptotic markers. In vitro analysis exhibits statistically significant antioxidant activity, whereas in vivo analysis exhibits normalization of the genetic expression of leukemia biomarkers STMN1 and S1009A, accompanied by the restoration of the hematological and morphological traits of leukemic blood cells in nanomedicine-treated rats. Likewise, a substantial improvement in hepatic and renal biomarkers is also observed. In addition to these findings, the nanomedicine successfully normalizes the elevated expression of GAPDH and mTOR induced by exposure to benzene. Further, the nanomedicine downregulates pro-survival components of the NF-kappa B pathway and upregulated P53 expression. Additionally, in the TRAIL pathway, it enhances the expression of pro-apoptotic players TRAIL and DR5 and downregulates the anti-apoptotic protein cFLIP. Conclusions: Our data suggest that MSNPs loaded with caffeine, i.e., CcNP/nanomedicine, can potentially inhibit transformed cell proliferation and induce pro-apoptotic TRAIL machinery to counter benzene-induced leukemia. These results render our nanomedicine as a potentially excellent therapeutic agent against AML. [ABSTRACT FROM AUTHOR]

Background and aims: Phosphate-solubilizing bacteria (PSB) possess significant potential for enhancing soil phosphorus bioavailability, but their efficacy may be constrained by carbon and nitrogen availability. Algae exhibit synergistic interactions with bacteria through producing active organic carbon. However, the influence of algae and PSB together on phosphorus bioavailability under varying nitrogen levels remains unclear.We conducted a microcosm experiment to explore the effects of applying Chlorella-Bacillus biofertilizer, along with various nitrate addition amounts, on both soil microbial community composition and phosphorus bioavailability. In addition, we employed a co-culture of Chlorella and Bacillus with different nitrogen concentrations to investigate the possible effects of nitrate addition on the production of organic anions and phosphatases of the Chlorella-Bacillus communities by using metabolomic analysis.Chlorella-Bacillus biofertilizer significantly increased soil Olsen-P concentration via strong interactive effects correlating with the various nitrate addition amounts in the microcosm experiment. These effects were due mainly to reducing the algal diversity, soil pH, and changing dissolved organic matter (DOM) characteristics, especially increasing the humification index (HIX). The metabolomic analyses of co-culture confirm that pathways related to the biosynthesis of fatty acids and phosphatases production are enhanced when nitrogen levels are high.Chlorella-Bacillus biofertilizer has significantly interactive effects with nitrate addition on soil phosphorus bioavailability by influencing soil DOM, pH and production of organic anions and phosphatases. These insights are useful for optimizing bio-fertilizer-nitrate combinations for increasing phosphorus bioavailability thereby reducing chemical fertilizer requirements.Methods: Phosphate-solubilizing bacteria (PSB) possess significant potential for enhancing soil phosphorus bioavailability, but their efficacy may be constrained by carbon and nitrogen availability. Algae exhibit synergistic interactions with bacteria through producing active organic carbon. However, the influence of algae and PSB together on phosphorus bioavailability under varying nitrogen levels remains unclear.We conducted a microcosm experiment to explore the effects of applying Chlorella-Bacillus biofertilizer, along with various nitrate addition amounts, on both soil microbial community composition and phosphorus bioavailability. In addition, we employed a co-culture of Chlorella and Bacillus with different nitrogen concentrations to investigate the possible effects of nitrate addition on the production of organic anions and phosphatases of the Chlorella-Bacillus communities by using metabolomic analysis.Chlorella-Bacillus biofertilizer significantly increased soil Olsen-P concentration via strong interactive effects correlating with the various nitrate addition amounts in the microcosm experiment. These effects were due mainly to reducing the algal diversity, soil pH, and changing dissolved organic matter (DOM) characteristics, especially increasing the humification index (HIX). The metabolomic analyses of co-culture confirm that pathways related to the biosynthesis of fatty acids and phosphatases production are enhanced when nitrogen levels are high.Chlorella-Bacillus biofertilizer has significantly interactive effects with nitrate addition on soil phosphorus bioavailability by influencing soil DOM, pH and production of organic anions and phosphatases. These insights are useful for optimizing bio-fertilizer-nitrate combinations for increasing phosphorus bioavailability thereby reducing chemical fertilizer requirements.Results: Phosphate-solubilizing bacteria (PSB) possess significant potential for enhancing soil phosphorus bioavailability, but their efficacy may be constrained by carbon and nitrogen availability. Algae exhibit synergistic interactions with bacteria through producing active organic carbon. However, the influence of algae and PSB together on phosphorus bioavailability under varying nitrogen levels remains unclear.We conducted a microcosm experiment to explore the effects of applying Chlorella-Bacillus biofertilizer, along with various nitrate addition amounts, on both soil microbial community composition and phosphorus bioavailability. In addition, we employed a co-culture of Chlorella and Bacillus with different nitrogen concentrations to investigate the possible effects of nitrate addition on the production of organic anions and phosphatases of the Chlorella-Bacillus communities by using metabolomic analysis.Chlorella-Bacillus biofertilizer significantly increased soil Olsen-P concentration via strong interactive effects correlating with the various nitrate addition amounts in the microcosm experiment. These effects were due mainly to reducing the algal diversity, soil pH, and changing dissolved organic matter (DOM) characteristics, especially increasing the humification index (HIX). The metabolomic analyses of co-culture confirm that pathways related to the biosynthesis of fatty acids and phosphatases production are enhanced when nitrogen levels are high.Chlorella-Bacillus biofertilizer has significantly interactive effects with nitrate addition on soil phosphorus bioavailability by influencing soil DOM, pH and production of organic anions and phosphatases. These insights are useful for optimizing bio-fertilizer-nitrate combinations for increasing phosphorus bioavailability thereby reducing chemical fertilizer requirements.Conclusion: Phosphate-solubilizing bacteria (PSB) possess significant potential for enhancing soil phosphorus bioavailability, but their efficacy may be constrained by carbon and nitrogen availability. Algae exhibit synergistic interactions with bacteria through producing active organic carbon. However, the influence of algae and PSB together on phosphorus bioavailability under varying nitrogen levels remains unclear.We conducted a microcosm experiment to explore the effects of applying Chlorella-Bacillus biofertilizer, along with various nitrate addition amounts, on both soil microbial community composition and phosphorus bioavailability. In addition, we employed a co-culture of Chlorella and Bacillus with different nitrogen concentrations to investigate the possible effects of nitrate addition on the production of organic anions and phosphatases of the Chlorella-Bacillus communities by using metabolomic analysis.Chlorella-Bacillus biofertilizer significantly increased soil Olsen-P concentration via strong interactive effects correlating with the various nitrate addition amounts in the microcosm experiment. These effects were due mainly to reducing the algal diversity, soil pH, and changing dissolved organic matter (DOM) characteristics, especially increasing the humification index (HIX). The metabolomic analyses of co-culture confirm that pathways related to the biosynthesis of fatty acids and phosphatases production are enhanced when nitrogen levels are high.Chlorella-Bacillus biofertilizer has significantly interactive effects with nitrate addition on soil phosphorus bioavailability by influencing soil DOM, pH and production of organic anions and phosphatases. These insights are useful for optimizing bio-fertilizer-nitrate combinations for increasing phosphorus bioavailability thereby reducing chemical fertilizer requirements. [ABSTRACT FROM AUTHOR]