Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disorder that primarily affects females. Estrogen deficiency plays a key role in its development, prompting interest in phytoestrogens as safer alternatives to synthetic estrogen therapies. Our previous in-silico analysis identified Bavachin (BVN) as a potent phytoestrogen capable of targeting the NF-κB complex. This study investigates the therapeutic and mechanistic effects of BVN in mitigating the pathogenesis and inflammation associated with RA. BVN treatment significantly reduced the levels of key inflammatory markers, including IL-6, IL-1β, TNF-α, and NF-κB p65, in RA fibroblast-like synoviocytes (RA-FLS). Additionally, BVN demonstrated a protective effect by significantly decreasing the expression of cell adhesion and angiogenesis factors, such as VTN, SPARC, VEGF, and Cadherin, in TNF-α-induced synovial cells and RA-FLS, as assessed using Western blotting and immunocytochemistry assays. BVN also affected the binding of VTN and SPARC protein, inhibiting angiogenic progression. The therapeutic effects of BVN were confirmed via in vivo studies using a collagen-induced arthritis (CIA) rat model. Treatment with BVN significantly reduced paw inflammation, arthritic scores, immune cell infiltration, and plasma levels of IL-6, IL-1β, and TNF-α while also decreasing the deposition of VTN and SPARC in the rat synovial tissues. Our findings thus suggest that BVN has the potential to serve as a natural therapy for managing RA pathogenesis and reducing associated inflammation.

Introduction: Indiscriminate application of poultry litter (PL) often exceeds crop nutrient demand, resulting in nitrate (NO3-N) and phosphate (PO4-P) leaching to groundwater. Conventional amendments, i.e., alum and iron sulfate, effectively immobilize nutrients but may induce soil acidification. Biochar (BC), a carbon-rich byproduct, has emerged as a potentially sustainable alternative. However, a systematic comparison with established amendments is required, along with the role of manure-derived dissolved organic carbon (DOC) on nutrient leaching dynamics, before broader adoption. Materials and methods: An in-situ pot experiment was conducted using coarse-textured soil in 24 leaching columns under open-field conditions with corn (Zea mays) as the test crop. Six treatments were evaluated: (i) soil without PL, (ii) soil with 20 t ha(-1) PL (iii) soil with 20 t ha(-1) PL + 10% BC-1 (w/w relative to PL), (iv) soil with 20 t ha(-1) PL + 10% BC-2, (v) soil with 20 t ha(-1) PL + 10% alum, and (vi) soil with 20 t ha(-1) PL + 10% iron sulfate. Leachate samples across five natural rainfall events were analyzed for NO3-N, PO4-P, and DOC. Results: In unamended PL-treated soil, NO3-N and PO4-P concentrations ranged from 0.53-51.5 and 3.88-20.5 mg L-1, respectively. With amendments, NO3-N concentrations ranged from 1.94-42.0 (BC-1), 1.72-39.2 (BC-2), 1.07-22.1 (alum), and 1.55-46.7 mg L-1 (iron sulfate), while PO4-P concentrations ranged from 3.20-13.9, 3.18-13.6, 1.51-8.25, and 1.99-11.6 mg L-1, respectively. Across, five rainfall events, amendments reduced cumulative average PO4-P loading by 14.5% (BC-1), 33% (BC-2), 48% (alum), and 52% (iron sulfate) and NO3-N loading by 37% (BC-2), 41% (alum), and 33% (iron sulfate), whereas BC-1 increased cumulative average NO3-N loading by 10% compared to unamended manure soil. DOC exhibited significant positive correlations with NO3-N (r = 0.54, p < 0.05) and PO4-P (r = 0.83, p < 0.001). Grain yield was similar in unamended and BC-amended soils, significantly higher than alum- and iron sulfate-amended soils. Conclusion: The role of amendments (BC-2, alum, and iron sulfate) was significant for PO4-P retention. The NO3-N retention was modest and influenced by crop growth stages, while PO4-P loss was governed by rainfall amount.

Hypothyroidism (HT) is a common endocrine disorder that adversely affects different body functions. Saraca asoca (SA) is traditionally used as a remedy for gynaecological disorders. Although thyroid hormones are essential for reproductive function, no data are available so far on the impact of SA on thyroid function. Therefore, the current study attempted to evaluate the effects of SA in regulating HT through in vivo and in silico approaches. HT was induced in rats by administering 0.05

Biochar has emerged as a promising soil amendment for mitigating phosphorus (P) losses from agricultural runoff; however, untreated biochar often exhibits limited P adsorption capacity due to inherent P content and negatively charged surface functional groups. To overcome these limitations, this study synthesized and evaluated three pinewood-derived biochar variants: untreated, Fe-modified, and DI-washed, for their P sorption-desorption behavior and soil performance. Biochar variants were characterized using XRD, SEM, FTIR, and BET analyses, and P sorption was modeled using the Langmuir isotherm. Fe-modified biochar exhibited the highest sorption maxima (Smax: 1250-2000 mg kg(-1)), followed by DI-washed (1181-1339 mg kg(-1)) and untreated variants (310-390 mg kg(-1)). Desorption studies revealed stark contrasts: Fe-modified biochar released <0.1 % of sorbed P, DI-washed released similar to 10 %, and untreated released similar to 63 %, indicating strong retention in Fe-modified samples. An incubation experiment mimicking field conditions in high-P coastal plain sandy soil confirmed that Fe-modified biochar reduced cumulative water-extractable P by up to 34 % compared to the control, while DI-washed biochar provided moderate retention and controlled release, offering agronomic benefits. These findings demonstrate that Fe modification substantially enhances P immobilization, whereas DI washing offers a cost-effective alternative for balancing environmental protection and agronomic nutrient availability. The novelty of the study lies in systematically comparing Fe-modified and DI-washed biochars derived from the same feedstock across multiple production batches, thereby linking sorption-desorption dynamics with soil incubation performance to simulate real-world conditions. Overall, biochar modification strategies can be tailored to mitigate P losses from high-risk soil and improve water quality in agricultural landscapes.

Hypothyroidism (HT) is the most common endocrine disorder in women and female reproduction is adversely affected by hypothyroidism. Saraca asoca (Roxb.) de Wilde (SA) is traditionally used as a remedy for gynaecological disorders. Although thyroid hormones are essential for reproductive function no data are available so far on the impact of SA on thyroid function. Therefore, the current study attempted to evaluate the effects of SA in regulating HT through in vivo and in silico approaches. HT was induced in rats by administering 0.05% 6-propyl-thiouracil (PTU) in their drinking water for 4 weeks and the effect of standardized dose of SA extract (100 mg/kg body weight) examined in HT-induced rats for 28 days. LC–MS/MS analysis identified the active constituents in SA. Molecular docking was used to predict the interaction between active component and key targets. Oral administration of SA effectively ameliorated HT initiated with PTU as revealed by decreased TSH, increased thyroid hormones,5’D1 activity, antioxidants and decreased inflammatory marker, TNF-α with improved liver histology. LC-MS analysis identified the notable presence of betulinic acid (BA) and lupeol (LPL) in extract. Molecular docking study predicted strong binding energies between BA and LPL and thyroid receptors, TRβ and TSHR, supporting BA and LPL as the active principles of SA for the management of hypothyroidism. Our study proposed for the first time that BA and LPL as potential thyroid agonist playing a crucial role in the thyroid stimulatory role of SA. However, further mechanistic study is needed to solidify our findings.

The rapid growth of the U.S. broiler industry has generated a large amount of poultry litter (PL). This bulky waste is often applied in excessive amounts in nearby agricultural fields due to limited handling, contributing to nutrient runoff and degradation of water quality. A sustainable solution is needed to convert this PL into a value-added resource, offering broader agricultural utilization and nutrient retention to minimize the environmental risks. Biochar (BC) was mixed with PL at different ratios: 0

Phosphorus index (P-index) was developed to assess field vulnerability to phosphorus (P) loss and guide P management decisions. The original structure of the P-index was additive, and with continued refinement, multiplicative and component-based indices were developed. Alabama adopted the additive version in early 2000; however, the tool was never tested for its performance. The objectives of this study were to (i) evaluate the Alabama P-index using edge-of-field P loss data, (ii) test if multiplicative (Tennessee) and component-based (Georgia) P-indices perform better, and (iii) improve and test the performance of a modified Alabama P-index. We evaluated the performance by examining the strength and directional relationship between P-index scores and annual P loads. The Alabama P-index showed weak correlations (r < 0.50) between risk scores and measured dissolved reactive phosphorus (DRP), total particulate phosphorus (TPP), and total phosphorus (TP) loads. Additionally, directional inaccuracies were observed, indicating that the index misclassified the relative risk of P loss. Further, we evaluated multiplicative and component-based indices but found similar discrepancies between predicted risk scores and actual P loading. Subsequently, we modified the Alabama P-index by replacing soil test P with the phosphorus saturation ratio and substituting the underground outlet system factor with the timing of P application. Minor adjustments to weighting factors were made. The modified P-index demonstrated statistically significant correlations (r > 0.51) and directional alignment with DRP, TPP, and TP loads, suggesting it can serve as a reliable interim tool for assessing P losses. Future research should focus on restructuring and validating a component-based P-index tailored to Alabama's agricultural systems.

Phosphorus (P) loading from farmland to water bodies through surface runoff is a major water quality concern. Soil test P (STP) methods developed for fertilizer recommendations are commonly used for estimating environmental P loss. This research evaluated the relationship between P concentration in runoff and STP concentrations determined by different methods (water‐soluble P, Mehlich‐1 [M1], and Mehlich‐3 [M3]) and quantified the differences in P loads in runoff from soils having distinct STP levels. Artificial rainfall simulations (RS) were conducted at four sites (1, 2, 3, and 4), having mean M1‐P values of 143, 236, 28, and 5 mg kg −1 , respectively. Runoff samples were analyzed for dissolved reactive P (DRP) and total P (TP). The correlation between DRP and TP concentrations with M1 and M3 was similar in direction, but M3 had a greater correlation coefficient and was reliable for estimating environmental P loss from Coastal Plain soils. Among the four sites, cumulative DRP and TP loadings (118.4 and 232.3 g ha −1 ) from the first RS at site 2 with the highest M1 values were significantly higher than the other three sites (range: 3.48–37.5 g ha −1 for DRP and 6.03–83.1 g ha −1 for TP). Similarly, site 2 had the highest loading for both DRP and TP (123.5 and 194.8 g ha −1 ) during the second RS. No statistical differences were found between the first and second RS for both DRP and TP loads, indicating rainfall events of similar intensity occurring 24 h apart produced the same amount of P loss in runoff.

Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by joint damage and disrupted vitamin D signaling, leading to calcium deposition in joints. This study explores the therapeutic potential of Bavachin (BVN), a phytoestrogen from Psoralea corylifolia, in modulating vitamin D signaling in RA. Vitamin D receptor (VDR) structure was modeled using SWISS-MODEL, AlphaFold, and I-TASSER, followed by docking with BVN and Estradiol (E2) via AutoDock Vina. BVN’s effects on VDR mRNA and protein levels in RA-FLS were assessed by qRT-PCR and Western blot(WB). VDR-related BVN targets in RA were explored through protein-protein interaction (PPI) network and pathway analysis in Cytoscape. BVN’s impact on RXRα expression and VDR–RXRα interaction was examined by WB and immunofluorescence. Alizarin staining evaluated calcium deposition, while qRT-PCR analyzed BVN’s regulation of calcium-binding proteins. In silico analysis revealed a strong interaction of VDR with BVN with Gibbs-free energy of -7.2 Kcal/mol with prominent H-bonds. Further, in vitro study in RA-FLS revealed that BVN treatment increased VDR mRNA and protein expression. PPI and pathway enrichment analysis retrieved RXRα as the prominent protein to be targeted by BVN in Vitamin D signaling. BVN treatment also significantly upregulated RXRα expression and enhanced the interaction between VDR and RXRα. Further, BVN modulated associated calcium signaling, reduced calcium deposition in RA-FLS and significantly downregulated calcium-binding proteins CALB1, CALB2, NCX1, TRPV5, and TRPV6. Collectively, this study depicted a prominent therapeutic efficacy of BVN in targeting Vitamin D signaling and associated calcium deposition to alleviate RA pathogenesis.

Broiler litter (BL) has the potential to emit ammonia (NH3) and greenhouse gas (GHG) emissions such as carbon dioxide (CO2), nitrous oxide (N2O), and methane (CH4), which have a greater impact on climate change. Understanding the impact of stockpiling methods on emissions is essential, as they influence the emission rates. This study focused on quantifying the emissions of N2O, CO2, CH4, and NH3 from the BL stockpiles during 126 days of storage under three stockpiling conditions a) Broiler litter stockpile covered with tarp (treatment-T), b) uncovered litter stockpile (treatment-U), c) Broiler litter stockpile covered with a 0.08 m layer of soil (treatment-S). Gas emissions were measured with an INNOVA-1512 photoacoustic gas analyzer. Daily emission rates were calculated by using the ideal gas equation, and cumulative emissions were calculated from interpolated daily emission rates. The results suggested that over the 126 days of storage period, treatment-T emitted significantly lower (P < 0.05) cumulative NH3-N (89.5 g m-2), N2O-N (47.85g m-2), CO2-C (9708.5 g m-2), and CH4-C (123.27 g m-2) emissions compared to treatments -U and -S. Covering the BL stockpiles with a tarp reduced the NH3-N, N2O-N, CO2-C, and CH4-C emissions by 38 %, 54 %, 28 %, and 19 %, respectively, compared to the control (treatment -U). In contrast, covering BL with soil (treatment-S) increased the NH3-N, N2O-N, CO2-C, and CH4-C emissions by 13 %, 17 %, 123 %, and 9 %, respectively, compared to the control (treatment-U). Overall global warming potential (GWP) expressed as CO2 equivalents (CO2-eq) was also low for treatment-T, indicating its effectiveness in mitigating emissions.

Objective RA is a chronic inflammatory disease characterized by synovial membrane hyperplasia and joint degeneration. Aberrant protein expression has shed light on their association with disease pathogenesis. This study emphasized the mechanistic role of one of the major altered proteins, Inter-alpha-trypsin-inhibitor heavy chain 4 (ITIH4), in RA pathogenesis.Methods The expression level of ITIH4 was validated in RA patients' plasma and peripheral blood mononuclear cells (PBMCs) using ELISA and western blotting. The interaction of ITIH4 with the C-X-C chemokine receptor type 4 (CXCR4) complex was analysed by molecular dynamics simulation. In vitro studies targeting ITIH4 with siRNA were conducted to confirm its interaction with CXCR4 and its mediated downstream signalling molecules in apoptosis and inflammation in RA fibroblast-like synoviocytes (RA-FLS). An in vivo study was conducted to validate the in vitro findings using a CIA rat model.Results Increased levels of ITIH4 were observed in RA patients' plasma and PBMCs. In vitro studies show that, ITIH4 was positively interacted with CXCR4, leading to increased apoptosis and reduced pro-inflammatory cytokine production by regulating Phosphoinositide 3-kinase (PI3K)/Akt signalling after ITIH4 knockdown in RA-FLS. ITIH4 knockdown also significantly led to inhibit the progression of arthritis-like symptoms in the CIA rat model, shown by decreased arthritis index, cellular infiltration, cytokines production and pannus formation.Conclusion The study suggests that the ITIH4-CXCR4 interaction is linked to apoptosis and inflammation in RA through PI3K/Akt signalling. Targeting ITIH4 could represent a promising therapeutic strategy for RA management.

Mitochondrial dysfunction drives Rheumatoid Arthritis (RA) progression by disturbing energy metabolism and promoting inflammation. Additionally, the female predominance of RA highlights estrogen deficiency as an important contributor to disease development. The effect of estrogen in RA has been investigated; however, its specific effects on the mitochondrial proteome and function have yet to be studied. This study investigated the effects of 17-β estradiol (E2) on the mitochondrial proteome of patient-derived RA fibroblast-like synoviocytes (RA-FLS) using Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS) analysis, followed by an assessment of key mitochondrial functional parameters and in vitro validation. The results identified an upregulated expression of two mitochondrial proteins, Acyl-CoA dehydrogenase very long chain (ACADVL) and ATP synthase subunit O (ATP5O), after E2 treatment in RA-FLS. This was further validated by increased real-time ATP production and reduced glycolytic capacity, along with increased expression of proteins related to fatty acid β-oxidation. In addition, E2 influenced mitochondrial dynamics by modulating the fission–fusion balance, resulting in improved mitochondrial morphology. E2 treatment also reduced the expression of mitophagy markers and increased mitochondrial membrane potential, indicating improved mitochondrial function. It also lowered mitochondria-centered oxidative stress by upregulating mitochondrial antioxidant enzymes. Mitochondrial proteomics analysis thus, demonstrated that E2 has the potential to enhance mitochondrial energy metabolism and alleviate mitochondrial dysfunction in RA. These findings provide a foundation for further exploration of mitochondria-targeted therapeutic approaches in RA management.

Estrogen metabolites, a subset of female sex hormones, are known to play a role in autoimmunity and the inflammatory response associated with rheumatoid arthritis (RA). Current therapeutic approaches have focused on the development of small molecules that can easily alter intracellular components within a signaling pathway, thereby selectively targeting the disease physiology. In the present study, small mole- cule 2-hydroxyestradiol (2-OHE2) was utilized to investigate the potential anti-inflammatory effects by in vitro studies using primary fibroblast-like synoviocytes (RA-FLS) and in vivo studies using collagen-induced arthritis (CIA) rat model. A biophysical interaction study between 2-OHE2 and TNF-alpha was conducted using tyrosine quenching and thermal shift assay, and the maximum fluorescence quenching of the tyrosine residue was observed at a ligand concentration of 1 mM. Further, the impact of 2-OHE2 on the TNF-alpha signaling pathway was evaluated in RA-FLS, focusing on the inhibition of inflammation, cell proliferation, and apoptosis activation, using Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), caspase 3/7 activity, scratch assays, and immunocytochemistry. We found that 2-OHE2 effectively down-reg- ulates inflammatory mediators, adhesion markers, and metalloproteinases and regulates apoptotic markers in RA-FLS. 2-OHE2 also exhibited anti-inflammatory effects in the CIA rat model. Our findings indicate that 2-OHE2 may be a promising potential anti-inflammatory compound. It targets TNF-alpha signaling, exhibiting pro-apoptotic and anti-proliferative effects, suggesting that 2-OHE2 could have therapeutic implications in the pathophysiology of RA.

Non-point-source pollution due to loss of phosphate (PO43–P), nitrate (NO3–N), ammonium (NH4+-N), zinc (Zn) and copper (Cu) from agricultural-lands receiving broiler-litter (BL) has been a serious concern. Although biochar application for reducing such pollution is considered ecofriendly, its efficacy is limited by low-functionality. An attempt was made to engineer biochar for immobilizing these anionic (PO43–P, NO3–N) and cationic (NH4+-N, Zn2+, Cu2+) non-point-source pollutants in BL-manured soils. Engineered-biochar (FeBC) was synthesized by oxidizing pine-wood derived biochar with HNO3-H2SO4 followed by iron (FeCl3.6H2O) impregnation and characterized using microscopic (SEM) and spectral (XRD and FTIR) techniques. The efficacy of FeBC was compared with that of water-washed-biochar (WBC) and inorganic-amendments (alum and ferrous-sulfate) in reducing the solubility of these pollutants in the BL-mixed Marlboro and Decatur soils. For each soil-type, BL was first mixed with the soil (5

Rheumatoid arthritis (RA) is an autoimmune disease caused by intricate signal transductions, where chronic inflammation is manifested in the joints and has a higher prevalence observed in females. To address RA pathogenesis, Estradiol (E2), a prominent form of estrogen, has been used in this study, identifying differentially expressed proteins in RA-Fibroblast-like synoviocytes by SWATH-MS, as well as exploring its mechanistic pathways. In-silico pathway enrichment analysis depicted the major involvement of the proteins in extracellular matrix organization, with Vitronectin (VTN) and Secreted protein acidic and rich in cysteine (SPARC) proteins as prominent protein targets. E2 was found to reduce VTN and SPARC expression and its downstream, angiogenesis, and cell proliferation factors, validated by qRT-PCR, Western blotting, and Scratch assay. VTN and SPARC interaction was also hindered by E2, demonstrated by molecular docking, followed by Immunofluorescence, and co-immunoprecipitation assay. E2 effected the VTN-SPARC dynamics, marking a significant reduction in RA symptoms, validated using the ovariectomized collagen-induced arthritis rat model. Our findings suggested that E2 diminished RA pathogenesis by altering the VTN and SPARC dynamics and their downstream signal transductions.

Poultry litter (PL) can be used as a viable alternative to phosphate fertilizers. However, there is a lack of information about phosphorus (P) distribution in inorganic (Pi) and organic (Po) forms and its transformation in soils amended with PL of varying age (based on litter clean-out frequency) and application rate. This study aimed to determine the effect of PL age and application rate on soil P forms and their bioavailability. Soils were amended with 5 and 10 Mg ha-1 PL using 6-, 18-, and 30-month-old litter and incubated for 6 months. Soil P fractionation was performed following the Hedley protocol. Soil P availability and soil P storage capacity (SPSC) were determined using Mehlich 3 (M3) extraction. Results indicated that P transformation from labile to stable P forms occurred over 150-day incubation. Litter age had no significant effect on the distribution of soil P forms. However, the highly reactive Pi (HRPi) form was higher for treatments with 10 Mg ha-1 PL on Day 0, indicating a risk for P loss, which was also revealed by negative SPSC for those treatments. At Day 0, M3-P was positively correlated to HRPi. However, from Day 30 to 150, M3-P was strongly correlated to both HRPi and moderately reactive Pi (MRPi) forms, indicating MRPi contribution to soil P availability. The negative relationship between HRPi and SPSC further confirms that high HRPi on Day 0 may be an environmental concern.

Elevated levels of Inter-alpha-trypsin-inhibitor heavy chain 4 (ITIH4) have grabbed attention in rheumatoid arthritis (RA) pathogenesis, though its precise mechanisms remain unexplored. To elucidate these mechanisms, a comprehensive strategy employing network pharmacology and molecular docking was utilized. RA targets were sourced from the DisGeNET Database while interacting targets of ITIH4 were retrieved from the STRING and Literature databases. Venny 2.1 was used to identify overlapping genes, followed by Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) through Cytoscape 3.10.2 software, and molecular docking was performed in the ClusPro server. The study identified 18 interacting proteins of ITIH4 associated with RA, demonstrating their major involvement in the chemokine signaling pathway by enrichment analysis. Molecular docking of ITIH4 with the 18 proteins revealed that C-X-C chemokine-receptor type 4 (CXCR4), a major protein associated with chemokine signaling, has the highest binding affinity with ITIH4 with energy −1705.7 kcal/mol forming 3 Hydrogen bonds in the active site pocket of ITIH4 with His441, Arg288, Asp443 amino acids. The effect of ITIH4 on CXCR4 was analyzed via knockdown studies in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), demonstrating the significant downregulation of CXCR4 protein expression validated by Western blot in RA-FLS. In conclusion, it was speculated that CXCR4 might serve as a potential receptor for ITIH4 to activate the chemokine signaling, exacerbating RA pathogenesis.

Manure is an important source of plant nutrients and organic matter that can benefit soil health over time. However, indiscriminate use of manure can lead to environmental problems including eutrophication of water bodies caused by nutrient runoff during precipitation events. There is a need to understand the effect of manure source and application rate on nitrogen (N) and phosphorus (P) forms and their losses during runoff events. In this study, we assessed the impact of application rate of broiler litter (BL) and swine liquid manure (SLM) on runoff volume, soil, N, and P losses using a rainfall simulator and three consecutive 2.45 cm rainfall events. Surface Decatur silty clay loam (0-0.06 m) was collected and packed in trays (0.55 x 0.30 × 0.06 m3). Manure was surface-applied to the soil at equivalent P rates ranging from 62 to 249 kg ha-1 for BL and 5-18 kg ha-1 for SLM, respectively. Rainfall events took place 7, 14, and 21 d after manure application. Results indicated that the runoff volume decreased at the highest manure application rate compared to the lowest manure application rate. The total suspended solids (TSS) loss was lower in control compared to BL and SLM treatments. The loss of nitrate-N (NO3-N) dissolved reactive P (DRP) and dissolved organic P (DOP) in runoff water was maximum at the highest application rates for both the BL and SLM with respect to control. Mehlich 3 extractable P (M3P) and water soluble P (WSP) increased with increasing P application rates for both manure types in soils following post rainfall simulation study. An increase in M3P and WSP, along with a decrease in soil P storage capacity following post-rainfall simulation for higher P application rates, indicates caution should be taken for considering the manure application rate to prevent environmental nutrient loss during runoff events.

Rheumatoid arthritis (RA) is a metabolic joint disorder influenced by hormonal regulation, notably estrogen, which plays a cytoprotective role against inflammation. While estrogen’s impact on RA pathogenesis has been studied, the altered metabolite expression under estrogen’s influence remains unexplored. This study investigated the changes in the metabolome of synovial fibroblasts isolated from RA patients under 17β-estradiol (E2) using the liquid chromatography with tandem mass spectrometry (LC-MS/MS) approach followed by multivariate and biological pathway analysis along with in vitro validation. Results identified 3624 m/z, among which eight metabolites were significant (p < 0.05). Nicotinate and nicotinamide metabolism was found to be highly correlated with the treatment of E2, with metabolites NAD+ and 1-methynicotinamide (1-MNA) upregulated by E2 induction in RA-FLS. PharmMapper analysis identified potential gene targets of 1-MNA, which were further matched with RA gene targets, and thus, STAT1, MAPK14, MMP3, and MMP9 were concluded to be the common targets. E2 treatment affected the expression of these gene targets and ameliorated the development of oxidative stress associated with RA inflammation, which can be attributed to increased concentration of 1-MNA. Thus, an LC-MS/MS-based metabolomics study revealed the prominent role of estrogen in preventing inflammatory progression in RA by altering metabolite concentration, which can support its therapeutic capacity in remitting RA.