Fumarate Research Articles

Metabolomic Analysis Reveals the Linkage between Sleep-Enhancing Effects and Metabolite Biomarkers and Pathways of Different Casein Hydrolysates in Chronic Unpredictable Mild Stressed Mice.

Casein hydrolysates have been proven to exert varying sleep-enhancing and anxiolytic effects due to their distinct release of potential peptides. However, their underlying sleep-enhancing mechanisms at the metabolic level remain unclear. This study aims to investigate the potential sleep-enhancing mechanism of casein hydrolysates through an integrated approach of untargeted and targeted metabolomics in CUMS-induced anxiety mice for the first time. The results showed seven potential biomarkers were identified and screened using orthogonal partial least-squares discriminant analysis, random forest model, and pathway analysis, including ornithine, l-proline, l-prolinamide, inhibitory neurotransmitters gamma-aminobutyric acid, 5-HIAA, fumaric acid, and 4-oxoglutaramate. Moreover, casein hydrolysates exerted sleep-enhancing effects through multiple metabolic pathways, mainly including the GABAergic system, tryptophan metabolism, and cAMP response signaling pathway, which was validated by targeted metabolomics and vital protein expressions. It was interesting that casein hydrolysates with diverse representative peptide compositions exhibited varying activity, which could be attributed to distinct alterations in metabolites via different pathways.

Analysis of GCRV Pathogenesis and Therapeutic Measures Through Proteomic and Metabolomic Investigations in GCRV-Infected Tissues of Grass Carp (Ctenopharyngodon idella)

Hemorrhagic disease caused by grass carp reovirus (GCRV) infection is a major problem affecting the grass carp aquaculture industry. Therefore, inhibiting the spread of GCRV infection is of great economic significance. Herein, we sequenced five tissues (gill, liver, intestine, kidney, and muscle) from grass carp before and after GCRV infection using data-independent acquisition proteomic and untargeted metabolomic technologies, and quantitatively identified 10,808 proteins and 4040 metabolites. Then, we analyzed the differentially expressed proteins (DEPs) and metabolites (DEMs) before and after GCRV infection in the five tissues. Gene ontology analysis revealed that the five tissue DEPs were enriched in metabolic, including carbohydrate and lipid metabolic processes. Chemical taxonomy analysis showed that the categories of DEMs mainly included carbohydrates and lipids, such as fatty acids, glycerophospholipids, steroids, and their derivatives. Both the proteomic and the metabolomic data showed that GCRV affected the carbohydrate and lipid metabolism in the host. Shared pathway analysis was performed at both the protein and metabolic levels, showing significant enrichment of the glycolysis and pentose phosphate pathways (p < 0.001). Further analysis of glycolysis and pentose phosphate pathway inhibitors revealed that these two pathways are important for GCRV replication. As the kidney was the most affected among the five tissues, we analyzed the butanoate metabolism in the kidney, which revealed that most of the differentially expressed proteins and differently expressed metabolites in the butanoate metabolism were related to the TCA cycle. Further investigation showed that fumaric acid, an intermediate product in the TCA cycle, significantly inhibited GCRV replication in the CIK cells (p < 0.001), and that this inhibitory effect may be related to its induction of interferon system activation. The addition of fumaric acid to feed increased the survival rate of juvenile grass carp by 19.60% during GCRV infection, and protected the tissues of those infected with GCRV, making it a potential anti-GCRV feed additive. Our results provide new perspectives on GCRV pathogenesis and antiviral strategies for grass carp.

Altered serum metabolome is associated with disease activity and immune responses in rheumatoid arthritis.

Rheumatoid arthritis (RA) is widespread globally, with the emergence of metabolites derived from both the host and microbes playing a pivotal role in its pathogenesis. This study aims to elucidate the relationships between serum metabolites and the immunological and clinical features of RA. Serum samples were collected from 35 RA patients and 37 healthy controls (HC). Metabolite profiling was performed using gas chromatography-mass spectrometry (GC/MS). Principal component analysis revealed a significant distinction between the RA and HC cohorts. Employing univariate statistical analysis, we identified 36 differential metabolites. Among these, 9 metabolites, including galactose and glucose, were found to be enriched, while the remaining metabolites, such as citric acid, fumaric acid, and inosine, were depleted in RA. These diverse metabolites encompassed various metabolic processes, including the biosynthesis of fatty acids, amino acids, and glucose. The enrichment of glucose and galactose in RA exhibited a substantial correlation with elevated IgG levels, as determined through correlation analysis. Conversely, the depletion of citric acid was correlated with elevated levels of C3 and CRP. Methionine, which also declined in RA patients, displayed a negative correlation with ESR. Furthermore, galactose and glucose exhibited significant positive correlations with naïve B cells, while the decreased eicosanoic acid level in RA was significantly associated with an increase in natural killer cells. Our findings suggest that the altered serum metabolite profile in RA is closely linked to disease severity and the dysregulated immune responses observed in RA patients. Key Points • Identified nine metabolites with upregulated expression and twenty-seven metabolites with downregulated expression. • Established a correlation between alterations in serum metabolite levels and inflammatory markers in RA patients. • Discovered a significant association between changes in serum metabolites and immune cell profiles in RA patients.

Arsenic, Mercury, Lead and Iron Induced Lipid Peroxidation in Phospholipids Liposomes and Protective Effect of Fumaric Acid

Arsenic, Mercury, Lead and Iron Induced Lipid Peroxidation in Phospholipids Liposomes and Protective Effect of Fumaric Acid

The tale of two Ions Na+ and Cl−: unraveling onion plant responses to varying salt treatments

BackgroundExploring the adaptive responses of onions (Allium cepa L.) to salinity reveals a critical challenge for this salt-sensitive crop. While previous studies have concentrated on the effects of sodium (Na+), this research highlights the substantial yet less-explored impact of chloride (Cl−) accumulation. Two onion varieties were subjected to treatments with different sodium and chloride containing salts to observe early metabolic responses without causing toxicity.ResultsThe initial effects of salinity on onions showed increased concentrations of both ions, with Cl− having a more pronounced impact on metabolic profiles than Na+. Onions initially adapt to salinity by first altering their organic acid concentrations, which are critical for essential functions such as energy production and stress response. The landrace Birnförmige exhibited more effective regulation of its Na+/K+ balance and a milder response to Cl− compared to the hybrid Hytech. Metabolic alterations were analyzed using advanced techniques, revealing specific responses in leaves and bulbs to Cl− accumulation, with significant changes observed in organic acids involved in the TCA cycle, such as fumaric acid, and succinic acid, in both varieties. Additionally, there was a variety-specific increase in ethanolamine in Birnförmige and lysine in Hytech in response to Cl− accumulation.ConclusionThis comprehensive study offers new insights into onion ion regulation and stress adaptation during the initial stages of salinity exposure, emphasizing the importance of considering both Na+ and Cl− when assessing plant responses to salinity.

Conformational Geometry Matters: The Case of the Low-Melting-Point Systems of Tetrabutylammonium Triflate with Fumaric or Maleic Acid

For this article, the interaction of tetrabutylammonium trifluoromethanesulfonate (TBATFO) with either fumaric (FUM) or maleic (MAL) acid has been investigated. These acids are isomers and can be considered the trans and cis configurations of the same molecular geometry. When TBATFO is mixed with FUM, an eutectic point is obtained for a relative composition of 90-10 (molar ratio), with a melting point of ≈90 °C. If maleic acid is mixed with TBATFO, one obtains an inhomogeneous phase with the retention of a solid portion immersed in a liquid phase, even above 90 °C. DFT calculations helped to model the interaction between the components. It is suggested herein that TBATFO interacts more strongly with FUM than with MAL, due to possible interactions in two different sites for hydrogen bonding (HB) in FUM. In MAL, one of the HB sites is instead retained in the intramolecular interactions; therefore, fewer sites are available for intermolecular interactions. Infrared spectroscopy measurements have confirmed this scenario, in which the hydrogen bonds of the acid molecules are replaced by HB between the acid and the ionic couple: for both kinds of mixtures, the vibration region of the OH bonds is strongly affected by mixing. However, in the case of FUM, the vibrations of the SO3 group of the TFO anion are displaced, while they remain in practically the same frequency position in the case of MAL.

Mammalian Diaphanous-related formin 1 (mDia1) inducing diabetic cardiomyopathy by regulating metabolic reprogramming

Abstract Background Mammalian Diaphanous-related formin 1 (mDia1) is one of the formin family proteins and acts as a rho-effector molecule which is involved in actin organization. Previous studies showed that mDia1 aggravated compensatory cardiac hypertrophy in response to pressure overload. However, the role of mDia1 in diabetic cardiomyopathy and its mechanisms remain elusive. Objective To clarify the mechanisms of mDia1 in DCM through mediating metabolic reprogramming. Methods 5-week-old of mDia1 ko mice were used to induce DCM by feeding high-fat diet (HFD) for 16 weeks. The blood glucose and body weight of the mice were measured regularly. Echocardiography was used to evaluate cardiac function. HE and WGA staining were used to evaluate hypertrophy of cardiomyocytes. Transmission electron microscopy and mitotracker staining were used to observe the morphology of mitochondrial in heart. Proteomics and metabolomics were used to explore the metabolites in hearts of mice. Primary neonatal cardiomyocytes were isolated and stimulated with 35 mM glucose and 250 μM palmitate in vitro. Adenovirus expressing shRNA of mDia1 was used to knockdown mDia1 in cardiomyocytes. Mitochondria were isolated from primary cardiomyocytes to verify the translocation of mDia1. Co-Immunoprecipitation was used to confirm the interaction between mDia1 with succinate dehydrogenase subunits A (SDHA). Results mDia1 had no effects to blood glucose and body weight after 16-week HFD feeding. Loss of mDia1 ameliorated diastolic dysfunction in DCM mice with shorter isovolumic relaxation time (IVRT) and increased E/A ratio in left ventricular. In addition, cardiac hypertrophy was significantly improved in mDia1 ko mice. mDia1 deficiency tended to maintain the normal mitochondrial structure. Results of proteomics showed that mDia1 was involved in mitochondrial function, ATP synthesis and metabolic pathways. Metabolomics showed that HFD induced accumulation of α-ketoglutaric acid in wild type mice compared with mDia1 ko mice. However, mDia1 ko significantly increased fumaric acid but did not affect succinyl-CoA and succinic acid compared with wild type mice. Furthermore，we found that mDia1 translocated into mitochondrial with high glucose and palmitate stimuli. Results of CoIP showed mDia1 interacted with SDHA both in cardiomyocytes and HEK293 cells. Conclusions mDia1 deteriorated DCM through translocating into mitochondrial and interacting with SDHA, a process dependent on metabolic pathways.Figure of Mechanism

Multi-omics profiling reveals the molecular mechanism of Bifidobacterium animalis BB04 in co-culture with Wickerhamomyces anomalus Y-5 to induce bifidocin A synthesis.

Bacteriocin is a kind of natural substance that can effectively inhibit bacteria, but its production usually limited by environment. Co-culture is a strategy to stimulate bacteriocin production. Bifidocin A produced by Bifidobacterium animalis BB04, is a novel bacteriocin with a broad-spectrum antimicrobial active of foodborne bacteria. In order to enhance bifidocin A production, bacteriocin-inducing strains were screened firstly in co-cultivation. Then, the molecular mechanism of co-cultural induction was investigated by transcriptomic and proteomic analysis. Finally, the key inducing metabolites were identified by using targeted metabolomic technology. The results showed that Wickerhamomyces anomalus Y-5 in co-cultivation could significantly enhance bifidocin A production, with a 3.00-fold increase compared to mono-culture. The induction may not depend on direct contact with cells and may instead be attributed to be continuous exposure to inducing substances at specific concentration. In co-cultivation, W. anomalus Y-5 up-regulated Hxk2 and Tap42 to activate Glucose-cAMP and Tor and HOG-MAPK pathway, stimulated the expression of the retrograde gene, produced glutamine and glycerol to maintain activity. During this process, glutamine, inosine, guanosine, adenine, uracil, fumaric acid and pyruvic acid produced by W. anomalus Y-5 could induce the synthesis of bifidocin A. In conclusion, W. anomalus Y-5 in co-cultivation induced the synthesis of bifidocin A by regulating various signaling pathways to produce inducing substances. These findings establish a foundation for high-efficient synthesis of bifidocin A and provide a new perspective into the industrial production of bacteriocin.

Trace Amounts of Multifunctional Electrolyte Additives Enhance Cyclic Stability of High-Rate Aqueous Zinc-Ion Batteries.

Aqueous zinc ion batteries (AZIBs) are renowned for their exceptional safety and eco-friendliness. However, they face cycling stability and reversibility challenges, particularly under high-rate conditions due to corrosion and harmful side reactions. This work introduces fumaric acid (FA) as a trace amount, suitable high-rate, multifunctional, low-cost, and environmentally friendly electrolyte additive to address these issues. FA additives serve as prioritized anchors to form water-poor Inner Helmholtz Plane on Zn anodes and adsorb chemically on Zn anode surfaces to establish a unique in situ solid-electrolyte interface. The combined mechanisms effectively inhibit dendrite growth and suppress interfacial side reactions, resulting in excellent stability of Zn anodes. Consequently, with just tiny quantities of FA, Zn anodes achieve a high Coulombic efficiency (CE) of 99.55 % and exhibit a remarkable lifespan over 2580 hours at 5mA cm-2, 1 mAh cm-2 in Zn//Zn cells. Even under high-rate conditions (10mA cm-2, 1 mAh cm-2), it can still run almost for 2020 hours. Additionally, the Zn//V2O5 full cell with FA retains a high specific capacity of 106.95 mAh g-1 after 2000 cycles at 5 A g-1. This work provides a novel additive for the design of electrolytes for high-rate AZIBs.

Mixed-Linker Zr-Metal-Organic Framework with Improved Lewis Acidic Sites for CO2 Fixation Reaction Catalysis.

Applying the mixed-linker strategy in synthesizing metal-organic frameworks (MOFs) has drawn considerable attention as a heterogeneous catalyst owing to their easy synthesis and different functional ligands in their frameworks. Following this strategy, we have developed a mixed linker Zr(IV)-based MOF, [Zr6O4(OH)4(FUM)n(PZDC-NO2)6-n] (PZDC-NO2 = 4-nitro-3,5-pyrazoledicarboxylic acid, FUM = fumaric acid) denoted as MOF-801(PZDC-NO2) synthesized via this strategy which possess an electron-withdrawing group (-NO2) on secondary linkers. The MOF-801(PZDC-NO2) has been fully characterized via various analyses, such as Fourier transform infrared, powder X-ray diffraction, 13C/1H nuclear magnetic resonance, XPS, TGA, and N2 adsorption/desorption, SEM, EDX, etc. By considering the concurrent existence of acid-base active sites and the synergistic role of these sites, this mixed-linker MOF was used as a catalyst for the cycloaddition reaction of CO2 and epoxides under mild without-solvent conditions. MOF-801(PZDC-NO2) displays significant catalytic performance by producing the highest catalytic conversion of epoxide to cyclic carbonate (93%) with a turnover number of 130.7 in 8 h reaction time and 100 °C temperature under low-pressure CO2 pressure. The mixed-linker Zr-MOF exhibits exceptional stability and reusability, maintaining its structure and functionality after consecutive cycles of utilization. Finally, the reaction mechanism was further investigated by density functional theory calculations. The total energy of the reactants, intermediates, and products involved in the process.

Metabolomic signature of sperm in men with obesity-associated asthenozoospermia.

Obese men have a significantly increased risk of developing asthenozoospermia. Sperm motility is directly related to cellular energy supply and metabolic status. Sperm metabolomics research based on Gas chromatography-mass spectrometry (GC-MS) technology can provide useful information for the pathological mechanism, diagnosis, and treatment of obesity-associated asthenozoospermia. Sperm samples were obtained from a healthy control group (n = 49) and patients with obesity-associated asthenozoospermia (n = 40). After the analysis of sperm samples using GC-MS, various multivariate statistical methods such as principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal partial least squares-discriminant analysis (OPLS-DA) were conducted. A total of 56 metabolites were identified in the sperm samples. Among them, 19 differential metabolites were found between the two groups. Metabolites such as glutamic acid, fumaric acid, and cysteine were significantly downregulated in the sperm of patients with obesity-associated asthenozoospermia, while metabolites like palmitic acid, stearic acid, and alanine were significantly upregulated. The differential metabolites were enriched in D-glutamine and D-glutamate metabolism; proline, aspartate, and glutamate metabolism; glutathione metabolism and the other metabolic pathways. Obesity may influence the composition of metabolic products in sperm, and metabolomic analysis proves beneficial for the future diagnosis and treatment of obesity-associated asthenozoospermia.

Multi-omics reveals the molecular mechanisms of rapid growth in distant hybrid fish

Distant hybridization usually results in heterosis. In previous studies, we obtained an improved fish (WR-II, 2n = 100) with rapid growth through distant hybridization. To investigate the molecular mechanisms underlying the rapid growth of WR-II, the intestinal structure, microbiome and metabolome of the gut and the transcriptome of muscle were compared between WR-II and its parents (WCC and RCC, 2n = 100). The results revealed that WR-II had more intestinal folds, and the height, width and goblet cell density of the intestinal folds were greater than those of its parents. The absolute abundances of the probiotics Ralstonia and Salinivibrio were significantly greater in WR-II than in the parents (p < 0.05), and the probiotic Cupriavidus was found in only WR-II. A total of 481 and 718 differentially abundant metabolites (DMs) were identified in WR-II vs. WCC and WR-II vs. RCC, respectively. These DMs were enriched mainly in pathways related to metabolism, protein synthesis and development, such as fumaric acid, sphingosine, betaine and 5′-adenylic acid (AMP). A total of 5680 and 11,795 differentially expressed genes (DEGs) were identified in WR-II vs. WCC and WR-II vs. RCC, respectively. These DEGs were enriched mainly in pathways related to protein synthesis and substance metabolism. Growth-related genes such as irs1, irs2, foxo1, igf1r, and akt were upregulated in WR-II. Multi-omics analysis revealed that Salinivibrio can promote the level of AMP, which then regulates the expression of irs1 and foxo1, thus promoting the growth of WR-II. This study revealed the mechanism of rapid growth of WR-II from the probiotics, metabolites and genes, which provides evidence for the molecular mechanism of heterosis.

Crystal structures of two different multi-component crystals consisting of 1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline and fumaric acid

Two different multi-component crystals consisting of papaverine [1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline, C20H21NO4] and fumaric acid [C4H4O4] were obtained. Single-crystal X-ray structure analysis revealed that one, C20H21NO4·1.5C4H4O4 (I), is a salt co-crystal composed of salt-forming and non-salt-forming molecules, and the other, C20H21NO4·0.5C4H4O4 (II), is a salt–co-crystal intermediate (i.e., in an intermediate state between a salt and a co-crystal). In this study, one state (crystal structure at 100 K) within the salt–co-crystal continuum is defined as the ‘intermediate’.

Physiological and metabolomic analyses reveal the mechanism by which exogenous spermine improves drought resistance in alfalfa leaves (Medicago sativa L.).

Alfalfa (Medicago sativa L.) is a globally important legume crop with high nutritional and ecological value. Drought poses a serious threat to alfalfa acreage and yields. Spermine (Spm) has been shown to protect plants from drought damage. The aim of this study was to clarify the mechanism of exogenous Spm to improve drought resistance of alfalfa. In this study, we root applied 0.1, 0.5, and 1 mM Spm to Gannong No. 3 (G3) alfalfa under drought stress, and then determined their physiological and metabolic changes. The results showed that exogenous Spm increased chlorophyll content, chlorophyll fluorescence parameters and gas exchange parameters, enhanced antioxidant enzymes activity, improved ascorbic acid-glutathione (AsA-GSH) cycle, increased osmoregulatory substances content, reduced hydrogen peroxide and superoxide anion levels, and inhibited malondialdehyde accumulation in alfalfa under drought stress, thereby increasing plant height and leaf relative water content and enhancing drought tolerance of alfalfa. The redundancy analysis of the above physiological indicators showed that the addition of the optimal Spm to improve drought tolerance of alfalfa under drought stress was mainly achieved by increasing catalase activity and improving the ASA-GSH cycle. In addition, metabolomics analysis revealed that exogenous Spm increased the content of oxobutanedioic acid, citric acid, fumaric acid and malic acid to enhance the tricarboxylic acid cycle. Meanwhile, exogenous Spm increased endogenous Spm and proline (Pro) content to resist drought stress by enhancing Spm and Pro metabolism. Moreover, exogenous Spm increased the accumulation of the signaling substance abscisic acid. In conclusion, exogenous Spm enhanced drought resistance of alfalfa leaves under drought stress.

Integration analysis of transcriptome and metabolome revealed the potential mechanism of spermatogenesis in Tibetan sheep (Ovis aries) at extreme high altitude

Testis has an indispensable function in male reproduction of domestic animals. Numerous genes and metabolites were related to testicular development and spermatogenesis. However, little is known about the biological regulation pathways associated with fecundity in male Tibetan sheep. In this study, Testes were collected from Huoba Tibetan sheep (HB, 4614 m) and Gangba Tibetan sheep (GB, 4401 m) at extreme high altitude, and Alpine Merino sheep (AM, 2500 m, control group) at medium-high altitude, investigating the genes and metabolites levels of them. The histological analysis of testicular tissue using hematoxylin-eosin (HE) staining was performed for Tibetan sheep and Alpine Merino sheep, and the testes of them were analyzed by transcriptomics and metabolomics to explore the potential mechanism of testicular development and spermatogenesis. The statistical results showed that the cross-sectional area of testicular seminiferous tubules, diameter of seminiferous tubules, and spermatogenic epithelium thickness were significantly smaller in HB and GB than in AM (P < 0.05). Overall, 5648 differentially expressed genes (DEGs) and 336 differential metabolites (DMs) were identified in three sheep breeds, which were significantly enriched in spermatogenesis and other related pathways. According to integrated metabolomic and transcriptomic analysis, glycolysis/gluconeogenesis, AMPK signaling pathway, and TCA cycle, were predicted to have dramatic effects on the spermatogenesis of Tibetan sheep. Several genes (including Wnt2, Rab3a, Sox9, Hspa8, and Slc38a2) and metabolites (including L-histidinol, Glucose, Fumaric acid, Malic acid, and Galactose) were significantly enriched in pathways related to testicular development and spermatogenesis, and might affect the reproduction of Tibetan sheep by regulating the acrosome reaction, meiotic gene expression, and the production of sex hormones. Our results provide further understanding of the key genes and metabolites involved in testicular development and spermatogenesis in Tibetan sheep.

Tailoring Fumaric Acid Delivery: The Role of Surfactant-Enhanced Solid Lipid Microparticles via Spray-Congealing.

Fumaric acid, a naturally occurring preservative with antimicrobial properties, has been widely used in the baking industry. However, its direct addition interferes with yeast activity and negatively impacts the gluten structure. This study investigates the potential of spray-congealing as a method for encapsulating fumaric acid within solid lipid microparticles. The selection of lipid carriers and surfactants is critical, so hydrogenated palm stearin, hydrogenated rapeseed oil, and Compritol ATO 888 (glyceryl behenate) were chosen as lipid carriers, and propylene glycol monostearate and glyceryl monolaurate were utilised as surfactants with varying concentrations. Rheological properties, encapsulation efficiency, particle size, moisture content, and thermal behaviour were assessed, along with the release profiles under different temperature conditions simulating the baking process. The findings indicate that the addition of surfactants significantly impacts the viscosity and stability of the molten mixtures, which in turn affects the spray-congealing process and the release of fumaric acid. The temperature-dependent and time-dependent release profiles demonstrate the potential for customising release kinetics to suit specific applications, such as the baking industry. This study may contribute to the development of a controlled-release system that synchronises with the baking process, thereby optimising fumaric acid's functionality while preserving the quality of baked goods.

Effects of using different dentin conditioners on dentin regeneration.

This experiment aimed to evaluate the impact of several dentine etching and conditioning agents on growth factors (GFs) liberation from dentine slices. Eighteen dentine slices were obtained from nine premolars divided in to six groups, the slices immersed in one mL test solutions for 5 min; Group 1: white Mineral trioxide aggregate (MTA), Group 2: Phosphate buffered saline (PBS), Group 3: 37% phosphoric acid, Group 4: 17% Ethylenediaminetetraacetic Acid (EDTA), Group 5: 10% Maleic acid (MAc), and Group 6: 0.7% Fumaric acid. The solutions were removed and stored directly at for further detection and quantification of transforming GF beta 1 (TGF-b1), bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA was used to compare the mean release and standard deviation between groups (α = 0.05). Tukey's post hoc applied for multiple comparisons. After five min conditioning of dentine slices, white MTA released the highest level of TGF-b1, BMP2 and VEGF among all groups, followed by 0.7% Fumaric acid with no significant difference between them, but compared to 37% phosphoric acid and PBS groups significant difference observed, which they released the least amount of GFs amongst all groups. Based on the results of this research the detectable release of TGF-b1, BMP2 and VEGF by 0.7% fumaric acid was comparable with white MTA from dentin slices.

Defect-Engineered MOF-801/Sodium Alginate Aerogel Beads for Boosting Adsorption of Pb(II).

Metal-organic frameworks (MOFs) are attractive adsorbents for heavy metal capture due to their superior stability, easy modification, and adjustable pore size. However, their inherent microporous structure poses challenges in achieving a higher adsorption capacity. Defect engineering is considered a simple method to create hierarchical MOFs with larger pores. Here, we employed l-aspartic acid as a mixed linker to bind Zr4+ clusters in competition with fumaric acid of MOF-801 to create defects, and the pore size was increased from 4.66 to 15.65 nm. Mercaptosuccinic acid was subsequently used as a postexchange ligand to graft the resultant MOF-801 by acid-ammonia condensation to further expand the pore size to 22.73 nm. Notably, the -NH2, -COOH, and -SH groups contributed by these two ligands increased the adsorption sites for Pb(II). The obtained defective MOF-801 with larger pores was thereafter loaded onto sodium alginate to form aerogel beads as adsorbents, and an adsorption capacity of 375.48 mg/g for Pb(II) was achieved, which is ∼51 times that of pristine MOF-801. The aerogel beads also exhibited outstanding reusability with a removal efficiency of ∼90.23% after 5 cycles of use. The adsorption mechanism of Pb(II) included ion-exchange interaction, as well as chelation interactions of Pb-O, Pb-NH2, and Pb-S. The versatile combination of defect engineering and composite beads provides novel inspirations for MOF modification for boosting heavy metal adsorption.

Effects of phosphate-solubilizing bacteria Aspergillus flavus AF-LRH1 on promoting phosphorus solubilization, wheat growth and soil heavy metal remediation

Increasing nutrient supply level and eliminating pollution risk are essential to promote farmland soil use. In the soil-plant nutrition cycle, phosphorus is a limiting nutrient, toxic metals such as Cd and Pb are stress threats. Utilizing microorganisms as a bio-amendment could be a viable approach to enhance the cycling of soil phosphorus nutrients and immobilize Cd and Pb in the soil. This study involved the isolation of Aspergillus flavus AF-LRH1, a phosphate solubilizing fungal strain from soil. The strain exhibited the capacity to solubilize calcium phosphate, attaining a phosphorus concentration of 220.73 mg L−1 in the medium. High performance liquid chromatography analysis showed that AF-LRH1 produced a combination of organic acids (tartaric acid 260.7 mg L−1, fumaric acid 0.8 mg L−1, citric acid 911.9 mg L−1) to dissolve Ca3(PO4)2 by providing H+ ions. AF-LRH1 also utilizes NH4+ for the biosynthesis of amino acids and releases protons, which facilitate the dissolution of insoluble Ca3(PO4)2 and calcium phytate. Through these processes, calcium phosphate is partly converted into hydroxyapatite because of biological solubilization. AF-LRH1 strain showed the capability to recover phosphorus from various types of sludge-based solid residue by increasing the solubility of insoluble phosphate compounds for plant nutrient supply. In addition, the combining addition of AF-LRH1 strain and phosphate-containing amendments (calcium phosphate, sludge ash and biochar) benefited the decontamination of Pb and Cd contaminated soil. This finding confirmed the AF-LRH1 could be a promising environmental-friendly biofertilizer suitable for agricultural applications and bioremediation of heavy metal contaminated soil.

Effects of complex probiotics on intestinal function and its regulatory mechanism in patients with constipation.

Chronic constipation is a multi-symptomatic, multifactorial, and heterogeneous gastrointestinal disorder. Current pharmacological treatments for chronic constipation are limited and might negatively impact the patients' quality of life. Although probiotics have been shown to improve constipation symptoms, their specific regulatory mechanisms remain unclear. This study sought to explore how probiotic complexes may affect chronic constipation by improving patients' defecation habits. Furthermore, microbial profiles and non-targeted metabolites were assessed to explore the metabolic pathways involved in the improvement of constipation by probiotics. Patients with chronic constipation were treated using a single-blind, randomised, placebo-controlled trial design. The experimental group was administered Lactobacillus powder prepared from 15 probiotic products, and maltodextrin was used as a placebo. Samples were collected twice daily for 4 weeks, and faecal samples were analysed using 16S rRNA sequencing and untargeted metabolic histology. Probiotic treatment changed the makeup of the gut microbiota, enhanced the quantity of Bifidobacterium and Lactobacillus, and markedly reduced clinical symptoms. The 16S rRNA analysis revealed that the abundance of Bifidobacterium and Prevotella increased while that of Thickettsia declined. Moreover, there was a decrease in the abundance of Faecalibacterium and Roseburia. Non-targeted metabolomics analysis identified several differential metabolites, including succinic acid, fumaric acid, cholesterol, xanthurenic acid, 3-alpha,7-alpha-trihydroxy-5beta-cholestan-26-oic, and N-methyltryptamine. KEGG analysis showed that these metabolites were mainly associated with metabolic pathways such as primary bile acid biosynthesis, tryptophan metabolism, alanine, aspartate and glutamate metabolism, phenylalanine metabolism, cholesterol metabolism, and propanoate metabolism. In this study, gut microbiome and non-targeted metabolome analyses were performed on collected faecal samples to compare characteristic microorganisms and differential metabolites to provide new insights and references for probiotic intervention in constipation. Trial registered at chictr.org.cn under number: ChiCTR2200056274.