Search Results (140)

Protein phosphorylation and dephosphorylation reactions of intracellular molecules catalyzed by enzymes such as kinases and phosphatases are essential reactions in a lot of cellular functions such as intracellular signal transduction in living systems. The design and synthesis of artificial enzyme mimics are important research topics in bioorganic and bioinorganic chemistry. In this paper, we report on the construction of artificial phosphatases via the supramolecular self-assembly of compounds such as an amphiphilic bis(Zn²⁺-cyclen) (cyclen = 1,4,7,10-tetraazacyclododecane) complex, barbital derivatives modified with benzocrown ethers and boronophenyl groups, and a copper(II) ion in a two-phase solvent system. We have developed a hypothesis whereby a mono(4-nitrophenyl)phosphate (MNP) substrate coordinates to the Cu₂(µ-OH)₂ core in supramolecular complexes and is activated either by Lewis acidic units such as alkali metal (Li⁺, Na⁺ and K⁺)-benzocrown ether complexes or by boronophenyl moieties. The findings suggest that supramolecular phosphatase functionalized with a benzo-12-crown-4-Li⁺ complex shows a higher level of activity in the MNP hydrolysis of a two-phase solvent system compared with that of our previous supramolecular phosphatases in terms of hydrolysis activity and catalytic turnover. Full article

The alpine grassland ecosystem of the Tibetan Plateau is a vital base for animal husbandry and a key ecological security barrier in China. Phosphorus (P), an essential nutrient, is among the primary factors limiting grassland productivity. However, the spatial distribution of soil P fractions across alpine grasslands on the Tibetan Plateau and their environmental drivers remain unclear, limiting our understanding of P cycling and grassland productivity. This study examined the composition and distribution of soil P in three representative alpine grasslands (meadow, steppe, and desert) using a combination of chemical fractionation and ³¹P nuclear magnetic resonance (NMR) spectroscopy. The results revealed pronounced spatial heterogeneity, with total soil P content varying by approximately 2.4-fold among the grassland types. Alpine meadows had the highest total P (0.73 g kg⁻¹) and available P (4.02 mg kg⁻¹) concentrations, with the latter being nearly twice that of alpine steppes and deserts. Alpine meadows were characterized by a predominance of labile and moderately labile organic P (e.g., NaOH-Po) and a diverse array of phosphate monoesters and diesters, whereas alpine deserts were dominated by stable, calcium-bound inorganic P (HCl-Pi). Temperature, precipitation, pH, and phosphatase activity were identified as key factors regulating the distribution and transformation of P fractions. The distinct P fractions and availability uncovered in this study are essential for predicting grassland ecosystem responses to environmental change and guiding sustainable pasture management on the Tibetan Plateau. Full article

Background: Prostate cancer (PCa) remains the second leading cause of cancer-related deaths in men in the United States. Fatty acid-binding protein 5 (FABP5), a member of a class of intracellular lipid transporters, promotes PCa progression via enhanced lipid metabolism and trafficking of lipid ligands. Previous work from our group has demonstrated that small-molecule FABP5 inhibitors based on the truxillic-acid monoester scaffold reduce PCa growth. Methods: Here, we assessed the effect of third-generation FABP5 inhibitors on the PCa cell cycle, proliferation, apoptosis, signaling pathway activity, and transcriptomic landscape. Results: We demonstrate that the third-generation FABP5 inhibitor SBFI-1143 significantly inhibits the viability of PCa cells by arresting them at the G0/G1 and G2/M phases of the cell cycle, inducing apoptosis, and promoting cell death. Strikingly, SBFI-1143 efficiently inhibited the growth of PCa spheroids compared to its predecessor, SBFI-103. RNA-seq and Gene Set Enrichment Analysis demonstrated that SBFI-1143 more effectively suppressed pathways involved in cell cycle progression, cell cycle division, and chromosome organization while upregulating genes associated with endoplasmic reticulum stress, responses to incorrectly folded proteins, and regulating apoptosis, compared to SBFI-103. Notably, SBFI-1143 treatment downregulated genes associated with the subpopulation of PCa cells characterized by a lineage plasticity-related signature, related to trans-differentiation, recurrence, and poor cancer prognosis. Conclusions: Our findings demonstrate that SBFI-1143 significantly alters the transcriptomic landscape of prostate cancer and may serve as a potentially effective therapeutic option for this disease. Full article

Phosphorus (P) is a key limiting nutrient in alpine meadows. Analyzing the spatial distribution of soil P and its forms along altitudinal gradients is crucial to understand soil nutrient cycling and sustain productivity under climate change. In this study, changes in the total P, available P, inorganic P (Pi), and organic P (Po) contents in soil along an altitudinal gradient of 4400–5200 m on the Qinghai–Tibetan Plateau were investigated using sequential chemical fractionation and solution ³¹P nuclear magnetic resonance (NMR). The results showed that the contents of total soil P, available P, Pi, and Po forms showed vertical distribution patterns. At an altitude of 4400–4950 m, the dominance of NaOH-Po was observed, whereas HCl-Pi was predominant at 5200 m. With increasing elevation, total soil P, orthophosphate, NaHCO₃-Pi, NaOH-Pi, HCl-Pi, and HCl-Po contents increased gradually. In contrast, the concentrations of available P, H₂O-Pi, H₂O-Po, NaHCO₃-Po, NaOH-Po, pyrophosphate, orthophosphate monoester, and diester initially increased, peaked at approximately 4950 m, and subsequently decreased. Both climatic factors (i.e., mean annual temperature and precipitation) and biological factors (aboveground biomass and enzyme activity) jointly regulated the vertical distribution of soil P forms in the alpine ecosystems. Full article

Heliotropium procumbens, a Boraginaceae species native to Panama, has remained largely unexplored regarding its nitrogen-containing metabolites, including pyrrolizidine alkaloids (PAs). In the current study, a comprehensive phytochemical investigation of its aerial parts is presented using HPLC-DAD-IT-MS, UHPLC–HRMS, and GC-MS primarily to profile its PA composition. A total of twelve PAs and N-oxides (PANOs) were identified, along with two phenolamides—including N¹, N¹⁰-diferuloylspermidine, which is biosynthetically related to PAs—and the distinctive metabolite heliotropamide. The detected PAs included unsaturated necines, primarily monoesters of retronecine and heliotridine, as well as saturated PAs such as a platynecine-type PA and the less commonly encountered triol necines and their N-oxides. Among these, helifoline-N-oxide was isolated and structurally elucidated by NMR spectroscopy for the first time as a natural product. Comparison with the chemodiversity of PAs within the Heliotropium genus revealed a high degree of diversity in H. procumbens, which can be attributed both to the species’ inherent biosynthetic capacity for chemical variation and to the more comprehensive and extensive studies conducted on it, which naturally enrich the apparent diversity observed. This work expands the phytochemical knowledge of H. procumbens and contributes to a broader understanding of PA diversity in the genus, offering new insights into their potential ecological and toxicological significance. Full article

The pigmentation and coloration of P. vannamei are primarily determined by the type and concentration of dietary carotenoids, with carotenoid-rich macroalgae serving as effective dietary supplements to enhance pigment accumulation and improve commercial quality. Five experimental diets were formulated with 3% brown algae (Saccharina japonica, SJ group; Sargassum fusiforme, SF group), red algae (Neoporphyra haitanensis, NH group), or 0.1% purified carotenoids (zeaxanthin, ZT group; fucoxanthin, FX group). The results showed that both macroalgae and carotenoid supplementation significantly enhanced weight gain rate (WGR) and specific growth rate (SGR) compared to the control group, with the zeaxanthin and fucoxanthin groups exhibiting the greatest improvements (1.6-fold and 1.3-fold, respectively). The N. haitanensis-supplemented diet, which had the highest carotenoid content, resulted in the most pronounced carotenoid accumulation (2.58-fold increase). Carotenoids were mainly deposited in the exoskeleton, followed by the hepatopancreas, with minimal accumulation in muscle tissue. α-Carotene and β-carotene contributed most to exoskeleton deposition, while lutein and zeaxanthin had weaker effects, and fucoxanthin showed no significant influence. Tissue-specific distribution patterns were observed: α-carotene and β-carotene were localized in the exoskeleton; fucoxanthin and zeaxanthin were found only in the exoskeleton and hepatopancreas, and astaxanthin was present in all three tissues. Furthermore, astaxanthin diesters (C20:5 and C22:6) were primarily detected in the exoskeleton and hepatopancreas, while monoesters (C16:0 and C18:0) were specific to muscle. These findings suggest that targeted supplementation of algal-derived carotenoids can enhance both growth and pigmentation in P. vannamei, providing a theoretical basis for the development of functional feeds to improve shrimp commercial quality. Full article

Sucrose esters are biodegradable surfactants widely used in the food and cosmetic industries due to their vast range of hydrophilic to lipophilic balance (HLB) values. However, their application has mostly been reported in aqueous media. With the rising demand for water-free products, a gap in the literature exists with regards to water-free colloids stabilized by sucrose esters. In particular, only two articles exist on sucrose ester-stabilized water-free foams, or oleofoams. This article explores for the first time the effects of sucrose ester HLB value on the physical properties of foams. The effects of oil triglyceride content on foamability were studied. The results showed that higher temperatures (90–100 °C) were needed to solubilize more hydrophilic sucrose esters, and these rendered the most encapsulated air (up to 62%) due to their high monoester content (>50%). Surface tension results also showed that the more hydrophilic sucrose esters reduced the oil/air surface tension the most. Regarding the oil triglyceride profile, results showed that with longer fatty acid chains, more air was incorporated into the foam. Sucrose esters have important untapped potential for use in the formation and stabilization of water-free foams. Full article

Processed Fu-Zi (the lateral roots of Aconitum carmichaeli) is beneficial for the cardiac system, but, because it contains toxins, raw Fu-Zi produces arrhythmia and breathing difficulties. C₁₉ diester diterpenoid alkaloids (DDAs), including aconitine, mesaconitine, and hypaconitine, are toxic Aconitum alkaloids found in Fu-Zi and can be hydrolyzed to nontoxic monoester diterpenoid alkaloids (MDAs), including benzoylaconine, benzoylmesaconine, and benzoylhypaconine. In this study, six processed Fu-Zi decoction pieces and herbal medicines were analyzed. The highest DDA contents were found in Shengfupian, the raw Fu-Zi samples. A processing quality index (Grades A to D) was established to evaluate the processing quality of Fu-Zi. The data demonstrated that few Fu-Zi decoction pieces did not conform to the government regulation. The results of testing the inorganic elements showed that the calcium content increased by approximately 5 to 30 fold compared to raw Fu-Zi due to substances assisting with processing. Raw Fu-Zi processed by boiling, without additional substances, may have a decreased DDA content. This study provides a method of determining the quality status of pieces of Fu-Zi decoction and establishes a processing quality index for pieces of Fu-Zi decoction and herbal medicine. Furthermore, our results suggest that it is not necessary to use additional substance to assist with the processing of Fu-Zi. Through the established processing quality index, Fu-Zi may be used more safely and may demonstrate a greater consistency in quality. Full article

This study explored the effect of the combined application of chemical and organic fertilizers on phosphorus morphology and its conversion to an active state. A long-term field positioning experiment comprising five treatments was conducted in black soil. The results concluded that the soil total phosphorus (TP), available phosphorus (AP), inorganic phosphorus, and organic phosphorus contents of all treatments ranked as follows: 1.5M1NPK > M2NPK > M1NPK > NPK > CK. The long-term application of chemical and organic fertilizers increased the proportion of soil reactive phosphorus and moderately reactive phosphorus but decreased the proportion of mildly active phosphorus and residual phosphorus. A phosphorus-31 nuclear magnetic resonance (³¹P NMR) spectral analysis showed that the contents of orthophosphate, pyrophosphate, phosphoric acid diesters, and orthophosphate acid monoesters increased with the application of chemical and organic fertilizers, of which 1.5M1NPK usually resulted in the highest increases. In conclusion, the long-term application of chemical fertilizers could promote the conversion of soil phosphorus into active phosphorus and improve the effectiveness of soil phosphorus, and the long-term use of organic and chemical fertilizers was more effective than the use of chemical fertilizers only, with 1.5M1NPK providing the best effects. Full article

Certain secondary carotenoids, such as astaxanthin and canthaxanthin, are of growing economic interest in the fields of human nutrition, food, health and cosmetics, as well as feed and aquaculture, particularly due to their numerous biological activities, such as their remarkable antioxidant properties. The present study was devoted to assessing, in a photobioreactor, the feasibility of cultivating newly isolated Dysmorphococcus strains from the biodiversity of Reunion Island for the production of these valuable xanthophylls. The results showed that all these strains were capable of producing and accumulating canthaxanthin and astaxanthin in response to environmental stresses. Among them, a strain which presented interesting morphological, genetic and biochemical properties as compared to the other Dysmorphococcus strains was further cultivated in a 3 L benchtop photobioreactor and was found to produce maximum carotenoid-rich biomass concentrations and productivities of about 4 g L⁻¹ dw and 0.055 g L⁻¹ d⁻¹ dw, respectively. We also found that the biomass contained up to 1.2 mg g⁻¹ dw of canthaxanthin and 0.7 mg g⁻¹ dw of different forms of astaxanthin, mainly astaxanthin monoesters. The productivity of these carotenoids was found to be lower than those observed for other microalgal species previously reported, and we suggested that further optimizations with respect to the cultivation and the carotenogenesis induction processes are needed to improve productivities and to make this locally isolated Dysmorphococcus strain useful for future commercial production of natural canthaxanthin and astaxanthin. Full article

Introduction: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have greatly improved outcomes in persons with CF (pwCF); however, there is still significant heterogeneity in clinical responses, particularly with regard to respiratory infection and inflammation. Exogenous administration of ketones has profound systemic anti-inflammatory effects and produces several nutrient-signaling and metabolic effects that may benefit multiple organ systems affected in pwCF. This pilot study was designed to determine the feasibility of administration of a ketone monoester (KME) to increase circulating D-beta hydroxybutyrate concentrations (D-βHB) and to improve subjective measures of CF-specific quality of life and markers of inflammation in serum and sputum in adults with CF. Methods: Fourteen participants receiving modulator therapy were randomized to receive either KME (n = 9) or placebo control (PC, n = 5) for 5–7 days during hospitalization for treatment of acute pulmonary exacerbation or as outpatients under standard care. Results: The KME was well tolerated, with only mild reports of gastrointestinal distress. D-βHB concentrations increased from 0.2 ± 0.1 mM to 1.6 ± 0.6 mM in the KME group compared to 0.2 ± 0.0 to 0.3 ± 0.1 in the PC group (p = 0.011) within 15 min following consumption and remained elevated, relative to baseline, for over 2 h. Pulmonary function was not altered after single- or short-term KME administration, but participants in the KME group self-reported higher subjective respiratory scores compared to PC in both cases (p = 0.031). Plasma inflammatory markers were not statistically different between groups following the short-term (5–7 d) intervention (p > 0.05). However, an exploratory analysis of plasma pre- and post-IL-6 concentrations was significant (p = 0.028) in the KME group but not PC. Sputum IFNγ (p = 0.057), IL-12p70 (p = 0.057), IL-1β (p = 0.100), IL-15 (p = 0.057), IL-1α (p = 0.114), and MPO (p = 0.133) were lower in the KME group compared to PC but did not achieve statistical significance. Conclusions: With the emerging role of exogenous ketones as nutrient signaling molecules and mediators of metabolism, we showed that KME is well tolerated, increases circulating D-βHB concentrations, and produces outcomes that justify the need for large-scale clinical trials to investigate the role of KME on whole-body and tissue lipid accumulation and inflammation in pwCF. Full article

Haematococcus lacustris is a freshwater green microalgae species able to produce and accumulate astaxanthin in response to environmental stresses such as high light and nutrient deprivation. Astaxanthin is a xanthophyll carotenoid of growing economic interest due to its numerous biological activities, notably its strong antioxidant properties, which can be valued in the fields of nutrition, health, feed and aquaculture. The present study aims at evaluating the capacity of two newly isolated Haematococcus strains from the biodiversity of Reunion Island, to be cultivated in a photobioreactor and to produce astaxanthin. The results showed that both strains were able to grow in various nutritive media and to produce and accumulate astaxanthin in response to stresses, mainly in the form of astaxanthin monoesters, which represented up to 2% of the dry biomass weight and which were mostly composed of linoleic and linolenic acids. In fed-batch cultures using 3 L benchtop photobioreactors, the concentrations of biomass enriched in astaxanthin reached up to 3 g L⁻¹ (dry weight) with biomass productivities of 0.04 and 0.02 g L⁻¹ d⁻¹ based on the durations of the vegetative stage and of the entire culture, respectively. In these cultures, the astaxanthin productivities were found to reach on average around 0.25 mg L⁻¹ d⁻¹. Although these results were relatively low compared to the literature, the possibility of improving growth conditions in order to improve biomass and astaxanthin yields, to guarantee economic viability for cultivation at a commercial scale, was further discussed. Full article

Hydroxytyrosol (HT) is a nutraceutical compound, mainly found in the fruit, leaves and waste from the olive oil industry, known for exhibiting one of the highest antioxidant activities among molecules of natural origin. To harness this bioactivity in cosmetics, pharmaceuticals and the food industry, it is essential to modify the hydrophilicity of HT to enhance its compatibility with lipid-based mixtures. This chemical modification must be carried out with high selectivity to avoid compromising its radical scavenging activity. This work presents a highly efficient and selective approach to perform the biocatalytic esterification of free fatty acids (FFAs) of different alkyl chain lengths with HT in a reaction medium based on the SLIL [C₁₂mim][NTf₂]. By using a 1:2 (mol/mol) HT:FFA mixture of substrates, the HT-monoester derivative was obtained up to 77% yield after 2 h at 80 °C. The optimized molar ratio of substrates, combined with the ability to recover the SLIL for further reuse, significantly reduces waste accumulation compared to other reported strategies and results in a more sustainable approach as demonstrated by different green metrics. The antioxidant activity of HT-monoester products was fully maintained with respect to that presented by the natural HT, being stable for at least 3 months at 4 °C, as demonstrated by the DPPH and FRAP antioxidant analysis. Full article

Spinal cord injury (SCI) pathology and pathophysiology can be attributed to both primary physical injury and secondary injury cascades. Secondary injury cascades involve dysregulated metabolism and energetic deficits directly linked to compromised mitochondrial bioenergetics. Rescuing mitochondrial function and reducing oxidative stress are associated with neuroprotection. In this regard, ketosis after traumatic brain injury (TBI), or after SCI, improves secondary neuropathology by decreasing oxidative stress, increasing antioxidants, reducing inflammation, and improving mitochondrial bioenergetics. Here, we follow up on our previous study and have used an exogenous ketone monoester, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE), as an alternative to a ketogenic diet, focusing on mitochondrial function between 1 and 14 days after injury. Starting 3 h following a cervical level 5 (C5) hemi-contusion injury, animals were fed either a standard control diet (SD) or a ketone ester diet (KED) combined with KE administered orally (OKE). We found that mitochondrial function was reduced after SCI at all times post-SCI, accompanied by reduced expression of most of the components of the electron transport chain (ETC). The KE rescued some of the bioenergetic parameters 1 day after SCI when D-β-Hydroxybutyrate (BHB) concentrations were ~2 mM. Still, most of the beneficial effects were observed 14 days after injury, with BHB concentrations reaching values of 4–6 mM. To our knowledge, this is the first report to show the beneficial effects of KE in rescuing mitochondrial function after SCI and demonstrates the suitability of KE in ameliorating the metabolic dysregulation that occurs after traumatic SCI without requiring a restrictive dietary regime. Full article

Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug extensively used by people living with HIV. The TDF molecule is hydrolysed in vivo and liberates tenofovir, the active part of the molecule. Tenofovir is a very stable drug and the discharge of its residues into the environment can potentially lead to risk for aquatic species. This study evaluated the TDF biodegradation and removal by cultures of Microcystis novacekii with the bacteria Pseudomonas pseudoalcaligenes. Concentrations of TDF of 12.5, 25.0, and 50.0 mg/L were used in this study. The process occurred in two stages. In the first 72 h, TDF was de-esterified, forming the tenofovir monoester intermediate by abiotic and enzymatic processes associated in an extracellular medium. In a second step, the monoester was removed from the culture medium by intracellular processes. The tenofovir or other by-products of TDF were not observed in the test conditions. At the end of the experiment, 88.7 to 94.1% of TDF and its monoester derivative were removed from the culture medium over 16 days. This process showed higher efficiency of TDF removal at the concentration of 25 mg/L. Tenofovir isoproxil monoester has partial antiviral activity and has shown to be persistent, maintaining a residual concentration after 16 days in the culture medium, therefore indicating the need to continue research on methods for total removal of this product from the aquatic environment. Full article