Evaluating appropriateness of 18F-fluciclovine PET/CT relative to standard of care imaging guidelines and the impact of ADT on positivity: a prospective study in 62 Veterans Administration patients at a single institution.

BACKGROUND: According to the National Comprehensive Cancer Network Guidelines, 18F-fluciclovine PET/CT is considered appropriate after negative standard of care (SOC) imaging. OBJECTIVE: To prospectively compare 18F-fluciclovine to SOC imaging, investigate whether it should be done when SOC imaging is (+), and evaluate its detection rate in patients receiving androgen deprivation therapy. METHODS: We recruited 57 prostate cancer patients with biochemical recurrence with 18F-fluciclovine PET/CT and SOC imaging within 30 days. Prostate-specific antigen (PSA) level, Gleason score (GS), history of radical prostatectomy (RP), radiation therapy (RT) or hormone therapy (HT) were reviewed. RESULTS: The 57 patients had a median PSA of 2.6 and average GS of 7.4; 27 (47.4%) had RP, 28 (49.1%) had RT, 1 (1.75%) had HT and 1 (1.75%) observation only. 18F-fluciclovine identified disease recurrence in 45/57 patients (78.9%), including oligometastasis in 18/45 (40%). SOC imaging identified recurrent disease in 12/57 patients (21.1%) while 18F-fluciclvoine identified additional sites of disease in 11/12 (91.7%). The (+) 18F-fluciclovine studies had a median PSA 2.6 ng/ml compared to 6.0 ng/ml in the (+) SOC studies. CONCLUSION: 18F-fluciclovine was superior to SOC imaging for lesion detection, identification of oligometastasis and identification of additional sites of disease.

Biosynthesis of Chryseno[2,1,c]oxepin-12-Carboxylic Acid from Glycyrrhizic Acid in Aspergillus terreus TMZ05-2, and Analysis of Its Anti-inflammatory Activity.

Glycyrrhizic acid, glycyrrhetinic acid, and their oxo, ester, lactone, and other derivatives, are known for their anti-inflammatory, anti-oxidant, and hypoglycemic pharmacological activities. In this study, chryseno[2,1-c]oxepin-12-carboxylic acid (MG) was first biosynthesized from glycyrrhizic acid through sequential hydrolysis, oxidation, and esterification using Aspergillus terreus TMZ05-2, providing a novel in vitro biosynthetic pathway for glycyrrhizic acid derivatives. Assessing the influence of fermentation conditions and variation of strains during culture under stress-induction strategies enhanced the final molar yield to 88.3% (5 g/L glycyrrhizic acid). CCK8 assays showed no cytotoxicity and good cell proliferation, and anti-inflammatory experiments demonstrated strong inhibition of NO release (36.3%, low-dose MG vs. model), transcriptional downregulation of classical effective cellular factors tumor necrosis factor-α (TNF-α; 72.2%, low-dose MG vs. model), interleukin-6 (IL-6; 58.3%, low-dose MG vs. model) and interleukin-1ß (IL-1ß; 76.4%, low-dose MG vs. model), and decreased abundance of P-IKK-α, P-IKB-α, and P-P65 proteins, thereby alleviating inflammatory responses through the NF-κB pathway in LPS-induced RAW264.7 cells. The findings provide a reference for the biosynthesis of lactone compounds from medicinal plants.

Constituents from the Polar Extract of Pisolithus arhizus and Their Anti-inflammatory Activity.

The phytochemical study of the Pisolithus arhizus fruiting body methanol extract led to the isolation of six new triterpenoids (1-6) and one new naphthalenoid pulvinic acid derivative (7), together with five known compounds, including norbadione A (8). Their structure was established from 1D and 2D NMR spectroscopy and HRESIMS analyses. The absolute configuration of the triterpenoids was determined by circular dichroism. The two pulvinic acid derivatives 7 and 8, showing the highest activity in modulating IL-6 secretion, were tested for their effect on COX-2, STAT3, and p-STAT3 proteins; both compounds were able to downregulate p-STAT3.

Multidrug-resistant Gram-negative clinical isolates with reduced susceptibility/resistance to cefiderocol: which are the best present and future therapeutic alternatives?

PURPOSE: To evaluate the different present and future therapeutic ß-lactam/ß-lactamase inhibitor (BL/BLI) alternatives, namely aztreonam-avibactam, imipenem-relebactam, meropenem-vaborbactam, cefepime-zidebactam, cefepime-taniborbactam, meropenem-nacubactam, and sulbactam-durlobactam against clinical isolates showing reduced susceptibility or resistance to cefiderocol in Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa. METHODS: MIC values of aztreonam, aztreonam-avibactam, cefepime, cefepime-taniborbactam, cefepime-zidebactam, imipenem, imipenem-relebactam, meropenem, meropenem-vaborbactam, meropenem-nacubactam, sulbactam-durlobactam, and cefiderocol combined with a BLI were determined for 67, 9, and 11 clinical Enterobacterales, P. aeruginosa or A. baumannii isolates, respectively, showing MIC values of cefiderocol being ≥1 mg/L. If unavailable, the respective ß-lactam breakpoints according to EUCAST were used for BL/BLI combinations. RESULTS: For Enterobacterales, the susceptibility rates for aztreonam, cefepime, imipenem, and meropenem were 7.5%, 0%, 10.4%, and 10.4%, respectively, while they were much higher for cefepime-zidebactam (91%), cefiderocol-zidebactam (91%), meropenem-nacubactam (71.6%), cefiderocol-nacubactam (74.6%), and cefiderocol-taniborbactam (76.1%), as expected. For P. aeruginosa isolates, the higher susceptibility rates were observed for imipenem-relebactam, cefiderocol-zidebactam, and meropenem-vaborbactam (56% for all combinations). For A. baumannii isolates, lower susceptibility rates were observed with commercially or under development BL/BLI combos; however, a high susceptibility rate (70%) was found for sulbactam-durlobactam and when cefiderocol was associated to some BLIs. CONCLUSIONS: Zidebactam- and nacubactam-containing combinations showed a significant in vitro activity against multidrug-resistant Enterobacterales clinical isolates with reduced susceptibility to cefiderocol. On the other hand, imipenem-relebactam and meropenem-vaborbactam showed the highest susceptibility rates against P. aeruginosa isolates. Finally, sulbactam-durlobactam and cefiderocol combined with a BLI were the only effective options against A. baumannii tested isolates.

Synergistic improvements in energy recovery and bio-oil quality through integrated thermochemical valorization of agro-industrial waste of varying moisture content.

Two thermochemical valorization schemes were investigated for co-upgrading dry and wet agricultural wastes through integrated hydrothermal carbonization (HTC) and pyrolysis. In the first pathway, dry and wet wastes were co-carbonized. The resulting hydrochar was pyrolyzed to yield an energy dense biochar (26-32 MJ/kg) high in fixed carbon (41-86 wt%) and low in volatile matter (6-12 wt%). The resulting bio-oil was lower in carboxylic acids and higher in phenols than predicted based on an additive scheme. In pathway two, wet waste (only) underwent HTC and the resulting hydrochar was mixed with dry waste and the mixture pyrolyzed. This pathway showed a lower biochar yield (32-67 wt%) and lower HHV values (24-31 MJ/kg) but higher fixed carbon content (65-84 wt%). The bio-oil contained more carboxylic acids than pathway 1 bio-oil. Pathway 1 biochars were more thermally reactive than pathway 2 biochars, reflecting a synergistic deoxygenation that occurs when incorporating dry waste in HTC prior to pyrolysis.

Phosphorus absorption kinetics and exudation strategies of roots developed by three lupin species to tackle P deficiency.

MAIN CONCLUSION: Different lupin species exhibited varied biomass, P allocation, and physiological responses to P-deprivation. White and yellow lupins had higher carboxylate exudation rates, while blue lupin showed the highest phosphatase activity. White lupin (Lupinus albus) can produce specialized root structures, called cluster roots, which are adapted to low-phosphorus (P) soil. Blue lupin (L. angustifolius) and yellow lupin (L. luteus), which are two close relatives of white lupin, do not produce cluster roots. This study characterized plant responses to nutrient limitation by analyzing biomass accumulation and P distribution, absorption kinetics and root exudation in white, blue, and yellow lupins. Plants were grown in hydroponic culture with (64 µM NaH2PO4) or without P for 31 days. Under P limitation, more biomass was allocated to roots to improve P absorption. Furthermore, the relative growth rate of blue lupin showed the strongest inhibition. Under + P conditions, the plant total-P contents of blue lupin and yellow lupin were higher than that of white lupin. To elucidate the responses of lupins via the perspective of absorption kinetics and secretion analysis, blue and yellow lupins were confirmed to have stronger affinity and absorption capacity for orthophosphate after P-deprivation cultivation, whereas white lupin and yellow lupin had greater ability to secrete organic acids. The exudation of blue lupin had higher acid phosphatase activity. This study elucidated that blue lupin was more sensitive to P-scarcity stress and yellow had the greater tolerance of P-deficient condition than either of the other two lupin species. The three lupin species have evolved different adaptation strategies to cope with P deficiency.

Deep Eutectic Solvents Based on Carboxylic Acids and Glycerol or Propylene Glycol as Green Media for Extraction of Bioactive Substances from Chamaenerion angustifolium (L.) Scop.

Chamaenerion angustifolium (L.) Scop. is one of the promising sources of biologically active compounds and a valuable industrial crop. Recently, green extraction methods have become more topical. One of them is the application of deep eutectic solvents (DESs). The aim of this work was the synthesis and characterization of DES consisting of glycerin or propylene glycol with malonic, malic, or citric acids, evaluation of their effectiveness for extracting useful substances from C. angustifolium during ultrasonic extraction, description of kinetics, and optimization of extraction conditions. DESs were obtained and characterized with FTIR. Their effectiveness in the process of ultrasound-assisted extraction of biologically active substances from C. angustifolium was estimated. Kinetic parameters describing the dependence of the total phenolic, flavonoids, and antioxidant content, free radical scavenging of DPPH, and concentration of flavonoid aglycons (myricetin, quercetin, and kaempferol) via time in the range of 5-60 min at 45 °C are obtained. Extraction conditions were optimized with the Box-Behnken design of experiment. The results of this work make it possible to expand the scope of DES applications and serve the development of C. angustifolium processing methods.

Hydraulic Retention Time as an Operational Tool for the Production of Short-Chain Carboxylates via Anaerobic Fermentation of Carbohydrate-Rich Waste.

The carboxylate platform is a sustainable and cost-effective way to valorize wastes into biochemicals that replace those of fossil origin. Short-chain fatty acids (SCFAs) are intermediates generated during anaerobic fermentation (AF) and are considered high-value-added biochemicals among carboxylates. This investigation aimed to produce SCFAs through the AF of sugar beet molasses at 25 °C and semi-continuous feeding mode in completely stirred tank reactors. A particular focus was devoted to the role of hydraulic retention time (HRT) variation in SCFAs production and distribution profile. The highest SCFAs concentration (44.1 ± 2.3 gCOD/L) was reached at the HRT of 30 days. Caproic acid accounted for 32.5-35.5% (COD-concentration basis) at the long HRTs of 20 and 30 days due to the carbon chain elongation of shorter carboxylic acids. The findings of this study proved that HRT could be used to steer the anaerobic process toward the targeted SCFAs for specific uses. Furthermore, the successful operation at low-temperature conditions (i.e., 25 °C) makes the process economically promising.

Biodegradation of saturate fraction of crude oil and production of signature carboxylic acids.

Bacteria degrading large portion of saturated hydrocarbons are important for crude oil bioremediation. This study investigates Novosphingobium sp. S1, Gordonia amicalis S2 and Gordonia terrae S5 capability of degrading wide range of saturated hydrocarbons from Congo Bilondo crude oil and discusses the degradation pathway. A parallel analytical approach combining GC-MS and LC-HRMS enabled characterization of saturated hydrocarbons and comprehensive determination of carboxylic acid metabolites produced during biodegradation, respectively. Results showed that the three strains could efficiently degrade the n-alkanes (C10-C28) as well as methyl-substituted alkanes (C11-C26). The series of mono-, hydroxy- and dicarboxylic acids identified in this study confirmed the active biodegradation of the saturate fraction and suggest their degradation was via the bi-terminal oxidation pathway. This is the first study linking these bacterial species to bi-terminal oxidation of the saturated hydrocarbons. The study highlights the potential application of the bacterial strains in the bioremediation of crude oil contaminated sites. Additionally, while carboxylic acids is indicated as a suitable and valuable metabolic biomarker, its application is considered feasible and cost effective for rapid monitoring and evaluation of hydrocarbon biodegradation.

Site-specific spatiotemporal occurrence and molecular congener distributions of naphthenic acids in Athabasca oil sands wetlands of Alberta, Canada.

The Athabasca oil sands region (AOSR) of Alberta, Canada is notable for its considerable unconventional petroleum extraction projects, where bitumen is extracted from naturally-occurring oil sands ore. The large scale of these heavy crude oil developments raises concerns because of their potential to distribute and/or otherwise influence the occurrence, behaviour, and fate of environmental contaminants. Naphthenic acids (NAs) are one such contaminant class of concern in the AOSR, so studies have examined the occurrence and molecular profiles of NAs in the region. We catalogued the spatiotemporal occurrence and characteristics of NAs in boreal wetlands in the AOSR over a 7-year period, using derivatized liquid chromatography-tandem mass spectrometry (LC-MS/MS). Comparing median concentrations of NAs across these wetlands revealed a pattern of NAs suggesting NAs in surface waters derived from oil sands deposits. Opportunistic wetlands that formed adjacent to reclaimed overburden and other reclamation activities had the highest concentrations of NAs and consistent patterns suggestive of bitumen-derived inputs. However, similar patterns in the occurrence of NAs were also observed in undeveloped natural wetlands located above the known surface-mineable oil sands deposit that underlies the region. Intra-annual sampling results along with inter-annual comparisons across wetlands demonstrated that differences in the spatial and temporal NA concentrations were dependent on local factors, particularly when naturally occurring oil sands ores were observed in the wetland or drainage catchment.

Modulatory properties of Thespesia garckeana (F. Hoffm.) Exell & Hillc. Aqueous fruit extract on female rats reproductive hormones and tissues histology and potential inhibitory activity of its constituents against SRD5α2.

ETHNOPHARMACOLOGICAL RELEVANCE: Thespesia garckeana (F. Hoffm.) Exell & Hillc. is called Gorontula (Kola of Tula) in Nigeria, Morojwa in Bostwana, and Thespesia garckeana in South Africa and is widely distributed across Africa. Its parts reportedly possess multiple medicinal properties and are employed for treating various diseases. In Tula, Gombe State, Nigeria, the ripe fruit decoction is taken as remedy for female infertility as documented by Ochokwu and co in the Journal of Biology, Agriculture and Healthcare in 2015. AIM OF THE STUDY: This research examined the effects of aqueous fruit extract of T. garckeana (F. Hoffm.) Exell & Hillc. (AFETG) on selected reproductive tissues and hormones in female rats and also evaluated the inhibitory potentials of its phytoconstituents against human 5-alpha reductase 2 (SRD5α2) using in silico approach. METHODS: Twenty-five (25) sexually matured female rats were randomized into 5 groups (i.e. A - E). Oestrous in the rats was synchronized (subcutaneous oestradiol conjugate [10 µg/100 g BW]). Group A received distilled water (control). Group B received standard drug, clomiphene citrate (0.85 mg/kg BW), while groups C, D, and E received AFETG at 50, 100, and 200 mg/kg BW respectively. The animals were treated for five (5) days and sacrificed 24 h after. Their blood was collected and prepared for analysis of serum prolactin, oestradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) while ovaries, uteruses, and oviducts were studied for histological and histomorphometric changes. For the in silico study, the target protein, human steroid 5α-reductase 2 (SRD5α2) was prepared and its receptor grid was generated using Optimized Potential for Liquid Simulations-2005. The ligand 2D structures were prepared using LigPrep 2.4 software and docked using Glide. The binding energy of the ligands to the protein receptor was predicted using Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis. RESULTS: AFETG significantly increased serum levels of E2 but did not alter serum levels of prolactin, LH and FSH when compared with distilled water and clomiphene citrate. AFETG also significantly increased ovarian tertiary follicular diameter, oviductal epithelial height and serosa thickness as well as uterine endometrial epithelial height, endometrial thickness, and myometrial thickness when compared with control. Ovarian secondary follicular diameter and oviductal submucosa thickness and muscular thickness were significantly decreased by AFETG when compared with control. Two compounds in T. garckeana (F. Hoffm.) Exell & Hillc.; D-Melezitose (-12.55 kcal/mol XP GScore) and 1, 3, 4-trihydroxy-5-oxo cyclohexane-1-carboxylic acid (-9.136 kcal/mol XP GScore) exhibited higher binding affinities for SRD5α2 than the reference ligand, epristeride (-8.096 kcal/mol XP GScore). In conclusion, the ability of AFETG to increase serum E2 level, thickness of uterine endometrium and ovarian tertiary follicles size can be explored for the treatment of female infertility caused by thinning of the uterine endometrium and reduced follicular size. Two compounds in AFETG (i.e. D-Melezitose and 1, 3, 4-trihydroxy-5-oxo cyclohexane-1-carboxylic acid are potential inhibitors of SRD5α2, thus aiding the biosynthesis of E2. Available evidence therefore corroborate the traditional use of T. garckeana (F. Hoffm.) Exell & Hillc fruit as a female fertility enhancer in Northern Nigeria.

Comparison of chromatographic conditions for the targeted tandem mass spectrometric determination of 354 mammalian metabolites.

Metabolomics is becoming increasingly popular in livestock research, but no single analytical method can cover the entire metabolome. As such, we compared similar and complementary chromatographic methods with respect to analyte coverage and chromatographic properties of mammalian metabolites. We investigated 354 biologically relevant primary metabolites from 19 compound classes including amino acids, bile acids, biogenic amines, carboxylic acids, lipids, nucleotides and sugars. A total of 2063 selected reaction monitoring transitions were optimized on a triple quadrupole mass spectrometer. We then determined the retention profiles and peak parameters of our compounds using an anion exchange chromatography (AIC), three reversed-phase (RP) and three hydrophilic interaction liquid chromatography (HILIC) methods. On average, HILIC methods covered 54% of all metabolites with retention factors >1, while average RP coverage was 41%. In contrast to RP, HILIC methods could also retain polar metabolites such as amino acids and biogenic amines. Carboxylic acids, nucleotides, and sugar related compounds were best separated by AIC or zwitterionic pHILIC with alkaline eluents. Combining two complementary HILIC and RP methods increased the library coverage to 92%. By further including important short chain fatty acids, a combination of HILIC, RP and AIC methods achieved a coverage of 97%. The resulting dataset of LC and MS/MS parameters will facilitate the development of tailor-made quantitative targeted LC-MS/MS methods to investigate the mammalian metabolome.

Root morphological and physiological traits are committed to the phosphorus acquisition of the desert plants in phosphorus-deficient soils.

BACKGROUND: Phosphorus (P) deficiency in desert ecosystems is widespread. Generally, desert species may allocate an enormous proportion of photosynthetic carbon to their root systems to adjust their P-acquisition strategies. However, root P-acquisition strategies of deep-rooted desert species and the coordination response of root traits at different growth stages to differing soil P availability remains unclear. In this study, a two-year pot experiment was performed with four soil P-supply treatments (0, 0.9, 2.8, and 4.7 mg P kg-1 y-1 for the control, low-, intermediate-, and high-P supply, respectively). Root morphological and physiological traits of one- and two-year-old Alhagi sparsifolia seedlings were measured. RESULTS: For two-year-old seedlings, control or low-P supply significantly increased their leaf Mn concentration, coarse and fine roots' specific root length (SRL), specific root surface area (SRSA), and acid phosphatase activity (APase), but SRL and SRSA of one-year-old seedlings were higher under intermediate-P supply treatment. Root morphological traits were closely correlated with root APase activity and leaf Mn concentration. One-year-old seedlings had higher root APase activity, leaf Mn concentration, and root tissue density (RTD), but lower SRL and SRSA. Two-year-old seedlings had higher root APase activity, leaf Mn concentration, SRL and SRSA, but a lower RTD. Root APase activity was significantly positively correlated with the leaf Mn concentration, regardless of coarse or fine roots. Furthermore, root P concentrations of coarse and fine roots were driven by different root traits, with root biomass and carboxylates secretion particularly crucial root traits for the root P-acquisition of one- and two-year-old seedlings. CONCLUSIONS: Variation of root traits at different growth stages are coordinated with root P concentrations, indicating a trade-off between root traits and P-acquisition strategies. Alhagi sparsifolia developed two P-activation strategies, increasing P-mobilizing phosphatase activity and carboxylates secretion, to acclimate P-impoverished in soil. The adaptive variation of root traits at different growth stages and diversified P-activation strategies are conducive to maintaining the desert ecosystem productivity.

Zinc supplementation and light intensity affect 2-acetyl-1-pyrroline (2AP) formation in fragrant rice.

BACKGROUND: Improving the yield and aroma content of fragrant rice is the focus of fragrant rice research. Light and Zinc (Zn) management generally cause regulations in the 2-acetyl-1-pyrroline (2AP) accumulation in fragrant rice. In addition, Zn promotes rice growth and improves rice yield, which has the potential to compensate for the negative impact of low light on fragrant rice yield. However, the potential of Zn to improve fragrant rice yield and 2AP content under shading conditions has not been verified. METHODS: Field experiments were conducted in the rice season (May-September) in 2019 to 2021. Two light i.e., normal light (NL) and low light (LL) and four Zn levels i.e., 0 kg Zn ha- 1 (N0), 1 kg Zn ha- 1 (Zn1), 2 kg Zn ha- 1(Zn2), and 3 kg Zn ha- 1 (Zn3), which applied at booting stage was set up. The grain yield, 2AP contents, Zn content in polished rice, photosynthesis related indicators, MDA content, antioxidant enzyme activity and the biochemical parameters related to 2AP formation were investigated. RESULTS: Shading reduced yield by 8.74% and increased 2AP content by 24.37%. In addition, shading reduced net photosynthetic rate (Pn), superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), and increased proline, γ-aminobutyric acid (GABA), and pyrroline-5-carboxylic acid (P5C), proline dehydrogenase (PDH), △1-pyrroline-5-carboxylic acid synthetase (P5CS), malondialdehyde (MDA). With increasing Zn application levels, yield, 2AP, Zn content in polished rice, Pn, proline, P5C, GABA, PDH, P5CS, SOD, CAT and POD increased, and MDA decreased. Significant Light and Zn interaction effect on 2AP content was detected, and both shading and increasing Zn application increased the 2AP content. CONCLUSION: Shading can increase the 2AP content but reduce the yield of fragrant rice. Increasing Zn application under shading conditions can further promote the biosynthesis of 2AP, but the effect of improving yield is limited.

The Influence of Solid and Liquid Systems In Vitro on the Growth and Biosynthetic Characteristics of Microshoot Culture of Spiraea betulifolia ssp. aemiliana.

The paper focuses on the growth dynamics and biosynthetic characteristics of the microshoot culture of Spiraea betulifolia ssp. aemiliana obtained in vitro in agar-solidified and liquid media. Microshoots cultured in either type of media showed similar growth dynamics. The most active culture growth was observed from day 35 to day 60. A comparative analysis of the contents of flavonoids and phenol carboxylic acids showed a higher level of phenol carboxylic acids (5.3-6.84%) and a stronger 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity (half-maximal inhibitory concentration: 341 µg/mL) in S. betulifolia ssp. aemiliana microshoots grown in the liquid medium compared to the microshoots cultured in the solid medium. The flavonoid content of the cultured microshoot did not depend on the consistency of the medium. High-performance liquid chromatography (HPLC) was employed to study the profile and levels of phenolic compounds in microshoots, intact plants, and ex vitro-acclimated S. betulifolia ssp. aemiliana plants. The concentration of kaempferol glycosides was found to be higher in microshoots (1.33% in the solid medium, 1.06% in the liquid medium) compared to intact plants and ex vitro-acclimated plants. Thus, the microshoots of S. betulifolia ssp. aemiliana cultured in the liquid medium rapidly increase their biomass and are an inexpensive promising source of biologically active antioxidant substances, mainly phenol carboxylic acids and kaempferol glycosides.

Treatment Response to Lycopene in Recurrent Prostate Cancer Confirmed on 18 F-Fluciclovine PET/CT.

ABSTRACT: 18 F-fluciclovine (Axumin; Blue Earth Diagnostics, Ltd, Oxford, United Kingdom) PET has shown value in detecting biochemical recurrent prostatic cancer. Lycopene, a plant-based carotenoid, is reported to have potential inhibitory effect on prostate cancer, as a complementary treatment. We report a case of biochemically recurrent prostate cancer showing treatment response to lycopene as seen on an 18 F-fluciclovine PET/CT correlating with serum prostate-specific antigen response.

Sustainable extraction of antioxidants from out-of-caliber kiwifruits.

Valorisation of discarded kiwifruits is proposed by extracting bioactive compounds using sustainable solvents namely deep eutectic solvents (DES). A screening of fifteen DES and several hydrogen bonding donor solvents was carried out. Extraction efficiency was measured in terms of antioxidant activity using DPPH and FRAP tests. The influence of solvents characteristics in particular DES structure, presence of ethanol or water, and pH of DES/water mixture on the antioxidant properties of the extracts was studied. Results show that kiwi peels extracts obtained with DES based on carboxylic acids exhibit enhanced antioxidant activity compared to conventional solvents and alcohol-based DES with a maximum DPPH scavenging activity of 42.0 mg TE/g DW. Glycerol or ethylene glycol are also efficient at extracting antioxidant compounds with DPPH scavenging activity of 33.1 and 36.7 mg TE/g DW. Finally, a chemical analysis of extracts using HPTLC revealed that most active compounds extracted are polyphenolic compounds, presumably tannins.

Plasma levels of carboxylic acids are markers of early kidney dysfunction in young people with type 1 diabetes.

BACKGROUND: We compared plasma metabolites of amino acid oxidation and the tricarboxylic acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and related the metabolites to glomerular filtration rate (GFR), renal plasma flow (RPF), and albuminuria. Metabolites associated with impaired kidney function may warrant future study as potential biomarkers or even future interventions to improve kidney bioenergetics. METHODS: Metabolomic profiling of fasting plasma samples using a targeted panel of 644 metabolites and an untargeted panel of 19,777 metabolites was performed in 50 youth with T1DM ≤ 10 years and 20 controls. GFR and RPF were ascertained by iohexol and p-aminohippurate clearance, and albuminuria calculated as urine albumin to creatinine ratio. Sparse partial least squares discriminant analysis and moderated t tests were used to identify metabolites associated with GFR and RPF. RESULTS: Adolescents with and without T1DM were similar in age (16.1 ± 3.0 vs. 16.1 ± 2.9 years) and BMI (23.4 ± 5.1 vs. 22.7 ± 3.7 kg/m2), but those with T1DM had higher GFR (189 ± 40 vs. 136 ± 22 ml/min) and RPF (820 ± 125 vs. 615 ± 65 ml/min). Metabolites of amino acid oxidation and the TCA cycle were significantly lower in adolescents with T1DM vs. controls, and the measured metabolites were able to discriminate diabetes status with an AUC of 0.82 (95% CI: 0.71, 0.93) and error rate of 0.21. Lower glycine (r:-0.33, q = 0.01), histidine (r:-0.45, q < 0.001), methionine (r: -0.29, q = 0.02), phenylalanine (r: -0.29, q = 0.01), serine (r: -0.42, q < 0.001), threonine (r: -0.28, q = 0.02), citrate (r: -0.35, q = 0.003), fumarate (r: -0.24, q = 0.04), and malate (r: -0.29, q = 0.02) correlated with higher GFR. Lower glycine (r: -0.28, q = 0.04), phenylalanine (r:-0.3, q = 0.03), fumarate (r: -0.29, q = 0.04), and malate (r: -0.5, q < 0.001) correlated with higher RPF. Lower histidine (r: -0.28, q = 0.02) was correlated with higher mean ACR. CONCLUSIONS: In conclusion, adolescents with relatively short T1DM duration exhibited lower plasma levels of carboxylic acids that associated with hyperfiltration and hyperperfusion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03618420 and NCT03584217 A higher resolution version of the Graphical abstract is available as Supplementary information.

A Comprehensive Phytochemical Analysis of Sideritis scardica Infusion Using Orbitrap UHPLC-HRMS.

Sideritis scardica Griseb, also known as "mountain tea" and "Olympus tea" (Lamiaceae family) is an endemic plant from the mountainous regions of the Balkan Peninsula. In this study, we focused on an in-depth phytochemical analysis of S. scardica infusion using ultra-high-performance liquid chromatography hyphenated with high-resolution mass spectrometry (UHPLC-HRMS). Quantitative determination of the main secondary metabolites was carried out by UHPLC-HRMS analyses using the external standard method. The results revealed more than 100 metabolites, including five sugar acids and saccharides, 21 carboxylic, hydroxybenzoic, hydroxycinnamic acids, and derivatives, 15 acylquinic acids, 10 phenylpropanoid glycosides, four iridoid glycosides, 28 flavonoids, seven fatty acids, and four organosulfur compounds. Furthermore, a dereplication and fragmentation patterns of five caffeic acids oligomers and four acylhexaric acids was performed for the first time in S. scardica. Regarding the quantitative analysis, the phenylethanoid verbascoside (53) (151.54 ± 10.86 mg/g lyophilized infusion, li), the glycosides of isoscutellarein (78) (151.70 ± 14.78 mg/g li), methylisoscutelarein (82) (107.4 ± 9.07 mg/g li), and hypolaetin (79) (78.33 ± 3.29 mg/g li), as well as caffeic acid (20) (87.25 ± 6.54 mg/g li), were found to be the major compounds in S. scardica infusion. The performed state-of-the-art phytochemical analysis of S. scardica provides additional knowledge for the chemical constituents and usage of this valuable medicinal plant.

Optimized Coordination of Uranyl in Engineered Calmodulin Site 1 Provides a Subnanomolar Affinity for Uranyl and a Strong Uranyl versus Calcium Selectivity.

As an alpha emitter and chemical toxicant, uranium toxicity in living organisms is driven by its molecular interactions. It is therefore essential to identify main determinants of uranium affinity for proteins. Others and we showed that introducing a phosphoryl group in the coordination sphere of uranyl confers a strong affinity of proteins for uranyl. In this work, using calmodulin site 1 as a template, we modulate the structural organization of a metal-binding loop comprising carboxylate and/or carbonyl ligands and reach affinities for uranyl comparable to that provided by introducing a strong phosphoryl ligand. Shortening the metal binding loop of calmodulin site 1 from 12 to 10 amino acids in CaMΔ increases the uranyl-binding affinity by about 2 orders of magnitude to log KpH7 = 9.55 ± 0.11 (KdpH7 = 280 ± 60 pM). Structural analysis by FTIR, XAS, and molecular dynamics simulations suggests an optimized coordination of the CaMΔ-uranyl complex involving bidentate and monodentate carboxylate groups in the uranyl equatorial plane. The main role of this coordination sphere in reaching subnanomolar dissociation constants for uranyl is supported by similar uranyl affinities obtained in a cyclic peptide reproducing CaMΔ binding loop. In addition, CaMΔ presents a uranyl/calcium selectivity of 107 that is even higher in the cyclic peptide.