Search

BackgroundHyperpolarized 13C spectroscopic magnetic resonance spectroscopy (MRS) is an advanced imaging tool that may provide important real-time information about brain metabolism.MethodsMice underwent unilateral hypoxia-ischemia (HI) on postnatal day (P)10. Injured and sham mice were scanned at P10, P17, and P31. We used hyperpolarized 13C MRS to investigate the metabolic exchange of pyruvate to lactate in real time during brain development following HI. 13C-1-labeled pyruvate was hyperpolarized and injected into the tail vein through a tail-vein catheter. Chemical-shift imaging was performed to acquire spectral-spatial information of the metabolites in the brain. A voxel placed on each of the injured and contralateral hemispheres was chosen for comparison. The difference in pyruvate delivery and lactate to pyruvate ratio was calculated for each of the voxels at each time point. The normalized lactate level of the injured hemisphere was also calculated for each mouse at each of the scanning time points.ResultsThere was a significant reduction in pyruvate delivery and a higher lactate to pyruvate ratio in the ipsilateral (HI) hemisphere at P10. The differences decreased at P17 and disappeared at P31. The normalized lactate level in the injured hemisphere increased from P10 to P31 in both sham and HI mice without brain injury.ConclusionWe describe a method for detecting and monitoring the evolution of HI injury during brain maturation which could prove to be an excellent biomarker of injury.

BackgroundHyperpolarized carbon-13 (HP-13C) MRI is a non-invasive imaging technique for probing brain metabolism, which may improve clinical cancer surveillance. This work aimed to characterize the consistency of serial HP-13C imaging in patients undergoing treatment for brain tumors and determine whether there is evidence of aberrant metabolism in the tumor lesion compared to normal-appearing tissue.MethodsSerial dynamic HP [1-13C]pyruvate MRI was performed on 3 healthy volunteers (6 total examinations) and 5 patients (21 total examinations) with diffuse infiltrating glioma during their course of treatment, using a frequency-selective echo-planar imaging (EPI) sequence. HP-13C imaging at routine clinical timepoints overlapped treatment, including radiotherapy (RT), temozolomide (TMZ) chemotherapy, and anti-angiogenic/investigational agents. Apparent rate constants for [1-13C]pyruvate conversion to [1-13C]lactate (kPL) and [13C]bicarbonate (kPB) were simultaneously quantified based on an inputless kinetic model within normal-appearing white matter (NAWM) and anatomic lesions defined from 1H MRI. The inter/intra-subject consistency of kPL-NAWM and kPB-NAWM was measured in terms of the coefficient of variation (CV).ResultsWhen excluding scans following anti-angiogenic therapy, patient values of kPL-NAWM and kPB-NAWM were 0.020 s-1 ± 23.8% and 0.0058 s-1 ± 27.7% (mean ± CV) across 17 HP-13C MRIs, with intra-patient serial kPL-NAWM/kPB-NAWM CVs ranging 6.8-16.6%/10.6-40.7%. In 4/5 patients, these values (0.018 s-1 ± 13.4% and 0.0058 s-1 ± 24.4%; n = 13) were more similar to those from healthy volunteers (0.018 s-1 ± 5.0% and 0.0043 s-1 ± 12.6%; n = 6) (mean ± CV). The anti-angiogenic agent bevacizumab was associated with global elevations in apparent rate constants, with maximum kPL-NAWM in 2 patients reaching 0.047 ± 0.001 and 0.047 ± 0.003 s-1 (±model error). In 3 patients with progressive disease, anatomic lesions showed elevated kPL relative to kPL-NAWM of 0.024 ± 0.001 s-1 (±model error) in the absence of gadolinium enhancement, and 0.032 ± 0.008, 0.040 ± 0.003 and 0.041 ± 0.009 s-1 with gadolinium enhancement. The lesion kPB in patients was reduced to unquantifiable values compared to kPB-NAWM.ConclusionSerial measures of HP [1-13C]pyruvate metabolism displayed consistency in the NAWM of healthy volunteers and patients. Both kPL and kPB were globally elevated following bevacizumab treatment, while progressive disease demonstrated elevated kPL in gadolinium-enhancing and non-enhancing lesions. Larger prospective studies with homogeneous patient populations are planned to evaluate metabolic changes following treatment.

We developed methods for the preparation of hyperpolarized (HP) sterile [2-13C]pyruvate to test its feasibility in first-ever human NMR studies following FDA-IND & IRB approval. Spectral results using this MR stable-isotope imaging approach demonstrated the feasibility of investigating human cerebral energy metabolism by measuring the dynamic conversion of HP [2-13C]pyruvate to [2-13C]lactate and [5-13C]glutamate in the brain of four healthy volunteers. Metabolite kinetics, signal-to-noise (SNR) and area-under-curve (AUC) ratios, and calculated [2-13C]pyruvate to [2-13C]lactate conversion rates (kPL) were measured and showed similar but not identical inter-subject values. The kPL measurements were equivalent with prior human HP [1-13C]pyruvate measurements.

Abstract Pyruvic acid is an important organic acid and a key industrial raw material. It is widely used in the chemical, agricultural, and food fields. Candida glabrata is the preferred strain for pyruvic acid production. The waste yeast cell for pyruvic acid fermentation with C. glabrata are rich in protein, amino acid, nucleic acid, and vitamins, as potential and cost-effective nitrogen source raw material. In this study, the potential of C. glabrata to produce pyruvic acid using spent yeast cell dry powder was evaluated. When 30 g/L of spray-dried spent yeast cell powder was used as the seed nitrogen source, a high titer of pyruvic acid was obtained. The pyruvic acid production reached 63.4 g/L with a yield of 0.59 g/g in a 5 L bioreactor. After scale-up to a 50 L bioreactor using the fermented spent yeast cell dry powder as a seed nitrogen source, 65.1 g/L of pyruvic acid was harvested, with a yield of 0.61 g/g. This study proposes a promising approach for increasing the pyruvic acid titer and reducing the costs. Graphical Abstract

Low throughput is one of dissolution Dynamic Nuclear Polarization (dDNP) main shortcomings. Especially for clinical and preclinical applications, where direct 13C nuclei polarization is usually pursued, it takes hours to generate one single hyperpolarized (HP) sample. Being able to hyperpolarize more samples at once represents a clear advantage and can expand the range and complexity of the applications. In this work, we present the design and performance of a highly versatile and customizable dDNP cryogenic probe, herein adapted to a 5 T "wet" preclinical polarizer, that can accommodate up to three samples at once and, most importantly, it is capable of monitoring the solid-state spin dynamics of each sample separately, regardless of the kind of radical used and the nuclear species of interest. Within 30 min, the system was able to dispense three HP solutions with high repeatability across the channels (30.0 ± 1.2% carbon polarization for [1-13C]pyruvic acid doped with trityl radical). Moreover, we tested multi-nucleus NMR capability by polarizing and monitoring simultaneously 13C, 1H and 129Xe. Finally, we implemented [1-13C]lactate/[1-13C]pyruvate polarization and back-to-back dissolution and injection in a healthy mouse model to perform multiple-substrate HP Magnetic Resonance Spectroscopy (MRS) at 14.1 T. [ABSTRACT FROM AUTHOR]

Improving the quality of life (QoL) of patients with various chronic diseases has become a challenge and priority of contemporary medicine. The aim of this study was to assess the impact of pyruvic acid peeling on the QoL of patients with acne vulgaris. The study group consisted of 200 young patients (mean age 23.04 ± 4.71) with acne vulgaris of mainly mild or moderate severity. Basic data about the patient were collected using a self-reported questionnaire. The assessment of QoL was carried out using standardized questionnaires: CADI (Cardiff Acne Disability Index), DLQI (Dermatology Life Quality Index), SWLS (Satisfaction With Life Scale), and BDI (Beck Depression Inventory). The cosmetic intervention consisted of chemical peeling with 35% pyruvic acid for acne lesions on the body and included four series repeated at 7-day intervals. This study demonstrated that acne vulgaris impairs the quality of life of young people. There were no significant differences between the severity of acne and the lifestyles of the subjects. The applied cosmetic procedure significantly decreased the severity of the acne and improved the quality of life of the patients. [ABSTRACT FROM AUTHOR]

The function of the aminotransferase Aat (GenBank Protein WP_159211138) from Pediococcus acidilactici FAM 18098 was studied in vivo. For this purpose, the gene was replaced with an erythromycin resistance gene using the temperature-sensitive Escherichia coli-Pediococcus shuttle plasmid pSET4T_Δaat. The knockout was verified by PCR and genome sequencing. Subsequently, the differences between the metabolism of the knockout and of the wild-type strain were investigated by determining the free amino acids and organic acids in culture supernatants. It was found that the knockout mutant no longer synthesized 3-phenyllactic acid (PLA) and 4-hydroxyphenyllactic acid (HPLA). Additionally, the mutant strain no longer catabolized phenylalanine. Metabolic pathway analysis using the KEGG database indicate that P. acidilactici cannot synthesize a-ketoglutarate that is a predominant amino-group acceptor in many transamination reactions. To study the transfer of the amino group of phenylalanine, the wild-type strain was incubated with [15N] phenylalanine. Mass spectrometry showed that during fermentation, [15N] alanine was formed, indicating that pyruvic acid is an amino group acceptor in P. acidilactici. The present study shows that Aat plays a crucial role in PLA/HPLA biosynthesis and pyruvic acid is an amino acceptor in transamination reactions in P. acidilactici. [ABSTRACT FROM AUTHOR]

Sucrose is an abundant, cheap, and renewable carbohydrate which makes it an attractive feedstock for the biotechnological production of chemicals. Escherichia coli W, one of the few safe E. coli strains able to metabolize sucrose, was examined for the production of pyruvate. The repressor for the csc regulon was deleted in E. coli W strains expressing a variant E1 component of the pyruvate dehydrogenase complex, and these strains were screened in a shake flask culture for pyruvate formation from sucrose. The pyruvate accumulated at yields of 0.23–0.57 g pyruvate/g sucrose, and the conversion also was accompanied by the accumulation of some fructose and/or glucose. Selected strains were examined in 1.25 L controlled batch processes with 40 g/L sucrose to obtain time–course formation of pyruvate and monosaccharides. Pyruvate re-assimilation was observed in several strains, which demonstrates a difference in the metabolic capabilities of glucose- and sucrose-grown E. coli cultures. An engineered strain expressing AceE[H106M;E401A] generated 50.6 g/L pyruvate at an overall volumetric productivity of 1.6 g pyruvate/L·h and yield of 0.68 g pyruvate/g sucrose. The results demonstrate that pyruvate production from sucrose is feasible with comparable volumetric productivity and yield to glucose-based processes. [ABSTRACT FROM AUTHOR]

One critical step in new drugs development is the investigation of the interactions between drug candidate and target protein. Nuclear Magnetic Resonance Spectroscopy (NMR) is a well-established technique for studding these interactions. Due to its availability and structural similarities to human albumin, bovine serum albumin (BSA) is widely accepted as a model for investigating the binding of small molecules to serum albumin. We report here on the evaluation of binding interactions between BSA and 18 metabolites using saturation transfer difference (STD) NMR experiments. Positive STD signals that indicate metabolite-protein interactions were obtained for leucine, pyruvic acid, valine, threonine, alanine, 4-aminohippuric acid and tryptophan. [ABSTRACT FROM AUTHOR]

Pyruvic acid is an organic compound used in various fields (e.g., the pharmaceutical, cosmetic, food, and chemical industries) and subject to constantly growing demand. Pyruvic acid is liquid at room temperature, rendering manipulation less straightforward. Furthermore, in the liquid phase, pyruvic acid is air-sensitive. We here present a multi-component crystal engineering strategy to render pyruvic acid solid under ambient conditions, focusing on cocrystallization and salt formation. Out of 73 screened cocrystal and salt formers, eight were found to form novel crystalline forms with pyruvic acid. Four of these were studied in detail, with pyruvic acid stable in a solid phase at temperatures up to 120 °C. These results illustrate the effectiveness of cocrystallization as a tool to convert unstable liquid compounds into stable crystalline solid forms. [ABSTRACT FROM AUTHOR]

Background. Garlic (Allium sativum) peeling is one of the crucial steps in its use and is a significant challenge for maintaining the peeled garlic’s quality. The peeling of garlic on a mass scale is required to produce dehydrated garlic flakes, powder, grits, paste, garlic pickle, and for use as a critical wet spice in various processed products. Materials and methods. Manual peeling (MP), normal water peeling (NWP), hot water peeling (HWP), flame peeling (FP), and lye peeling (LP) methods were assessed for the quality characteristics of peeled garlic cloves based on antioxidant activities (AOA), total phenolic content (TPC), total flavonoid content (TFC), anti-nutritional properties, ascorbic acid (AA), reducing sugar, allicin, and pyruvic acid content. Principal component analysis (PCA) was used to develop the correlations between the garlic peeling methods and the measured parameters. Morphological and Energy Dispersive X-Ray (EDX) analyses were used to verify the difference between the optimized method of peeled garlic over the manually peeled garlic. Results. All peeling methods of garlic resulted in the respective peeled garlic having a pH in the acidic range (6.08–6.14). Reducing sugar is an important component affecting the color of the dehydrated garlic, which was found to be minimal in NWP (275.64 mg/g, fresh weight) and LP (335.26 mg/g, fresh weight). Allicin content, pyruvic acid, TPC, TFC, and AOA were similar for manually and lye-peeled garlic. MP garlic had the highest levels of anti-nutritional factors, such as saponin, phytic acid, and tannin. Whereas, the minimum level of saponin was found in HWP garlic. Phytic acid and tannin content were found to be minimum in LP and FP garlic. Multivariate analysis showed that the estimated chemical attributes were found to have the maximum number of positive correlations with the LP methods of garlic. At the same time, it also showed less correlation with anti-nutritional properties and a negative correlation with reducing sugar. Thus, the lye peeling (LP) method may be applied commercially for garlic peeling on a commercial scale due to it maintaining the quality characteristics; the morphological and EDX analyses also support this finding. Conclusions. LP method was found to be the best method of peeling since it maintained the allicin content, antioxidant properties, and reduced anti-nutritional properties and doesn’t reduce sugar. [ABSTRACT FROM AUTHOR]

Until now, the solubilization capacities of insoluble mineral P by soil microorganisms have been screened in vitro with media containing NH4+ as a nitrogen source. This presence of NH4+ will lead to an acidification of the medium responsible for the solubilization of the insoluble P. However, besides proton release, the production of organic acids can play a very important role in the release of free P. This physiological mechanism can largely depend on the source of nitrogen (NH4+vs NO3-) assimilated by the bacteria but the influence of the N source on the production of organic acids has yet to be studied. Our aim was to investigate if the N source assimilated by bacteria and the soil characteristics such as the dominant N source (NH4+vs NO3-) and CaCO3 contents might influence the bacterial capacities to solubilize rock phosphate. To fill this objective, we screened the capacity of bacteria isolated from 3 soils to solubilize rock phosphate in vitro in presence of NH4+or NO3-. Then, we selected the most efficient bacterial strains to identify and quantify the release of organic anions into the medium. Among the two hundred and forty-three bacterial strains isolated from the 3 soils, nine and seven isolates were identified with the highest % rock phosphate-solubilization values with NH4+ or NO3- as the sole N-source. Only one strain was able to release free Pi with NH4+ or NO3- as the sole N-source. The most predominant organic acids released by almost all isolates were gluconic acid, lactic acid, glycolic acid, acetic acid, formic acid and pyruvic acid regardless the N-source. However, with NO3- as source of N, the highest concentrations on those acids were found together with the highest release of free Pi into the medium. Molecular analysis of 16S rRNA indicated that almost all strains belonged to Bacillus and Paenibacillus genera. The PCA analysis between soil properties and bacterial capacities to release organic acids and free Pi also revealed that soil factors such as CaCO3 and soil NO3- content positively influenced the release of organic acids by bacteria grown in vitro. Our results concluded that the bacterial rock phosphate-solubilization was intimately related to organic acids production which in turn seemed to be driven by the assimilation of NO3- by bacteria. Therefore, the N-source might be considered a key factor to take into consideration during the screening and selection of suitable strains involved in the P-solubilization. [ABSTRACT FROM AUTHOR]

To figure out the differentially changed metabolites and disturbed pathways in follicular fluid (FF) of patients with OHSS in comparison to the control group undergoing in vitro fertilization (IVF), we conducted this metabolomic analysis between two groups, the OHSS group included 30 patients treated with oocyte retrieval and developed OHSS in the next 7-14 days, while another 30 patients without OHSS tendency were selected as the control group. The FF samples were obtained during the process of oocyte retrieval. FF samples were analyzed using ultra-high liquid chromatography-tandem mass spectrometry (UPLC-MS). The results identified a total of 59 differentially changed metabolites, including 33 decreased metabolites (P < 0.01) and 26 increased metabolites (P < 0.01) in FF of OHSS compared with the control group. 12 metabolites could be the most valuable biomarkers for OHSS based on ROC results. Our correlation analyses showed that deoxyinosine levels were found positively correlated with serum estradiol (E2) levels in OHSS patients, while L-isoleucine, pyruvic acid, maleamate, and arachidonic acid were found to be positively correlated with the number of retrieved oocytes. Furthermore, 4-hydroxyphenylacetaldehyde, deoxycorticosterone, creatinine, and creatine were found to be negatively associated with serum E2 levels, while 4-hydroxyphenylacetaldehyde, L-carnitine, isovaleric acid and L-2-hydroxyglutaric acid were negatively related with the number of oocytes retrieved in OHSS patients. Taken together, our study provides better identification of OHSS FF metabolic dynamics, suggesting the metabolic compounds can be used as valuable predictors or treatment targets of OHSS. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Chinese Institute of Food Science & Technology is the property of Journal of Chinese Institute of Food Science & Technology Periodical Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The herb of Trigonella caerulea (Fabaceae), commonly known as blue fenugreek, is used for the production of traditional cheese and bread varieties in the Alpine region. Despite its frequent consumption, only one study so far has focused on the constituent pattern of blue fenugreek, revealing qualitative information on some flavor-determining constituents. However, with regard to the volatile constituents present in the herb, the applied methods were insufficient and did not take relevant terpenoids into account. In the present study, we analyzed the phytochemical composition of T. caerulea herb applying a set of analytical methods, such as headspace-GC, GC-MS, LC-MS, and NMR spectroscopy. We thus determined the most dominant primary and specialized metabolites and assessed the fatty acid profile as well as the amounts of taste-relevant α-keto acids. In addition, eleven volatiles were quantified, of which tiglic aldehyde, phenylacetaldehyde, methyl benzoate, n-hexanal, and trans-menthone were identified as most significantly contributing to the aroma of blue fenugreek. Moreover, pinitol was found accumulated in the herb, whereas preparative works led to the isolation of six flavonol glycosides. Hence, our study shows a detailed analysis of the phytochemical profile of blue fenugreek and provides an explanation for its characteristic aroma and its health-beneficial effects. [ABSTRACT FROM AUTHOR]

Onions have a high moisture content, which makes them more susceptible to microbial growth. Drying is one of the postharvest preservation methods applied to decrease onion moisture content, thereby increasing its storage life. In this study, onions were peeled, washed, cut into quarters, hot water blanched, and pureed. The puree was further dried using two different drying methods: refractance window drying (RWD) (water temperature: 70 °C) and convective drying (CD) (50 °C). The puree was spread on prefabricated trays at varying thicknesses of 2 mm, 4 mm, and 6 mm. It was observed that, irrespective of the drying method, moisture ratio (MR) decreased and drying time and effective moisture diffusivity increased with respect to the thickness of the puree. In addition, the Lewis model and the Wang and Singh model showed the highest R2 and lowest SEE value for RWD and CD, respectively. Moreover, the MR of onion puree during RWD and CD was predicted using a multi-layer feed-forward (MLF) artificial neural network (ANN) with a back-propagation algorithm. The result showed that the ANN model with 12 and 18 neurons in the hidden layer could predict the MR, with a high R2 value for RWD and CD, respectively. The results also showed that the thickness of the puree and drying method significantly affected the physicochemical quality (color characteristics, pyruvic acid content, total phenolic content, total flavonoid content, antioxidant capacity, and hygroscopicity) of onion powder. It was concluded that RWD proved to be a better drying method than CD in terms of the quality of dried powder and reduced drying time. Irrespective of the drying method, 2 mm-thick puree dried yielded the best-dried onion powder in terms of physicochemical quality, as well yielding the lowest drying time. These samples were further analyzed for calculating the glass transition temperature. [ABSTRACT FROM AUTHOR]

Fermented beverages, particularly wines, exhibit variable concentrations of organic and phenolic acids, posing challenges in their accurate determination. Traditionally, enzymatic methods or chromatographic analyses, mainly high-performance liquid chromatography (HPLC), have been employed to quantify these compounds individually in the grape must or wine. However, chromatographic analyses face limitations due to the high sugar content in the grape must. Meanwhile, phenolic acids, found in higher quantities in red wines than in white wines, are typically analyzed using HPLC. This study presents a novel method for the quantification of organic acids (OAs), glycerol, and phenolic acids in grape musts and wines. The approach involves liquid-liquid extraction with ethyl acetate, followed by sample derivatization and analysis using gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring (SIM) detection mode. The results indicated successful detection and quantification of all analyzed compounds without the need for sample dilution. However, our results showed that the method of adding external standards was more suitable for quantifying wine compounds, owing to the matrix effect. Furthermore, this method is promising for quantifying other metabolites present in wines, depending on their extractability with ethyl acetate. Fermented beverages, particularly wines, exhibit variable concentrations of organic and phenolic acids, posing challenges in their accurate determination. Traditionally, enzymatic methods or chromatographic analyses, mainly high-performance liquid chromatography (HPLC), have been employed to quantify these compounds individually in the grape must or wine. The approach of this proposed method involves (i) methoximation of wine compounds in a basic medium, (ii) acidification with HCl, (iii) liquid-liquid extraction with ethyl acetate, and (iv) silyl derivatization to analyze samples with gas chromatography-mass spectrometry (GC-MS) in ion monitoring detection mode (SIM). The results indicated successful detection and quantification of all analyzed compounds without the need for sample dilution. However, our results showed that the method of adding external standards was more suitable for quantifying wine compounds, owing to the matrix effect. Furthermore, this method is promising for quantifying other metabolites present in wines, depending on their extractability with ethyl acetate. In other words, the proposed method may be suitable for profiling (targeted) or fingerprinting (untargeted) strategies to quantify wine metabolites or to classify wines according to the type of winemaking process, grape, or fermentation.

Lipopolysaccharide (LPS) is a commonly used agent for induction of neuroinflammation in preclinical studies. Upon injection, LPS causes activation of microglia and astrocytes, whose metabolism alters to favor glycolysis. Assessing in vivo neuroinflammation and its modulation following therapy remains challenging, and new noninvasive methods allowing for longitudinal monitoring would be highly valuable. Hyperpolarized (HP) 13 C magnetic resonance spectroscopy (MRS) is a promising technique for assessing in vivo metabolism. In addition to applications in oncology, the most commonly used probe of [1-13 C] pyruvate has shown potential in assessing neuroinflammation-linked metabolism in mouse models of multiple sclerosis and traumatic brain injury. Here, we aimed to investigate LPS-induced neuroinflammatory changes using HP [1-13 C] pyruvate and HP 13 C urea. 2D chemical shift imaging following simultaneous intravenous injection of HP [1-13 C] pyruvate and HP 13 C urea was performed at baseline (day 0) and at days 3 and 7 post-intracranial injection of LPS (n = 6) or saline (n = 5). Immunofluorescence (IF) analyses were performed for Iba1 (resting and activated microglia/macrophages), GFAP (resting and reactive astrocytes) and CD68 (activated microglia/macrophages). A significant increase in HP [1-13 C] lactate production was observed at days 3 and 7 following injection, in the injected (ipsilateral) side of the LPS-treated mouse brain, but not in either the contralateral side or saline-injected animals. HP 13 C lactate/pyruvate ratio, without and with normalization to urea, was also significantly increased in the ipsilateral LPS-injected brain at 7 days compared with baseline. IF analyses showed a significant increase in CD68 and GFAP staining at 3 days, followed by increased numbers of Iba1 and GFAP positive cells at 7 days post-LPS injection. In conclusion, we can detect LPS-induced changes in the mouse brain using HP 13 C MRS, in alignment with increased numbers of microglia/macrophages and astrocytes. This study demonstrates that HP 13 C spectroscopy has substantial potential for providing noninvasive information on neuroinflammation.

Lipopolysaccharide (LPS) is a commonly used agent for induction of neuroinflammation in preclinical studies. Upon injection, LPS causes activation of microglia and astrocytes, whose metabolism alters to favor glycolysis. Assessing in vivo neuroinflammation and its modulation following therapy remains challenging, and new noninvasive methods allowing for longitudinal monitoring would be highly valuable. Hyperpolarized (HP) 13 C magnetic resonance spectroscopy (MRS) is a promising technique for assessing in vivo metabolism. In addition to applications in oncology, the most commonly used probe of [1-13 C] pyruvate has shown potential in assessing neuroinflammation-linked metabolism in mouse models of multiple sclerosis and traumatic brain injury. Here, we aimed to investigate LPS-induced neuroinflammatory changes using HP [1-13 C] pyruvate and HP 13 C urea. 2D chemical shift imaging following simultaneous intravenous injection of HP [1-13 C] pyruvate and HP 13 C urea was performed at baseline (day 0) and at days 3 and 7 post-intracranial injection of LPS (n = 6) or saline (n = 5). Immunofluorescence (IF) analyses were performed for Iba1 (resting and activated microglia/macrophages), GFAP (resting and reactive astrocytes) and CD68 (activated microglia/macrophages). A significant increase in HP [1-13 C] lactate production was observed at days 3 and 7 following injection, in the injected (ipsilateral) side of the LPS-treated mouse brain, but not in either the contralateral side or saline-injected animals. HP 13 C lactate/pyruvate ratio, without and with normalization to urea, was also significantly increased in the ipsilateral LPS-injected brain at 7 days compared with baseline. IF analyses showed a significant increase in CD68 and GFAP staining at 3 days, followed by increased numbers of Iba1 and GFAP positive cells at 7 days post-LPS injection. In conclusion, we can detect LPS-induced changes in the mouse brain using HP 13 C MRS, in alignment with increased numbers of microglia/macrophages and astrocytes. This study demonstrates that HP 13 C spectroscopy has substantial potential for providing noninvasive information on neuroinflammation.

The goal of the study was to establish early hyperpolarized (HP) 13 C MRI metabolic and perfusion changes that predict effective high-intensity focused ultrasound (HIFU) ablation and lead to improved adjuvant treatment of partially treated regions. To accomplish this a combined HP dual-agent (13 C pyruvate and 13 C urea) 13 C MRI/multiparametric 1 H MRI approach was used to measure prostate cancer metabolism and perfusion 3-4 h, 1 d, and 5 d after exposure to ablative and sub-lethal doses of HIFU within adenocarcinoma of mouse prostate tumors using a focused ultrasound applicator designed for murine studies. Pathologic and immunohistochemical analysis of the ablated tumor demonstrated fragmented, non-viable cells and vasculature consistent with coagulative necrosis, and a mixture of destroyed tissue and highly proliferative, poorly differentiated tumor cells in tumor tissues exposed to sub-lethal heat doses in the ablative margin. In ablated regions, the intensity of HP 13 C lactate or HP 13 C urea and dynamic contrast-enhanced (DCE) MRI area under the curve images were reduced to the level of background noise by 3-4 h after treatment with no recovery by the 5 d time point in either case. In the tissues that received sub-lethal heat dose, there was a significant 60% ± 12.4% drop in HP 13 C lactate production and a significant 30 ± 13.7% drop in urea perfusion 3-4 h after treatment, followed by recovery to baseline by 5 d after treatment. DCE MRI Ktrans showed a similar trend to HP 13 C urea, demonstrating a complete loss of perfusion with no recovery in the ablated region, while having a 40%-50% decrease 3-4 h after treatment followed by recovery to baseline values by 5 d in the margin region. The utility of the HP 13 C MR measures of perfusion and metabolism in optimizing focal HIFU, either alone or in combination with adjuvant therapy, deserves further testing in future studies.

Mammalian organs continually exchange metabolites via circulation, but systems-level analysis of this shuttling process is lacking. Here, we compared, in fasted pigs, metabolite concentrations in arterial blood versus draining venous blood from 11 organs. Greater than 90% of metabolites showed arterial-venous differences across at least one organ. Surprisingly, the liver and kidneys released not only glucose but also amino acids, both of which were consumed primarily by the intestine and pancreas. The liver and kidneys exhibited additional unexpected activities: liver preferentially burned unsaturated over more atherogenic saturated fatty acids, whereas the kidneys were unique in burning circulating citrate and net oxidizing lactate to pyruvate, thereby contributing to circulating redox homeostasis. Furthermore, we observed more than 700 other cases of tissue-specific metabolite production or consumption, such as release of nucleotides by the spleen and TCA intermediates by pancreas. These data constitute a high-value resource, providing a quantitative atlas of inter-organ metabolite exchange.

PurposeTo compare the performance of an 8-channel surface coil/clamshell transmitter and 32-channel head array coil/birdcage transmitter for hyperpolarized 13 C brain metabolic imaging.MethodsTo determine the field homogeneity of the radiofrequency transmitters, B1 + mapping was performed on an ethylene glycol head phantom and evaluated by means of the double angle method. Using a 3D echo-planar imaging sequence, coil sensitivity and noise-only phantom data were acquired with the 8- and 32-channel receiver arrays, and compared against data from the birdcage in transceiver mode. Multislice frequency-specific 13 C dynamic echo-planar imaging was performed on a patient with a brain tumor for each hardware configuration following injection of hyperpolarized [1-13 C]pyruvate. Signal-to-noise ratio (SNR) was evaluated from pre-whitened phantom and temporally summed patient data after coil combination based on optimal weights.ResultsThe birdcage transmitter produced more uniform B1 + compared with the clamshell: 0.07 versus 0.12 (fractional error). Phantom experiments conducted with matched lateral housing separation demonstrated 8- versus 32-channel mean transceiver-normalized SNR performance: 0.91 versus 0.97 at the head center; 6.67 versus 2.08 on the sides; 0.66 versus 2.73 at the anterior; and 0.67 versus 3.17 on the posterior aspect. While the 8-channel receiver array showed SNR benefits along lateral aspects, the 32-channel array exhibited greater coverage and a more uniform coil-combined profile. Temporally summed, parameter-normalized patient data showed SNRmean,slice ratios (8-channel/32-channel) ranging 0.5-2.00 from apical to central brain. White matter lactate-to-pyruvate ratios were conserved across hardware: 0.45 ± 0.12 (8-channel) versus 0.43 ± 0.14 (32-channel).ConclusionThe 8- and 32-channel hardware configurations each have advantages in particular brain anatomy.

PurposeVarious excitation strategies have been proposed for dynamic imaging of hyperpolarized agents such as [1-13 C]-pyruvate, but the impact of these strategies on quantitative evaluation of signal evolution remains unclear. To better understand their relative performance, we compared the accuracy and repeatability of measurements made using variable excitation angle strategies and conventional constant excitation angle strategies.MethodsSignal evolution for constant and variable excitation angle schedules was simulated using a pharmacokinetic model of hyperpolarized pyruvate with 2 chemical pools and 2 physical compartments. Noisy synthetic data were then fit using the same pharmacokinetic model with the apparent chemical exchange term as an unknown, and fit results were compared with simulation parameters to determine accuracy and reproducibility.ResultsConstant excitations and a variable excitation strategy that maximizes the HP lactate signal yielded data that supported quantitative analyses with similar accuracy and repeatability. Variable excitation angle strategies that were designed to produce a constant signal level resulted in lower signal and worse quantitative accuracy and repeatability, particularly for longer acquisition times.ConclusionsThese results suggest that either constant excitation angle or variable excitation angles that attempt to maximize total signal, as opposed to maintaining a constant signal level, are preferred for metabolic quantification using hyperpolarized pyruvate.

PurposeTo develop and translate a metabolite-specific imaging sequence using a symmetric echo planar readout for clinical hyperpolarized (HP) Carbon-13 (13 C) applications.MethodsInitial data were acquired from patients with prostate cancer (N = 3) and high-grade brain tumors (N = 3) on a 3T scanner. Samples of [1-13 C]pyruvate were polarized for at least 2 h using a 5T SPINlab system operating at 0.8 K. Following injection of the HP substrate, pyruvate, lactate, and bicarbonate (for brain studies) were sequentially excited with a singleband spectral-spatial RF pulse and signal was rapidly encoded with a single-shot echo planar readout on a slice-by-slice basis. Data were acquired dynamically with a temporal resolution of 2 s for prostate studies and 3 s for brain studies.ResultsHigh pyruvate signal was seen throughout the prostate and brain, with conversion to lactate being shown across studies, whereas bicarbonate production was also detected in the brain. No Nyquist ghost artifacts or obvious geometric distortion from the echo planar readout were observed. The average error in center frequency was 1.2 ± 17.0 and 4.5 ± 1.4 Hz for prostate and brain studies, respectively, below the threshold for spatial shift because of bulk off-resonance.ConclusionThis study demonstrated the feasibility of symmetric EPI to acquire HP 13 C metabolite maps in a clinical setting. As an advance over prior single-slice dynamic or single time point volumetric spectroscopic imaging approaches, this metabolite-specific EPI acquisition provided robust whole-organ coverage for brain and prostate studies while retaining high SNR, spatial resolution, and dynamic temporal resolution.

Effective coil combination methods for human hyperpolarized 13C spectroscopy multi-channel data had been relatively unexplored. This study implemented and tested several coil combination methods, including (1) the sum-of-squares (SOS), (2) singular value decomposition (SVD), (3) Roemer method by using reference peak area as a sensitivity map (RefPeak), and (4) Roemer method by using ESPIRiT-derived sensitivity map (ESPIRiT). These methods were evaluated by numerical simulation, thermal phantom experiments, and human cancer patient studies. Overall, the SVD, RefPeak, and ESPIRiT methods demonstrated better accuracy and robustness than the SOS method. Extracting complex pyruvate signal provides an easy and excellent approximation of the coil sensitivity map while maintaining valuable phase information of the coil-combined data.

Hyperpolarized 13 C MRI takes advantage of the unprecedented 50 000-fold signal-to-noise ratio enhancement to interrogate cancer metabolism in patients and animals. It can measure the pyruvate-to-lactate conversion rate, kPL , a metabolic biomarker of cancer aggressiveness and progression. Therefore, it is crucial to evaluate kPL reliably. In this study, three sequence components and parameters that modulate kPL estimation were identified and investigated in model simulations and through in vivo animal studies using several specifically designed pulse sequences. These factors included a magnetization spoiling effect due to RF pulses, a crusher gradient-induced flow suppression, and intrinsic image weightings due to relaxation. Simulation showed that the RF-induced magnetization spoiling can be substantially improved using an inputless kPL fitting. In vivo studies found a significantly higher apparent kPL with an additional gradient that leads to flow suppression (kPL,FID-Delay,Crush /kPL,FID-Delay  = 1.37 ± 0.33, P

PurposeAcquisition timing and B1 calibration are two key factors that affect the quality and accuracy of hyperpolarized 13 C MRI. The goal of this project was to develop a new approach using regional bolus tracking to trigger Bloch-Siegert B1 mapping and real-time B1 calibration based on regional B1 measurements, followed by dynamic imaging of hyperpolarized 13 C metabolites in vivo.MethodsThe proposed approach was implemented on a system which allows real-time data processing and real-time control on the sequence. Real-time center frequency calibration upon the bolus arrival was also added. The feasibility of applying the proposed framework for in vivo hyperpolarized 13 C imaging was tested on healthy rats, tumor-bearing mice and a healthy volunteer on a clinical 3T scanner following hyperpolarized [1-13 C]pyruvate injection. Multichannel receive coils were used in the human study.ResultsAutomatic acquisition timing based on either regional bolus peak or bolus arrival was achieved with the proposed framework. Reduced blurring artifacts in real-time reconstructed images were observed with real-time center frequency calibration. Real-time computed B1 scaling factors agreed with real-time acquired B1 maps. Flip angle correction using B1 maps results in a more consistent quantification of metabolic activity (i.e, pyruvate-to-lactate conversion, kPL ). Experiment recordings are provided to demonstrate the real-time actions during the experiment.ConclusionsThe proposed method was successfully demonstrated on animals and a human volunteer, and is anticipated to improve the efficient use of the hyperpolarized signal as well as the accuracy and robustness of hyperpolarized 13 C imaging.

Vorinostat is a histone deacetylase (HDAC) inhibitor that inhibits cell proliferation and induces apoptosis in solid tumors, and is in clinical trials for the treatment of glioblastoma (GBM). The goal of this study was to assess whether hyperpolarized 13 C MRS and magnetic resonance spectroscopic imaging (MRSI) can detect HDAC inhibition in GBM models. First, we confirmed HDAC inhibition in U87 GBM cells and evaluated real-time dynamic metabolic changes using a bioreactor system with live vorinostat-treated or control cells. We found a significant 40% decrease in the 13 C MRS-detectable ratio of hyperpolarized [1-13 C]lactate to hyperpolarized [1-13 C]pyruvate, [1-13 C]Lac/Pyr, and a 37% decrease in the pseudo-rate constant, kPL , for hyperpolarized [1-13 C]lactate production, in vorinostat-treated cells compared with controls. To understand the underlying mechanism for this finding, we assessed the expression and activity of lactate dehydrogenase (LDH) (which catalyzes the pyruvate to lactate conversion), its associated cofactor nicotinamide adenine dinucleotide, the expression of monocarboxylate transporters (MCTs) MCT1 and MCT4 (which shuttle pyruvate and lactate in and out of the cell) and intracellular lactate levels. We found that the most likely explanation for our finding that hyperpolarized lactate is reduced in treated cells is a 30% reduction in intracellular lactate levels that occurs as a result of increased expression of both MCT1 and MCT4 in vorinostat-treated cells. In vivo 13 C MRSI studies of orthotopic tumors in mice also showed a significant 52% decrease in hyperpolarized [1-13 C]Lac/Pyr when comparing vorinostat-treated U87 GBM tumors with controls, and, as in the cell studies, this metabolic finding was associated with increased MCT1 and MCT4 expression in HDAC-inhibited tumors. Thus, the 13 C MRSI-detectable decrease in hyperpolarized [1-13 C]lactate production could serve as a biomarker of response to HDAC inhibitors.

PurposeAcquisition timing and B1 calibration are two key factors that affect the quality and accuracy of hyperpolarized 13 C MRI. The goal of this project was to develop a new approach using regional bolus tracking to trigger Bloch-Siegert B1 mapping and real-time B1 calibration based on regional B1 measurements, followed by dynamic imaging of hyperpolarized 13 C metabolites in vivo.MethodsThe proposed approach was implemented on a system which allows real-time data processing and real-time control on the sequence. Real-time center frequency calibration upon the bolus arrival was also added. The feasibility of applying the proposed framework for in vivo hyperpolarized 13 C imaging was tested on healthy rats, tumor-bearing mice and a healthy volunteer on a clinical 3T scanner following hyperpolarized [1-13 C]pyruvate injection. Multichannel receive coils were used in the human study.ResultsAutomatic acquisition timing based on either regional bolus peak or bolus arrival was achieved with the proposed framework. Reduced blurring artifacts in real-time reconstructed images were observed with real-time center frequency calibration. Real-time computed B1 scaling factors agreed with real-time acquired B1 maps. Flip angle correction using B1 maps results in a more consistent quantification of metabolic activity (i.e, pyruvate-to-lactate conversion, kPL ). Experiment recordings are provided to demonstrate the real-time actions during the experiment.ConclusionsThe proposed method was successfully demonstrated on animals and a human volunteer, and is anticipated to improve the efficient use of the hyperpolarized signal as well as the accuracy and robustness of hyperpolarized 13 C imaging.

Specific metabolic underpinnings of androgen receptor (AR)-driven growth in prostate adenocarcinoma (PCa) are largely undefined, hindering the development of strategies to leverage the metabolic dependencies of this disease when hormonal manipulations fail. Here we show that the mitochondrial pyruvate carrier (MPC), a critical metabolic conduit linking cytosolic and mitochondrial metabolism, is transcriptionally regulated by AR. Experimental MPC inhibition restricts proliferation and metabolic outputs of the citric acid cycle (TCA) including lipogenesis and oxidative phosphorylation in AR-driven PCa models. Mechanistically, metabolic disruption resulting from MPC inhibition activates the eIF2α/ATF4 integrated stress response (ISR). ISR signaling prevents cell cycle progression while coordinating salvage efforts, chiefly enhanced glutamine assimilation into the TCA, to regain metabolic homeostasis. We confirm that MPC function is operant in PCa tumors in-vivo using isotopomeric metabolic flux analysis. In turn, we apply a clinically viable small molecule targeting the MPC, MSDC0160, to pre-clinical PCa models and find that MPC inhibition suppresses tumor growth in hormone-responsive and castrate-resistant conditions. Collectively, our findings characterize the MPC as a tractable therapeutic target in AR-driven prostate tumors.

Parkinson disease is a chronic progressive neurodegenerative disorder with a prevalence that increases with age. The glycolytic end-product pyruvate, has antioxidant and neuroprotective feature. Here, we investigated the effects of ethyl pyruvate (EP), a pyruvic acid derivative, on 6-hydroxydopamine-induced SH-SY5Y cell apoptosis. Ethyl pyruvate decreased protein levels of cleaved caspase-3, phosphorylated endoplasmic reticulum kinase (pERK), and extracellular signal-regulated kinase (ERK), suggesting that EP reduces apoptosis via the ERK signaling pathway. Ethyl pyruvate also decreased oxygen species (ROS) and neuromelanin contents, suggesting that it suppresses ROS-mediated neuromelanin synthesis. Furthermore, increased protein levels of Beclin-1 and LC-II, and LC-II:LC-I ratios indicated that EP upregulates autophagy. [ABSTRACT FROM AUTHOR]

In this study, expanded graphite (EG) was prepared by the oxidation and intercalation of the natural flake graphite using perchloric acid and potassium permanganate at different expansion temperatures (300, 400, 500, and 600°C), and were characterized by scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). EG prepared at 500°C was found to be highly effective for the mineralization of oxalic acid aqueous solution during ozonation at pH 3, which was ascribed to the formation of hydroxyl radicals from the surface reaction of surface hydroxyl groups on EG with ozone. The performance of expanded graphite in this catalytic system was basically unchanged after three repeated use. The presence of Cl−, SO 4 2 − , HPO 4 2 − / H 2 PO 4 − and NO 3 − could inhibit the degradation of oxalic acid in catalytic ozonation with EG. Degradations of oxamic acid and pyruvic acid in catalytic ozonation with EG were pH-dependent, which were lower than that of oxalic acid. The degradations of oxalic acid and oxamic acid were identified as mineralization process by the determination of TOC, while pyruvic acid may transform into organic products such as acetic acid by O3/EG. Manganese ion (Mn2+) could promote the degradation of oxalic acid by O3/EG at pH 3 because permanganate was produced by O3/EG in oxalic acid solution and then reacted with oxalic acid readily at acidic pH. Catalytic ozonation by EG exhibited great application potential for the destruction of refractory organic compounds. [ABSTRACT FROM AUTHOR]

The iron(III) anionic complex based on a pyruvic acid thiosemicarbazone ligand with the lithium cation Li[FeIII(thpy)2]·3H2O (1) has been synthesized and characterized by FTIR spectroscopy, powder and single crystal X-ray diffraction, direct current magnetic susceptibility measurements, and 57Fe Mössbauer spectroscopy. Moreover, the molecular structure of the [Fe(thpy)2]− anion has been determined for the first time. The [Fe(thpy)2]− units in the triclinic P1¯ lattice of 1 are assembled into layers parallel to the bc plane. The Li+ cations and water molecules are located between the layers and the structure is stabilized by hydrogen bonding. The [Fe(thpy)2]− anions form interconnected dimer pairs through hydrogen bonds and short contacts with Fe⋯Fe separation of 6.7861(4) Å. According to dc magnetic measurements, compound 1 demonstrates an incipient spin-crossover transition from the LS (S = 1/2) to the HS (S = 5/2) state above 250 K. The Bleaney–Bowers equation for a model of an isolated LS dimer with a mean-field correction was applied to fit the experimental data of magnetic susceptibility dependence on temperature in the temperature range of 2–250 K. The intra-dimer J1 = −1.79(1) K and inter-dimer J2 = −0.24(3) K antiferromagnetic coupling constants were defined. The analysis of the 57Fe Mössbauer spectra at 80 K and 296 K confirms the presence of the shortened distances between the iron nuclei. Moreover, the influence of the lithium cation on the stabilization of the LS state was shown for the [Fe(thpy)2]− anion. BS-DFT calculations for the optimized structure of two isolated [Fe(thpy)2]− anions also correctly predict a weak exchange J1(calc) = −0.92 K. DFT calculations revealed the OPBE (GGA-type) functional that correctly predicts the spin-crossover transition for the iron(III) thpy compounds. Besides, the effect of the N2O4, N2S2O2, and N2Se2O2 coordination environments on the energy stabilization of the LS state of iron(III) anionic thpy complexes was noted as well. [ABSTRACT FROM AUTHOR]

We explored a co‐dissolved strategy to embed mono‐dispersed Pt center into V2O5 support via dissolving [PtV9O28]7− into [V10O28]6− aqueous solution. The uniform dispersion of [PtV9O28]7− in [V10O28]6− solution allows [PtV9O28]7− to be surrounded by [V10O28]6− clusters via a freeze‐drying process. The V centers in both [PtV9O28]7− and [V10O28]6− were converted into V2O5 via a calcination process to stabilize Pt center. These double separations can effectively prevent the Pt center agglomeration during the high‐temperature conversion process, and achieve 100 % utilization of Pt in [PtV9O28]7−. The resulting Pt‐V2O5 single‐atom‐site catalysts exhibit a CH4 yield of 247.6 μmol g−1 h−1, 25 times higher than that of Pt nanoparticle on the V2O5 support, which was accompanied by the lactic acid photooxidation to form pyruvic acid. Systematical investigations on this unambiguous structure demonstrate an important role of Pt−O atomic pair synergy for highly efficient CO2 photoreduction. [ABSTRACT FROM AUTHOR]

In this study, the growth of fungi Trichoderma guizhouense NJAU4742 was significantly inhibited under acid stress, and the genes related to acid stress were identified based on transcriptome analysis. Four genes including tna1, adh2/4, and bna3 were significantly up‐regulated. Meanwhile, intracellular hydrogen ions accumulated under acid stress, and ATP synthesis was induced to transport hydrogen ions to maintain hydrogen ion balance. The enhancement of glycolysis pathway was also detected, and a large amount of pyruvic acid from glycolysis was accumulated due to the activity limitation of PDH enzymes. Finally, acetaldehyde accumulated, resulting in the induction of adh2/4. In order to cope with stress caused by acetaldehyde, cells enhanced the synthesis of NAD+ by increasing the expression of tna1 and bna3 genes. NAD+ effectively improved the antioxidant capacity of cells, but the NAD+ supplement pathway mediated by bna3 could also cause the accumulation of kynurenine (KYN), which was an inducer of apoptosis. In addition, KYN had a specific promoting effect on acetaldehyde synthesis by improving the expression of eno2 gene, which led to the extremely high intracellular acetaldehyde in the cell under acidic stress. Our findings provided a route to better understand the response of filamentous fungi under acid stress. [ABSTRACT FROM AUTHOR]

Cystinosis is a rare, devastating hereditary disease secondary to recessive CTNS gene mutations. The most commonly used diagnostic method is confirmation of an elevated leukocyte cystine level; however, this method is expensive and difficult to perform. This study aimed to identify candidate biomarkers for the diagnosis and follow-up of cystinosis based on multiomics studies. The study included three groups: newly-diagnosed cystinosis patients (patient group, n = 14); cystinosis patients under treatment (treatment group, n = 19); and healthy controls (control group, n = 30). Plasma metabolomics analysis identified 10 metabolites as candidate biomarkers that differed between the patient and control groups [L-serine, taurine, lyxose, 4-trimethylammoniobutanoic acid, orotic acid, glutathione, PE(O-18:1(9Z)/0:0), 2-hydroxyphenyl acetic acid, acetyl-N-formil-5-metoxikinuramine, 3-indoxyl sulphate]. As compared to the healthy control group, in the treatment group, hypotaurine, phosphatidylethanolamine, N-acetyl-d-mannosamine, 3-indolacetic acid, p-cresol, phenylethylamine, 5-aminovaleric acid, glycine, creatinine, and saccharic acid levels were significantly higher, and the metabolites quinic acid, capric acid, lenticin, xanthotoxin, glucose-6-phosphate, taurine, uric acid, glyceric acid, alpha-D-glucosamine phosphate, and serine levels were significantly lower. Urinary metabolomic analysis clearly differentiated the patient group from the control group by means of higher allo-inositol, talose, glucose, 2-hydroxybutiric acid, cystine, pyruvic acid, valine, and phenylalanine levels, and lower metabolite (N-acetyl-L-glutamic acid, 3-aminopropionitrile, ribitol, hydroquinone, glucuronic acid, 3-phosphoglycerate, xanthine, creatinine, and 5-aminovaleric acid) levels in the patient group. Urine metabolites were also found to be significantly different in the treatment group than in the control group. Thus, this study identified candidate biomarkers that could be used for the diagnosis and follow-up of cystinosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acne scars are a permanent disfiguring sequel of acne. OBJECTIVE: To compare the efficacy of microneedling with 15% trichloroacetic acid (TCA) peel versus microneedling with 25% pyruvic acid peel in the management of postacne scars. MATERIAL AND METHODS: Thirty patients with atrophic acne scars were randomized into 2 groups receiving microneedling on both sides of the face at 0,6, and 12 weeks and 15% TCA on one side and 25% pyruvic acid on other side at 3,9, and 15 weeks. Acne scar scoring performed using the Echelle D'Evaluation Clinique des Cicatrices D'Acne (ECCA) and visual analogue scales by patient and physician were used to grade improvement at all visits and at 21 weeks. RESULTS: The mean ECCA score on the TCA side declined from 151.17 ± 26.90 to 138.83 ± 30.56 and on the pyruvic side declined from 151.83 ± 27.53 to 141.33 ± 28.92 after 21 weeks (statistically significant: p -value <.05). Comparing the ECCA on the TCA and pyruvic sides at 21 weeks was not significant. VAS showed moderate-to-marked improvement after 3 months in both groups. CONCLUSION: In our study, the combination modality showed early reduction in rolling and boxcar compared with icepick scars. These peels led to improvement in overall texture of the skin, hence more patient satisfaction. On comparing ECCA, a significant difference was not observed. [ABSTRACT FROM AUTHOR]

The conversion of lignite to clean energy has won considerable attention and plays an important role in achieving the goal of carbon reduction. The effects of corn straw on hydrogen production from lignite was explored by using lignite as the substrate and corn straw as an exogenous substance. The fermentation mechanism was elucidated through the analysis of total and daily hydrogen production; the concentration of humic acid, benzoic acid, pyruvate, and glucose, as well as pH value. In addition, total solid (TS), and volatile solid (VS) from activated sludge before and after fermentation are examined. The results showed that corn straw could accelerate hydrogen production from lignite with an optimal content of corn straw of 40%. The fermentative hydrogen production with 40% corn straw was up to 186.20 mL, 3.40 times higher than that of the control group. Corn straw effectively improved the concentration of humic acid and benzoic acid, accelerating the anaerobic fermentation of lignite to produce hydrogen. The concentration of pyruvic acid, glucose, pH, and the changes in TS and VS before and after fermentation showed that the group of 40% corn straw had a better promotion effect than other systems for hydrogen production. This provides a new idea for improving hydrogen production through lignite anaerobic fermentation. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) has recently become the most prevalent malignancy in women. There are many alternative treatments for BC, and for aesthetic and postoperative quality of life concerns, breast-conserving surgery and corresponding adjuvant therapy have become the predominant treatment for early invasive BC. Currently, the main method used to assess the margins for breast-conserving surgery is intraoperative pathological diagnosis. However, the designation of surgical margins is controversial, and metabolomics may be a novel approach to evaluate surgical margins. Methods: We collected specimens from 10 breast cancer patients and samples from its surrounding tissues and divided them into cancerous tissue and 1 mm, 2 mm, 3 mm, 5mmand 10mmcutting edge tissues, with a total of 60 samples. The samples were analyzed by mass spectrometry on an ultra-performance liquid chromatography-quadrupole/Orbitrap high resolution platform. The data were then statistically analyzed to detect metabolic changes in the different cutting edges and to identify possible surgical cutting edges with statistically significant findings. Abnormal metabolic pathways were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG), which elucidated potential markers. Results: Statistical analysis indicated that there were substantial differences between the 1 mm margin tissue and the cancer tissue, while there were no statistically significant differences between the 1 mm tissue and tissues from the other margins. The levels of 6 metabolites in the 1 mm tissue were significantly different from those in the cancer tissue and were not significantly different from those in the 2 mm tissue. The six metabolites were pyruvate, N-acetyl-L-aspartate, glutamic acid, γ-aminobutyric acid, fumaric acid, and citric acid. Metabolic pathways such as amino acid metabolism and amino t-RNA synthesis in the margin tissue were significantly distinct from those in cancer tissues based on KEGG analysis. Conclusion: There was a significant difference between the 1mmmargin tissue and the cancerous tissue. Based on metabolomic analysis, the 1 mm negative margin is sufficient for surgery, and the six metabolites that we identified as abnormal, including pyruvic acid, N-acetyl-L-aspartic acid, glutamic acid, gamma-aminobutyric acid, fumaric acid and citric acid, may serve as biomarkers for a negative margin and help surgeons select an appropriate surgical margin. [ABSTRACT FROM AUTHOR]

α-Ketoglutaric acid (KGA) is a valuable compound with a wide range of applications, e.g., in the cosmetics, pharmaceutical, chemical and food industries. The present study aimed to enhance the efficiency of KGA production by Yarrowia lipolytica CBS146773 from renewable carbon sources. In the investigation, various factors that may potentially affect KGA biosynthesis were examined in bioreactor cultures performed on a simple medium containing glycerol (20 g/L) and fed with four portions of a substrate mixture (15 + 15 g/L of glycerol and rapeseed oil). It was found that the process may be stimulated by regulation of the medium pH and aeration, application of selected neutralizing agents, supplementation with thiamine and addition of sorbitan monolaurate, whereas presence of biotin and iron ions had no positive effect on KGA biosynthesis. Adjustment of the parameters improved the process efficiency and allowed 82.4 g/L of KGA to be obtained, corresponding to productivity of 0.57 g/L h and yield of 0.59 g/g. In addition, the production of KGA was characterized by a low level (≤6.3 g/L) of by-products, i.e., citric and pyruvic acids. The results confirmed the high potential of renewable carbon sources (glycerol + rapeseed oil) for effective KGA biosynthesis by Yarrowia lipolytica. [ABSTRACT FROM AUTHOR]

Pre‐stroke exercise conditioning reduces neurovascular injury and improves functional outcomes after stroke. The goal of this study was to explore if post‐stroke exercise conditioning (PostE) reduced brain injury and whether it was associated with the regulation of gluconeogenesis. Adult rats received 2 h of middle cerebral artery (MCA) occlusion, followed by 24 h of reperfusion. Treadmill activity was then initiated 24 h after reperfusion for PostE. The severity of the brain damage was determined by infarct volume, apoptotic cell death, and neurological deficit at one and three days after reperfusion. We measured gluconeogenesis including oxaloacetate (OAA), phosphoenolpyruvate (PEP), pyruvic acid, lactate, ROS, and glucose via ELISA, as well as the location and expression of the key enzyme phosphoenolpyruvate carboxykinase (PCK)‐1/2 via immunofluorescence. We also determined upstream pathways including forkhead transcription factor (FoxO1), p‐FoxO1, 3‐kinase (PI3K)/Akt, and p‐PI3K/Akt via Western blot. Additionally, the cytoplasmic expression of p‐FoxO1 was detected by immunofluorescence. Compared to non‐exercise control, PostE (*p <.05) decreased brain infarct volumes, neurological deficits, and cell death at one and three days. PostE groups (*p <.05) saw increases in OAA and decreases in PEP, pyruvic acid, lactate, ROS, glucose levels, and tissue PCKs expression on both days. PCK‐1/2 expressions were also significantly (*p <.05) suppressed by the exercise setting. Additionally, phosphorylated PI3K, AKT, and FoxO1 protein expression were significantly induced by PostE at one and three days (*p <.05). In this study, PostE reduced brain injury after stroke, in association with activated PI3K/AKT/FoxO1 signaling, and inhibited gluconeogenesis. These results suggest the involvement of FoxO1 regulation of gluconeogenesis underlying post‐stroke neuroprotection. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is the most devastating subtype of stroke, but effective prevention and treatment strategies are lacking. Recently, gut microbiome and its metabolitesis are considered to be an influencing factor of stroke. However, little is known about the effects of the gut microbiome on ICH and host metabolic activity. Therefore, we used 16S sequencing, macrogenomics sequencing and untargeted metabolomics to explore the differences in gut microbial-metabolome interactions between patients with intracerebral hemorrhage and healthy control populations. We found a significant decrease in the phylum of Firmicutes and a significant increase of Bacteroidetes in ICH patients. At the genus level, Streptococcus, Bifidobacterium, Akkermansia, and Lactobacillus were more abundant in ICH patients. Macrogenomic analysis revealed active glycosaminoglycan degradation, heme synthesis, galactose degradation, lipopolysaccharide core region synthesis, and beta-Lactam resistance in ICH patients. Serum untargeted metabolomic analysis combined with ROC curves showed that octanoylcarnitine, decanoylcarnitine, dodecanoylcarnitine, glyceric acid, pyruvic acid, aspartic acid, methylcysteine, pyroglutamic acid, 9E-tetradecenoic acid, N-Acetylneuraminic acid, and aconitic acid were the best markers for the diagnosis of ICH. Correlation analysis showed that microbiome enriched in the gut of ICH patients were significantly correlated with serum metabolites, revealing a close correlation between the gut microbiome of ICH patients and the host metabolome, and significant differences from the healthy population. microbiota-host co-metabolites including pyruvic acid and 9E-tetradecenoic acid is associated with the the National Institutes of Health Stroke Scale (NIHSS) scores. In conclusion, microbiome-related metabolites in ICH patients was associated with the severity of ICH, the microbiota-host co-metabolites may be a potential may be potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Application of regenerated thermodynamic inhibitor (THI) is a cost-effective way of hydrate inhibition in oil industries. There have been literature reports for application of regenerated THI monoethylene glycol (MEG) in order to keep the process economical and also to avoid releasing the used MEG to the environment in order to reduce its impact. In our previous studies, thermodynamic gas hydrate equilibrium curves were established for pure propylene glycol. So, in continuation to previous work, thermal degradation of propylene glycol is studied in this research to be applicable for gas hydrate inhibition as regenerated product. A laboratory batch distillation setup is utilized for conducting thermal degradation of propylene glycol (40 and 80 wt%). Degraded products were collected at different time intervals to identify generated organic acids. Major degradation product observed was lactic acid and other generated acids include formic, acetic and pyruvic acid. Results showed increase of degradation product concentration with increasing retention time and higher propylene glycol concentration. The degradation characteristics studied in the research work will be helpful to identify the parameters affecting the degraded propylene glycol efficiency to be tested as gas hydrate inhibitor in our future research work. [ABSTRACT FROM AUTHOR]

Iron is one of the most abundant elements in the Universe and Earth's surfaces, and undergoes a redox change of approximately 0.77 mV in changing between its +2 and +3 states. Many contemporary terrestrial organisms are deeply connected to inorganic geochemistry via exploitation of this redox change, and iron redox reactions and catalysis are known to cause significant changes in the course of complex abiotic reactions. These observations point to the question of whether iron may have steered prebiotic chemistry during the emergence of life. Using kinetically naive in silico reaction modeling we explored the potential effects of iron ions on complex reaction networks of prebiotic interest, namely the formose reaction, the complexifying degradation reaction of pyruvic acid in water, glucose degradation, and the Maillard reaction. We find that iron ions produce significant changes in the connectivity of various known diversity-generating reaction networks of proposed prebiotic significance, generally significantly diversifying novel molecular products by ~20%, but also adding the potential for kinetic effects that could allow iron to steer prebiotic chemistry in marked ways. [ABSTRACT FROM AUTHOR]

Background: In the course of glycolysis, the intracellular enzyme lactate dehydrogenase (LDH) transforms pyruvic acid into lactic acid. The main source of energy in the placenta is glycolysis. In PE, hypoxia further boosts glycolysis and raises LDH activity. Studies have revealed that PE placentas had more LDH activity and gene expression than placentas from healthy pregnancies. OBJECTIVES: To compare serum LDH levels in the normal pregnant women and in women with preeclampsia and eclampsia in the antepartum period. To study the correlation of maternal and perinatal outcomes with serum LDH levels. Material & Methods: Study Design: Prospective hospital based cross - sectional study. Study area: study conducted in the Department of Obstetrics and Gynaecology in collaboration with the department of Biochemistry, Murshidabad Medical College, Berhampore, Murshidabad, West Bengal. Study Period: June 2021 - May 2022. Study population: Pregnant women in the third trimester were enrolled in the study. Sample size: study consisted a total of 100 cases and 100 controls. Sampling Technique: Simple Random sampling method. Study tools and Data collection procedure: The rest of the women were enrolled in the study and divided into the following groups Group 1: Healthy normal pregnant women (controls) Group 2: Patients of preeclampsia and eclampsia (c a s e s). They were subdivided into two groups based on severity of preeclampsia 2a: Patients with non-severe preeclampsia 2b: Patients with severe pre-eclampsia. Results: In the control group, all had levels of LDH < 600 IU/L, the mean value of LDH being 395.16 ± 92.54 IU/L. Majority of the patients (77.4%) in the non-severe preeclampsia group had LDH levels < 600 IU/L, 6 (9.2%) patients had LDH in the range of 600-800 IU/L, 8(12.9%) patients had LDH in the range of > 800 IU/L. The mean LDH Level in the nonsevere preeclampsia group is 513 ± 306.08. CONCLUSION: A helpful biochemical indicator of the severity and occurrence of preeclampsia problems is lactic dehydrogenase. These issues may be avoided by identifying high-risk patients with increased levels of lactic dehydrogenase, closely monitoring them, and providing timely, appropriate care, which will reduce maternal and foetal morbidity and mortality. [ABSTRACT FROM AUTHOR]

Pyruvic acid has numerous applications in the food, chemical, and pharmaceutical industries. The high costs of chemical synthesis have prevented the extensive use of pyruvate for many applications. Metabolic engineering and traditional strategies for mutation and selection have been applied to microorganisms to enhance their ability to produce pyruvate. In the past decades, different microbial strains were generated to enhance their pyruvate production capability. In addition to the development of genetic engineering and metabolic engineering in recent years, the metabolic transformation of wild-type yeast, E. coli, and so on to produce high-yielding pyruvate strains has become a hot spot. The strategy and the understanding of the central metabolism directly related to pyruvate production could provide valuable information for improvements in fermentation products. One of the goals of this review was to collect information regarding metabolically engineered strains and the microbial fermentation processes used to produce pyruvate in high yield and productivity. [ABSTRACT FROM AUTHOR]

Alcohol abuse, which affects almost one-fifth of the world’s population, is one of the most socially significant in the world. It is known that from 25 to 85 % of patients are in a state of alcohol intoxication during hospitalization to the Polytrauma Department. The study was aimed to determine the content of major metabolites of carbohydrate metabolism, in particular glucose, pyruvic acid, and lactic acid in the blood of patients with combined trauma and alcoholic delirium, depending on the method of sedation. Materials and methods. The study included 80 patients with moderate polytrauma and alcohol withdrawal complicated by alcohol delirium. The median age was 45 years [39–54]. Patients in group 1 (n = 40) were given dexmedetomidine as a sedation method, and in group 2 (n = 40), diazepam sedation was used according to the symptom-trigger protocol. The CAM-ICU method was used to diagnose delirium. The concentration of glucose, lactic acid, and pyruvic acid (pyruvate) was determined in the patients’ blood. Results. The blood content of glucose of patients of group 1 on admission to ICU was 7.45 [6.52; 8.97] mmol/L, which is 1.7 times higher than this indicator in the control group; on the 3rd day, it decreased by 9.4 % compared to the first day of admission to ICU and was 6.75 [6.13; 8.0] mmol/L but did not reach the level of glucose in the control group and remained higher by 55.1 % compared to the control. On the 7th day, the blood glucose content decreased to normal values and amounted to 5.55 [4.9; 5.9] mmol/L. In patients of group 2, the glucose level was 8.3 [7.2; 9.87] mmol/L, which is 1.9 times hig­her than in the control group. On the 3rd day, the blood glucose level decreased by 6 % to 7.8 [6.95; 9.2] mmol/L, and a week after admission, it was 6.6 [4.9; 5.9] mmol/L. In patients of group 1, the level of pyruvate at the admission to the ICU was 0.127 [0.115; 0.130] mmol/L, lactate — 2.345 [2.11; 2.66] mmol/L, lactate/pyruvate ratio — 18.46. The same rates in patients of group 2 were slightly higher: pyruvate — 0.129 [0.104; 0.147] mmol/L, lactate — 2.535 [2.33; 2.81] mmol/L, lactate/pyruvate ratio — 19.65. On the 7th day, among the patients of group 1, the level of pyruvate reached 0.103 [0.098; 0.111] mmol/L, lactate — 2.040 [1.86; 2.19] mmol/L, lactate/pyruvate ratio — 19.81. In patients of group 2, on the 7th day the level of pyruvate reached 0.108 [0.093; 0.129] mmol/L, lactate — 2.455 [2.26; 2.748] mmol/L, lactate/pyruvate ratio — 22.73. Thus, hyperglycemia was observed in the blood of patients with polytrauma and alcohol withdrawal syndrome complicated by alcoholic delirium on admission, on the 3rd day of hospital stay (groups 1 and 2) and the 7th day in patients of group 2, indicating violation of biochemical mechanisms that promote blood glucose homeostasis. Conclusions. The use of dexmedetomidine for sedation of patients with alcohol withdrawal and alcoholic delirium and polytrauma reduces the manifestations of carbohydrate metabolism disorders.

A core-shell structured catalyst 3Ni-7Co@SiO 2 -0.2 was created to facilitate the reductive amination of pyruvic acid into alanine and the yield of alanine is up to 99 %. The SiO 2 shell played a crucial role in spatial isolation effect, preventing the direct hydrogenation of pyruvic acid and improving the selectivity of alanine. By inter-doping Ni and Co, the electronic structure and properties are adjusted, the d-band center is reduced which is beneficial to the desorption of the product and the reaction barrier is reduced. Furthermore, it is proposed that catalysts exhibit better reductive amination reaction performance when there is a smaller difference in adsorption energy between NH 3 and H 2 atoms on the metal surface. [Display omitted] • Core-shell structured catalysts for reductive amination of pyruvic acid to alanine. • The yield of alanine reached up to 99 %. • The spatial isolation effect of SiO2 shell. • Lattice doping of Ni and Co. [ABSTRACT FROM AUTHOR]