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Zacharias Dische's discovery of feedback inhibition in metabolism was one of the most important in the history of biochemistry. However, his paper was written and published under very difficult circumstances in wartime and passed almost completely unnoticed. It is almost never cited, and the discovery itself is usually attributed to later work of others. Here I provide a discussion of Dische's work, a translation of his paper into English, and a transcription of the original French version, which is almost unobtainable anywhere. [ABSTRACT FROM AUTHOR]

Waste paper can serve as a feedstock for ethanol production due to being rich in cellulose and not requiring energy-intensive thermophysical pretreatment. In this study, an efficient process was developed to convert waste paper to ethanol. To accelerate enzymatic saccharification, pH of waste paper slurry was adjusted to 4.5–5.0 with H 2 SO 4 . Presaccharification and simultaneous saccharification and fermentation (PSSF) with enzyme loading of 40 FPU/g waste paper achieved an ethanol yield of 91.8% and productivity of 0.53 g/(L h) with an ethanol concentration of 32 g/L. Fed-batch PSSF was used to decrease enzyme loading to 13 FPU/g waste paper by feeding two separate batches of waste paper slurry. Feeding with 20% w/w waste paper slurry increased ethanol concentration to 41.8 g/L while ethanol yield decreased to 83.8%. To improve the ethanol yield, presaccharification was done prior to feeding and resulted in a higher ethanol concentration of 45.3 g/L, a yield of 90.8%, and productivity of 0.54 g/(L h). Ethanol fermentation recovered 33.2% of the energy in waste paper as ethanol. The biochemical methane potential of the stillage eluted from ethanol fermentation was 270.5 mL/g VTS and 73.0% of the energy in the stillage was recovered as methane. Integrating ethanol fermentation with methane fermentation, recovered a total of 80.4% of the energy in waste paper as ethanol and methane. [ABSTRACT FROM AUTHOR]

Abstract: A cost-effective HPLC method for determination of pyrimethamine (PYR) in human whole blood samples dried on filter paper (Whatman®) is reported. Trimethoprim (TMP) was used as an internal standard. Whole blood spiked with PYR was transferred (100μl) onto filter paper and dried at room temperature. Capillary blood samples (100μl) after ingestion of three tablets of sulfadoxine-pyrimethamine (SP) by one subject were also tested. PYR and an internal standard (IS) TMP were extracted into di-isopropyl ether as bases and then re-extracted with 150μl mobile phase. A C-18 column was used and the mobile phase consisted of phosphate buffer (0.05M, pH 5):acetonitrile:concentrated perchloric acid (750:300:2.5, v/v/v). The absorbances of PYR and IS were monitored at 270nm. The limit of quantification was 40ng/ml. The within- and between-assay coefficient of variations were <10% at the limit of quantification. [Copyright &y& Elsevier]

The effect of pulp and paper-mill effluents on terrestrial animals was investigated using male albino rats as a test organism, under controlled laboratory conditions. Effluent consumption for 15 days caused a reduction in the relative weight of the testis (mg/100 g body weight), compared to the control rats. The effects were not so pronounced in other regions of the male reproductive tract. Biochemical analysis revealed a drop in the activity of epididymal α-glucosidase in the effluent-treated animals. Although sperm collected from the cauda epididymis appeared morphologically normal, a decline in total sperm count and number of motile sperm was seen. The circulating level of testosterone in effluent-treated rats was slightly lower in some groups of rats given effluent treatment compared to controls. The level of progesterone and oestradiol, however, remained unaffected. Hematological and serological analyses suggest that effluents could produce anemia, liver and kidney dysfunction in rats. This inference stems from the altered blood cell counts, enhanced bilirubin and urea concentration in blood and high activity of serum GOT and GPT observed in effluent fed animals compared to controls. It is concluded that besides the general toxicity, the effluent affects the male reproductive system predominantly at the level of the testis. [Copyright &y& Elsevier]

Abstract: A bioanalytical method for the determination of lumefantrine in 100μl blood applied onto sampling paper, by solid-phase extraction and liquid chromatography, has been developed and validated. Whatman 31 ET Chr sampling paper was pre-treated with 0.75M tartaric acid before sampling capillary blood to enable a high recovery of lumefantrine. Lumefantrine was extracted from the sampling paper, then further purified using solid-phase extraction and finally quantified with HPLC. The between-day variation was below 10% over the range 0.4–25μM. The lower limit of quantification was 0.25μM in 100μl capillary blood. No decrease in lumefantrine concentration in dried blood spot is seen after 4 months storage at 22°C. The method was also evaluated in field samples from patients in Tanzania after treatment with lumefantrine/artemether. Lumefantrine could be estimated accurately enough to assess bioavailability and treatment compliance on day 7 (i.e. 4 days after the last dose) after a standard regimen with the lumefantrine/artemether combination. [Copyright &y& Elsevier]

Abstract: Lipophilic low molar-mass constituents in wood chips for the paper industry result in low quality pulp, pitch deposition, and effluent toxicity. New biotechnological solutions such as fungal pre-treatment of wood chips can reduce pitch problems. This laboratory-scale study focuses on the potential and limitations of a fungal bio-treatment of Norway spruce chips with the white-rot fungus Trametes versicolor. Different fungal treatment conditions were compared. A 4-week fungal treatment reduced the concentration of resin acids and triglycerides by 40% and 100%, respectively, but neither lowered the energy requirements of the TMP process nor significantly affected the morphological fiber characteristics and the physical pulp properties. The pre-treatment led to slightly poorer optical properties. The Trametes versicolor fungal treatment contributed to a less toxic effluent and improved the biodegradability. A treatment of 2–3 weeks appears optimal. [Copyright &y& Elsevier]

The world has been encountered with COVID-19 pandemic since at the beginning of 2020 and the number of infected people by COVID-19 is increasing every day. Despite various studies conducted by researchers and doctors, no treatment has been developed until now, therefore self-protection and isolation are strongly recommended to stop the spread of the virus. The elderly population and people with chronic diseases such as hypertension, cardiovascular diseases, diabetes, and cancer are categorized as risk groups, however, we suggest that people with hemoglobinopathies or porphyria can be described as risk groups as well. Current in silico studies have revealed that the COVID-19 virus can attack heme and hemoglobin metabolisms which are responsible for the oxygen transport to the tissues, iron metabolism, elevated levels of oxidative stress, and tissue damage. Data of the in silico study have been supported with the biochemistry and hemogram results of the COVID-19 patients, for instance hemoglobin levels decreased and serum ferritin and C-reactive protein levels increased. Indicated biochemistry biomarkers are tightly associated with inflammation, iron overload, and oxidative stress. In conclusion, since people with hemoglobinopathies or porphyria have already impaired heme and hemoglobin metabolism, COVID-19 infection can enhance the adverse effects of impaired hemoglobin metabolism and accelerate the progression of severe symptoms in patients with hemoglobinopathies or porphyria compared to the normal individuals. Thus those people can be considered as a risk group and extra precautions should be applied for them to protect them. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the structure and properties of one TA system from the bacterial prophage P1. It says that the crystal structure of the Doc toxin, in complex with the C-terminal portion of Phd, reveals that Doc adopts an all-helical fold different from the other known TA toxins. It notes that structural studies also demonstrated that the Phd C-terminal domain is inherently disordered and folds into an a-helix upon binding to Doc, where it hinders toxic activity.

The article presents a study wherein the researchers use an innovative approach to explaining enzyme-substrate complex. It says that visualizing enzymes with their bound substrates is fundamental to fully understand the catalytic process. They cryo-cooled crystals of human carbonic anhydrase II, under high pressure to capture the first step of such reaction. They then solved the substrate-bound structures of both the full enzyme and an apo form lacking the catalytic zinc.

The xanthones represent an important and widely spread class of specialized metabolites in the plant kingdom, fungi, and lichens. Their aromatic and highly oxygenated structures owe them the ability to undergo a series of chemical reactions to form an important number of derivatives as well as to exert a large scale of excellent activities that particularly increased their interest for several researchers. Amongst the reactions observed on their basic nucleus, C-glycosylation leads to the formation of C-glycosylxanthones, a rare subclass of xanthones encountered in nature. Until July 2023, the literature survey on chemical and pharmacological investigations of medicinal plants indicated that a total of 41 distinct natural C-glycosylxanthones have been isolated from 31 plant species belonging to 10 families. Mangiferin (1) was the most reported one and the most biologically screened. Antioxidant activity was the most performed test on isolated compounds, while some strong and good anti-inflammatory, antiplasmodial, and α-glucosidase inhibitory activities have been also reported in the literature for some C-glycosylxanthones. This paper is a mini-review summarizing the occurrence, chemistry, and biological activities of C-glycosylxanthones. The writing of this paper has been done using the literature collected from online libraries including SciFinder, PubMed, Web of Science, and Google Scholar using keywords xanthone, glycosyl, C-glycosylxanthone, without language restriction. This review represents therefore the easiest access to the information on C-glycosylxanthones for researchers intending to also continue the research investigations on this topic. [Display omitted] • This review summarizes the occurrence, the chemistry and pharmacology of C-glycoxanthones. • Forty-one naturally occurring C-glycosylxanthones have been identified and reported in the literature so far. • The distribution, classification and biosynthesis of C-glycosylxanthones are discussed. • The pharmacology of the C-glycosylxanthones is discussed. [ABSTRACT FROM AUTHOR]

Abstract: Produced water, discharged from offshore oil and gas operations, contains chemicals from formation water, condensed water, and any chemical added down hole or during the oil/water separation process. Although, most of the contaminants fall below the detection limits within a short distance from the discharge port, a few of the remaining contaminants including naturally occurring radioactive materials (NORM) are of concern due to their bioavailability in the media and bioaccumulation characteristics in finfish and shellfish species used for human consumption. In the past, several initiatives have been taken to model human health risk from NORM in produced water. The parameters of the available risk assessment models are imprecise and sparse in nature. In this study, a fuzzy possibilistic evaluation using fuzzy rule based modeling has been presented. Being conservative in nature, the possibilistic approach considers possible input parameter values; thus provides better environmental prediction than the Monte Carlo (MC) calculation. The uncertainties of the input parameters were captured with fuzzy triangular membership functions (TFNs). Fuzzy if-then rules were applied for input concentrations of two isotopes of radium, namely 226Ra, and 228Ra, available in produced water and bulk dilution to evaluate the radium concentration in fish tissue used for human consumption. The bulk dilution was predicted using four input parameters: produced water discharge rate, ambient seawater velocity, depth of discharge port and density gradient. The evaluated cancer risk shows compliance with the regulatory guidelines; thus minimum risk to human health is expected from NORM components in produced water. [Copyright &y& Elsevier]

• First-of-its-kind general framework for a CTMC theory of stochastic rewriting systems for rules with conditions. • New rule-algebraic restricted rewriting theory formalism. • First-of-its-kind encoding of bio- and organo-chemical reaction systems via rule-algebraic restricted rewriting theory. The Kappa biochemistry and the MØD organic chemistry frameworks are amongst the most intensely developed applications of rewriting-based methods in the life sciences to date. A typical feature of these types of rewriting theories is the necessity to implement certain structural constraints on the objects to be rewritten (a protein is empirically found to have a certain signature of sites, a carbon atom can form at most four bonds,...). In this paper, we contribute a number of original developments that permit to implement a universal theory of continuous-time Markov chains (CTMCs) for stochastic rewriting systems. Our core mathematical concepts are a novel rule algebra construction for the relevant setting of rewriting rules with conditions, both in Double- and in Sesqui-Pushout semantics, augmented by a suitable stochastic mechanics formalism extension that permits to derive dynamical evolution equations for pattern-counting statistics. A second main contribution of our paper is a novel framework of restricted rewriting theories, which comprises a rule-algebra calculus under the restriction to so-called constraint-preserving completions of application conditions (for rules considered to act only upon objects of the underlying category satisfying a globally fixed set of structural constraints). This novel framework in turn renders a faithful encoding of bio- and organo-chemical rewriting in the sense of Kappa and MØD possible, which allows us to derive a rewriting-based formulation of reaction systems including a full-fledged CTMC semantics as instances of our universal CTMC framework. While offering an interesting new perspective and conceptual simplification of this semantics in the setting of Kappa , both the formal encoding and the CTMC semantics of organo-chemical reaction systems as motivated by the MØD framework are the first such results of their kind. [ABSTRACT FROM AUTHOR]

Background: Postpartum depression (PPD) is the most frequent psychiatric complication during the postnatal period and its mechanisms are not fully understood. Metabolomics, can quantitatively measure metabolites in a high-throughput method, and thus uncover the underlying pathophysiology of disease.Objectives: In this study, we reviewed metabolomics studies conducted on PPD, aiming to understand the changes of metabolites in PPD patients and analyze the potential application of metabolomics in PPD prediction and diagnosis.Methods: Relevant articles were searched in PubMed, Google scholar, and Web of Science databases from January 2011 to July 2022. The metabolites involved were systematically examined and compared. MetaboAnalyst online software was applied to analyze metabolic pathways.Results: A total of 14 papers were included in this study. There were several highly reported metabolites, such as kynurenine, kynurenic acid, and eicosapentaenoic acid. Dysregulation of metabolic pathways involved amino acids metabolism, fatty acids metabolism, and steroids metabolism.Limitations: The included studies are relatively inadequate, and further work is needed.Conclusions: This study summarized significant metabolic alterations that provided clues for the prediction, diagnosis, and pathogenesis of PPD. [ABSTRACT FROM AUTHOR]

Many transition metal complexes have been explored for their therapeutic properties after the discovery of cisplatin. Schiff bases have an efficient complexation tendency with the transition metals and several medicinal properties have been reported. However, fewer studies have reported the medicinal utility of vanadium and its Schiff base complexes. This paper provides a comprehensive overview of vanadium complexes with Schiff bases along with their mechanistic insight. Vanadium complexes in + 4 and + 5 oxidation states have exhibited well-defined geometry and found to be thermodynamically stable. The studies have reported the G0/G1 phase cell cycle arrest and decreased delta psi m, inducing mitochondrial membrane depolarization in cancer cell lines along with the alterations in the metabolism of the cancer cells upon dosing with the vanadium complexes. Cancer cell invasion and growth are also found to be markedly reduced by peroxo complexes of vanadium. The studies included in the review paper have been taken from leading indexing databases and focus was laid on recent reports in literature. The biological potential of vanadium complexes of Schiff bases opens new horizons for future interdisciplinary studies and investigation focussed on understanding the biochemistry of these complexes, along with designing new complexes which have better bioavailability, solubility and low or non-toxicity. [ABSTRACT FROM AUTHOR]

Taste is one of the five human senses, but it contains differences and ambiguities among people. Therefore, some researchers consider that taste expression, which cannot be clearly defined, is influenced by the expressions used by others. In this study, we propose a method for quantitatively evaluating user comments on a recipe-sharing website. In evaluating KOKU as an example of a taste expression using the proposed method, we confirmed that expressions from others have a statistically significant influence on KOKU. Although there have been attempts to clarify the influence of other information on taste in cognitive linguistics and biochemistry, these attempts have been based on cognitive linguistics and chemical analysis. The series of analytical methods presented in this paper enables us to quantitatively evaluate the influence of others' comments on taste expressions the general public has used without clear definitions. [ABSTRACT FROM AUTHOR]

Steroids are farnesyl diphosphate-derived triterpene derivatives widely distributed in Meliaceae plants that can have several health benefits due to their biological activities. This literature survey on chemical and pharmacological studies of steroids from the Meliaceae plants indicates that 157 distinct steroids classified into six subclasses including (in decreasing number): pregnane-, stigmastane-, ergostane-, cholestane-, androstane- and ecdysterone-type steroids have been reported from a total of 49 plant species. This review aims to provide a reference document compiling information about the occurrence, chemistry and biological activities of meliaceous steroids for the period from 1988 to July 2023. In particular, generalities about the chemistry of steroids with unusual skeletons and underlying biosynthetic pathways are highlighted. In addition, some structural relationships between different compound types and their biological activities are presented. The information used during the writing of this paper was collected from the online libraries PubMed, Google Scholar and Scifinder using the keywords steroids and Meliaceae with no language restriction. This review points out new avenues for further investigations of steroids from plants of the Meliaceae family. A comprehensive compilation of literature and discussion on the occurrence, chemistry and biological activities of a total of 153 natural occurring steroids and 4 synthetic analogues reported from 49 Meliaceae plant species between 1988 and July 2023. [Display omitted] • This is the first comprehensive review on steroids from Meliaceae. • A total of 157 steroids from 49 plant species are reported in the literature so far. • The distribution, classification and biosynthesis of Meliaceous steroids are discussed. • Pregnane-type steroids represent the most abundant ones. • Biological activities of the reported steroids are discussed. [ABSTRACT FROM AUTHOR]

Although the papers of Kacser and Burns (1973) and Heinrich and Rapoport (1974a,b) are commonly taken as the birth of metabolic control analysis, many of the ideas in them are foreshadowed in earlier papers, from 1956 onwards, when Kacser first argued for taking a systemic view of genetics and biochemistry. [ABSTRACT FROM AUTHOR]

Abstract: This paper reports on the influence of independent variables in the pulping of olive wood trimmings [viz. cooking temperature (165–195°C) and time (30–90min), ethanolamine concentration (5–15%), soda concentration (2.5–7.5%) and liquid/solid ratio (4–6)], on the yield and kappa number of the pulps and breaking length, burst index and tear index of the resulting paper sheets. By using a central composite factorial design, equations that relate each dependent variable to the different independent variables were obtained that reproduced the experimental results for the dependent variables with errors less than 15%. These equations could be used to find the suitable operations conditions, so that operating with not too high values of operating variables (with the consequent minor costs of capital and of operation) pulps could be obtained by acceptable strength properties. Optimizing pulp yield, the kappa number and the strength properties of the resulting paper sheets entails using rather different conditions in each case. Obtaining acceptably strong paper sheets while saving on immobilized capital through the use of smaller facilities and less chemical reagents entails using a medium soda concentration and low values of all other independent variables. In this way, the yield is 22.2% lower, the kappa number 42.5% higher, and the breaking length, burst index and tear index 6.2, 29.1 and 29.6%, respectively, lower than their optimum values; in any case, the strength properties increase although the pulp was suitably refining. [Copyright &y& Elsevier]

The usual BOD measuring systems used for monitoring the degradation of biodegradable materials are applied for the assessment of biodegradation exclusively in aquatic tests by detecting the amount of O2 consumed during degradation. In our study, a new, solid test application of a BOD system optionally capable to detect CO2 evolved during degradation is presented. After the optimisation of sample concentration and test temperature, the measurement set-up possessing relatively small reaction vessels of 250 ml with 80 g of soil mix proved to supply reliable and reproducible results. The system was optimised with microcrystalline cellulose—used as reference material in aquatic and solid test as well—showing 89.3±3.2% degree of degradation after 21 days, and it was applied for the assessment of biodegradation of commercially available non-powdered (films and kraft-paper) samples indicating degrees of degradation between 24.9 and 55.4%. [Copyright &y& Elsevier]

This document is a withdrawal notice for an article titled "Carbon monoxide protects against hyperoxia-induced endothelial cell apoptosis by inhibiting reactive oxygen species formation." The authors of the article have withdrawn it, except for one author who could not be contacted. The journal determined that there were issues with the reuse of images and potential reuse of data from a previously published paper. These issues could not be resolved due to the lack of original data. [Extracted from the article]

Theoretical estimates based on the Mie solution for single droplets show that infrared irradiation of droplet clusters levitating over the heated water surface prevents the ordinary growth of droplets and subsequent coalescence of the droplet cluster with water layer. As a result, this irradiation can be used to stabilize the levitating clusters for a long time. This prediction is confirmed in the paper by a series of experiments with obtaining the required power of infrared irradiation. The resulting stable droplet clusters are considered as an appropriate laboratory model of atmospheric droplets to study biochemical processes in the droplets of natural mists and clouds. Possible use of sub-millimeter electromagnetic radiation to reach a similar stabilization effect is also analyzed in the paper. [ABSTRACT FROM AUTHOR]

A multidisciplinary study of the implementation potential of a biorefinery, using forestry residues as feedstock, is performed by assessing techno-economic factors, system integration and feedstock supply. The process is based on biochemical conversion of logging residues to produce ethanol, biogas, pellets, heat and electricity. Nine models were designed in Aspen Plus based on the available feedstock and the required co-products. Focus was on the product ratio of pellets and heat. The net present value of the plants was calculated and thermal integration with district-heating systems in areas with regional feedstock availability was investigated. Also co-location with pulp and paper mills in Sweden was investigated to replace fossil fuels with pellets. Seven of the nine models showed a positive net present value assuming an 11% discount rate and 30% corporate tax. Five counties in Sweden were identified as potential feedstock suppliers to a biorefinery processing 200 kt dry feedstock/y. [ABSTRACT FROM AUTHOR]

Docking is now routine in virtual screening or lead optimization for drug screening and design. The number of papers related to docking has dramatically increased over the past decade. However, there are many issues to consider when undertaking a docking study. Frequent problems or issues arise, such as the wrong binding site of the target protein, screening using an unsuitable small-molecule database, the choice of docking pose, high dock score but failed in molecular dynamics (MD) simulation, and lack of clarity over whether the compound is an inhibitor or agonist. These problems should be cause for caution and concern before performing docking. Some papers show comprehensive biochemistry experiments but only a simple docking figure. This review presents some evidence to show that the docking might be questionable, despite a high score. In some cases, the accuracy of docking can even change from 0% to 92.66%. Thus, please beware of docking! [ABSTRACT FROM AUTHOR]

In this paper, we presented an integrated C5-based biorefinery concept to produce C5-platform of biofuels and biochemicals using corn fiber from Dried Distillers Grains (DDG). The process utilizes a selective hydrolysis process to generate a xylose-rich hydrolyzate stream and two co-product streams: fine fraction generated during mechanical pretreatment of DDG using Mesh 20 sieve and residual fiber after hydrolysis. Utilization of these two co-product streams is critical to the success of the biorefinery. This paper discusses how the two streams are generated, their composition, and their potential value in animal feed applications. Composition analysis of the first co-product stream showed that it is enriched in proteins compared to original DDG (11% higher crude protein content; 36% higher lysine content). The second co-product stream has 113% higher fat content compared to original DDG, as well as 15% higher total digestible nutrients, and 15% higher digestible energy. The results of this study suggest that these co-product side streams can be potentially applied as additives in animal feed, allowing for cost-effective utilization of DDG for bio-products without negatively impacting feed markets associated with DDG. [ABSTRACT FROM AUTHOR]

• Poor BBB passage and fast elimination limit use of oximes in OPs treatment. • Cucurbit[7]uril (CB7)was tested as a delivery vehicle for bisquaternary oximes. • The encapsulation process, cell toxicity, in vivo safety and influence of CB7 on oxime pharmacokinetics and pharmacodynamics were studied. • The encapsulation of K027 increased and accelerated the blood-brain-barrier penetration. • The CB7 protects the circulating oxime from rapid renal clearance. Oxime-based acetylcholinesterase reactivators (briefly oximes) regenerate organophosphate-inactivated acetylcholinesterase and restore its function. Poor blood-brain-barrier passage and fast elimination from blood limit their actual use in treatment of patients exposed to organophosphates. Previous in vitro results implicated further testing of cucurbit[7]uril as a delivery vehicle for bisquaternary oximes. The present paper focuses on cell toxicity, in vivo safety and influence of cucurbit[7]uril on oxime pharmacokinetics and pharmacodynamics. Neither the K027 nor the complex caused any cell toxicity, changes in blood biochemistry or hepato- or nephrotoxicity in tested concentrations. The encapsulation of K027 increased and accelerated the blood-brain-barrier penetration. The peripheral oxime exposure also increased, supporting the suggestion that cucurbit[7]uril protects the circulating oxime from rapid renal clearance. Contrary to the comparable in vitro reactivation power of K027 and the encapsulated K027, we failed to confirm this in vivo. In theory, this might result from the non-specific binding of molecules to the cucurbit[7]uril or the interaction of K027 with cucurbit[7]uril being too strong for acetylcholinesterase reactivation. Precise explanation requires additional in silico , in vitro and also in vivo experiments. [ABSTRACT FROM AUTHOR]

Since its conception some fifty years ago, metabolic control analysis (MCA) aims to understand how cells control their metabolism by adjusting the activity of their enzymes. Here we extend its scope to a whole-cell context. We consider metabolism in the evolutionary context of growth-rate maximisation by optimisation of protein concentrations. This framework allows for the prediction of flux control coefficients from proteomics data or stoichiometric modelling. Since genes compete for finite biosynthetic resources, we treat all protein concentrations as interdependent. We show that elementary flux modes (EFMs) emerge naturally as the optimal metabolic networks in the whole-cell context and we derive their control properties. In the evolutionary optimum, the number of expressed EFMs is determined by the number of protein-concentration constraints that limit growth rate. We use published glucose-limited chemostat data of S. cerevisiae to illustrate that it uses only two EFMs prior to the onset of fermentation and that it uses four EFMs during fermentation. We discuss published enzyme-titration data to show that S. cerevisiae and E. coli indeed can express proteins at growth-rate maximising concentrations. Accordingly, we extend MCA to elementary flux modes operating at an optimal state. We find that the expression of growth-unassociated proteins changes results from classical metabolic control analysis. Finally, we show how flux control coefficients can be estimated from proteomics and ribosome-profiling data. We analyse published proteomics data of E. coli to provide a whole-cell perspective of the control of metabolic enzymes on growth rate. We hope that this paper stimulates a renewed interest in metabolic control analysis, so that it can serve again the purpose it once had: to identify general principles that emerge from the biochemistry of the cell and are conserved across biological species. [ABSTRACT FROM AUTHOR]

NAD+ is crucial for cellular balance in all organisms. Recent interest has focused on its metabolism. Deficiency-related issues can be countered using NMN and NR, potential therapies available through diet or supplementation. These compounds are emerging as nutraceuticals and bioactive food elements. Bibliometric analysis was used to study the scientific output and impact of research on the NAD+ metabolome. For this, the terms "nicotinamide adenine dinucleotide" or "NAD+" or "NAD+ precursors" or "nicotinamide riboside" or "nicotinamide mononucleotide" were searched in the topic title in The Web of Science™ database. Only original articles and articles review were considered. VOSviewer was used for constructing and visualizing the bibliometric networks maps. A total of 10,568 papers were published, with a consistent increase in the number of publications, especially over the last decade. Biochemistry molecular biology, biophysics, cell biology, chemistry multidisciplinary and microbiology were the top 5 field research in the subject. The majority of the publications came from the 'Journal of biological chemistry' and 'Biochemistry' journals. The prominent research topics included longevity, sirtuins, NAD+ precursors, oxidation and reduction reactions, enzymes, microbial biotechnology, cancer therapy, and crop science. Finally, a guide for future investigation in nutrition and food sciences areas was proposed, which holds immense potential for developing innovative strategies to enhance food quality, promote optimal nutrition, and explore new avenues for improving human health. To our knowledge, this is the first bibliometric analysis of NAD+ metabolome, which can provide valuable insights into the research landscape in this multidisciplinary rapidly growing field. [Display omitted] • Initial research of NAD + has focused on biochemistry and cellular biology fields. • The most cited topic was related with sirtuins and lifespan extension. • Current focus is on strategies targeting NAD + for reverting diseases. • There are many unexplored topics related to NAD+ in nutrition and food sciences. • NAD + metabolome holds promise for nutrition, food quality, and health improvements. [ABSTRACT FROM AUTHOR]

Metabolomics is the study of small molecules, primarily metabolites, that are produced during metabolic processes. Analysis of the composition of an organism's metabolome can yield useful information about an individual's health status at any given time. In recent years, the development of large-scale, targeted metabolomic methods has allowed for the analysis of biological samples using analytical techniques such as LC-MS/MS. This paper presents a large-scale metabolomics method for analysis of biological samples, with a focus on quantification of metabolites found in blood plasma. The method comprises a 10-min chromatographic separation using HILIC and RP stationary phases combined with positive and negative electrospray ionization in order to maximize metabolome coverage. Complete analysis of a single sample can be achieved in as little as 40 min using the two columns and dual modes of ionization. With 540 metabolites and the inclusion of over 200 analytical standards, this method is comprehensive and quantitatively robust when compared to current targeted metabolomics methods. This study uses a large-scale evaluation of metabolite recovery from plasma that enables absolute quantification of metabolites by correcting for analyte loss throughout processes such as extraction, handling, or storage. In addition, the method was applied to plasma collected from adjuvant breast cancer patients to confirm the suitability of the method to clinical samples. [Display omitted] • Large-scale targeted metabolomics 560 metabolites in human plasma • Rapid (40 min per sample) analysis using RP and HILIC chromatography • % Recovery for 228 compounds in human plasma enables absolute quantification [ABSTRACT FROM AUTHOR]

Reaction systems are an abstract model of interactions among biochemical reactions, developed around two opposite mechanisms: facilitation and inhibition. The evolution of a reaction system is driven by the external objects which are sent into the system by the environment at each step. In order to increase the modelling expressiveness of the calculus, we consider an extension of reaction systems with restriction , which allows the hiding of entities, such as those occurring inside membranes. To this purpose, we recently developed the Reaction Algebra , a calculus resembling reaction systems extended with a restriction operator. In the present paper, three equivalent semantics for the Reaction Algebra are presented: a reduction semantics, and two state-abstract compositional semantics. The reduction semantics is meant to capture the behaviour of Reaction Algebra models at a high-level, while the two compositional semantics make the interactive nature of reaction systems explicit. The difference between the two compositional semantics lies in how the behaviour with respect to the contextual entities is described: one uses an extensional description, while the other uses an intensional one. We also define, in the settings of both compositional semantics, a behavioural equivalence subsuming the functional equivalence of reaction systems, which is also shown to be congruence, thus providing a formal ground to the modular description of models. Finally, as an example of application of the techniques developed in the paper, we compare the semantics of two different Reaction Algebra models of the functioning of the lac operon in the E. coli bacterium. [ABSTRACT FROM AUTHOR]

Abstract: Aim of study: To build an early warning score (EWS) based exclusively on routinely undertaken laboratory tests that might provide early discrimination of in-hospital death and could be easily implemented on paper. Materials and methods: Using a database of combined haematology and biochemistry results for 86,472 discharged adult patients for whom the admission specialty was Medicine, we used decision tree (DT) analysis to generate a laboratory decision tree early warning score (LDT-EWS) for each gender. LDT-EWS was developed for a single set (n =3496) (Q1) and validated in 22 other discrete sets each of three months long (Q2, Q3…Q23) (total n =82,976; range of n =3428 to 4093) by testing its ability to discriminate in-hospital death using the area under the receiver-operating characteristic (AUROC) curve. Results: The data generated slightly different models for male and female patients. The ranges of AUROC values (95% CI) for LDT-EWS with in-hospital death as the outcome for the validation sets Q2–Q23 were: 0.755 (0.727–0.783) (Q16) to 0.801 (0.776–0.826) [all patients combined, n =82,976]; 0.744 (0.704–0.784, Q16) to 0.824 (0.792–0.856, Q2) [39,591 males]; and 0.742 (0.707–0.777, Q10) to 0.826 (0.796–0.856, Q12) [43,385 females]. Conclusions: This study provides evidence that the results of commonly measured laboratory tests collected soon after hospital admission can be represented in a simple, paper-based EWS (LDT-EWS) to discriminate in-hospital mortality. We hypothesise that, with appropriate modification, it might be possible to extend the use of LDT-EWS throughout the patient's hospital stay. [Copyright &y& Elsevier]

Abstract: The paper gives a review on the importance of distribution of Al in biological fluids, primarily in the lights of the works of the author in Al chemistry. It starts with studies of interactions of Al(III) with small biomolecules, such as aliphatic and aromatic hydroxycarboxylic acids, and inorganic and organic phosphates. A significant part of this review deals with the problems of description of the biospeciation of Al(III) in serum, where besides the thermodynamic conditions the role of time is also considered in the case of this sluggish metal ion. The Al(III) complexes of the other large group of biomolecules, proteins and their building blocks (oligo)peptides and amino acids are also discussed, where the role of the type of the side chain donors and the extent of preorganisation are considered in the efficiency of metal ion binding. The application of low molecular mass chelator molecules in restoring the dysfunctioning metal ion (including Al(III)) homeostasis in the treatment of Alzheimer's disease is also discussed in the paper. [Copyright &y& Elsevier]

Abstract: Metabolic engineering has been playing important roles in developing high performance microorganisms capable of producing various chemicals and materials from renewable biomass in a sustainable manner. Synthetic and systems biology are also contributing significantly to the creation of novel pathways and the whole cell-wide optimization of metabolic performance, respectively. In order to expand the spectrum of chemicals that can be produced biotechnologically, it is necessary to broaden the metabolic capacities of microorganisms. Expanding the metabolic pathways for biosynthesizing the target chemicals requires not only the enumeration of a series of known enzymes, but also the identification of biochemical gaps whose corresponding enzymes might not actually exist in nature; this issue is the focus of this paper. First, pathway prediction tools, effectively combining reactions that lead to the production of a target chemical, are analyzed in terms of logics representing chemical information, and designing and ranking the proposed metabolic pathways. Then, several approaches for potentially filling in the gaps of the novel metabolic pathway are suggested along with relevant examples, including the use of promiscuous enzymes that flexibly utilize different substrates, design of novel enzymes for non-natural reactions, and exploration of hypothetical proteins. Finally, strain optimization by systems metabolic engineering in the context of novel metabolic pathways constructed is briefly described. It is hoped that this review paper will provide logical ways of efficiently utilizing ‘big’ biological data to design and develop novel metabolic pathways for the production of various bulk chemicals that are currently produced from fossil resources. [Copyright &y& Elsevier]

Abstract: With the increasing ease of measuring and calculating multiple descriptors per molecule in quantitative structure–activity relationship, the importance of variable selection for data reduction and improving interpretability is gaining importance. While variable selection has been extensively studied in the context of supervised learning, in this paper, an unsupervised learning method is proposed for variable selection and its performance is assessed using a typical QSAR data set. Whereas there is no real dependent variable in the proposed variable selection algorithm, applied variable selection is unsupervised indeed. Besides, scores that are the linear combination of the data variables are set as dependent variables (artificial dependent variables). It includes 107 derivatives of HEPT molecule, characterized by 160 descriptors encoding the steric, hydrophobic, electronic and structural features of HEPT derivatives. The aims of this procedure are generating a subset of descriptors from a data set with the relevant variables, eliminating redundancy, and reducing multicollinearity. The core of this methodology is based on jack-knife resampling method. In this paper, using jack-knife led to selection of 48 out of 160 initial descriptors, so that the data information was preserved. Lastly, using influence effect on prediction resulted in eight descriptors as representative of the 160 descriptors. Constructed model with final 8 descriptors has Q 2 IN =0.67, R 2 =0.74, Q 2 EXT =0.85. It represents adequacy of our strategy for preserving data structure. [Copyright &y& Elsevier]

Abstract: Reaction systems are a formal model based on the regulation mechanisms of facilitation and inhibition between biochemical reactions, which underlie the functioning of living cells. The aim of this paper is to explore the expressive power of reaction systems as a modeling framework, showing how their basic assumptions and properties can be exploited to formalize computer science and biology oriented problems. In this view, we first provide a reaction-based description of an iterative algorithm to solve the Tower of Hanoi puzzle. Then, we show how the regulation of gene expression in the lac operon, involved in the metabolism of lactose in Escherichia coli cells, can be formalized in terms of reaction systems. Finally, we present a method to derive, given a reaction system with reactions, a functionally equivalent system with reactions using simplification methods of boolean expressions. Some final remarks and directions for future research conclude the paper. [Copyright &y& Elsevier]

Abstract: To ensure constant and satisfactory product quality, close monitoring of batch processes is an absolute requirement in the (bio)chemical industry. Principal Component Analysis (PCA)-based techniques exploit historical databases for fault detection and diagnosis. In this paper, the fault detection and diagnosis performance of Batch Dynamic PCA (BDPCA) and Auto-Regressive PCA (ARPCA) is compared with Multi-way PCA (MPCA). Although these methods have been studied before, the performance is often compared based on few validation batches. Additionally, the focus is on fast fault detection, while correct fault identification is often considered of lesser importance. In this paper, MPCA, BDPCA, and ARPCA are benchmarked on an extensive dataset of a simulated penicillin fermentation. Both the detection speed, false alarm rate and correctness of the fault diagnosis are taken into account. The results indicate increased detection speed when using ARPCA as opposed to MPCA and BDPCA at the cost of fault classification accuracy. [Copyright &y& Elsevier]

Abstract: Polycyclic aromatic hydrocarbons (PAH) are hydrophobic environmental contaminants with petrogenic, biogenic, and pyrogenic sources. Alkylated PAH predominate in crude oils, are found in sediment downstream of pulp and paper mills, and can be more toxic than their non-alkylated homologues. The enzymatic metabolism of alkyl phenanthrenes generates ring and chain hydroxylated derivatives. The main objective of this research was to estimate the potential role of hydroxylation in PAH toxicity and secondly to better understand the relative risk of different PAH in complex mixtures. This project assessed the toxicity of ring and chain hydroxylated 1-methylphenanthrenes to the early life stages of Japanese medaka (Oryzias latipes). Phenols were more toxic than benzylic alcohols, and some phenols were more than four times more toxic than their non-hydroxylated counterpart. Ring hydroxylation can increase PAH toxicity, and metabolism may enhance alkyl-PAH toxicity through the generation of such metabolites. This paper is the first to describe the relative toxicity of a suite of hydroxylated alkyl-PAH to the early life stages of fish, proposing an association between the preferential formation of para-quinones and enhanced toxicity. [Copyright &y& Elsevier]

Apigenin and protoapigenone that both have the activities against various cancer cell lines co-exist in Macrothelypteris torresiana , while the extracts of M. torresiana couldn't achieve the fine anti-tumor effects for the existence of potent anti-tumor compounds. This study disclosed an antagonism between the two compounds on the protein level to elucidate the paradox. First, the study established the fingerprint for M. torresiana extract. The following anti-proliferation assay verified that the antagonism occurs between protoapigenone and apigenin. And then Western blot and qt-PCR were applied to evaluate the expression and transcription level of the Akt phosphorylation related targets to validate the antagonism at the protein level. Moreover, CETSA further validated the binding of PDK-1 with apigenin and protoapigenone, as well as the antagonism between the two compounds. Finally, the compound-protein complexes predicted by SYBYL-X gave the visual results for the antagonism. The results demonstrated that: Due to the structural similarity and close binding coefficients to the identical targets, when the cells were treated with apigenin and protoapigenone simultaneously, the Akt phosphorylation inhibition induced by protoapigenone would attenuate significantly. The antagonism disclosed in this paper could be a new explanation for the unsatisfied efficacy of M. torresiana extract. Unlabelled Image [ABSTRACT FROM AUTHOR]