Euglenids are a group of algae of great interest for biotechnology, with a large and complex metabolic capability. To study the metabolic network, it is necessary to know the subcellular locations of the component enzymes, but despite a long history of research into Euglena, the subcellular locations of many major pathways are only poorly defined. Euglena is phylogenetically distant from other commonly studied algae, they have secondary plastids bounded by three membranes, and they can survive after destruction of their plastids. These unusual features make it difficult to assume that the subcellular organization of the metabolic network will be equivalent to that of other photosynthetic organisms. Moreover, we show here that the presence of the secondary chloroplast means that it is not possible to make reliable predictions of the subcellular locations of enzymes in Euglena using existing informatics tools. In order to generate a model of the central metabolic pathway operating in Euglena we analysed biochemical and proteomic information from a variety of sources to assess the subcellular location of relevant enzymes. We use these assignments to propose the compartmentation of the core metabolic pathways in Euglena, a prerequisite for the further study of the metabolic network of Euglena. This model of the metabolic network shows that, other than photosynthesis, all major pathways present in the chloroplast are duplicated elsewhere in the cell, and that several biosynthetic pathways confined to plastids in higher plants are localized elsewhere in Euglena. Our model demonstrates how this organism can synthesise all the metabolites required for growth from simple carbon inputs, and can survive in the absence of chloroplasts.

Kidney disease is a significant health problem worldwide, affecting an estimated 10% of the global population. Kidney disease encompasses a diverse group of disorders that vary in their underlying pathophysiology, clinical presentation, and outcomes. These disorders include acute kidney injury (AKI), chronic kidney disease (CKD), glomerulonephritis, nephrotic syndrome, polycystic kidney disease, diabetic kidney disease, and many others. Despite their distinct etiologies, these disorders share a common feature of immune system dysregulation and metabolic disturbances. The immune system and metabolic pathways are intimately connected and interact to modulate the pathogenesis of kidney diseases. The dysregulation of immune responses in kidney diseases includes a complex interplay between various immune cell types, including resident and infiltrating immune cells, cytokines, chemokines, and complement factors. These immune factors can trigger and perpetuate kidney inflammation, causing renal tissue injury and progressive fibrosis. In addition, metabolic pathways play critical roles in the pathogenesis of kidney diseases, including glucose and lipid metabolism, oxidative stress, mitochondrial dysfunction, and altered nutrient sensing. Dysregulation of these metabolic pathways contributes to the progression of kidney disease by inducing renal tubular injury, apoptosis, and fibrosis. Recent studies have provided insights into the intricate interplay between immune and metabolic pathways in kidney diseases, revealing novel therapeutic targets for the prevention and treatment of kidney diseases. Potential therapeutic strategies include modulating immune responses through targeting key immune factors or inhibiting pro-inflammatory signaling pathways, improving mitochondrial function, and targeting nutrient-sensing pathways such as mTOR, AMPK, and SIRT1. This review highlights the importance of the interplay between immune and metabolic pathways in kidney diseases and the potential therapeutic implications of targeting these pathways.

Hydrogen is useful as a fuel and could be produced by a variety of means. One approach uses artificial photosynthesis where energy from sunlight powers the splitting of water into hydrogen and oxygen. But, biological methods for producing hydrogen has emerged strongly over the past decades. In particular, specific microorganisms could use different substrates to produce hydrogen at differing yields. Such fundamental discoveries with industrial applications thus motivated the use of metabolic engineering approaches and methodologies in enhancing biological hydrogen production through a series of enzyme over-expression, pathway debottlenecking, and gene deletion. However, such approaches heavily rely on the selection of an appropriate microbial chassis for biohydrogen production. With the proper strain in hand, use of alternative substrates may engender greater hydrogen productivities. But learning from the bioprocessing field, co-culture of two compatible microorganisms have been sought after for improving biohydrogen production. In addition, thermophilic microbes may also be useful candidates for exploiting hydrogen production from composting. Future outlook in the field looks into filling our gaps in understanding of the metabolic network that feeds into hydrogen production in different organisms. But, more importantly, problems such as reduced growth rate in engineered microbes point to fundamental issues with using genetically engineered microorganisms for improved biohydrogen production, to which clever bioprocess engineering may yield solutions.

Leishmaniasis is a tropical disease caused by a protozoan parasite Leishmania that is transmitted via infected female sandflies. At present, leishmaniasis treatment mainly counts on chemotherapy. The currently available drugs against leishmaniasis are costly, toxic, with multiple side effects, and limitations in the administration route. The rapid emergence of drug resistance has severely reduced the potency of anti-leishmanial drugs. As a result, there is a pressing need for the development of novel anti-leishmanial drugs with high potency, low cost, acceptable toxicity, and good pharmacokinetics features. Due to the availability of preclinical data, drug repurposing is a valuable approach for speeding up the development of effective antileishmanial through pointing to new drug targets in less time having low costs and risk. Metabolic pathways of this parasite play a crucial role in the growth and proliferation of Leishmania species during the various stages of their life cycle. Based on available genomics/proteomics information, known pathways-based (sterol biosynthetic pathway, purine salvage pathway, glycolysis, GPI biosynthesis, hypusine, polyamine biosynthesis) Leishmania-specific proteins could be targeted with known drugs that were used in other diseases, resulting in finding new promising anti-leishmanial therapeutics. The present review discusses various metabolic pathways of the Leishmania parasite and some drug candidates targeting these pathways effectively that could be potent drugs against leishmaniasis in the future.

Pharmaceutically active compounds and organic pollutants are becoming a major environmental dispute possessing serious threat to the water bodies and terrestrial ecosystem. Microorganisms are capable of the self-purification process, and hence the microbial degradation is considered a lucrative method to counteract the therapeutic and recalcitrant pollutants. Pharmaceutical toxicants in aquatic system can be treated by conventional wastewater treatment, but slow sludge settling, presence of mixture of pharmaceuticals and recalcitrant compounds often pose a potential ecological risk. Some microbial strains are very effective in reducing the chemical oxygen demand (COD), biological oxygen demand (BOD), total dissolved solids (TDS), and turbidity in pharmaceutical industrial wastewater treatment. The natural microbial community has a significant role in the ecological processes of pharmaceutical and organic compounds, including non-steroidal anti-inflammatory drugs, analgesics, blood lipid regulators and other micropollutants. Specific bacterial isolates can act as biodegraders, and fungal treatment could offer protection to the ecosystem. These microorganisms use the pollutants as their sole carbon source and transform the contaminants by co-metabolic pathways. Natural attenuation by native microorganisms, biostimulation and bioaugmentation are the processes employed to degrade the target contaminant. Microorganisms may also be genetically engineered to improve the neutralization efficiency, which would assist in the mineralization of the pollutants. Thus, employing microorganisms to detoxify the pollutants probably enhances the sustainable potential biodegradability, improves water quality standards and ensures eco-friendly alternative bioremediation strategy.

Obesity and metabolic syndrome involve chronic low-grade inflammation called metabolic inflammation as well as metabolic derangements from increased endotoxin and free fatty acids. It is debated whether the endoplasmic reticulum (ER) stress in monocytic cells can contribute to amplify metabolic inflammation; if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 monocytic cells by treatments with lipopolysaccharide (LPS), palmitic acid (PA), or oleic acid (OA), in the presence or absence of ER stressor thapsigargin (TG). Gene expression of tumor necrosis factor (TNF)-α and markers of ER/oxidative stress was determined by qRT-PCR, TNF-α protein by ELISA, ROS by DCFH-DA assay, HIF-1α/p38/ERK-1,2/NF-κB phosphorylation by immunoblotting, and insulin sensitivity by glucose-uptake assay. Regarding clinical analyses, adipose TNF-α was assessed by qRT-PCR/IHC and plasma TNF-α/hs-CRP/MDA/OX-LDL by ELISA. We found that the cooperative interaction between metabolic and ER stresses promoted TNF-α, ROS, CHOP, ATF6, SOD2, and NRF2 expression (P≤0.0183),. However, glucose uptake was not impaired. TNF-α amplification was dependent on HIF-1α/p38/NF-κB phosphorylation, while MAPK/NF-κB inhibitors and antioxidants/ROS scavengers attenuated TNF-α production (P≤0.05). Individuals with obesity displayed increased adipose TNF-α gene/protein expression as well as elevated plasma levels of TNF-α, CRP, MDA, and OX-LDL (P≤0.05). Our findings support a cooperative interaction between metabolic and ER stresses, favoring inflammation by triggering TNF-α production via the ROS/CHOP/HIF-1α and MAPK/NF-κB dependent mechanisms. This study also shows the therapeutic potential of ROS scavengers/anti-oxidants in inflammatory conditions involving metabolic/ER stresses.

The gastrointestinal tract is colonized by trillions of different microorganisms, named the gut microbiota, which is key to degrade undigested food such as dietary fibers. The fermentation of these food components leads to the production of short-chain fatty acids (SCFA) acetate, propionate, and butyrate, which exploit several beneficial roles for the host’s health. Their production and absorption happen in different ways in the human intestine and depend on the type of dietary fiber reaching the gut and the microorganisms involved in the fermentation. The supplementation of SCFAs, mostly butyrate, in treating gastrointestinal, metabolic, cardiovascular, and gut-brain-related diseases has been reported in the medical literature. This review aims to give an overview of the production and absorption dynamics of acetate, propionate, and butyrate in the human gut, with a final focus on the role played by these SCFAs on gastrointestinal and metabolic health and the present therapeutic implications.

Salidroside, a valuable phenylethanoid glycoside, is obtained from plants belonging to the Rhodiola genus, known for its diverse biological properties. At present, salidroside is still far from large-scale industrial production due to the lower titer and higher process cost. In this study, we constructed a biosynthetic pathway from L-tyrosine to salidroside in Saccharomyces cerevisiae. To increase sali-droside production, we for the first time constructed an in vivo UDP-glucose regeneration system that sucrose synthase GmSUS worked in conjunction with UDP-glucose transferase RrUGT33 to improve the UDP-glucose availability with inexpensive sucrose as the consumed substrate. Finally, the molar conversion rate of L-tyrosine could reach 95%. To further reduce the cost, co-culture with E. coli that synthesized L-tyrosine de novo resulted in an 81% reduction in the final substrate cost per 1 kg of salidroside compared to the initial cost. The final titer of salidroside obtained 3.8 g/L and was the highest titer achieved at the Shake-Flask-Level in the existing reports. And this marked the first successful synthesis of salidroside in an in situ enhanced UDP-glucose system using sucrose. This accomplishment laid a robust groundwork for further investigations into the synthesis of other notable glycosides and natural compounds.

The architecture, organization and functioning of biocatalytic reaction networks, which are coded in the cell specific genome and which work together in the small space of biological cells, are a fascinating feature of life evolved over more than 3 billion years. The knowledge about the diversity of biocatalytic functions and metabolic pathways sustaining life on our planet is highly important, especially as the currently occurring loss of biodiversity is considered a planetary boundary which is at high risk, and knowledge about the life of current biological organisms should be gained before they become extinct. In addition to the well-known enzymatic reactions involved in biochemical pathways, the enzyme universe offers numerous opportunities for discovering novel functions and pathways. Maintaining thousands of molecules and reactions functioning properly within biological cells, which may be exposed to various kinds of external hazards, environmental stress, enzymatic side reactions or non-enzymatic chemical reactions, is key for keeping cellular life healthy. This review aims at outlining advances in assigning enzyme functions to protein sequences and the discovery of novel biocatalytic functions and pathways.

The modification of GFP-CaaL sensor proteins by geranylgeranyl groups in plants requires an active plastidial mevalonate (MVA)-independent pathway. As a consequence, fosmidomycin, a specific inhibitor of 1-deoxy-D-xylulose (DX)-5 phosphate reductoisomerase/DXR, the second enzyme in this so-called methylerythritol phosphate (MEP) pathway, impedes protein prenylation, which results in GFP-labeling of nuclei instead of the plasma membrane. In tobacco cells, a visual screen of conditions that allowed membrane localization of GFP-CaaL proteins in the presence of fosmidomycin, pinpointed jasmonic acid methyl esther (Me-JA) as a chemical able to overcome the inhibition in a gradual manner. Using Arabidopsis protein prenyltransferase loss-of-function mutant lines expressing GFP-CaaL proteins, we demonstrated that Me-JA induces a modification in protein substrate recognition by protein farnesyltransferase (PFT). Similar to Me-JA, farnesol and MVA also alter the protein substrate specificity of PFT, whereas DX and geranylgeraniol have limited or no effect. Our data indicate that stimulation of the MVA pathway adjusts the protein substrate specificity of PFT, which is corroborated with metabolic cross-talk of the origin of the prenyl group used to modify the protein. To illustrate how activation of the MVA pathway impacting PFT substrate specificity benefits a plant under stress conditions, a model is proposed.

Chondroitin is a glycosaminoglycan that has gained widespread use in nutraceuticals and pharmaceuticals, mainly for treating osteoarthritis. Traditionally, it has been extracted from animal cartilage but recently, biotechnological processes have emerged as a commercial alternative to avoid the risk of viral or prion contamination and offer a vegan-friendly source. Typically, these methods involve producing the chondroitin backbone using pathogenic bacteria and then modifying it enzymatically through the action of sulfotransferases. Despite the challenges of expressing active sulfotransferases in bacteria, the use of eukaryotic microorganisms is still limited to a few works using Pichia pastoris. To create a safer and efficient biotechnological platform, we have constructed a biosynthetic pathway for chondroitin production in S. cerevisiae as a proof-of-concept. Up to 125 mg/L and 200 mg/L of intracellular and extracellular chondroitin were produced, respectively. Furthermore, as genome-scale models are valuable tools for identifying novel targets for metabolic engineering, a stoichiometric model of chondroitin-producing S. cerevisiae has been developed and used in optimization algorithms. Our research has yielded several novel targets, such as uridine diphosphate(UDP)-N-acetylglucosamine pyrophosphorylase (QRI1), glucosamine-6-phosphate acetyltransferase (GNA1) or N-acetylglucosamine-phosphate mutase (PCM1) overexpression that might enhance chondroitin production, which will guide future experimental research to develop more efficient host organisms for the biotechnological production process.

Cells have metabolic flexibility that allows them to adapt to changes in substrate availability. Two highly relevant metabolites are glucose and fatty acids (FA), and hence, glycolysis and fatty acid oxidation (FAO) are key metabolic pathways leading to energy production. Both pathways affect each other, and in the absence of one substrate, metabolic flexibility allows cells to maintain sufficient energy production. Here we show that glucose starvation or sustained pyruvate dehy-drogenase (PDH) activation by dichloroacetate (DCA) induce a large genetic remodeling to pro-pel FAO. The extracellular signal-regulated kinase 5 (ERK5) is a key effector of this multistep metabolic remodeling. First, there is an increase in the lipid transport by expression of low-density lipoprotein receptor-related proteins (LRP), e.g. CD36, LRP1 and others. Second, an increase of the expression of members of the acyl-CoA synthetase long-chain (ACSL) family acti-vates FA. Finally, the expression of the enzymes that catalyze the initial step in each cycle of FAO, i.e. the acyl-CoA dehydrogenases (ACADs), is induced. All of these pathways lead to enhanced cellular FAO. In summary, we show here that different families of enzymes, which are essential to perform FAO, are regulated by the signaling pathway, i.e. MEK5/ERK5, which transduces changes from the environment to genetic adaptations.

The framework proposed by Alison Druin about 20 years ago, which defined the roles children play in technology design, has been widely adopted by the Child-Computer Interaction (CCI) community. While some studies have adopted relevant roles as presented in the framework, others have argued for extending the framework to include newly identified roles. Still, other studies argue that Druin's framework failed to account for roles children may take up as they interact with peers or with tools. Consequently, this systematic literature review examines children’s emerging and changing roles in the codesign of new technologies. Specifically, we answered the research question: What new roles emerge in research as children co-design new technologies? Our effort aims at providing evidence of new roles children have adopted in literature, which may help researchers in the CCI community make more informed decisions about participatory design approaches with children.

Novel cultivation technologies demand the adaptation of existing analytical concepts. Metabolic flux analysis (MFA) requires stable-isotope labeling of biomass-bound protein as the primary information source. Obtaining the required protein in cultivation set-ups where biomass is scarce or inaccessible due to low cell densities and cell immobilization is difficult to date. We developed a non-disruptive analytical concept for 13C-based metabolic flux analysis based on secreted protein as an information carrier for isotope mapping in the protein-bound amino acids. This "metabolic flux probe" (MFP) concept was investigated in different cultivation set-ups with a recombinant, protein-secreting yeast strain. The obtained results grant insight into intracellular protein turnover dynamics. Experiments under metabolic but isotopically nonstationary conditions in continuous glucose-limited chemostats at high dilution rates demonstrated faster incorporation of isotope information from labeled glucose into the recombinant reporter protein than in biomass-bound protein. Our results suggest that the reporter protein was polymerized from intracellular amino acid pools with higher turnover rates than biomass-bound protein. The latter aspect might be vital for 13C-flux analyses under isotopically nonstationary conditions for analyzing fast metabolic dynamics.

Cell free systems are a widely used research tool in systems and synthetic biology and a promising platform for manufacturing of proteins and chemicals. In the past, cell free biology was primarily used to better understand fundamental biochemical processes. Notably, E. coli cell free extracts were used in the 1960s to decipher the sequencing of the genetic code. Since then, the transcription and translation capabilities of cell free systems have been repeatedly optimized to improve energy efficiency and protein yield. Today, cell free systems, in combination with the rise of synthetic biology, have taken on a new role as a promising technology for just in time manufacturing of therapeutically important biologics and high-value small molecules. They have also been implemented in an industrial scale for the production of antibodies and cytokines. In this review, we discuss the evolution of cell free systems, advancements in cell free protein synthesis, and cell free metabolic engineering, and conclude with discussing the importance and feasibility of mathematical modeling in cell free systems.

Ocean big data is the scientific practice of using big data technology in the marine field. Data from satellites, manned spacecraft, space stations, airship, unmanned aerial vehicles, shore-based radar and observation stations, exploration platforms, buoys, underwater gliders, submersibles, and submarine observation networks are seamlessly combined into the ocean’s big data. Increasing numbers of scholars have tried to fully analyze the ocean’s big data. To explore the key research technology knowledge graphs related to ocean big data, articles between 1990 and 2020 were collected from the “Web of Science”. By comparing bibliometric software and using the visualization software Cite-Space, the pivotal literature related to ocean big data, as well as countries, institutions, categories, and keywords, were visualized and recognized. Journal co-citation analysis networks can help determine the national distribution of core journals. Co-citation analysis networks for documents show authors who are influential at key technical levels. Key co-occurrence analysis network keywords can determine research hot spots and research frontiers. The three supporting elements of marine big data research are shown in the co-citation network. These elements are author, institution, and country. By examining the co-occurrence of keywords, the key technology research directions for future marine big data were determined.

Integrating sustainable processes and innovative waste utilization not only addresses environ-mental challenges but also aligns with evaluating energy sustainability and creating the circular waste management. This study presents a comparative analysis of liquid fuel production from waste tires and water hyacinth using two thermochemical methods: co-pyrolysis (direct method) and co-gasification integrated with the Fischer-Tropsch (FT) process (indirect method). The As-pen Plus simulation software version 9 is employed to develop models, determining optimal operating conditions for maximum liquid fuel, and assessing economic viability. Co-pyrolysis simulations reveal an increase in oil products and a decrease in gas products with higher blending weight ratios of waste tires/water hyacinth (W/B) and lower pyrolyser temperatures. Operating at 400°C with a blending weight ratio of 75:25 provided the maximum liquid fuel rate of 6649.22 gal/day. For co-gasification, optimal conditions (W/B = 50:50, T = 800°C, steam to feed ratio (S/F) = 1) result in the highest syngas yield of 115.92 kmol/h. Fischer-Tropsch simulations demonstrate an increase in gasoline and a decrease in diesel with rising reactor temperatures. At 230°C, the maximum liquid fuel rate reaches 8817.15 gal/day. The economic and production yield analysis indicates that the indirect method better than the direct method, providing higher liquid fuel yields and investment worthiness.

The severe respiratory distress syndrome (SRDS) has been a significant clinical issue in modern respiratory medicine. Its role in COVID-19 pandemic is not well defined. Outside-the-hospital SRDS is usually community-acquired septic pneumonia; however, in-hospitals incidences are complicated by co-infections. While SRDS is genetically selected in European and African origins, these are not clear in Middle East, particularly in COVID-19 backgrounds. There is a severe paucity in high quality data on correlations between COVID-19, ARDS, co-infectome, and patient demographics. We have conducted a comprehensive investigation on 298 patients for associations of SRDS, coinfections, and patient demographics on COVID-19 patients’ outcomes. Of these, 9.4% (n=28) had SRDS, and the rest (90.6%) had not. 54% of those with SRDS died while 84% survived; SRDS fatality was highly significant (Chi-square test P-value = 0.00000246). Irrespective of gender, the age of patients was significantly associated with SRDS (72.9 +/-8.9) compared to those without it (56.2 +/-15.1). However, there was no significant difference neither in the age of admitted patients before COVID-19 (58.5 +/-15.3) and during COVID-19 (57.2 +/-15.5) nor in the gender and COVID-19 fatality (Fisher Exact test 2-sided 1.000, 1-sided .546) ruling out that SRDS age-specificity were selected by virus susceptibility. A 100% of SRDS patients without bacterial co-infections survived while only 25% of those with co- infectome did not; this association was highly significant (P value= 0.00041). Co-infections alone without underlying SRDS was also associated with high fatality among patients (P value= 0.00000000076). Almost all COVID-19 patients without co-infectome (99.2%) survived while 28% of those with bacterial co-infection died. The major bacterial pathogens that potentially predisposed to SRDS, were Acinetobacter baumannii, and Escherichia coli either alone or in a mixed infection with Klebsiella pneumoniae were predominant species identified during SRDS attack. Thus, Gram-negative co-infectome potentially induced fatal SRDS aggravating COVID-19 outcome. These findings have significant clinical implications in specific differential diagnosis of SRDS syndromes for subsequent empiric therapy and patient management strategies. Future vertical investigation for similar mechanisms of cytokine-induced SRDS by Gram negative pathogens is imperative since hypervirulent strains are rapidly circulating in the region. The study is limited by a single center study confined to Ha’il hospitals; large scale investigation in major national hospitals would gain more insights.

Leishmania parasites present astonishing adaptative abilities that represent a matter of life or death within disparate environments during the heteroxenous parasite life cycle. From an evolutionary perspective, organisms develop methods of overcoming such challenges. Strategies that extend beyond the genetic diversity have been discussed and include variability between parasite cells during the infections of their hosts. The occurrence of Leishmania subpopulation fluctuations with variable structural genomic contents demonstrates that a single strain might shelter the variability required to overcome inconsistent environments. Such intrastrain variability provides parasites with an extraordinary ability to adapt and thus survive and propagate. However, different perspectives on this evolution have been proposed. Strains or species living in the same environment can cooperate but also compete. These interactions might increase the replication rate of some parasites but cause the loss of more aggressive competitors for others. Adaptive responses to intra- and interspecific competition can evolve as a fixed strategy (replication is adapted to the average genetic complexity of infections) or an optional strategy (replication varies according to the genetic complexity of the current infection). This review highlights the complexity of interspecies and intrastrain interactions among Leishmania parasites as well as the different factors that influence this interplay.

Introduction Urolithiasis, a prevalent urological condition (8-13% globally) exhibits regional variations, influenced by water quality, climate, health factors and diet. Sri Lanka with its tropical climate and dietary patterns is part of the "Stone Belt" of Asia. This study in Northern Sri Lanka examines urinary stone compositions and assesses the prevalence of metabolic disorders among urolithiasis patients. Methods This prospective cross-sectional study, conducted at tertiary urology centre from July 2022 to June 2023, focused on surgically treated urolithiasis patients. Institutional ethical clearance was obtained. Patient details and investigational findings were collected through questionnaires and data extraction forms. Stone analysis utilized Fourier transform infrared spectroscopy and detailed metabolic evaluation of 24 hour urine collection sample is carried out. Results This study followed 153 surgically treated urolithiasis patients, primarily male (64.3%), mean age 48.64. Ureteric colic (48.4%) was common, with kidney stones (45.8%) prevalent; 57.52% had recurrent stones. Diabetes mellitus (DM=23.5%) was the top comorbidity. Calcium oxalate monohydrate (COM) stones (78.4%) were most frequent, followed by uric acid (12.4%). COM predominated in 40-59 age group. No significant gender-stone type association. 86.9% had metabolic abnormalities, notably hypocitraturia (60.1%). 23% had both hypocitraturia and hypomagnesuria. Some metabolic disorders showed gender differences, with a marginal age-metabolic disorders association (p < 0.061). Urine oxalate levels were normal with higher variability in males. Conclusion Middle-aged males with urolithiasis commonly presented with ureteric colic and predominantly had calcium oxalate monohydrate stones. Recurrent stones were common, often accompanied by metabolic abnormalities such as hypocitraturia and hypomagnesuria, with diabetes mellitus as the primary comorbidity.

New setting is introduced to study types of coloring numbers, degree of vertices, degree of hyperedges, co-degree of vertices, co-degree of hyperedges, neutrosophic degree of vertices, neutrosophic degree of hyperedges, neutrosophic co-degree of vertices, neutrosophic co-degree of hyperedges, neutrosophic number of vertices, neutrosophic number of hyperedges in neutrosophic hypergraphs. Different types of procedures including neutrosophic (r, n)−regular hypergraphs and neutrosophic complete r−partite hypergraphs are proposed in this way, some results are obtained. General classes of neutrosophic hypergraphs are used to obtain chromatic number, the representatives of the colors, degree of vertices, degree of hyperedges, co-degree of vertices, co-degree of hyperedges, neutrosophic degree of vertices, neutrosophic degree of hyperedges, neutrosophic co-degree of vertices, neutrosophic co-degree of hyperedges, neutrosophic number of vertices, neutrosophic number of hyperedges in neutrosophic hypergraphs. Using colors to assign to the vertices of neutrosophic hypergraphs and characterizing representatives of the colors are applied in neutrosophic (r, n)−regular hypergraphs and neutrosophic complete r−partite hypergraphs. Some questions and problems are posed concerning ways to do further studies on this topic. Using different ways of study on neutrosophic hypergraphs to get new results about number, degree and co-degree in the way that some number, degree and co-degree get understandable perspective. Neutrosophic (r, n)−regular hypergraphs and neutrosophic complete r−partite hypergraphs are studied to investigate about the notions, coloring, the representatives of the colors, degree of vertices, degree of hyperedges, co-degree of vertices, co-degree of hyperedges, neutrosophic degree of vertices, neutrosophic degree of hyperedges, neutrosophic co-degree of vertices, neutrosophic co-degree of hyperedges, neutrosophic number of vertices, neutrosophic number of hyperedges in neutrosophic (r, n)−regular hypergraphs and neutrosophic complete r−partite hypergraphs. In this way, sets of representatives of colors, degree of vertices, degree of hyperedges, co-degree of vertices, co-degree of hyperedges, neutrosophic degree of vertices, neutrosophic degree of hyperedges, neutrosophic co-degree of vertices, neutrosophic co-degree of hyperedges, neutrosophic number of vertices, neutrosophic number of hyperedges have key points to get new results but in some cases, there are usages of sets and numbers instead of optimal ones. Simultaneously, notions chromatic number, the representatives of the colors, degree of vertices, degree of hyperedges, co-degree of vertices, co-degree of hyperedges, neutrosophic degree of vertices, neutrosophic degree of hyperedges, neutrosophic co-degree of vertices, neutrosophic co-degree of hyperedges, neutrosophic number of vertices, neutrosophic number of hyperedges are applied into neutrosophic hypergraphs, especially, neutrosophic (r, n)−regular hypergraphs and neutrosophic complete r−partite hypergraphs to get sensible results about their structures. Basic familiarities with neutrosophic hypergraphs theory and hypergraph theory are proposed for this article.

At Mae-Moh power plant, Thailand, superheater tubes, which are exposed in fly ash environ-ment, often degrade due to solid particle erosion. To extend the service lifetime of the superheater tubes, the high velocity oxy-fuel (HVOF) thermal spray technique is used to deposit a protective coating on the material, SA213-T22 steel. In this work, the solid particle erosion of the Co-28Cr and WC-12Co coatings was investigated using erodent particle impingement at the angles of 30o and 90o with an average particle size of 60 μm. The erosion behavior of SA213-T22 with and without Co-28Cr and WC-12Co coatings was explained using ductile and brittle erosion modes. The erosion test resulted in the brittle mode for both Co-28Cr and WC-12Co coatings, while SA213-T22 without coating indicated the ductile mode. On the investigation of surface morphology, the Co-28Cr coating showed mostly microcracks in contrast with the WC-12Co coating, fracture, de-bonding and deep cavities were also observed. Erosion resistance of the Co-28Cr coating was significantly higher than the WC-12Co coating, due to high hardness, low porosity and high density of the coating.

The main objective of this paper is to identify the major research areas of ChatGPT through term and keyword co-occurrence network mapping techniques. For conducting the present study, total of 577 publications were retrieved from the Lens database for the network visualization. The findings of the study showed that “chatgpt” occurrence in maximum number of times followed by its related terms such as artificial intelligence, large language model, gpt, study etc. This study will be helpful to library and information science as well as computer or information technology professionals.

(1) Background: Metabolic syndrome is a strong predictor of cardiovascular disease thus the objective of the study was to verify the prevalence of metabolic syndrome in farmers, as well as to verify the association with sociodemographic, work and lifestyle factors. (2) Methods: Cross-sectional, observational study, carried out with 790 individuals. For the diagnosis of metabolic syndrome, the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) and International Diabetes Federation (IDF) criteria were used. Pearson's chi-square test and binary logistic regression were used to verify factors associated with metabolic syndrome (3) Results: The prevalence of MS according to the IDF criteria was 16.3% overall, with 9.7% of women (95% CI: 6.66–16.16) and 6.6% of men (95% CI: 5.17–11.97). According to the NCEP/ATP III criterion, it was 12.3% overall, with 7.5% corresponding to women (95% CI: 6.62 – 13.13) and 4.8% to men (95% CI: 3.5 – 8.70). With regard to the conditions that make up metabolic syndrome, it was found that high density lipoprotein, high blood pressure and high waist circumference were the most prevalent. (4) Conclusions: The prevalence of metabolic syndrome is considerable in the population when compared to other regions, both rural and urban, in Brazil.

The increasing need for effective analytical tools to evaluate beef quality has prompted the development of new procedures to improve the animal sector’s performance. In this study, three beef breeds—Thai native (TN), crossbred Brahman x Thai native (BT), and crossbred Charolais x Brahman (CB)—were compared in terms of their physicochemical and metabolic profiles. The findings demonstrated that TN beef was lighter and tougher than other beef. Beef odor was stronger in BT. In addition, CB beef was the most tender and the highest intramuscular fat content. Twenty-one different metabolites were found overall through NMR and chemometric approaches. High levels of lactate and creatine were found in all species. The primary factors contributing to the difference in OPLS-DA loading plots were acetylcholine, valine, adenine, leucine, and phosphocreatine, β-hydroxypyruvate, ethanol, adenosine diphosphate, creatine, acetylcholine, and lactate. The multivariate analysis indicated that these metabolites in beef cattle breeds could be distinguished using NMR spectroscopy. The results of this study provide valuable information on the quality and meat metabolites in different breeds. This could help in the development of a more accurate assessment of the quality of beef in future research.

In the last decade, different omic technologies have experiences an exponential technological advancement. However, metabolomics has not followed a similarly vertiginous improving improvement and are far from genomics or transcriptomics in terms of throughput, cost and even accuracy. Therefore, genome-scale in-silico methodologies to estimate metabolic activities from genomic data constitute an active field. The solutions available fall into two extremes: those with few assumptions about the relationships among proteins and metabolites, which are easy-to-use but less accurate and those that account for the complex relationships among molecules and proteins defined in the metabolic pathways, which are more accurate but require mathematical skills. Here, we introduce Metabolica, an algorithm that considers the complex functional relationships among all the molecules and proteins involved in the metabolic pathway analyzed but keeping an easy use that do not require of advanced mathematical skills. Metabolica has been implemented in a freely available software R package. The software inputs transcriptomic data and infers the activities of the reactions that produce the different metabolites in the pathway analyzed. An example shows how detected dysregulated metabolites in several cancers are related to patient survival.

Inflammation is known to be risk factors for metabolic diseases. The purpose of this study was to develop a Food-based Index of Dietary Inflammatory Potential (FBDI) and conduct its validation assessment. This study analyzed raw data from Korean Genome and Epidemiology Study 2012–2014 data of 17,771 people. We carried out the correlation analysis between 51 food groups and hs-CRP. The FBDI was developed by multiple regression method with hs-CRP and selected 17 food group. For the validation of FBDI, 7795 people in the 6th Korea National Health and Nutrition Examination Survey (KNHAES) was used. Binary logistic regression analysis was used for risk analysis of metabolic syndrome and FBDI. The FBDI model included that 7 were composed of anti-inflammatory food groups and 3 of inflammatory food groups. The FBDI was calculated by multiplying the intake of food group by β coefficients. KNHAES were included in the validation of FBDI. The risk of metabolic syndrome was found to be 2.152 times higher in the group with the highest FBDI than in the group with the lowest one (95% Cl:1.458–3.178, p for trend = 0.000). This study developed FBDI reflecting food intake for Koreans, which showed a significant relationship with the risk of metabolic syndrome.

Drug functionalization through formation of hydrophilic groups is the norm in phase I metabolism of drugs for modification of drug action. The reactions involved are mainly oxidative catalyzed mostly by CYP isoenzymes. The benzene ring, as phenyl or fused with other rings, is the most common hydrophobic pharmacophoric moiety in drug molecules. On the other hand the alkoxy group (mainly methoxy) bonded to the benzene ring assumes an important and sometimes essential pharmacophoric status in some drug classes. Upon metabolic oxidation, both moieties, i.e. the benzene ring and the alkoxy group, produce hydroxy groups; the products are arenolic in nature. Through a pharmacokinetic effect, the hydroxy group enhances the water solubility and elimination of the metabolite with the consequent termination of drug action. However, through hydrogen bonding, the hydroxy group may modify the pharmacodynamics of the interaction of the metabolite with the site of parent drug action (i.e. the receptor). Accordingly, the expected pharmacologic outcome will be enhancement, retaining, attenuation, or loss of activity of the metabolite relative to the parent drug. All the above issues have been presented and discussed in this review using selected members of different classes of drugs with inferences regarding mechanisms, drug design and drug development.

Abstract: Patient blood samples are invaluable in clinical omics databases, yet current methodologies often fail to fully uncover the molecular mechanisms driving patient pathology. While Genome-scale Metabolic Models (GEMs) show promise in systems medicine by integrating various omics data, having only exometabolomic data remains a limiting factor. To address this gap, we introduce a comprehensive pipeline integrating GEMs with patient plasma metabolome. This pipeline constructs case-specific GEMs using literature-based and patient-specific metabolomic data. Novel computational methods, including adaptive sampling and an in-house developed algorithm for the rational exploration of the sampled space of solutions, enhance integration accuracy while improving computational performance. Model characterization involves task analysis in combination with clustering methods to identify critical cellular functions. The new pipeline was applied to a cohort of trauma patients to investigates shock-induced endotheliopathy using patient plasma metabolome data. By analyzing endothelial cell metabolism comprehensively, the pipeline identified critical substrates and contributed to the development of targeted therapeutic strategies. Our study demonstrates the efficacy of integrating patient plasma metabolome data into computational models to analyze endothelial cell metabolism in disease contexts. This approach offers a deeper understanding of metabolic dysregulations and provides insights into diseases with metabolic components and potential treatments.

The sustainable metabolic engineering (SME) concept was defined by Stalidzans and Dace as an approach for the selection of most sustainable metabolic engineering designs taking the economic, environmental and social components of sustainability into account. In the centre of sustainability calculations is a genome scale metabolic model that provides full balance of all incoming and outgoing metabolic fluxes at steady state. Therefore, sustainability indicators are assigned for each exchange reaction enabling calculation of sustainability features of consumption or production of each metabolite. The further development of the SME concept depends on its implementation at the computational level to acquire applicable results – sustainable production strain designs. This study proposes for the first time a workflow and tools of SME implementation using constraint based stoichiometric modelling, genome scale metabolic models and growth coupled product synthesis approach. For SME application demonstration purposes, a relatively simple engineering task has been carried out. The most sustainable designs have been identified using Escherichia coli as chassis organism, glucose as a substrate and gene deletions as metabolic engineering tool. A growth coupled production design tool has been used to reduce the variability of sustainability. The 10 000 most sustainable designs were producing succinate as the main product with the number of deleted genes ranging from two to ten. A big number of similar designs has been identified due to the combinatorial explosion of different alternative combinations of gene deletion sets that result in interruption of the same metabolic pathways with the same impact on the metabolism.

Iron overnutrition has been implicated with higher risk of developing metabolic and cardiovascular diseases, including metabolic syndrome (MetS), while iron deficiency anemia exacerbates many underlying chronic conditions. Hemoglobin (Hb) concentration in the blood, which reflects a major functional iron (i.e., heme iron) in the body, may serve as a surrogate of iron nutrition status. We conducted sex-specific observational association studies where we carefully titrated the association between Hb deciles and MetS and its components among the Taiwanese Han Chinese (HC) from the Taiwan Biobank and Europeans of White ancestry from the UK Biobank, representing two large ethnicities. Our data show that at higher-than-normal levels of Hb, increasing deciles of Hb concentration were significantly associated with MetS across all sex subgroups in both ethnicities, with the highest deciles resulting in up to three times greater risks than the reference group [Taiwanese HC: OR=3.17 (95% CI, 2.75-3.67) for Hb >16.5 g/dL in men, OR=3.11 (2.78-3.47) for Hb >14.5 g/dL in women; European Whites: OR=1.89 (1.80-1.98) for Hb >16.24 g/dL in men, OR=2.35 (2.24-2.47) for Hb >14.68 g/dL in women]. The association between stronger risks and increasing Hb deciles was similarly observed with all metabolic components except diabetes. Here we found that both the highest Hb decile groups and contrarily the lowest ones, with respect to the reference, were associated with higher odds of diabetes in both ethnic groups [e.g., Taiwanese HC men: OR=1.64 (1.33-2.02) for Hb >16.5 g/dL, OR=1.71 (1.39-2.10) for Hb <13.5 g/dL; European Whites women: OR=1.39 (1.26-1.45) for Hb >14.68 g/dL, OR=1.81 (1.63-2.01) for Hb <12.39 g/dL]. These findings confirm that elevated Hb concentrations, a potential indicator of iron overnutrition, may play a role in the pathophysiology of MetS and metabolic components.

Frailty, an age-related decline in homeostatic reserves, markedly proceeded during the coronavirus disease 2019 pandemic. To continuously assess frailty status, a remote system is urgently required. We aimed to co-design/co-develop an online frailty check (FC) application alongside FC supporters who were facilitators in a pre-existing onsite FC program. The online FC included a screening measurement for sarcopenia and an 11-item questionnaire covering dietary, physical, and social behaviors. Using prototype applications, 55 opinions obtained from 32 FC supporters (median 74.0 years) were categorized and reflected refinement. Regarding the self-efficacy of FC supporters, a significant increase in social positioning was seen after the mock test (P=.031). For FC supporters and participants, the average system usability scale (SUS) score was 70.2±10.3 points, which was “marginally high” for acceptability and “good” for the adjective range. Multiple regression analysis showed that the SUS score was significantly correlated with online-onsite reliability but not online communication, even after adjusting by age, sex, education level, and ICT proficiency (b=0.400, 95% CI: 0.243-1.951, P=.013). Additionally, a significant association between onsite and online FC scores was observed (R=0.670, P=.001). Our online FC application was evaluated to be a valuable tool to practically assess frailty status remotely.

Metastasis is a systemic condition and the major challenge among cancer types, as it can lead to multiorgan vulnerability. Recently, attention has been drawn to cellular senescence, a complex stress response condition, as a factor implicated in metastatic dissemination and outgrowth. Here, we examine the current knowledge of the features required for cells to invade and colonize secondary organs and how senescent cells can contribute to this process. First, we described the role of senescence in placentation, itself an invasive process which has been linked to higher rates of invasive cancers. Second, we describe how senescent cells can contribute to metastatic dissemination and colonization. Third, we discuss several metabolic adaptations by which senescent cells could promote cancer survival along the metastatic journey. In conclusion, we posit that targeting cellular senescence may have a potential therapeutic efficacy to limit metastasis formation.

(1) Background: Metabolic syndrome is associated with cardiovascular complications. Therefore, this study aims to establish cut points for the conicity index based on the components of the metabolic syndrome and to associate it with characteristics sociodemographic, food consumption and occupational factors in Brazilian rural workers; (2) Methods: Cross-sectional study carried out with farmers. The receiver operating characteristic curve was calculated and the cutoff points for the conicity index were identified by the area under the curve, sensitivity and specificity. The variables included in the binary logistic regression analysis were selected by considering p &lt; 0.20 in the bivariate test; (3) Results: The cut points were similar in females according to both criteria, resulting in a single cut-off of 1.269. In males, the cut points showed differences, resulting in 1.272 according to the NCEP-ATP III and 1.252 according to the IDF. We have shown that younger people, those who work more than 40 hours a week and the lowest contribution of culinary ingredients are associated with increased odds of abdominal obesity. While the consumption of the products they sell or produce decreases these chances; (4) Conclusions: The conicity index showed high discriminatory power for the identification of abdominal obesity in rural workers.

Background: Metabolic syndrome (MS) is associated with a greater risk of morbimortality. Ob-jective: To estimate the prevalence of Metabolic Syndrome (MS) and associated factors in patients of a Psychosocial Care Center (CAPS) in the city of Salvador, state of Bahia, Brazil. Method: Cross-sectional study set at CAPS in the city of Salvador-Bahia, between August 2019 and February 2020. MS was evaluated according to the National Cholesterol Education Program's Adult Treatment Panel III. In addition to descriptive statistics, gross and adjusted prevalence ratios were described. Results: MS was found in 100 (35.2%) individuals, 116 (40.9%) were obese and 165 (58.1%) had increased waist circumference. Polypharmacy was identified in 63 (22.3%) patients and 243 (85.9%) used antipsychotics. In the gross evaluation, the female (PR = 1.88; 95% CI: 1.35-2.63) and the use of antidepressants (PR = 1.41; 95%CI: 1.05-1.88) were associated with MS. After logistic re-gression, depression (PR = 1.86; 95%CI: 1.38-2.51), acanthosis (PR = 1.50; 95%CI: 1.18 - 1.90), use of antipsychotics (PR = 1.88; 95%CI: 1.13 - 2.75) and the hypertriglyceremic waist (PR = 3.33; 95%CI: 2.48- 4.46) were associated with MS. Conclusion: The prevalence of MS alerts to multimorbidity among individuals with mental disorders and the need for clinical screening.

Metabolic flexibility is the ability of an organism to adapt its energy source based on nutrient availability and energy requirements. In humans, this ability has been linked to cardio-metabolic health and healthy aging. Genome-scale metabolic models have been employed to simulate metabolic flexibility by computing the Respiratory Quotient (RQ), which is defined as the ratio of carbon dioxide produced to oxygen consumed, and varies between values of 0.7 for pure fat metabolism and 1.0 for pure carbohydrate metabolism. While the nutritional determinants of metabolic flexibility are known, the role of low energy expenditure and sedentary behavior in the development of metabolic inflexibility is less studied. In this study we present a new description of metabolic flexibility in genome-scale metabolic models which accounts for energy expenditure, and we study the interactions between physical activity and nutrition in a set of patient-derived models of skeletal muscle metabolism in older adults. The simulations show that fuel choice is sensitive to ATP consumption rate in all models tested. The ability to adapt fuel utilization to energy demands is an intrinsic property of the metabolic network

Depression and metabolic diseases often coexist having several features in common, e.g., chronic low-grade inflammation and intestinal dysbiosis. Different microbiota interventions have been proposed to be used as a treatment for these disorders. In the paper we review the efficacy of probiotics in depressive disorders, obesity, metabolic syndrome and its liver equivalent based on the published experimental studies, clinical trials and meta-analyses. Probiotics seem to be effective in reducing depressive symptoms when administered in addition to antidepressants. Additionally, probiotics intake may ameliorate some of the clinical components of metabolic diseases. However, standardized methodology regarding probiotics clinical trials has not been established yet. In this narrative review we discuss current knowledge on the recently used methodology with its strengths and limitations and propose criteria that may be implemented to create a new study of the effectiveness of probiotics in depressive disorders comorbid with metabolic abnormalities. We put across our choice on type of study population, probiotics genus, strains, dosages and formulations, intervention period, as well as primary and secondary outcome measures.

The expression "metabolic reprogramming" is more and more encountered in the literature since the mid-1990s. It seems to encompass several notions depending on the author, but the lack of a clear definition allows it to be used as a "catch-all" expression. With the increased interest in metabolism, and more specifically, in the Warburg effect in cancer research, it seems appropriate to discuss this expression and related concepts in detail.

Rare diseases are characterized by a wide diversity of signs and symptoms and vary not only from disease to disease, but also from person to person, and living with a disease leads patients to peculiar experiences and treatments, without limits of time and space, as they extend to various environments and relationships of their lives. The objective of this study is the theoretical interaction between Value Co-creation (VC) and the Stakeholder Theory (ST) with the Shared Decision Making (SDM) health care theory. It is configured as a multiparadigmatic proposal by enabling the analysis of multiple perspectives of different stakeholders in health care. Thus, Co-created Decision Making (CDM) emerges in a logic dominated by service, with emphasis on intangible aspects and the interactivity of the relationships. It goes beyond the clinical office and the doctor-patient relationships, as studied in SDM, extending to all environments and interactions that add value to the patient's treatment. It was concluded that the essence of this new theory proposed here is neither in patient-centered care nor in patient self-care, but in co-created relationships with and between stakeholders in both directions, including non-health care environments that are important to the patient, such as relationships with friends, family, other patients with the same disease, social media, public policies, and the practice of pleasurable activities.

Recently, many authors have been interested to introduce fuzzy implications over t-norms and t-conorms. In this paper, we introduce (S,N) and residuum fuzzy implication for Dubois t-norm and Hamacher's t-norm. Also, new concepts so-called (T,N) and residual fuzzy co-implication in dual Heyting Algebra are investigated. Some examples as well as application are discussed as well.

As one of the important components of underwater propulsion systems, water lubricated bearings are often failure due to mechanical wearing and vibrating, especially under high loads and prolonged friction. In this paper, a dual-network co-crosslinking strategy based on HNBR is proposed, in which the epoxy network connects with the rubber network through Epoxidized Eommia ulmoides gum. The damping, tribological and mechanical properties of the prepared composite are systematically investigated. The results show that this material has excellent friction and vibration damping properties, with a water-lubricated coefficient of friction as low as 0.022 and a wear resistance as high as 3.87 × 10-6mm3/Nm. Preparing HNBR-based composite by dual network co-crosslinked is proved being a feasible solution to improve the reliability and service life of water-lubricated bearings.

The 2022-2023 influenza season in Romania was characterized by high pediatric hospitalization rates, predominated by influenza A subtypes H1N1 and H3N2. Lowered population immunity to influenza after the SARS-CoV-2 pandemic and subsequent stoppage of influenza circulation, particularly in children who had limited pre-pandemic exposures, influenced hospitalization among children immunosuppressed, and patients with concurrent medical conditions who are at increased risk for developing severe forms of influenza. This study focused on the characteristics of influenza issues among paediatric patients, as well as the relationship between different influenza virus types and viral and bacterial coinfections and illness severity in the 2022-2023 season after the SARS-CoV-2 pandemic. We conducted a retrospective clinical analysis on 301 cases of influenza in pediatric inpatients (age ≤ 18 years), hospitalized at the National Institute of Infectious Diseases "Prof. Dr. Matei Balș" IX Pediatric Infectious Diseases Clinical Section between October 2022 and February 2023. The most significant age group was 57.8% representing children between one to four years old and female. The average clinical forms were found in 61.7%, whereas severe versions represented 18.2% of cases. Most of the complications were respiratory (acute interstitial pneumonia, 76.1%), hematological (72.1%), represented by intra-infectious and deficiency anemia, leukopenia, thrombocytopenia), 33.6% were digestive, such as diarrheal disease, liver cytolysis syndrome, and the acute dehydration syndrome associated with electrolyte imbalance (71.4%). Severe complications were associated with a risk of unfavorable evolution: acute respiratory failure and neurological complications (convulsions, encephalitis). No deaths were reported. We noticed that the flu season 2022-2023 was characterized by the association of co-infections (viral, bacterial, fungal and parasitic) more frequent than in previous years (26.2% vs. 16%), which evolved more severely, with prolonged hospitalization and more complications (p<0.05), and time of use of oxygen therapy was statistically significant (p > 0.05); influenza vaccination in this group was zero. In conclusion, coinfections with respiratory viruses increase the severity of the pediatric population's immunity to influenza, especially among young children who are more vulnerable to developing a serious illness. All people above the age of six months should get vaccinated against influenza to prevent the illness and its severe complications.

Recently, the amount of waste generated has been rapidly increasing, there have been difficulties disposing of waste in Korea. As a solution to this, treating waste using a cement kiln has suggested, but the environmental and economic effects have not been specifically studied. In this study, the effects of alternative resources, and reducing the social costs(Installation and Operation) associated with waste treatment facilities were analyzed. Through a co-processing method, a reduction of approximately 53kg of CO2 can be realized during the production of one ton of cement, and cost savings of about 3,815 milion USD. Another effect is an extension of the expiration date for landfills by 7.55 years.

New setting is introduced to study quasi-degree and quasi-co-degree arising from co-neighborhood. quasi-degree and quasi-co-degree is about a vertex which are applied into the setting of neutrosophic graphs. . The structure of set is studied and general results are obtained. Also, some classes of neutrosophic graphs namely path-neutrosophic graphs, cycle-neutrosophic graphs, complete-neutrosophic graphs and star-neutrosophic graphs, complete-bipartite-neutrosophic graphs and complete-multipartite-neutrosophic graphs are investigated in the terms of a vertex which is called either quasi-degree or quasi-co-degree. Neutrosophic number is reused in this way. It’s applied to use the type of neutrosophic number in the way that, three values of a vertex are used and they’ve same share to construct this number to compare with other vertices. Summation of three values of vertex makes one number and applying it to a comparison. This approach facilitates identifying vertices which form quasi-degree and quasi-co-degree. Quasi-degree is a value of a vertex which is maximum amid all values of vertices which are neighbors to a fixed vertex. Quasi-co-degree is a value of an edge which is maximum amid all values of edges which are neighbors to a fixed vertex but corresponded vertex is representative for this notion. Using different values which are related to a vertex inspire us to focus on edge and vertices which are corresponded to a fixed vertex. The notion of neighborhood is used to collect either vertices are titled neighbors or edges are incident to fixed vertex. In both settings, some classes of well-known neutrosophic graphs are studied. Some clarifications for each result and each definitions are provided. Using fixed vertex has key role to have these notions in the form of vertex or edge. The value of an edge has eligibility to call quasi-co-degree but the value of a vertex has eligibility to call quasi-degree. Some results get more frameworks and perspective about these definitions. The way in that, two vertices have connection together, open the way to define neighborhood and co-neighborhood. The maximum values in neighborhood and co-neighborhood introduces quasi-degree and quasi-co-degree, respectively. New name is chosen from degree. Since amid all vertices with different degrees, one vertex is chosen. In other words, one vertex is fixed and its degree turns out quasi-degree where two degrees could be assigned to a vertex. Degree of edges and degree of vertices. The number of edges which are incident to the vertex and the number of vertices which are neighbors to the vertex. Degree and co-degree are the notions which are transformed to use in quasi-style. Two neutrosophic values introduce two neutrosophic vertices separately in each settings. These notions are applied into neutrosophic graphs as individuals but not family of them as drawbacks for these notions. Finding special neutrosophic graphs which are well-known, is an open way to purse this study. Some problems are proposed to pursue this study. Basic familiarities with graph theory and neutrosophic graph theory are proposed for this article.

Potential of co-digestion mixing thickened secondary sludge (TS) from extended aeration wastewater treatment plant and locally available substrates (whey, grease and septage) has been studied using three steps. The first step was a batch test to determine biological methane potential (BMP) of different mixtures of the three co-substrates with TS. The second step has been carried out with lab-scale reactors (20 L) simulating anaerobic continuous stirred tank reactors fed by three mixtures of co-substrates determined according to previous step results. Modelling using ADM1 as a mechanistic model was applied in the third step to help understanding the co-digestion process. According to BMP step, septage used as co-substrate has a negative effect on performance and addition of 10 to 30% grease or 10% whey would lead to a higher production of biogas and with an increase of the methane content. The results from the reactor showed less evi-dence of the positive effects observed with the BMP assay. Protein and lipid fractions of particu-late biodegradable COD are important variables for digester stability and methane production as predicted by modelling. Results of simulations with ADM1 model adapted to co-digestion confirmed that this model is a powerful tool to optimize the process of biogas production.

There is compelling evidence that the nuclear receptor TRβ, a member of the thyroid hormone receptor (TR) family, is a tumor suppressor in thyroid, breast and other solid tumors. Cell-based and animal studies reveal that the liganded TRβ induces apoptosis, reduces an aggressive phenotype, decreases stem cell populations, and slows tumor growth through modulation of a complex interplay of transcriptional networks. TRβ-driven tumor suppressive transcriptomic signatures include repression of known drivers of proliferation such as PI3K/Akt pathway and activation of novel signaling (JAK1/STAT1) and metabolic reprogramming in both thyroid and breast cancers. The presence of TRβ is also correlated with a positive prognosis and response to therapeutics in BRCA+ and triple-negative breast cancers respectively. Ligand activation of TRβ enhances sensitivity to chemotherapeutics. TRβ co-regulators and bromodomain-containing chromatin remodeling proteins are emergent therapeutic targets. This review considers TRβ as a potential biomolecular diagnostic and therapeutic target.

The sense of uncertainty and fragility due to the effects and magnitude of global challenges we are facing (from pandemic circumstances to climate change impacts) requires – much more than in the past – the capacity to generate a visionary and forefront design approach in the young gen-erations aiming at stimulating their reaction attitude rather than providing consolidated tools from past conditions that no longer exist or will rapidly evolve. Within this general framework, we have investigated the effectiveness and impacts of experienced-based methods of learning and innovative educational tools in architecture aimed at shaping expertise in which the environ-mental dimension and the climate-change challenge dialogues with the context's complexity in terms of socio-cultural dynamics, real potentialities and constrains, addressing their transdisci-plinary trajectories. The paper analyses 5 international pioneering teaching experiences that provide the opportunity to understand the outcomes of collaborative and experiential learning processes in which the educational activities leverage a dialogue between diverse communities (academia-citizens-policymakers-practitioners). The study outcomes show that shifting the pedagogical paradigm towards in-field-experience-based models can improve the awareness of future practitioners for climate implications of architectural design, implement their analysis and project skills while triggering processes of knowledge transfer and co-production at community level, and allow them to better address the societal and cultural issues involved within decision making.

The purpose of this study is to explore conceptual approaches in co-production studies and to examine current research trends of the study. The conceptual paper includes research articles related to co-production in public administration field. By thoroughly scrutinizing 32 research works of co-production, this study highlights major loopholes in the field of the study. The contributions of the study are: (1) identifying two common characteristics of co-production, (2) categorising three types of co-producing by end-users, and (3) finding that goals and success of co-production are more beneficial for service providers though its initial approach is citizen-centric approach. We suggest that future studies should be (1) to focus on reasons for co-production failures or success, (2) to discover further hindrances for co-production in service production, (3) to examine influencing factors on service providers as well as institutional impacts on co-production process, and (4) to include practical assessment in co-production study.

Elevated antimony concentrations in aqueous environments from anthropogenic sources is becoming of global concern, here iron oxides are known to strongly adsorb aqueous antimony species with different oxidation states, but the effect of silica on the removal characteristics is not well understood despite being a common component in the environment. In this study, ferrihydrite was synthesized at various Si/Fe molar ratios to investigate its adsorption and co-precipitation behaviors with aqueous antimony anionic species, Sb(III) and Sb(V). The XRD analyses of the precipitates showed two broad diffraction features at approximately 35° and 62° 2θ, which are characteristic of 2-line ferrihydrite, no significant shifts in peak positions in the ferrihydrite regardless of the Si/Fe ratios. The infrared spectra showed a sharp band at ~990 cm⁻¹, corresponding to asymmetric stretching vibrations of Si-O-Fe bonds which increased in intensity with increasing Si/Fe molar ratios. Further, the surface charge on the precipitates became more negative with increasing Si/Fe molar ratios. The adsorption experiments indicated that Sb(V) was preferentially adsorbed at acidic conditions and decreased dramatically with increasing pH while the adsorption rate of Sb(III) ions was independent of pH, however, the presence of silica suppressed the adsorption of both Sb(III) and Sb(V) ions. The results showed that Sb(III) and Sb(V) ions were significantly inhibited by co-precipitation with ferrihydrite even in the presence of silica by isomorphous substitution in the ferrihydrite crystal structure.

Background: Previously, our laboratory has provided evidence that pre-administration of the antioxidant, lipoic acid covalently bonded to various naturally occurring antioxidants, enhanced neuroprotective capacity compared to the administration of lipoic acid on its own. The naturally occurring compound scopoletin, a coumarin derivative, has been shown in various in vitro studies to have both antioxidant and anti-inflammatory mechanism of actions. To date, the effect of scopoletin on neuronal cell death in an in vivo model of ischemia or ischemia-reperfusion has not been investigated. Therefore, the present investigation was designed to determine if scopoletin on its own, or a co-drug consisting of lipoic acid and scopoletin covalent bond, named UPEI-400, would be capable of demonstrating a similar neuroprotective efficacy. Methods: Using a rodent model of stroke in male rats (anesthetized with Inactin®; 100 mg/kg, iv), the middle cerebral artery was permanently occluded for 6 hours (pMCAO), or in separate animals, occluded for 30 min followed by 5.5 hrs of reperfusion (ischemia/reperfusion; I/R). Results: Pre-administration of either scopoletin or UPEI-400 significantly decreased infarct volume in the I/R model (p<0.05), but not in the pMCAO model of stroke. However, UPEI-400 was ~1000 times more potent as compared to scopoletin on its own. The optimal dose of UPEI-400 was then injected during the occlusion and at several time points during reperfusion and significant neuroprotection was observed for up to 150 mins following the start of reperfusion (p<0.05). Conclusion: The data suggest that synthetic combination of scopoletin with lipoic acid (UPEI-400) is a more effective neuroprotectant that either compound on their own. Also, since UPEI-400 was only effective in a model of I/R, it is possible that it may act to enhance neuronal antioxidant capacity and/or upregulate anti-inflammatory pathways to prevent the neuronal cell death.

Poly(vinyl butyral-co-vinyl alcohol-co-vinyl acetate) named further PVBA was investigated as protective coating for copper corrosion in 0.9 % NaCl solution using electrochemical measurements such as, electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization associated with Atomic Force Microscopy (AFM). The PVBA coating on the copper surface (Cu-PVBA) was modeled in methanol containing PVBA. Its inhibitory properties against corrosion was comparatively discussed with those of the copper sample treated in methanol without polymer (Cu-Me) and of untreated sample (standard copper). A protective performance of PVBA coating of 80 % was computed from electrochemical measurements, for copper corrosion in NaCl solution. Also, AFM images designed a specific surface morphology of coated surface with PVBA, clearly highlighting a polymer film adsorbed on the copper surface, which presents certain deterioration after corrosion, but metal surface was not significantly affected compared to those of untreated samples or treated in methanol, in the absence of PVBA.

Previous investigations have illuminated the significant association between the gut microbiome and a broad spectrum of health conditions, including obesity, diabetes, cardiovascular diseases, and psychiatric disorders. Evidence from certain studies suggests that dysbiosis of the gut microbiota may play a role in the etiology of obesity and diabetes. Moreover, it is acknowledged that dietary habits, pharmacological interventions, psychological stress, and other exogenous factors can substantially influence the gut microbial composition. For instance, a diet rich in fiber has been demonstrated to increase the population of beneficial bacteria, whereas the consumption of antibiotics can reduce these advantageous microbial communities. In light of the established correlation between the gut microbiome and various pathologies, strategically altering the gut microbial profile represents an emerging therapeutic approach. This can be accomplished through the administration of probiotics or prebiotics, which aim to refine the gut microbiota and, consequently, mitigate the manifestations of associated diseases. The present manuscript evaluates recent literature on the relationship between gut microbiota and metabolic syndrome published over the past three years and anticipates future directions in this evolving field.

The microglia, displaying diverse phenotypes, play a significant regulatory role in the development, progression, and prognosis of Parkinson's disease. Research has established that glycolytic reprogramming serves as a critical regulator of inflammation initiation in pro-inflammatory macrophages. Furthermore, the modulation of glycolytic reprogramming has the potential to reverse the polarized state of these macrophages. Previous studies have shown that levetistilide A (LA), a phthalide component derived from Angelica sinensis, possesses a range of pharmacological effects, including anti-inflammatory, antioxidant, and neuroprotective properties. In our study, we have examined the impact of LA on inflammatory cytokines and glucose metabolism in microglia induced by lipopolysaccharide (LPS). Furthermore, we explored the effects of LA on the AMPK/mTOR pathway and assessed its neuroprotective potential both in vitro and in vivo. The findings revealed that LA notably diminished the expression of M1 pro-inflammatory factors induced by LPS in microglia, while leaving M2 anti-inflammatory factor expression unaltered. Additionally, it reduced ROS production and suppressed IκB-α phosphorylation levels as well as NF-κB p65 nuclear translocation. Notably, LA exhibited the ability to reverse microglial glucose metabolism reprogramming and modulate the phosphorylation levels of AMPK/mTOR. In vivo experiments further corroborated these findings, demonstrating that LA mitigated the death of TH-positive dopaminergic neurons and reduced microglia activation in the ventral SNpc brain region of the midbrain and the striatum. In summary, LA exhibited neuroprotective benefits by modulating the polarization state of microglia and altering glucose metabolism, highlighting its therapeutic potential.

Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 74% of the world's population still uses plant-based medicines, indicating the ongoing significance of phytochemicals for human health. The study emphasizes the growing body of research examining the role of polyphenols in uncovering their anti-adipogenic and anti-obesity properties. Functions of polyphenols including phenylpropanoids, flavonoids, terpenoids, alkaloids, glycosides, and phenolic acids are distinct due to changes in chemical diversity, and structural characteristics. This review methodically investigates the mechanism of how naturally occurring polyphenols mediate obesity and metabolic function. To this end, hormonal control of hunger has the potential to inhibit pro-obesity enzymes such as pancreatic lipase, the promotion of energy expenditure, and the modulation of adipocytokine production. Specifically, polyphenols affect insulin, a hormone that is essential for regulating blood sugar, and they also play a role in part in a complex web of factors that affect the progression of obesity. This review also explores the immunomodulatory properties of polyphenols, providing insight into their ability to improve immune function. The effects of polyphenols on gut health, improving the number of commensal bacteria, cytokine production suppression, and immune cell mediation, including natural killer cells and macrophages. Taken together, continuous studies are required for prudent and precise mechanisms underlying polyphenols' therapeutic potential in obesity and immunomodulation. In the interim, this review emphasizes the holistic approach to health and promotes the consumption of a wide range of foods and drinks high in polyphenols. This review lays the groundwork for future developments, indicating that the components of polyphenols and their derivatives may provide the answer to urgent worldwide health issues. This compilation of the body of knowledge paves the way for future discoveries in the global treatment of pressing health concerns in obesity and metabolic diseases.

Maternal obesity and gestational diabetes predispose to metabolic disturbances in the next generation. Moreover, the lactation phase also stands as critical for metabolic programming. Nevertheless, the precise mechanisms originating these changes remain unclear. Here we investigate the consequences of maternal diet lipid-rich diet during gestation and lactation, and its impact on metabolism and behavior in the offspring. Two experimental groups of Wistar female rats were used: a control group (NC) that fed a standard diet during gestation and lactation periods and an overnutrition group that fed a high-fat diet (HF, 60% lipid-rich) during the same phases. Offspring were analyzed at postnatal days 21, 28, and 2 months-old (PD21, PD28, PD60) for metabolic profile (weight, fasting glycemia insulin sensitivity, glucose tolerance) and euthanized for brain collection to evaluate by western blot markers of synaptic dynamics, metabolism and inflammation in the hypothalamus, hippocampus and prefrontal cortex. At 2 months-old, behavioral tests for anxiety, stress, cognition, and food habits were conducted. We observe that female offspring born from HF mothers exhibited increased weight gain and decreased glucose tolerance that attenuates with age. In offspring males, weight gain increased at P21 and worsened with age, while glucose tolerance remained unchanged. Offspring of HF mothers exhibited elevated levels of anxiety and stress during behavioral tests, displaying decreased predisposition for curiosity compared to the NC group. In addition, offspring from mothers with HF showed increased food consumption and a lower tendency towards food-related aggression. We conclude that exposure to HF diet during pregnancy and lactation induces dysmetabolism in the offspring accompanied by heightened stress and anxiety. There was sexual dimorphism in metabolic traits but not behavioral phenotypes.

In conclusion, the present study demonstrated the safety of practicing WFM at different TOD. Furthermore, it appears that practicing WF in the evening is safer, as indicated by HRR60s, [Gl], and MBP findings. The utilization of digital biomarkers for monitoring health status during WFM has been shown to be efficient.

This study assessed the associations between host genetic variants and subgingival microbiota in patients with metabolic syndrome (MetS); 103 patients with MetS underwent medical and periodontal examinations and had blood and subgingival plaque samples taken. DNA was extracted and processed (assessing a panel of selected single nucleotide polymorphisms (SNPs) first (hypothesis-testing), and then expanding to a discovery phase. The subgingival plaque microbiome from these patients was profiled. Analysis of associations between host genetic and microbial factors was performed, stratified for periodontal diagnosis. Specific SNPs within RUNX2, CAMTA1 and VDR genes were associated with diversity metrics, with no genome-wide associations detected for periodontitis severity or Mets components at p&lt;10-7. Severe periodontitis was associated with pathogenetic genera and species. Some SNPs correlated with specific bacterial genera, as well as with microbial taxa, notably VDR (rs12717991) with Streptococcus mutans and RUNX2 (rs3749863) with Porphyromonas gingivalis. This is the first study exploring the role of host genotype variation in subgingival microbial dysbiosis in patients with MetS and periodontitis. In conclusion, variation in host genotypes may play a role in the dysregulated immune responses characterizing periodontitis and thus the oral microbiome, suggesting that systemic health-associated host traits further interact with oral health and microbiome.

Modern research achievements support health-promoting effects of natural products and diets rich in polyphenols. Pomegranate (PG) (Punica granatum L.) contain a considerable number of bioactive compounds that exert a broad spectrum of beneficial biological activities, including antimicrobial, antidiabetic, antiobesity, and atheroprotective properties. In this view, the reviewed literature shows that PG intake might reduce insulin resistance, cytokine levels, redox gene expression, blood pressure elevation, vascular injuries and lipoprotein oxidative modifications. Lipid parameters corrective capabilities of PG-ellagitannins are also sufficiently reported to be significantly effective in reducing hyperlipidemia (TC, LDL-C, VLDL-C, and TAGs), plasma HDL-C concentrations, TC/HDL-C and LDL-C/HDL-C ratio. The health benevolent effects of pomegranate consumption appear to be produced through the amelioration of adipose tissue endocrine function, fatty acid utilization, GLUT receptor expression, paraoxonase activity enhancement, PPAR and NFκB modulation. Although the results from animal experiments are encouraging, human findings published in this field are inconsistent and still limited in many points of view. The present review discusses and provides a critical analysis of PG's bioeffects on metabolic syndrome components, type-2 diabetes, obesity, and dyslipidemia, as well as on some cardiovascular-related diseases. A brief overview of the pharmacokinetic properties, safety, and bioavailability of PG-ellagitannins is also included.

The purpose of this study was to examine the impact of fructose consumption during the peri-pubertal period on the later onset of metabolic syndrome in rats. Additionally, the study sought to explore the potential of moderate-intensity physical training as a non-pharmacological approach to mitigate the fructose effects. Male rats, 30 days old, received 10% fructose, and were submitted to concomitant moderate-intensity training until 60 days old. They were divided into 4 groups: sedentary control (SC), sedentary fructose (SF), trained control (TC), and trained fructose (TF). Fructose consumption mainly affected adult animals, resulting in glucose intolerance, increased periepididymal fat, and increased total cholesterol, triglycerides, and insulin levels. Furthermore, these rats exhibited reduced sympathetic nerve activity. The moderate running led to a decrease in periepididymal and retroperitoneal adipose tissue, as well as a reduction in total cholesterol and improved glucose tolerance. Peri-pubertal rats that received combination treatments exhibited lower levels of glucose and insulin during an intraperitoneal glucose tolerance test. The results indicate that 10% fructose supplementation during peripuberty predisposes to metabolic syndrome in adulthood. However, simultaneous moderate-intensity exercise training attenuates these effects and induces positive changes in glycemic homeostasis, lipid metabolism, and autonomic nervous system activity.

The aim of this study was to determine the association of metabolic syndrome (MetS) with kidney cancer and the impact of age and gender on such association. Using Korean National Health Insurance Service database, 9,932,670 subjects who had check-up in 2009 were followed up until the diagnosis of kidney cancer or death or until 2019. Kidney cancer was significantly associated with MetS (HR 1.56). This association was higher in the younger age group (HR: 1.82, 1.5, and 1.37 in 20-39 years, 40-64 years, and ≥65 years, respectively). In terms of the association of kidney cancer with obesity and central obesity, young-aged males showed higher HR for kidney cancer than old-aged ones (HR of obesity: 1.96, 1.52, and 1.25; HR of central obesity: 1.94, 1.53, and 1.3 in 20-39 years, 40-64 years, ≥65 years, respectively), while young-aged females showed lower HR. Kidney cancer was associated with obesity and MetS. The association was higher in younger aged population than in older ones. Regarding gender, MetS, obesity, and central obesity showed higher associations with kidney cancer in younger aged male population, while there was no significant difference in such association according to age in females.

The metabolic syndrome, first introduced by Hermann Haller in 1975, was sometimes also known as insulin resistance syndrome, syndrome X, and plurimetabolic syndrome. In 1989 it was rechristened by Kaplan as "Deadly Quartet" based on a consolidation of central obesity, impaired glucose tolerance, dyslipidemia, and systemic hypertension. Metabolic syndrome is positively associated with a pro-inflammatory and pro-thrombotic state, attributed to increased pro-thrombotic and inflammatory markers activity. Moreover, Metabolic syndrome is frequently associated with increased atherosclerotic cardiovascular disease, impaired glucose tolerance, hyperuricemia, obstructive sleep apnea, and chronic kidney disease. Despite concerted endeavors worldwide, the complexity of the pathophysiology of metabolic syndrome is still not clearly understood. Currently, therapeutic possibilities are confined to individual therapy of hyperglycemia, hypertension, hypertriglyceridemia, hyperuricemia, regular physical exercise, and a restricted diet.

One of the most interesting groups of fatty acid derivates is the group of conjugated fatty acids, from which the most researched are conjugated linoleic acid (CLA) and conjugated linolenic acid (CLNA), which are associated with countless health benefits. Sex pheromone mixture of some insect species, including tobacco horn-worm (Manduca sexta), are typical for the production of uncommon C16 long conjugated fatty acids with two and three conjugated double bonds, as opposed to C18 long CLA and CLNA. In this study, M. sexta desaturases MsexD2 and MsexD3 were expressed in multiple strains of Y. lipolytica with different genotypes. Experiments with supplementation of fatty acid methyl esters into the medium resulted in production of novel fatty acids. Using GCxGC-MS 20 new fatty acids with two or three double bonds were identified. Fatty acids with conjugated or isolated double bonds or combination of both were produced in trace amounts. Results of this study prove that Y. lipolytica is capable of synthesizing C16 conjugated fatty acids. Further genetic optimization of the Y. lipolytica genome and optimization of the fermentation process could lead to increased production of novel fatty acid derivatives with biotechnologically interesting properties.

Genome-scale metabolic models (GEMs) play an important role in the phenotype prediction of microorganisms, and their accuracy can be further improved by integrating other types of biological data such as enzyme concentrations and kinetic coefficients. Enzyme-constrained models (ecModels) have been constructed for several species and were successfully applied to increase the production of commodity chemicals. However, there was still no genome-scale ecModel for the important model organism Bacillus subtilis prior to this study. Here, we integrated enzyme kinetic and proteomic data to construct the first genome-scale ecModel of B. subtilis (ecBSU1) using the ECMpy workflow. We first used ecBSU1 to simulate overflow metabolism and explore the trade-off between biomass yield and enzyme usage efficiency. Then, we simulated the growth rate on eight previously published substrates and found that the simulation results of ecBSU1 were in good agreement with the literature. Finally, we identified target genes that enhance the yield of commodity chemicals using ecBSU1, most of which were consistent with the experimental data, and some of which may be potential novel targets for metabolic engineering. This work demonstrates that the integration of enzymatic constraints is an effective method to improve the performance of GEMs. The ecModel can predict overflow metabolism more precisely and can be used for the identification of target genes to guide the rational design of microbial cell factories.

Genome-scale metabolic model (GEM) is a powerful tool for interpreting and predicting cellular phenotypes under various environmental and genetic perturbations. However, GEM only consid-ers stoichiometric constraints, and the simulated growth and product yield values will show a monotonic linear increase with increasing substrate uptake rate, which deviates from the experi-mentally measured values. Recently, the integration of enzymatic constraints into stoichiometry-based GEMs was proven to be effective in making novel discoveries and predicting new engineer-ing targets. Here we present the first genome-scale enzyme-constrained model (eciCW773) for Corynebacterium glutamicum reconstructed by integrating enzyme kinetic data from various sources using ECMpy workflow based on the high-quality GEM of C. glutamicum (obtained by modifying the iCW773 model). The enzyme-constrained model improved the prediction of pheno-types and simulated overflow metabolism, while also recapitulating the trade-off between biomass yield and enzyme usage efficiency. Finally, we used eciCW773 to identify several gene modifica-tion targets for L-lysine production, most of which agree with previously reported genes. This study shows that incorporating enzyme kinetic information into the GEM enhances the cellular phenotypes prediction of C. glutamicum, which can help identify key enzymes and thus provide reliable guidance for metabolic engineering.

Background: A comparison of the amino acid (AA) plasma profile and markers of intestinal absorption-inflammation between healthy subjects aged 65-70 years and age-matched patients affected by stage 3b-4 chronic kidney disease (CKD3b-4) was performed. Methods: eleven healthy volunteers were compared with 12 CKD3b-4 patients at their first outpatient control (T0) and after 12-months (T12). Adherence to a low protein diet (LPD, 0.6±0.1 g/kg/day) was assessed by Urea Nitrogen Appearance. The following parameters were assessed: renal function, nutritional parameters, bioelectrical impedance analysis, plasma levels of 20 total aminoacids (TAAs), both essential (EAAs) including branched-chain amino acids (BCAAs) and non-essential (NEAAs). Zonulin and faecal Calprotectin markers were used to evaluate intestinal permeability/inflammation. Results: Four patients dropped out of the study; in the remaining 8 residual kidney function (RKF) remained stable, their LPD adherence had risen to 0.89g/kg/day, anaemia had worsened and extracellular body fluid had increased. In comparison to healthy subjects, TAA levels of histidine, arginine, asparagine, threonine, glycine, and glutamine had all increased. No variation in BCAAs was observed. A significant increase was detected in faecal calprotectin and zonulin levels in CKD patients as the disease progressed. Conclusions: This study confirms the finding in aged patients of an alteration in levels of several AAs secondary to uraemia. Intestinal markers provide confirmation of a relevant alteration to the intestinal function in CKD patients.

Flaxseed (Linum usitatissinum L.) oil is an important source of α-linolenic (C18:3 ω-3), this polyunsaturated fatty acid is well known for its nutritional role in human and animal diet. Understanding storage lipid biosynthesis in developing flaxseed embryos can lead to an increase in seed yield. While a tremendous amount of work has been done on different plant species to highlight their metabolism during embryos development, flaxseed metabolic flux analysis is still lacking. In this context, we have developed an in vitro cultured developing embryos of flaxseed and determined net fluxes by performing three complementary parallel labeling experiments with 13C-labeled glucose and glutamine. Metabolic fluxes were estimated by computer- aided modeling of the central metabolic network including 11 cofactors of 118 reactions of the central metabolism, 12 pseudo fluxes. A focus on lipid storage biosynthesis and the associated pathways was done in comparison with rapeseed, arabidopsis, maize and sunflower embryos. In our conditions, glucose was the main source of carbone of flaxseed embryos, leading to the conversion of phosphoenolpyruvate to pyruvate. The oxidative pentose phosphate pathway (OPPP) was identified as the producer of NADPH for fatty acid biosynthesis. Overall, the use of 13C-metabolic flux analysis provided new insight into flaxseed embryos metabolic processes involved in storage lipids biosynthesis. The elucidation of the metabolic network of this important crop plant reinforces the relevance of the application of this technique to the analysis of complex plant metabolic systems.

Introduction and objectives: a close association between metabolic syndrome among subjects with erectile dysfunction has been addressed, since mechanisms underlying metabolic syndrome compromise the blood flow to the penis in numerous ways. This study aims to analyze the relationship between erectile dysfunction and metabolic syndrome in a group of Mexican patients, to study the influence of other morbidity factors on erectile dysfunction, and to define the specific metabolic syndrome components most associated with erectile dysfunction severity. Methods: a descriptive and cross-sectional study was completed in a group of 86 adult Mexican patients with previous diagnosis of erectile dysfunction. Participants were classified as with or without metabolic syndrome. Erectile dysfunction severity, alcohol or tobacco consumption, and depressive behavior were identified through validated questionnaires and compared between both groups, as well as anthropometric, biochemical, and clinical parameters. Results: anthropometric measures, laboratory values, clinical characteristics and the Beck Depression Inventory score were significantly different among both groups. Additionally, more patients affected by severe and moderate erectile dysfunction were identified in the group with metabolic syndrome. Among the metabolic syndrome components, HbA1c >5.7% and fasting glucose >110 mg/dl were significantly associated to the development of erectile dysfunction (p = 0.004 and 0.04, respectively). Conclusions: metabolic syndrome components aggravate erectile dysfunction, particularly the lack of glycemic control manifested by Hb1Ac >5.7% and/or fasting glucose >110 mg/dL. The inclusion of fasting glucose and HbA1c as a complementary biochemical screening among patients with erectile dysfunction should be assessed.

Insulin resistance is a prominent pathophysiologic syndrome in a plethora of metabolic disorders including obesity, prediabetes, type 2 Diabetes Mellitus (Ten et al., 2007), impaired glucose tolerance, dyslipidemia, polycystic ovary syndrome and hypercoagulability (Smith & LeRoith, 2004). It is strongly associated with obstructive sleep apnea, hypoventilation syndrome, pancreatitis, nonalcoholic fatty liver disease, steatohepatitis, cirrhosis, gall bladder disease, multiple cancers (breasts, uterus, cervix prostate, kidney, colon, esophagus, pancreas and liver), stroke, cataracts, coronary heart disease, and hypertension. It is also associated with causation of abnormal menses, infertility, polycystic ovary syndrome, osteoarthritis, phlebitis and other venous diseases. Insulin resistance is thought to be caused by intrinsic and extrinsic factors that contribute to its development. Once present, insulin resistance affects the metabolism, behavior, physical appearance and has lasting effects. This paper will review the latest evidence in development of insulin resistance, its pathogenesis and manifestation and its relation to other conditions. The final aim is to raise awareness of its role on diet, metabolic, genetics and microbiome.

New setting is introduced to study co-neighborhood, neutrosophic t-neighborhood, neutrosophic quasi-vertex set, neutrosophic quasi-order, neutrosophic neighborhood, neutrosophic co-t-neighborhood, neutrosophic quasi-edge set, neutrosophic quasi-size, Neutrosophic number, neutrosophic co-neighborhood, co-neutrosophic number, quasi-number and quasi-co-number. Some classes of neutrosophic graphs are investigated.

Type 2 Diabetes Mellitus (T2DM) is one of the most common metabolic disorders, with a major involvement of oxidative stress in its onset and progression. Pioglitazone (Pio) is an antidiabetic drug which primarily works by reducing insulin resistance while Curcumin (Cur) is powerful antioxidant with o important hypoglycemic effect, also. The both drugs are associated with several drawbacks, such as reduced bioavailability, a short half-life time (Pio) as well as instability and poor water solubility (Cur), which limit their therapeutic use. In order to overcome these disadvantages, a new co-delivery (Pio, Cur) nanosystem based chitosan (CS) (CS-Pio-Cur NPs), was developed, and characterized in reference with simple nanosystems (CS-Pio NPs, CS-Cur NPs). The developed CS-based NPs (CS-Pio-Cur NPs, CS-Pio NPs, CS-Cur NPs) were physico-chemical characterized in terms of particle size (PS), entrapment efficiency (EF%) and loading capacity (LC%). The CS-Pio-Cur NPs proved increased or similar values of EE (88.95% ± 7.79 for Cur; 94.83% ± 9.89 for Pio) and LC% (24.25 % ± 1.62 for Cur; 3.5% ± 0.98 for Pio), in reference with simple nanosystems, CS-Cur NPs (EE = 82.46% ± 1.74; LC = 20.34% ± 0.94) and CS-Pio NPs) (EE = 96.31% ± 0.68; LC = 4.11% ± 0.47), respectively. The identification of APIs (Cur, Pio) loaded into CS matrix was performed using FR-IR spectroscopy and for simultaneously quantification of APIs (Cur, Pio) released from CS-Pio-Cur NPs, a HLPC method was developed and validated. Based on release study performed in different simulated fluids (SGF, SIF, SCF) it can be appreciated that developed CS-APIs NPs have favorable pharmacokinetic profile with good release in gastrointestinal tract.

The COVID-19 pandemic and tuberculosis have epidemiological similarities, being transmitted airborne, favored by direct contact, crowded environments and vulnerable biological status. We performed a retrospective study of 45 cases of pulmonary tuberculosis associated with COVID-19 (TB+COV+) compared to 45 cases with tuberculous monoinfection (TB+COV-), hospitalized during 2021-2022. The demographic characteristics were similar in the two groups, predominating men, a median age of 51 years, living in rural areas, medium level of education and smoking. Common symptoms of the two groups were cough, weight loss, profuse sweating, loss of appetite and hemoptysis, while fever, headache, myo-arthralgias and digestive symptoms characterized the TB+COV+ forms. The scores of radiological lesions in the TB+COV+ compared to TB+COV- group were significantly higher and persistent, revealing more frequent bilateral extensive lung lesions. There were no significant differences in the biological parameters between the two groups. Mortality was 2.2%, regardless of the association of COVID-19. The frequency of infections with Clostridioides difficile was higher in TB+COV+ cases. In conclusion, the co-infection of COVID-19 had an impact on the clinical and biological expression of tuberculosis diagnosed in a pandemic context.

The amalgamation of mineral and targeted bacterial preparations represents a new generation of agricultural technology. Inoculation with combined preparations of microorganisms is more effective than inoculation with a single microorganism in stimulating plant growth by providing a more balanced diet for various crops. In this work, the effect of inoculation of 20 consortium variants on the yield indicators of three crops (wheat, buckwheat, corn) and the soil microbiome in the open field was investigated. The soil microbiome was defined by 16S rRNA sequences through NGS. Species richness of the soil microbial community (alpha diversity) was similar for all studied samples. Beta-diversity analysis revealed that the microbial diversity of three soil samples (C.bw, F.bw and Soil.bw) differed significantly from all others. At the phylum level, the number of Acidobacteriota and Firmicutes in these samples was increased. For the combination “Consortium C (Rothia endophytic GMG9 and Azotobacter chroococcum GMG39) - buckwheat”, a systemic positive improvement in all growth and yield indicators was observed. The soil of the site where buckwheat grew, inoculated by Consortium C, contained significantly more available phosphorus than all other soil samples. Such results can be explained both by the direct action of a consortium of phosphate-immobilizing and nitrogen-fixing bacteria and to acidification of the medium due to an increase in phylum Acidobacteriota bacteria in the soil.

This paper presents a novel cheminformatics approach for the design and synthesis of hydroxyapatite/collagen nanocomposites, which have potential biomedical applications in tissue engineering, drug delivery, orthopedic and dental implants. The nanocomposites are synthesized by the co-precipitation method with different ratios of hydroxyapatite and collagen, and their mechanical, biological, and degradation properties are analyzed using various experimental and computational techniques, such as attenuated total reflection Fourier-transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, scanning electron microscopy with energy-dispersive X-ray spectroscopy, and molecular simulation. The antimicrobial activity of the nanocomposites is evaluated in vitro against several bacterial and fungal strains, demonstrating their medical potential. Additionally, in silico analyses are performed to predict the absorption, distribution, metabolism, and excretion properties and the bioavailability of the collagen samples. This work opens new avenues for the development of novel biomaterials using cheminformatics tools and methods, which can facilitate the optimization of the design and synthesis parameters, as well as the prediction of the biological outcomes. Future research directions include the investigation of the biocompatibility and bioactivity of the nanocomposites in vivo, as well as the exploration of other applications and functionalities of these nanocomposites.

Recently, there has been a lot of interest in the phenolics of pomegranate peels because of their health-promoting effects. The incorporation of encapsulated phenolic extracts in functional foods, beverages, and dietary supplements can enhance their nutritional and health benefits. This paper aims to provide an overview of the encapsulation of pomegranate peel phenolic extract by co-crystallization, focusing on the properties of the encapsulated extract. Pomegranate peel extract encapsulated in sucrose by co-crystallization at conditions determined in our previous work is characterized by evaluating its properties; moisture content, bulk density, solubility, hygroscopicity, color, degree of encapsulation by thermograms, crystallinity by X-ray scattering, microstructure by scanning electron microscope, and storage stability in terms of total phenolic content and antioxidant activity. The co-crystallized powder had a low moisture content (0.59%) and hygroscopicity (0.011%) and a high bulk density (0.803 g/cm3) and solubility (61 s). Its total phenolic content decreased by only 0.56% after storage at 60oC for 45 days, whereas its antioxidant activity was maintained at levels higher than 84%. The differential scanning calorimetry and the X-ray scattering techniques proved the successful encapsulation in the sucrose matrix and the fact that the extract remained liquid inside the porosity of the sucrose crystals.

This paper presents a bibliometric analysis of highly cited papers published in the journal Sustainability between 2009 and 2023. The aim is to identify influential countries, authors, and papers, as well as patterns in authorship and citation trends. The analysis focuses on frequently cited sources, the most cited research papers and references within the journal, and trends in author keywords. The analysis shows that Sustainability is a leading publication in sustainability research, with an annual growth rate of 53.57%. The selected papers, published between 2013 and 2022, have an average age of 2.11 years and an average of 88.12 citations each. The study highlights the most influential countries in sustainability research published in Sustainability, with China leading, followed by the United States and Germany. The most prolific authors are from China, Spain, and Italy. Interdisciplinary collaboration is essential to address complex sustainability challenges, as shown in the papers published in Sustainability. The study emphasizes the importance of staying informed about emerging trends and research directions in the field of sustainability published in this journal Sustainability. It underscores the significance of fostering international collaborations and partnerships to address complex sustainability challenges facing our world today, as evidenced by the papers published in Sustainability. Overall, this bibliometric analysis provides valuable insights into the current state of sustainability research published in Sustainability and its implications for policy and practice. It highlights key areas for future research and underscores the need for interdisciplinary collaboration to address complex sustainability challenges, as demonstrated by the papers published in Sustainability. These findings have important implications for policymakers, researchers, and practitioners interested in promoting sustainable development in the field of sustainability., as published in Sustainability.

Introduction: Increasing cannabis legalization raises concerns that tobacco use, frequently used with cannabis, will also increase. This study investigated the association between legal status of cannabis in place of residence and prevalence of cannabis and tobacco co-use, simultaneous use, and mixing by comparing the prevalence among adults in Canada (prior to cannabis legalization) vs. adults in US states that had legalized recreational cannabis vs. US states that had not as of September 2018. Methods: Data were drawn from the 2018 International Cannabis Policy Study, conducted with respondents aged 16-65 in Canada and the US recruited from non-probability consumer panels. Differences in the prevalence of co-use, simultaneous use, and mixing between tobacco and different cannabis products were examined using logistic regression models by legal status of place of residence among past 12-month cannabis consumers (N=6744). Results: Co-use and simultaneous use in the past 12 months were most common among respondents in US legal states. Among cannabis consumers, co-use and simultaneous use were less common in US legal states, while mixing was less frequent in US states with both legal and illegal cannabis compared to Canada. Use of edibles was associated with lower odds of all three outcomes, while smoking dried herb or hash was associated with higher odds. Conclusions: The proportion of cannabis consumers who used tobacco was lower in legal jurisdictions despite higher prevalence of cannabis use. Edible use was inversely associated with co-use suggesting that edible use does not appear to be associated with increased tobacco use.

As a typical form of value co-creation, crowdsourcing has been increasingly applied by firms to generate business value. By engaging a crowd, a platform, and other stakeholders, a crowdsourcer can foster the co-creation of a portfolio of value for diverse stakeholders. In analyzing the value co-creation in crowdsourcing, we propose a framework by combining the theories and frameworks in value co-creation and crowdsourcing. The framework examines the key stakeholders, joint purpose, engaged value co-creation processes, contributions, bidirectional relationships of the engagement, and perceived value, exhibiting a holistic view of the value co-creation in a crowdsourcing project. Results of the analysis reveal the business performance of the crowdsourcing project and identify areas of improvement regarding business sustainability. This is a major theoretical contribution of this study. The research design applied a case study approach to empirically investigate a crowdsourcing project. Both the theoretical and practical implications are discussed.

This pot-based study investigated the influence of co-composted wood-derived biochar on lettuce growth performance under salinity and drought stress conditions. Biochar of two particle sizes; > 2 mm and < 1 mm were co-composted with the mixture (1:1 ratio of dry weight) of cow and poultry manures. Co-composted biochars were applied at 5% and 7% rates in soil. Control treatments included the amendment of mixture of biochar with manure in soil. Pots were subjected to slight drought (48-55% water filled pore space (WFPS) of soil) and non-drought conditions (60% WFPS) and under 0 and 1.3 dS m-1 salinity. Results revealed that plants growth performance was significantly better under treatments of co-composted biochar and no salt stress conditions, than when mixture of biochar and manure was applied to soil as non-composted fertilizer. Under no stress condition, small particle-sized co-composted biochar increased root biomass by 786.2% than the large particle-sized co-composted biochar at same application rate. As compared to large-sized co-composted biochar, small sized co-composted biochar at high application rates increased root biomass by 167 – 245% but not leaf biomass under both stress conditions. Small particle-sized co-composted biochar amendment also increased the phosphorus use efficiency (PUE) of lettuce leaves than large particle-sized co-composted biochar under no stress condition. The amendment of small-sized co-composted biochar also increased significantly the concentration of Olsen phosphorus in soil than the amendment of large-particle-sized co-composted biochar. In conclusion, amendment of small particle-sized co-composted biochar has the potential of attenuating salinity and drought stress in lettuce and promoting P cycling in soil.

Applications in high-performance computing (HPC) may not use all available computational resources, leaving some of them underutilized. By co-scheduling, i.e. running more than one application on the same computational node, it is possible to improve resource utilization and overall throughput. Some applications may have conflicting requirements on resources and co-scheduling may cause performance degradation, so it is important to take it into account in scheduling decisions. In this paper, we formalized co-scheduling problem and proposed multiple scheduling strategies to solve it: an optimal strategy, an online strategy and heuristic strategies. These strategies vary in terms of the optimality of the solution they produce and a priori information about the system they require. We showed theoretically that the online strategy provides schedules with a competitive ratio that has a constant upper limit. This allowed us to solve the co-scheduling problem using heuristic strategies that approximate this online strategy. Numerical simulations showed how heuristic strategies compare to the optimal strategy for different input systems. We proposed a method for measuring input parameters of the model in practice and evaluated this method on HPC benchmark applications. We showed high accuracy of measurement method, which allows to apply proposed scheduling strategies in scheduler implementation.

The social distancing as a response to COVID 19 pandemic has led to the exceptional reductions of daily routine people activities and vehicle uses mainly in city. This same situation was also experienced by several busy, large, and populous cities in Southeast Asia (SA) countries. Correspondingly, this study aimed to test the hypothesis that the social distancing implementation period has increased the air quality in the term of carbon monoxide (CO) emission reduction as drawn from Jakarta city as an example of the one of populated cities in SA region. The CO was measured in parts per billions (ppb) and monitored on the daily basis employing remote sensor platform. The monitor periods were started from January, February, March, and April 2020 with 10 measurement days for each month. The social distancing was implemented from mid of March to the recent April. The CO measurement data were statistically tested to justify the significant effects of social distancing on the CO levels. Based on the CO data analysis, the order of CO mean by months is February > January > March > April. The CO levels for January, February, March, and April were 87.46 ppb (95%CI: 83.54-91.37), 88.20 ppb (95%CI: 81.65-94.74), 86.38 (95%CI: 81.06-91.69), and 78.68 (95%CI: 74.03-83.32) respectively. This study also find significant difference (p<0.05) of CO levels especially in April when social distancing has been implemented. Hence, these findings illustrate the potential air pollutant reduction gained from implementing social distancing as can be seen in April.

Degussa P25 is a benchmark form of TiO₂ used worldwide in photocatalysis studies. Currently no such benchmark exists for co-catalysts, which are essential for many photocatalytic reactions. Here, we present the preparation of Pt nanocluster co-catalysts on TiO₂ using an unmodified commercial source and equipment that is commonly available. Transmission electron microscopy reveals that the procedure produces TiO₂ decorated with Pt atom and nanoclusters (1-5 atoms). Optical reflectance and X-ray diffraction measurements show that the procedure does not affect the TiO₂ polymorph or UV-Vis absorbance. Gas phase photocatalytic splitting of heavy water (D₂O) shows that the Pt nanocluster decorated TiO₂ outperforms Pt nanoparticle (produced by photodeposition) decorated TiO₂ in D₂ production. Pt nanoclusters, produced directly from a commercial source, with high co-catalyst activity are prime candidates to be used in benchmark photocatalytic reactions.

In order to understand the effect of Pb-CuI co-doping on the thermoelectric performance of Bi₂Te₃, n-type Bi₂Te₃ co-doped with x at% CuI and 1/2x at% Pb (x = 0, 0.01, 0.03, 0.05, 0.07, and 0.10) were prepared via high temperature solid state reaction and consolidated using spark plasma sintering. Electron and thermal transport properties, i.e., electrical conductivity, carrier concentration, Hall mobility, Seebeck coefficient, and thermal conductivity, of CuI-Pb co-doped Bi₂Te₃ were measured in the temperature range from 300 K to 523 K and compared to corresponding x% of CuI-doped Bi₂Te₃ and undoped Bi₂Te₃. The addition of a small amount of Pb significantly decreased the carrier concentration, which could be attributed to the holes from Pb atoms, thus the CuI-Pb co-doped samples show a lower electrical conductivity and a higher Seebeck coefficient compared to CuI-doped samples with similar x values. The incorporation of Pb into CuI-doped Bi₂Te₃ rarely changed the power factor because of the trade-off relationship between the electrical conductivity and the Seebeck coefficient. The total thermal conductivity(κ_tot) of co-doped samples (κ_tot ~1.4 W/m∙K at 300 K) is slightly lower than that of 1% CuI-doped Bi₂Te₃ (κ_tot~1.5 W/m∙K at 300 K) and undoped Bi₂Te₃ (κ_tot ~1.6 W/m∙K at 300 K) due to the alloy scattering. The 1% CuI-Pb co-doped Bi₂Te₃ sample shows the highest ZT value of 0.96 at 370 K. All data on electrical and thermal transport properties suggest that the thermoelectric properties of Bi₂Te₃ and its operating temperature can be controlled by co-doping.

Cancer cells are adept at reprogramming energy metabolism and the precise manifestation of this metabolic reprogramming exhibits heterogeneity across individuals (and from cell to cell). In this study, we analyzed the metabolic differences between interpersonal heterogeneous cancer phenotypes. We used divergence analysis on gene expression data of 1156 breast normal and tumor samples from The Cancer Genome Atlas (TCGA) and integrated this information with a genome-scale reconstruction of human metabolism to generate personalized, context-specific metabolic networks. Using this approach, we classified the samples into four distinct groups based on their metabolic profiles. Enrichment analysis of the subsystems indicated that amino acid metabolism, fatty acid oxidation, citric acid cycle, androgen and estrogen metabolism and ROS detoxification distinguished these four groups. Additionally, we developed a workflow to identify potential drugs that can selectively target genes associated with the reactions of interest. MG-132 (a proteasome inhibitor) and OSU-03012 (a celecoxib derivative) were the top-ranking drugs identified from our analysis and known to have anti-tumor activity. Our approach has the potential to provide mechanistic insights into cancer-specific metabolic dependencies, ultimately enabling the identification of potential drug targets for each patient independently, contributing to a rational personalized medicine approach.

Infection with human immunodeficiency virus (HIV) and induced acquired immune deficiency syndrome (AIDS) represent one of the greatest health burdens worldwide. The complex pathophysiological pathways that link highly active antiretroviral therapy (HAART) and HIV infection per se with dyslipidemia make the management of lipid disorders and the subsequent increase in cardiovascular risk essential for the treatment of people living with HIV (PLHIV). Amongst the HAART regimens, darunavir and atazanavir in terms of protease inhibitors, tenofovir disoproxil fumarate, nevirapine or rilpivirine in terms of nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors respectively, and especially integrase inhibitors, have demonstrated the most favorable lipid profile emerging as sustainable options in HAART substitution. To this day, statins remain the cornerstone pharmacotherapy for dyslipidemia in PLHIV, although important drug-drug interactions with different HAART agents should be taken into account upon treatment initiation. For those intolerant or not meeting therapeutic goals, the addition of ezetimibe, PCSK9, bempedoic acid, fibrates or fish oils should also be considered. This review summarizes the current literature on the multifactorial etiology and intricate pathophysiology of hyperlipidemia in PLHIV, with an emphasis on the role of different HAART agents, while also providing valuable insights into potential switching strategies and therapeutic options.

Ischemic stroke is one of the leading causes of death and permanent disability in the world. Rapid diagnosis and intervention are crucial for reducing its consequences on individuals and societies. Identifying reliable biomarkers for early detection, prognostics and therapy is a criti-cal imperative for improving the stroke patient treatment. Metabolomics has been shown as a promising tool for biomarker discovery since many of the post-ischemic metabolites can found in the plasma or serum of the patient. In this research, we have performed comparative targeted metabolomic analysis of stroke thrombi, patient serums and healthy control serums in order to determine the alteration in the patients’ metabolome. The most statistically altered metabolites characterized in patient compared to control serums were glutamate and serotonin, followed by several lipid metabolites (phospholipids and triacylglycerols) and glucose. In stroke thrombi compared to patient’s serums, the most significantly altered metabolites were classified as li-pids, with choline-containing phospholipids and sphingomyelins having the highest discrimi-natory score. The results of this study could help in understanding the roles of different meta-bolic changes occurring during thrombosis and cerebral ischemia and possibly suggest new metabolic biomarkers of the ischemic stroke.

Metabolites are at the end of the gene-transcript-protein-metabolism cascade. As such, metabo-lomics is the omic approach that offers the most direct correlation with phenotype. This allows that, where genomics, transcriptomics and proteomics fail to explain a trait, metabolomics might give an answer. Complex phenotypes, which are determined by the influence of multiple small effect alleles, are an example of these situations. Consequently, the interest in metabolomics has increased ex-ponentially in the last years. As a newer discipline, the metabolomics bioinformatics analysis pipe-lines are not as standardized as in the other omic approaches. In this review we synthesized the different steps that need to be carried out to obtain biological insight from the annotated metabolite abundance raw data. These steps were grouped in three different modules: preprocessing, statistical analyses and metabolic pathway enrichment. We included within each one of them the different state-of-the art procedures and tools that can be used depending on the characteristics of the study, providing details about the characteristics of each method has, as well as the issues the reader might encounter. Finally, we introduce genome scale metabolic modeling as a tool for obtaining pseu-do-metabolomic data in situations where its acquisition is difficult, being possible to analyze the resulting data with the modules of the described workflow.

Evidence from large epidemiological studies has shown that obesity may predispose to increased Th2 inflammation and increase the odds of developing asthma. On the other hand, there is growing evidence suggesting that metabolic dysregulation that occurs with obesity, and more specifically hyperglycemia and insulin resistance, may modify immune cell function and in some degree systemic inflammation. Insulin resistance seldom occurs on its own, and in most cases constitutes a clinical component of metabolic syndrome, along with central obesity and dyslipidemia. Despite that, in some cases, hyperinsulinemia associated with insulin resistance has been proven a stronger risk factor than body mass in developing asthma. This finding has been supported by recent experimental studies showing that insulin resistance may contribute to airway remodeling, promotion of airway smooth muscle (ASM) contractility and proliferation, increase of airway hyper-responsiveness and release of pro-inflammatory mediators from adipose tissue. All these effects indicate the potential impact of hyperinsulinemia on airway structure and function, suggesting the presence of a specific asthma phenotype with insulin resistance. Epidemiologic studies have found that individuals with severe and uncontrolled asthma have a higher prevalence of glycemic dysfunction, whereas longitudinal studies have linked glycemic dysfunction to an increased risk of asthma exacerbations. Since the components of metabolic syndrome interact with one another so much, it is challenging to identify each one's specific role in asthma. This is why, over the last decade, additional studies have been conducted to determine whether treatment of type 2 diabetes mellitus affects comorbid asthma as shown by the incidence of asthma, asthma control and asthma-related exacerbations. The purpose of this review is to present the mechanism of action, and existing preclinical and clinical data, regarding the effect of insulin resistance in asthma.

The use of recombinant bovine somatotropin (rbST) leads to an increase, in variable amounts, of milk production in buffalo, but there is a lack of information on the influence of rbST on their metabolism. This study looked at the effects of a single 500 mg dose of rbST on lipid profile, liver and kidney function and physical, chemical and cellular constitution of milk in 14 buffalo over 14 days, from the 100th day of lactation, and compared them with 14 animals in a control group. From the 1st day after rbST, there was a rise in beta hydroxybutyrate (β-HBO), possibly due to the higher dry matter intake or by biotransformation of NEFA into β-HBO. Treatment did not influence blood glucose, non-esterified fatty acids (NEFA), triglycerides, cholesterol, total protein, albumin, AST, GGT, bilirubin, urea or creatinine. In 71.3% of the buffalo there was a gradual increase in milk production with maximal response in the first week that was then followed by a gradual decrease, whilst in 21.4%, the increase in production occurred between 7 and 10 days, and only 7.1% of animals did not respond. On the 3rd, 5th, 7th and 10th days after treatment, an increase was found in milk production between the two groups equal to 1.04, 1.52, 1.42 and 1.06 liters, respectively. In relative terms this means an increase in milk production, respectively, of 15.1%; 21.0%; 19.8 % and 15.1 %. The constitution of the milk showed no difference in the amounts of fat, lactose, total solids or somatic cell count; however, on the 3rd day after rbST, there was a decrease in protein; notably, from the 5th day, protein values show no statistical difference. It can be concluded that the application of rbST in buffalo from the 100th day of lactation is metabolically safe, since the treatment neither caused imbalances in fat metabolism nor overloaded the liver or renal function, and the changes in milk composition were transient and limited to a decrease in milk protein.

In recent years, the emergence of the concept of immunometabolism has shed light on the pivotal role that cellular metabolism plays in both the activation of immune cells and the development of immune programs. The antiviral response, a widely distributed defense mechanism used by infected cells, serves to not only control infections but also to attenuates their deleterious effects. The exploration of the role of metabolism in orchestrating the antiviral response represents a burgeoning area of research, especially considering the escalating incidence of viral outbreaks coupled with the increasing prevalence of metabolic diseases. Here, we present a review of current knowledge regarding immunometabolism and the antiviral response during viral infections. Initially, we delve into the concept of immunometabolism by examining its application in the field of cancer—a domain that has long spearheaded inquiries into this fascinating intersection of disciplines. Subsequently, we explore examples of immune cells whose activation is intricately regulated by metabolic processes. Progressing with a systematic and cellular approach, our aim is to unravel the potential role of metabolism in antiviral defense, placing significant emphasis on the innate and canonical interferon response.

Several factors, such as internal algorithm, sensor technology, and obsolescence might skew outcomes when comparing different gas analysers measurements during CPET. Besides aerosol borne infectious disease are a source of contamination during cardiopulmonary exercise tests (CPET). Thus, the main aim of this study was to determine the agreement degree between the Quark RMR and the Jaeger Oxycon Pro, using an antibacterial filter with the latter. Forty-two participants (19-54 years old) performed two non-consecutive maximal graded exercise tests on a cycle-ergometer on two counterbalance and different days using the Oxycon Pro and the Quark RMR in a randomized order. Differences between devices were tested using a generalized linear model adjusted by Bonferroni, and correlation and agreement was assessed using Pearson’s correlation coefficient (R), intraclass coefficient correlation (ICC), Lin’s concordance correlation coefficient (CCC) and Bland-Altman plots. No significant differences were found between devices in any of metabolic or ventilatory parameters for cardiorespiratory fitness assessment (VO_2max: 3131.3±882.1 vs. 3189.8±894.8, p=0.071, VCO_2max: 3436.3±936.0 vs. 3550.3±1043.2, p=0.071, for Quark RMR and Oxycon Pro, respectively). However, Bland-Altman plots showed a trivial tendency towards Oxycon Pro overestimation relative to Quark RMR as air flow volume increases. Both devices showed strong correlation and high level of agreement during maximal and submaximal exercise intensities (Pearson’s R: 0.974 & 0.977; ICC: 0.985 & 0.987; Lin’s CCC: 0.971 & 0.974, for VO₂ and VCO₂, respectively). Therefore, providing consistency to CPET data comparison between both devices, and insight into whether the use of these metabolic carts could be interchangeable or combined when a single device cannot be used for CPET assessment.

Aim: Evaluation of role of supplementation of omega-3 polyunsaturated fatty acids on endothelial function in patients with metabolic syndrome. Methods: Total of 80 patients with metabolic syndrome were enrolled to two groups. We evaluated endothelial function in subjects before and after three-month treatment with omega-3 polyunsaturated fatty acids in dose 2.4g daily (800mg 3 times a day) vs placebo. Using the Endo-PAT2000 device (Itamar Medical Ltd. Caesarea, Israel), reactive hyperemia index – a parameter of endothelial function and augmentation index– a parameter of arterial stiffness were measured. Plasmatic level of glutation peroxidase, homocysteine, apolipoprotein B and lipoprotein (a) were also evaluated. Results: The average values of reactive hyperemia index before the treatment with n-3PUFA was 1.62 ± 0.42 , whereas 1.96 ± 0.62 at the end of the study (p<0.005). Augmentation index changed from 14.66 ± 19.55 to 9.21 ± 15.64 after the treatment (p=0.003). We also observed statistically significant decrease of apolipopotein B (0.94 ± 0.36 vs 1.13 ± 0.35, p = 0.001) and homocysteine (19.31 ± 5.29 vs. 13.78 ± 3.05, p = 0.001) and increase of the glutathion perxidase plasma levels (41.65 ± 8.90 vs. 45.20 ± 8.01), p=0.001. Conclusion: We have observed significant improvement of the endothelial function in subjects with metabolic syndrome treated with omega-3 polyunsaturated fatty acids in dose 2.4g daily.

The number of published studies on curcuminoids in cancer research, including its lead molecule curcumin and synthetic analogs, has been increasing substantially during the past two decades. Insights on the diversity of inhibitory effects they produced on a multitude of pathways involved in carcinogenesis and tumor progression were provided. As this wealth of data was obtained in a setting of various experimental and clinical data, this review first aimed at presenting a chronology of discoveries and an update on their complex in vivo effects. Secondly, there are many interesting questions linked to their pleiotropic effects. One of them, which is a growing research topic, relates to their ability to modulate metabolic reprogramming. This review will also cover the use of curcuminoids as chemosensitizing molecules, that can be combined with several anticancer drugs for reversing the phenomenon of multidrug resistance. Finally, current investigations in these three complementary research fields raise several important questions that will be put in the prospects for the future research related to the importance of these molecules in cancer research.

The sustainable development goals(SDG) of the UNO would be difficult to achieve without prevention of metabolic diseases and other non-communicable diseases (NCDs). Western diet and lifestyle, which are major risk factors of NCDs, are known to cause oxidative stress and decrease in production of molecular hydrogen in the intestines which leads to a decline in endogenous antioxidant status in the body, leading to increase in systemic inflammation. Many experts consider molecular hydrogen as a potential nutrient, which may be administered as gas in the body. There are gaps in the knowledge about the role molecular hydrogen plays, in the treatment of metabolic diseases and other NCDs This review aims to discuss the role of hydrogen in the pathogenesis and prevention of NCDs. Molecular hydrogen (H2) has been studied extensively as a therapeutic gas, with an estimated 2000 publications to date, exploring its potential therapeutic use in 170 disease models across every organ in the mammalian body. Hydrogen therapy can be administered through several methods, such as H2 inhalation, dissolving H2 gas in water to make hydrogen-rich water (HRW) for oral consumption or topical application, or hydrogen-rich saline. The exact mechanism of action of molecular hydrogen is not known but it is in itself a potential antioxidant that can also inhibit hydroxyl and nitrosyl radicals in the cells and tissues. Hydrogen is known to cause a marked decline in oxidative stress, and inflammation that are crucial in the pathogenesis of NCDs. Hydrogen therapy has been found protective against NCDs, including, metabolic diseases, cardiovascular diseases (CVDs), neurodegenerative diseases, chronic kidney disease, cancer and chronic lung diseases.

Hexokinases (HKs) convert hexose sugars to hexose-6-phosphate, thus trapping them inside cells to meet the synthetic and energetic demands. HKs participate in various standard and altered physiological processes, including cancer, primarily through the reprogramming of cellular metabolism. Four canonical HKs have been identified with different expression patterns across tissues. HKs 1-3 play a role in glucose utilization, whereas HK 4 (glucokinase, GCK) also acts as a glucose sensor. Recently, a novel 5^th HK, hexokinase domain containing 1 (HKDC1), has been identified, which plays a role in whole-body glucose utilization and insulin sensitivity. Beyond the metabolic functions, HKDC1 is differentially expressed in many forms of human cancer. This review focuses on the role of HKs, particularly HKDC1, in metabolic reprogramming and cancer progression.

Ultraviolet (UV) radiation has both harmful and beneficial effects on human health. It can cause skin damage and cancer, but also provides the primary source of vitamin D. Additionally, UV radiation affects energy metabolism in mice with metabolic diseases and has protective effects on hypertension and cardiovascular diseases.Metabolic Syndrome is a collection of metabolic dysfunctions such as dyslipidemia, hypertension, hyperglycemia, abdominal/central obesity, and insulin resistance. Chronic UVR exposure suppressed obesity and type 2 diabetes in high-fat diet-fed mice, while vitamin D supplementation did not replicate these effects. On the other hand, topical application of nitric oxide (NO) donors replicated UV effects on mice, and NO scavengers prevented the positive impact of UV. UVR may prevent the development of obesity and metabolic syndrome through mechanisms that depend on UVR-induced NO, not vitamin D. Exposure to sunshine has a protective impact on blood pressure and cardiovascular disease. Although lower vitamin D concentration is linked to increased hypertension and the incidence of CVD, oral vitamin D supplementation does not decrease blood pressure or the risk of CVD, indicating that vitamin D may not mediate the beneficial effects of sun exposure. Instead, NO plays a crucial role as an endogenous vasodilator, produced by the vascular endothelium. Solar UVA may release nitrogen oxides from skin storage into the bloodstream, lowering blood pressure and cardiovascular mortality.In conclusion, UVR exposure could be a promising non-pharmacological intervention for metabolic syndrome, hypertension, and CVD prevention, and NO may play a crucial role in mediating these effects. Further research is needed to explore the precise mechanisms and identify the optimal doses and exposure times of UVR.

Gout is not only associated with obstructive sleep apnea (OSA), but the intermittent episodes of hypoxia that occur with OSA may also have a role in causing gout. Epidemiological studies have documented a higher incidence and prevalence of gout in individuals diagnosed with OSA than in individuals never diagnosed with OSA. The pathophysiology of OSA’s chronic episodes of hypoxia leading to hyperuricemia and gout involves boththe overproduction and underexcretion of uric acid. Treating OSA may be an additional way to control gout and its life-threatening comorbidities. Clinicians are urged to evaluate their patients with hyperuricemia/gout for OSA as it may lead to alternative ways to control gout with superior outcomes that simply pharmacologic treatment alone.

Cells produce reactive oxygen species (ROS) as by-products of metabolism, which can give rise to a two-sided effect on the body under balanced and imbalanced oxidant homeostasis conditions. Antioxidant supplements exert their beneficial efficacy in the treatment of metabolic diseases only when the oxidant homeostasis is imbalanced with the over-production of ROS. Over-supplementation of antioxidant(s) can also cause an imbalanced oxidant homeostasis to exert detriments to the induction of metabolic diseases. This commentary raises a concern that prior to precise supplementation of antioxidants, an establishment of oxidant homeostasis status is required in avoiding an imbalanced oxidant homeostasis in vivo. In searching for valid oxidant stress makers, 3-Nitrotyrosine seems to fit in with the selection criteria and its quantification can be correlated with the degree of oxidative stress in vivo.

Two putative boar pheromones (Androstenone and Androstenol) were discovered in endangered mouse deer during captive breeding program. This study further examined the molecular characteristics, pheromone synthesis pathway, and the functional role of these pheromones in reproduction of mouse deer. CYP17A1 and CYB5 genes were cloned and expressed in HEK-293, COS-7 cell lines and gonads of mouse deer to investigate CYP17A1 gene’s andien-β-synthase activity towards synthesis of sex pheromones in mouse deer. An enzyme immunoassay was also developed and standardized to measure the fecal androstenone during reproductive cycles of mouse deer. Results showed that mouse deer’s CYP17A1 gene possesses andien-β-synthase activity and could transform pregnenolone into 5,16-androstadien-3β-ol. The expression of CYP17A1 gene upregulated in the testis and ovary, compared to other tissues in mouse deer. Significantly elevated pheromones and estrogens were recorded prior to delivery and postpartum estrus / mating in mouse deer. Further, there were weak correlations between fecal pheromones and estrogens/ androgens in mouse deer during breeding season. The findings suggest that the boar pheromones might play a direct role in the reproductive activities of mouse deer which might be used for breeding of mouse deer elsewhere.

When exposed to a viral infection, the attacked cells promptly set up defence mechanisms. Part of antiviral responses, the innate immune interferon pathway and associated interferon stimulated genes are notably allowing the production of proteins bearing an antiviral activity. Numerous viruses are able to evade the interferon response, highlighting the importance of controlling this pathway to ensure their efficient replication. Several viruses are also known to manipulate the metabolism of infected cells to optimize the availability of amino acids, nucleotides and lipids. They then benefit from a reprogramming of the metabolism that favours glycolysis instead of mitochondrial respiration. Given the increasingly discussed crosstalk between metabolism and innate immunity, we wondered whether this switch from glycolysis to mitochondrial respiration would be beneficial or deleterious for an efficient antiviral response. We used a cell based model of metabolic reprogramming. Interestingly, we showed that increased mitochondrial respiration was associated with an enhanced interferon response following poly:IC stimulation. This suggests that during viral infection, the metabolic reprogramming towards glycolysis is also part of the virus' strategies to inhibit the antiviral response.

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n=55; approximately 800-1000 IU from combined sources) or monitored therapy (n=54; with an option of dose modification). 25(OH)D concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52±2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (&gt;90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p=0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.