Polycyclic aromatic hydrocarbons (PAHs), which consist of low-molecular-weight PAHs (LMW-PAHs) and high-molecular-weight PAHs (HMW-PAHs), form an important class of pollutants. Pyrene and benzo[a]pyrene (BaP) are the main pollutants belonging to HMW-PAHs, and their degradation by microorganisms remains an important strategy for their removal from the environments. Extensive studies have been carried out on the isolation and characterisation of microorganisms that actively degrade LMW-PAHs, and to a certain extent, the HMW-PAH pyrene. However, so far, limited work has been carried out on BaP biodegradation. BaP consists of five fused aromatic rings, which confers this compound a high stability, rendering it less amenable to biodegradation. The current review summarizes the emerging reports on BaP biodegradation. More specifically, work carried out on BaP bacterial degradation and current knowledge gaps that limit our understanding of BaP degradation are highlighted. Moreover, new avenues of research on BaP degradation are proposed, specifically in the context of the development of “omics” approaches

Triple negative breast cancer (TNBC) is the most aggressive breast cancer accounting for around 15% of identified breast cancer cases. TNBC, by lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), is unresponsive to current targeted therapies. Existing treatment relies on chemotherapeutic treatment but, despite an initial response to chemotherapy, the inception of resistance and relapse is unfortunately common. Dasatinib is an approved second-generation inhibitor of multiple tyrosine kinases and literature data strongly support its use in the management of TNBC. However, dasatinib binds to plasma proteins and undergoes extensive metabolism through oxidation and conjugation. To protect dasatinib from fast pharmacokinetic degradation and to prolong its activity, it was encapsulated on poly(styrene-co-maleic acid) (SMA) micelles. The obtained SMA-dasatinib nanoparticles (NPs) were evaluated for their physicochemical properties, in vitro antiproliferative activity in different TNBC cell lines, and in vivo anticancer activity in a syngeneic model of breast cancer. Obtained results showed that SMA-dasatinib is more potent against 4T1 TNBC tumor growth in vivo compared to free drug. This enhanced effect was ascribed to the encapsulation of the drug protecting it from a rapid metabolism. Our finding highlights the often-overlooked value of nanoformulations in protecting its cargo from degradation. Overall, results may provide an alternative therapeutic strategy for TNBC management.

Metabolic changes are an important component of tumor cell progression. Tumor cells adapt to environmental stresses via changes to carbohydrate and lipid metabolism. Autophagy, a physiological process in mammalian cells that digests damaged organelles and misfolded proteins via lysosomal degradation is closely associated with metabolism in mammalian cells acting as a meter of cellular ATP levels. In this review, we discuss the changes in glycolytic and lipid biosynthetic pathways in mammalian cells and their impact on carcinogenesis via the autophagy pathway. Also, we discuss the impact of these metabolic pathways on autophagy in lung cancer.

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.

In recent years, Atherosclerotic Cardiovascular Disease (ACVD), Obesity and Diabetes, have increase exponentially worldwide. In the present work, we evaluate the genoprotective effect of consuming a flavonoids-rich chocolate and the improvement in the biochemical parameters related to the prevention and treatment of cardiovascular risk and metabolic syndrome in young Mexican adults. A randomized, placebo-controlled, double-blind study was undertaken in the Autonomous University of Baja California. The treatments were a daily intake of 2 grams of dark chocolate containing 70% cooca or milk chocolate. Total phenolic compounds and flavonoids were evaluated in both chocolates. Anthropometrical and Biochemical parameters were measured in the 84 participants before and after the study. Buccal epithelial genotoxicity was also evaluated from the beginning to the end of the experiment in the participants. Result suggested that flavonoids of cocoa intake have protective effects against DNA damage, and Biochemical parameters (total cholesterol, triglycerides, and LDL-cholesterol level in blood) and anthropometrical parameters (waist circumference) were also improved after six months of daily intake of 2 grams of dark chocolate with a 70% of cocoa.

Colorectal cancer (CRC) is the second cause of cancer-related death where the CpG-island methylation pathways (CIMP) is associated to KRAS/BRAF mutations, two oncogenes rewiring cell metabolism, worst prognosis and resistance to classical chemotherapies. Despite this, the question of a possible metabolic rewiring in CIMPs has never been asked. Here we asked if metabolic dysregulations were associated to the methylation status of tumours by evaluating the transcriptome of CRC tumours. CIMP-high patients were found to present a hyper-metabolism activating mainly carbohydrates, folates, sphingolipids and arachidonic acid metabolic pathways. A third of these genes had epigenetic targets of Myc in their proximal promoter, activating carboxylic acid, tetrahydrofolate interconversion, nucleobase, and oxoacid metabolisms. Amongst the Myc signature, the expression of GAPDH, TYMS, DHFR, TK1 was enough to predict methylation levels, microsatellite instability (MSI) and mutations in the mismatch repair (MMR) machinery, which are strong indicators of responsiveness to immunotherapies. Finally, we discovered that CIMP patients harboured an increase in genes involved in the one-carbon metabolism, a pathway critical to provide nucleotides for cancer growth and methyl donors for DNA methylation which was associated to worse prognosis. Transcriptomics could hence become a tool to help clinicians stratify their patients better.

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.

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.

Sepsis is a serious disease that can lead to mortality. The etiology of the disease is connected to how the body as a host reacts toward microbes such as bacteria, viruses, and fungi invasion. Current research shows that during sepsis, the reaction toward microbe attacks takes two main phases. The first is known as a cytokine storm, while the second is a vicious cycle of pro-inflammatory responses followed by a strict anti-inflammatory response led by CD4+ Tregs. Various immunomodulatory therapies have been proposed to break the cycle of pro- and anti-inflammatory reactions to sepsis. However, clinical trials did not show promising results, indicating further research into the mechanism that Treg uses to inhibit proinflammatory reactions. We used next-generation sequencing (NGS) analysis of bulk RNA-seq and single-cell RNA-seq data to examine the exact molecular pathways used by Treg to inhibit the immune response in sepsis. Our approach identified ACOD1 (Aconitate Decarboxylase 1) as a primary mediator of Treg suppression of immune cells. We identified and validated CD36 as a downstream target of ACOD1. CD36 is a known metabolite regulator in Tregs. Taken together, our results indicate that targeting ACOD1 could prove valuable in regulating Treg function during sepsis.

Ferroptosis is an iron-dependent and lipid peroxidation-driven cell death cascade, occurring when there is an imbalance of redox homeostasis in the cell. Nuclear factor E2 related factor 2 (NFE2L2, also known as NRF2) is key for cellular antioxidant responses, which promotes downstream gene transcription by binding to their antioxidant response elements (AREs). Numerous studies suggest that NRF2 assumes an extremely important role in the regulation of ferroptosis, for its various functions on iron, lipid and amino acid metabolism and so on. Many pathological states are relevant to ferroptosis. In cancer cells, ferroptosis is frequently found abnormal suppression. While during tissue damages, ferroptosis is recurrently promoted, resulting in a large number of cell deaths and ultimately loss of the functions of the corresponding organs. Therefore, targeting NRF2-related signaling pathways, to induce or inhibit ferroptosis, has become a great potential therapy for combating cancers, as well as preventing neurodegenerative and ischemic diseases. In this review, a brief overview of the research process of ferroptosis over the past decade will be presented. In particular, the mechanisms of ferroptosis and a focus on the regulation of ferroptosis by NRF2 will be discussed. Finally, the review will briefly list some clinical applications of targeting the NRF2 signaling pathway in the treatment of diseases.

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.

New antibiotics are unquestionably needed in the fight to the emergence and spread of multidrug-resistant bacteria. So far, antibiotics targeting bacterial central metabolism have been poorly investigated. By determining the minimal inhibitory concentration (MIC) of desmethylphosphinothricin (Glu-γ-PH), an analogue of glutamate with a phosphinic moiety re-placing the γ-carboxyl group, we previously showed its promising antibacterial activity on Escherichia coli. Herein we synthetized and determined the growth inhibition exerted on E. coli by an L-Leu dipeptide derivative of Glu-γ-PH (L-Leu-D,L-Glu-γ-PH). Furthermore, we compared the growth inhibition obtained with this dipeptide with that exerted by the free amino acid, i.e. Glu-γ-PH, and by their phosphonic and non-desmethylated analogues. All tested compounds were more effective when assayed in chemically defined minimal medium. The dipeptide L-Leu-D,L-Glu-γ-PH had a significantly improved antibacterial activity (2 μg/mL), at a concentra-tion between the non-desmethytaled (0.1 μg/mL) and the phosphonic (80 μg/mL) analogues. Also in Bacillus subtilis the dipeptide L-Leu-D,L-Glu-γ-PH displayed an activity comparable to that of the antibiotic amoxicillin. This work highlights the antibacterial relevance of the phosphinic pharmacophore and proposes new avenues to the development of novel antimicrobial drugs containing the phosphinic moiety.

Olfactory Receptors (ORs) are a large family of G protein coupled receptors predominantly expressed by the main olfactory epithelium at nasal level and are responsible for the generation of smelling sense. Microarray and deep sequencing analyses, however, have demonstrated that ORs are ectopically expressed in various human tissues including testis, kidneys, adipose tissue and liver and their biological functions become to be unrevealed. Molecular and pharmacological approaches have shown that some of these ORs modulate glucose and lipid metabolism at multiple interfaces, suggesting that ORs might be part of the large family of nutrient sensors. i.e. molecular/ cellular machines that respond to a specific nutrient component. By using nutrients- derived agonists it has been shown that ORs effectively modulates glucose and lipid metabolism raising interest on their possible therapeutic application in the treatment of metabolic disorders including dyslipidemia, obesity and metabolic syndrome.

A view of life, based on sympoiesis, metabolism, and the second law of thermodynamics is proposed. Sympoiesis is the notion that organisms develop as teams, and that symbionts play roles in forming their partners. Metabolism is seen to occur not only within these developmental symbionts, but between them, as well. This occurs through thermodynamic principles of finding the lowest free energy states. Once one accepts the thermodynamics of metabolism and that holobionts emerge through sympoiesis, Gaia becomes readily understood. New ethical principles flow from these considerations.

Oxysterols have been implicated in the pathogenesis of cardiovascular diseases. Serum levels of oxysterols could be positively correlated with cholesterol absorption and synthesis. However, physiological regulation of various serum oxysterols is largely unknown. The aim of this study was to investigate the relationship between clinical factors and cholesterol metabolism markers, and identify oxysterols associated with cholesterol absorption and synthesis in patients with coronary artery disease. Subjects (n=207) who underwent coronary stenting between 2011 and 2013 were studied cross-sectionally. We measured lipid profiles including serum oxysterols. As for the serum biomarkers of cholesterol synthesis and absorption, oxysterol levels were positively correlated with campesterol and lathosterol. Covariance structure analysis revealed that dyslipidemia and statin usage had a positive correlation with “cholesterol absorption”. Statin usage also had a positive correlation with “cholesterol synthesis” Several oxysterols associated with cholesterol absorption and/or synthesis. In conclusion, we elucidated the potential clinical factors that may affect cholesterol metabolism, and the associations between various oxysterols with cholesterol absorption and/or synthesis in patients with coronary artery disease.

Background: The prevalence of obesity, defined as body mass index (BMI) ≥ 30 kg/m2, has reached epidemic levels. Obesity is associated with an increased risk of various cancers, including gastrointestinal ones. Recent evidence has suggested that obesity disproportionately impacts males and females with cancer, resulting in varied transcriptional and metabolic dysregulation. Methods: This study aimed to elucidate the differences in the metabolic milieu of adenocarcinomas of the gastrointestinal (GI) track both related and unrelated to sex in obesity. To demonstrate these obesity and sex-related effects, we utilized three primary data sources: serum metabolomics from obese and non-obese patients assessed via the Biocrates MxP Quant 500 mass spectrometry-based kit, the ORIEN tumor RNA-sequencing data for all adenocarcinoma cases to assess the impacts of obesity, and publicly available TCGA transcriptional analysis to assess GI cancers and sex-related differences in GI cancers specifically. We applied and integrated our unique transcriptional metabolic pipeline in combination with our metabolomics data to reveal how obesity and sex can dictate differential metabolism in patients. Results: Differentially expressed genes (DEG) analysis of ORIEN obese adenocarcinoma as compared to normal-weight adenocarcinoma patients resulted in large-scale transcriptional reprogramming (4029 DEGs, adj. p < 0.05 and |logFC|>0.58). Gene Set Enrichment and metabolic pipeline analysis showed genes enriched for pathways relating to immunity (inflammation, and CD40 signaling, among others) and metabolism. Specifically, we found alterations to steroid metabolism and tryptophan/kynurenine metabolism in obese patients, both of which are highly associated with disease severity and immune cell dysfunction. These findings were further confirmed using the TCGA colorectal adenocarcinoma (CRC) and esophageal adenocarcinoma (ESCA) data, which showed similar patterns of increased tryptophan catabolism for kynurenine production in obese patients. These patients further showed disparate alterations between males and females when comparing obese to non-obese patient populations. Alterations to immune and metabolic pathways were validated in 6 patients (2 obese and 4 normal weight) via CD8+/CD4+ peripheral blood mononuclear cell RNA-sequencing and paired serum metabolomics, which showed differential kynurenine and lipid metabolism, which corresponded with altered T-cell transcriptome in obese populations. Conclusions: Overall, obesity is associated with differential transcriptional and metabolic program in various disease sites. Further, these alterations, like kynurenine and tryptophan metabolism, which impact both metabolism and immune phenotype, vary with sex and obesity together. This study warrants further in-depth investigation into obesity and sex-related alterations in cancers that may better define biomarkers of response to immunotherapy.

Berberine (BBR) is an isoquinoline that inhibits the proliferation of transformed cells in vitro, but due to its poor solubility and bioavailability, it has only moderate therapeutic potential in vivo. Increasing evidence indicates that BBR specifically targets several metabolic, signaling and gene transcription events in transformed cells, altering their progression through the cell cycle and decreasing their metabolic rate and proliferation. In order to further develop BBR as a therapeutic, its mode of cellular internalization and localization within the cell needs to be further examined. BBR’s molecular targets and interactions with kinases, transcription factors and some enzymes are discussed in an attempt to better understand BBR’s role in these important pathways and how they may lead to changes in metabolism. Lastly, this review examines some of the benefits and challenges of using BBR as an inhibitor in cancer cell proliferation in breast cancer and glioblastoma, as two examples. BBR is a potent drug with multiple targets and it is this multiplicity of function that makes BBR such a promising drug for targeting cell metabolism and proliferation.

Metabolic adaptations are a hallmark of cancer and may be exploited to develop novel diagnostic and therapeutic tools. Only about 50% of the patients who undergo thyroidectomy due to suspicion of thyroid cancer actually have the disease, highlighting the diagnostic limitations of current tools. We explored the possibility of using non-invasive blood tests to accurately diagnose thyroid cancer. We analyzed blood and thyroid tissue samples from 2 independent cohorts of patients undergoing thyroidectomy at the Hospital Universitario 12 de Octubre (Madrid, Spain). As expected, histological comparisons of thyroid cancer and hyperplasia revealed higher proliferation and apoptotic rates and enhanced vascular alterations in the former. Notably, they also revealed increased levels of membrane-bound phosphorylated AKT, suggestive of enhanced glycolysis, and alterations in mitochondrial sub-cellular distribution. Both characteristics are common metabolic adaptations in primary tumors. These data together with reduced mtDNA copy number and elevated levels of the mitochondrial antioxidant Prx3 in cancer tissue samples suggest the presence of mitochondrial oxidative stress. In plasma, cancer patients showed higher levels of cfDNA and mtDNA. Of note, mtDNA plasma levels inversely correlated with those in the tissue, suggesting that higher death rates were linked to lower mtDNA copy number. In PBMCs, cancer patients showed higher levels of PGC-1, a positive regulator of mitochondrial function, but this increase was not associated with a corresponding induction of its target genes, suggesting a reduced activity in cancer patients. We also observed a significant difference in the PRDX3/PFKFB3 correlation at the gene expression level, between carcinoma and hyperplasia patients, also indicative of increased systemic metabolic stress in cancer patients. The correlation of mtDNA levels in tissue and PBMCs further stressed the interconnection between systemic and tumor metabolism. Evaluation of the mitochondrial gene ND1 in plasma, PBMCs and tissue samples, suggested that it could be a good biomarker for systemic oxidative metabolism, with ND1/mtDNA ratio positively correlating in PBMCs and tissue samples. In contrast, ND4 evaluation would be informative of tumor development, with ND4/mtDNA ratio specifically altered in the tumor context. Taken together, our data suggest that metabolic dysregulation in thyroid cancer can be monitored accurately in blood samples and might be exploited for the accurate discrimination of cancer from hyperplasia.

Laminopathies are a spectrum of diseases caused by LMNA mutations. In familial partial lipodystrophy of Dunnigan (FPLD), LMNA plays role in the differentiation and development of adipocytes and lipid metabolism. Changes in LMNA predict not only the differentiation of adipose-derived mesenchymal stem cells (AD-MSCs) but also the transformation of cancer cells. Hence, our in-depth study aimed to identify the molecular connection between disordered lipid metabolism and hepatic carcinogenesis. We first discovered significant positive correlations between pLMNA and two key rate-limiting enzymes in de novo fatty acid synthesis, acetyl-CoA-carboxylase 1 (ACC1) and fatty acid synthase (FASN), in the liver tissue but not in adipose tissue of obese model rats. Moreover, LMNA knockdown (KD) in rat AD-MSCs prevented the differentiation and maturation of adipocytes. To clarify the mechanistic relationship with lipogenesis, gain- and loss-of-function experiments in which functional changes and the related molecular pathways were investigated in a normal hepatocyte line (7701 cells). Adenosine 5'-monophosphate activated protein kinase α (AMPKα) was found to be activated by abnormalities in the LMNA structure under conditions of LMNA deletion, farnesyltransferase inhibitor (FTI) treatment and LMNA mutations associated with clinical FPLD pathogenic phenotype. Active AMPKα could directly phosphorylate ACC1 and thus inhibit lipid synthesis but induced glycolysis in both HCC cells and normal cells. The HCC cells could not survive with LMNA knockout (KO) or even KD. Lonafarnib (an FTI) combined with low-glucose conditions significantly decreased the proliferation of HepG2 and MHCC cells by inhibiting glycolysis and the maturation of prelamin A.

Autophagy is an essential mechanism to maintain cellular homeostasis. Besides its role in controlling the quality of cytoplasmic components, it participates in nutrient obtaining and lipid mobilization under stressful conditions. Furthermore, autophagy is involved in the regulation of systemic metabolic, a function mainly performed by neuronal populations of the arcuate nucleus of the hypothalamus. Several studies have shown that blockade of autophagy in these neurons can affect central regulation of metabolism and impact body energy balance. Moreover, hypothalamic autophagy can be altered during obesity. However, neurons are not the only cell type involved in the central regulation of metabolism. Astrocytes, essential cells for brain homeostasis, are key metabolic regulators. They can sense metabolic signals in the hypothalamus and modulate systemic functions as glucose homeostasis and feeding response. Moreover, the response of astrocytes to obesity has been widely studied. Astrocytes are important mediators of brain inflammation and can be affected by increased levels of saturated fatty acids associated to obesity. Although autophagy plays important roles for astrocyte homeostasis and functioning, the contribution of astrocyte autophagy to systemic metabolism has not been analysed. Furthermore, how obesity can impact astrocyte autophagy is poorly understood. More studies are needed in other to understand the contribution of astrocyte autophagy to metabolism.

Toll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected to C57BL/6J WT and C57BL/6-Aoc3^-/- (VAP-1 KO) mice on high-fat diet twice a week every two weeks for 10-weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration and lipolysis in visceral adipose tissue. Consequently, increased release of glycerol led to hepatic steatosis in WT but not KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT, while flagellin did not affect the gut microbiota. Our results suggest that by acting on visceral adipose tissue, flagellin increased leukocyte infiltration that induced lipolysis. Further, the released glycerol participated in hepatic fat accumulation. In conclusion, the results describe that gut microbial flagellin through VAP-1 induced hepatic steatosis.

Energy homeostasis is crucial for cell fate since all cellular activities are strongly dependent on the balance between catabolic and anabolic pathways. In particular, metabolic and energetic modulation has been reported in cancer cells long time ago, but have been neglected for a long time. Instead, during the past 20 years a recovery of the study of cancer metabolism has led to better consider metabolic alterations in tumors. Cancer cells must adapt their metabolism to meet the energetic and biosynthetic demands that accompany rapid growth of the primary tumor and colonization of distinct metastatic sites. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilization. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to deregulation in glucose metabolism, fatty acid synthesis, and glutamine utilization. Cancer cells exhibit a series of metabolic alterations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which responsible for cancer progression. Cholesterol metabolism is also altered in cancer cells and supports uncontrolled cell growth. In this context, we review the roles of PPARs transcription factors, master regulators of cellular energetic metabolism, in the control and deregulation of energetic homeostasis observed in cancer. We highlight the different contribution of the different PPAR isotypes in different cancers and the differential control of their transcription in the different cancer cells.

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.

After a Century it is time to turn the page on understanding of lactate metabolism and appreciate that lactate shuttling as an important component of intermediary metabolism in vivo. Cell-Cell and intracellular Lactate Shuttles fulfill purposes of energy substrate production and distribution as well as cell signaling under fully aerobic conditions. Recognition of lactate shuttling came first in studies of physical exercise where roles of driver and recipient cells and tissues were obvious. Moreover, the presence of lactate shuttling as part of postprandial glucose disposal has been recognized. Mitochondrial respiration creates the physiological sink for lactate disposal in vivo. Repeated lactate exposure from regular exercise results in adaptive processes such as mitochondrial biogenesis and other healthful circulatory and neurological characteristic such as improved physical work capacity, metabolic flexibility and cognition. The importance of lactate and lactate shuttling in healthful living is further emphasized when lactate signaling and shuttling are dysregulated as occur in illness and injury. Like a Phoenix, lactate rises again in importance in 21^st Century Biology.

Many microbes live in habitats below their optimum temperature. Retention of metabolic heat by aggregation or insulation would boost growth. Generation of excess metabolic heat may also provide benefit. A cell that makes excess metabolic heat pays the cost of production, whereas the benefit may be shared by neighbors within a zone of local heat capture. Metabolic heat as a shareable public good raises interesting questions about conflict and cooperation of heat production and capture. Metabolic heat may also be deployed as a weapon. Species with greater thermotolerance gain by raising local temperature to outcompete less thermotolerant taxa. Metabolic heat may provide defense against bacteriophage attack, by analogy with fever in vertebrates. This article outlines the theory of metabolic heat in microbial conflict and cooperation, presenting several predictions for future study.

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.

Glioblastoma is a central nervous system cancer type with a poor prognosis. One of its main features is the constant change of metabolism phenotype to support its development and progression. Mitochondria play a critical role in cellular metabolism. Acetylation on lysine residues of mitochondrial enzymes is a mechanism for regulating protein function. This modification negatively affects the mitochondrial proteome function and is counteracted by the enzyme sirtuin 3 (SIRT3). To better understand how SIRT3 regulates mitochondrial metabolism, we inhibited SIRT3 and examined by high-resolution mass spectrometry analysis the proteome and acetylome of two glioblastoma cell lines with different metabolic preferences. Our results indicate that protein synthesis machinery is regulated by lysine acetylation and plays a role in the metabolic phenotype. We also identified new SIRT3 targets not previously associated with specific functions, highlighting their potential as future targets for further study. This study shed light on the role of SIRT3 in mitochondria and its implication for cellular metabolism. We have generated knowledge at the proteome and acetylome levels on the dynamics between two glioblastoma cell lines with opposing metabolic phenotypes. Our results might guide in searching for biomarkers at both proteome and acetylome levels in glioblastoma.

Seaweed polysaccharides can substitute synthetic compounds present in commercial stimulants and fertilizers, used in agriculture to improve crops yield and vigor. In this study, three different poly-saccharides (alginate, agar and carrageenan) were extracted from one brown seaweed, Saccorhiza polyschides, and two red seaweeds, Gracilaria gracilis and Chondrus crispus, respectively, and applied on potted turnip greens (Brassica napus L.), with intention to analyze their impact on plant growth, development and metabolism. Turnip plants treated with polysaccharides, specially, carrageenan of Chondrus crispus showed the best results in improving the crop’s productivity, such as plant length and weight, number of leaves, nutrient and pigment content, and soil fertility, compared with turnip plants from the negative control or treated with a commercial leaf fertilizer. λ-carrageenan extracted from the tetrasporophyte generation of Chondrus crispus had the highest bioactivity and positive effect in turnip plants among all treatments. λ-carrageenan has shown that can improve plant growth, increase plant’s biomass, and root system, enhance photosynthetic activity, increase the uptake of soil nutrients, and protect plants against abiotic and biotic stresses, stimulating the production of secondary metabolites and manage its defense pathways. Seaweed extracted polysaccharides have the potential to be used in sustainable agriculture.

Yerba maté, an herbal tea derived from Ilex paraguariensis, has previously been reported to be protective against obesity-related and other cardiometabolic disorders. Using high-resolution respirometry and reverse-phase high-performance liquid chromatography, the effects of four weeks of yerba maté consumption on mitochondrial efficiency and cellular redox status in skeletal muscle, adipose, and liver, tissues highly relevant to whole body metabolism, were explored in healthy adult mice. Yerba maté treatment increased mitochondrial oxygen consumption in adipose, but not in other tissues examined. Yerba maté increased ATP concentration in skeletal muscle and decreased ATP concentration in adipose. Combined with observed changes in oxygen consumption, these data yielded a significantly higher ATP:O2, a measure of mitochondrial efficiency, in muscle and a significantly lower ATP:O2 in adipose, which were consistent with yerba maté-induced weight loss. Yerba maté treatment also altered the hepatic glutathione (GSH)/glutathione disulfide (GSSG) redox potential to a more reduced redox state, suggesting potential protective effects against oxidative stress and preservation of cellular function. Together, these data indicate beneficial, tissue-specific effects of yerba maté supplementation on mitochondrial bioenergetics and redox states in healthy mice that are protective against obesity.

Fruits, vegetables, and spices are natural sources of bioactive phytochemicals such as polyphenols, carotenoids, flavonoids, curcuminoids, terpenoids, and capsaicinoids, possessing multiple health benefits and relatively low toxicity. These compounds found in the diet play a central role in organism development and fitness. Given the complexity of the whole-body response to dietary changes, invertebrate model organisms can serve as valuable tools to examine the interplay between genes, signaling pathways, and metabolism. Drosophila melanogaster, an invertebrate model with its extensively studied genome, has more than 70% gene homology to humans and has been used as a model system in biological studies for a long time. The notable advantages of Drosophila as a model system, such as their low maintenance cost, high reproductive rate, short generation time and lifespan, and the high similarity of metabolic pathways between Drosophila and mammals, have encouraged the use of Drosophila in the context of screening and evaluating the impact of phytochemicals present in the diet. In this chapter, we summarize and review the benefits of Drosophila as a model system for use in the study of phytochemical ingestion and describe the previously reported effects of phytochemical consumption in Drosophila.

Water deficit is one of the factors that most influence plant growth and yield. Thus, this study aimed to evaluate the effect of silicon and salicylic acid application and water deficit on the growth and photosynthetic and osmoregulatory metabolism of Talisia esculenta Radlk seedlings and their recovery potential after the resumption of irrigation. Six treatments were performed: irrigation, irrigation suspension, irrigation suspension + silicon at 0.5 g L−1, irrigation suspension + silicon at 1.0 g L−1, irrigation suspension + salicylic acid at 50 mg L−1, and irrigation suspension + salicylic acid at 100 mg L−1. The evaluations were carried out at the beginning of the experiment (T0), at 10 and 15 (DIS) days after irrigation suspension, when the seedlings showed a photosynthetic rate close to zero, and at recovery (REC). The plants were submitted to water restriction for up to 15 days, being then re-irrigated until the recovery point, which was monitored based on the photosynthetic rate. Silicon application attenuated the harmful effects of water deficit on gas exchange, initial fluorescence, promoted proline accumulation in the leaf and root, and provided higher seedling quality. Salicylic acid application contributed to the maintenance of the relative water content of leaves during the water deficit period. Silicon and salicylic acid applications can attenuate the harmful effects of water stress, with silicon being the most effective agent in maintaining its growth and metabolism.

Saccharomyces cerevisiae (S. cerevisiae) ethanol fermentation has left an indelible trace in human history. It is regarded as the original beverage synthesis, and has developed into an essential energy supply for mankind today. However, the history of ethanol synthesis using S. cerevisiae, including the mechanism analysis process, has not been carefully and succinctly reported. In this paper, we review the history of ethanol synthesis using S. cerevisiae. In addition, we also review the substrates that drive S. cerevisiae ethanol synthesis, including the utilization of glucose, sucrose, starch and molasses, in order to summarize the current development status and to contribute to the further improvement of this field.

Metabolic dysfunction associated fatty liver disease (MAFLD) has gained worldwide attention as a public health problem. Nonetheless, lack of enough mechanistic knowledge restrains effective treatments. It is known that T3 regulate hepatic lipid metabolism, and mitochondrial function. Liver dysfunction of T3 contributes to MAFLD, but its role is not fully understood. Objective: To evaluate the role of T3 dysfunction in the progression of MAFLD in an animal model. Method-ology: Male/adult Sprague Dawley rats (n=20) were allocated to a control group (standard di-et–2.93kcal/g) and diet group (CDHF–4.3kcal/g). Euthanasia took place in the 28th week. D3 ac-tivity and expression, UCP2 and D1 expression, REDOX status, mitochondrial, Krebs cycle and endoplasmic reticulum homeostasis in liver tissue were measured. Results: We observed an in-crease in D3 activity/expression (P<0.001) related to increased TBARS and carbonyls and GSH reduction in the MAFLD group (P<0.05). There was a T3-dependent decrease in UCP2 expression (P=0.01), mitochondrial capacity, respiratory activity with increased endoplasmic reticulum stress in the MAFLD group (P < 0.001). Surprisingly, in and environment with lower T3 levels we observed an augmented alpha-ketoglutarate dehydrogenase (KGDH) and glutamate dehydro-genase (GDH) enzymes activity (P<0.05). Conclusion: Induced D3, triggered by changes in the REDOX state, decreases T3 availability, and hepatic mitochondrial capacity. The Krebs cycle en-zymes were altered as well as reticulum stress. Taken together, these results shed new light on the role of T3 metabolism in MAFLD and new treatment opportunities.

The model of T4 phage, Lambda phage and Escherichia coli is often used in research on virus-host interactions. This paper reports for the first time the thermodynamic driving force of biosynthesis, catabolism and metabolism for the three organisms, on the M9 medium. Moreover, the influence of activities of nutrients and metabolic products is analyzed. All three organisms were found to have very similar Gibbs energies of metabolism. Moreover, since they share the same catabolism, their Gibbs energies of catabolism are identical. However, Gibbs energies of biosynthesis differ. The calculated thermodynamic properties have been used to explain the coexistence of both bacteria and phages in a dynamic equilibrium in natural ecosystems.

Pancreatic cancer (pancreatic ductal adenocarcinoma: PDAC) is one of the most aggressive neoplastic diseases. Metformin use was associated with reduced pancreatic cancer incidence or better survival in diabetics. Metformin has been shown to inhibit PDAC cells survival and growth in vitro and in vivo. However, clinical trials using metformin failed to decrease pancreatic cancer progression in patients, raising important questions about molecular mechanisms that protect tumor cells from the antineoplastic activities of metformin. We confirm that metformin acts through inhibition of mitochondrial complex I, decreasing the NAD+/NADH ratio and that NAD+/NADH homeostasis determines metformin sensitivity in several cancer cell lines. Metabolites that can restore the NAD+/NADH ratio turned PDAC cells resistant to metformin. In addition, metformin treatment of PDAC cell lines induced a compensatory NAMPT expression increasing the pool of cellular NAD+. The NAMPT inhibitor FK866 sensitized PDAC cells to the antiproliferative effects of metformin in vitro and decreased cellular NAD+ pool. Intriguingly, FK866 combined with metformin increased survival in mice bearing KP4 cells xenografts but not in mice with PANC1 xenografts. Transcriptome analysis revealed that the drug combination reactivated genes in the p53 pathway and oxidative stress providing new insights about the mechanisms leading to cancer cell death.

Macrophages are essential innate immune cells characterized by a high diversity and plasticity. In vitro, their full dynamic range of activation profiles include the classical pro-inflammatory (M1) and the alternative anti-inflammatory (M2) program. Bistability usually arises in biological systems that contain a positive-feedback loop or a mutually inhibitory, double-negative-feedback loop, which are common regulatory motifs reported for macrophage transitions from one activation state to the other one. This switch-like behavior of macrophage is observed at four different levels. First, a decision-making module in signal transduction includes mutual inhibitory interactions between M1 (STAT1 and NF-KB/p50-p65) and M2 (STAT3 and NF-KB/p50-p50) signaling pathways. Second, a switch-like behavior at the gene expression level includes complex network motifs of transcription factors and miRNAs. Third, those changes impact metabolic gene expression leading to several switches in energy production, NADPH and ROS production, TCA cycle functionality, biosynthesis and nitrogen metabolism. Fourth, metabolic changes are monitored by specialized metabolic sensors coupled to AMPK and mTOR activity to provide stability by maintaining the signals to promote either M1 or M2 activation. The targeting of robust molecular switches has the potential to treat a broad range of widespread diseases such as sepsis, cancer or chronic inflammatory diseases.

Anhydrobiosis is the state of life when cells get into waterless conditions and gradually cease their metabolism. In this study, we determined the sequence of events in Saccharomyces cerevisiae energy metabolism during processes of dehydration and rehydration. The intensities of respiration and acidification of the medium, the amounts of Phenyldicarbaundecaborane (PCB-) bound to yeast membranes, and the capabilities of cells to accumulate K+ were assayed using electrochemical monitoring system, and intracellular content of ATP was measured using bioluminescence assay. Mesophilic, semi-resistant to desiccation S. cerevisiae strain 14 and thermotolerant, very resistant to desiccation S. cerevisiae strain 77 cells were compared. After 22 h of drying it was possible to restore the respiration activity of very resistant to desiccation strain 77 cells, especially when glucose was available. PCB- binding also indicated considerably higher metabolic activity of dehydrated S. cerevisiae strain 77 cells. Electrochemical K+ content and medium acidification assays indicated that permeabilization of the plasma membrane in cells of both strains started almost simultaneously, after 8-10 h of desiccation, but semi-resistant strain 14 cells were longer keeping K+ gradient and stronger acidifying the medium. For both cells, the fast rehydration in water was less efficient compared to reactivation in the growth medium, indicating the need for nutrients for the recovery. Higher viability of strain 77 cells after rehydration could be due to the higher stability of their mitochondria.

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.

Amino acid metabolism promotes cancer cell proliferation and survival by supporting building block synthesis, producing reducing agents to mitigate oxidative stress, and generating immunosuppressive metabolites for immune evasion. Malignant cells rewire amino acid metabolism to maximize their access to nutrients. Amino acid transporter expression is upregulated to acquire amino acids from the extracellular environment. Under nutrient depleted conditions, macropinocytosis can be activated where proteins from the extracellular environment are engulfed and degraded into the constituent amino acids. The demand for non-essential amino acids (NEAAs) can be met through de novo synthesis pathways. Cancer cells can alter various signaling pathways to boost amino acid usage for the generation of nucleotides, reactive oxygen species (ROS) scavenging molecules and oncometabolites. The importance of amino acid metabolism in cancer proliferation makes it a potential target for therapeutic intervention, including via small molecules and antibodies. In this review, we will delineate the targets related to amino acid metabolism and promising therapeutic approaches.

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3’-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair which holds considerable advantages over urinalysis for anti-doping tests.

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.

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.

Plant responses to different light and water availability are variable among species and their re-spective phenotypic plasticity, and the combination between these two abiotic factors can alleviate or intensify stressful effects. This study aimed to evaluate the impacts of exposure time of Cedrela fissilis Vell. seedlings to different water and light availability and the interaction of these factors. Seedlings were submitted to combinations of three shading levels – SH (0, 30 and 70%) and three water regimes based on the water holding capacity (WHC) in the substrate, constituting nine cul-tivation conditions: T1 – 0% SH + 40% WHC; T2 – 0% SH + 70% WHC; T3 – 0% SH + 100% WHC; T4 – 30% SH + 40% WHC; T5 – 30% SH + 70% WHC; T6 – 30% SH and 100% WHC; T7 – 70% SH + 40% WHC; T8 – 70% SH +70% WHC; T9 – 70% SH + 100% WHC. C. fissilis seedlings respond to water deficit, here represented by 40% WHC, regardless of exposure time, and when cultivated in full sun, the stressful effects were enhanced, acting in a synergistic manner. The condition that provided better gas exchange performance and greater total dry mass accumulation for C. fissilis seedlings was 30% shading combined with 100% WHC. C. fissilis seedlings have physiological plasticity and resilience to survive under different water and light conditions.

Sleep is an essential component of a healthy lifespan, influencing both physical and mental well-being along with good quality of life. Adequate sleep quality and quantity are associated with a host of health advantages, including enhanced immune function, learning and memory, emotional well-being, and cardiovascular health. Chronic sleep deprivation, or poor sleep quality, is associated with a variety of negative health outcomes, including an increased risk of obesity, diabetes, hypertension, depression, cancer, and even premature death. One compelling argument in favor of sleep as a predictor of a healthy lifespan is its effect on cellular repair and regeneration. During sleep, the body goes through important activities such as tissue repair, muscular growth, and memory consolidation. Sleep also helps the brain eliminate toxins and metabolic waste, which contributes to its optimal functioning. Without adequate sleep, these important processes are jeopardized, resulting in accelerated aging and greater susceptibility to chronic illnesses. Furthermore, sleep is essential for maintaining hormone balance, particularly those involved in appetite regulation and metabolism. Sleep disturbances can disrupt the regulation of these hormones, resulting in weight gain, metabolic diseases, and, ultimately, a shorter life span. Finally, prioritizing optimal sleep is pivotal for increasing longevity and general health. Emphasizing the importance of sleep hygiene and treating sleep-related dysfunctions should be part of the modern approach to extending healthy life.

Chronic kidney disease (CKD) affects approximately 12% of the global population posing a significant health threat. Inflammation plays a crucial role in the uremic phenotype of CKD contributing to elevated cardiovascular and overall mortality in affected individuals. This study aimed to explore novel metabolic pathways in non-dialysis dependent stage 5 CKD patients using semitargeted metabolomics. In a prospective observational design involving 50 patients, blood samples collected before the initial hemodialysis session underwent liquid chromatography and high resolution mass spectrometer analysis. Univariate (Mann-Whitney test) and multivariate (logistic regression with LASSO regularization) methods identified metabolomic variables associated with inflammation. Notably, adenosine-5’-phosphosulfate (APS), dimethylglycine, pyruvate, lactate, and 2-ketobutyric acid exhibited significant differences in the presence of inflammation. Cholic acid, homogentisic acid, and 2-phenylpropionic acid displayed opposing patterns. Multivariate analysis indicated increased inflammation risk with certain metabolites (N-Butyrylglycine, dimethylglycine, 2-Oxoisopentanoic acid, and pyruvate), while others (homogentisic acid, 2-Phenylpropionic acid, and 2-Methylglutaric acid) suggested decreased probability. These findings unveil potential inflammation-associated biomarkers related to defective mitochondrial fatty acid beta oxidation and branched-chain amino acid breakdown in CKD, shedding light on cellular energy production and offering insights for further clinical validation.

This review summarises the complex relationship between medications used to treat type 2 diabetes, and bone health. T2DM patients face an increased fracture risk despite higher bone mineral density, thus we analysed the impact of key drug classes, including Metformin, Sulphonylureas, SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 agonists, and Thiazolidinediones. Metformin, despite promising preclinical results, lacks a clear consensus on its role in reducing fracture risk. Sulphonylureas present conflicting data, with potential neutral effects on bone. SGLT-2 inhibitors seem to have a transient impact on serum calcium and phosphorus, but evidence on their fracture association is inconclusive. DPP-4 inhibitors emerge as promising contributors to bone health, as well as GLP-1 agonists exhibit positive effects on bone metabolism, reducing fracture risk. Thiazolidinediones, however, demonstrate adverse impacts on bone, inducing loss through mesenchymal stem cell effects. Insulin presents a complex relationship with bone health. While it has an anabolic effect on bone mineral density, its role in fracture risk remains inconsistent. In conclusion, a comprehensive understanding of diabetes medications' impact on bone health is crucial. Further research is needed to formulate clear guidelines for managing bone health in diabetic patients, considering individual profiles, glycemic control and potential medication-related effects on bone.

OBJECTIVE: Analyzing the effects of different physical exercise programs on the anthropometric, cardiovascular, metabolic, and strength variables of the elderly participating in health care programs. METHODS: Controlled clinical trial, with 60 elderly participants from health care groups, allocated into four groups: Group of resistance exercises in open-air gyms – GT1 (n = 17); Group of aerobic and localized exercises - GT2 (n = 11); Group of resistance exercises at GT3 gym (n = 17); Control group: non-exercise practitioners - CG (n = 15). Anthropometric (BMI, % body fat, and waist circumference), cardiovascular (SBP, DBP, HR, and DP), metabolic (total cholesterol, triglycerides, and glycemia), and strength variables were evaluated before and after 16 weeks of intervention. Descriptive statistics, Shapiro-Wilk and Kolmogorov-Smirnov normality test, equal variance test, T-Student test, non-parametric Mann-Witney test, ANOVA One Way, multivariate data analysis using data mining and machine learning techniques, Pearson and Spearman correlation tests, Classical Clustering (Agglomerative Hierarchical Method); Principal Component Analysis (PCA), Z score, Fruchterman-Reingold algorithm, Euclidian Similarity Index and, Cohen’s equations were applied. RESULTS: To observe effect size, morphofunctional variables for the GT1 group show a small effect for fat percentage, WHR, and ULS and a medium effect for LLS. For the GT2 group, there was a small effect for fat percentage, WHR, and ULS and a large effect for LLS. For the GT3 group, there was a small effect for the percentage of fat and HC, a medium effect for ULS, and a large effect for LLS. A small effect for glycemia in GT1, a medium effect for glycemia and triglycerides for GT2, a small effect for total cholesterol for GT3, and a large effect for glycemia in CG, with this effect being an increase in this analyte. For the cardiovascular variables, there is a small effect for SBP and HR in GT1, a small effect for DBP, HR, and DP, and a large effect for SBP in GT2, a small effect for SBP, DBP, and HR in GT3 and small effects for SBP and HR in CG. The correlation between BMI (P = 0.0007) and Body Fat% (P = 0.007) with ULS. The variables TG, LLS, and ULS were the ones that differed most in each type of stimulus chosen as an intervention in the present study. CONCLUSIONS: The results of this study indicate that GT2 caused more significant percentage reductions in body mass and BMI. However, GT3 caused greater fat percentage reduction. The GT2 caused the greatest decrease in waist circumference, while the GT3 caused the largest decline in hip circumference. The three groups induced an increase in strength (ULS and LLS). However, in ascending order, GT1 caused the smallest increase, GT2 an intermediate increase, and GT3 the greatest increase in strength, with considerable effects in GT2 and GT3. Finally, GT2 caused a greater percentage reduction in systolic blood pressure (large effect) and double product (small effect) than the other groups. The three methods proved to be efficient, but with particularities that may reflect the choice of one over another due to health conditions, objectives to be achieved, or characteristics of the patient at the time of their choice by the prescriber.

The following narrative review embarks on a comprehensive exploration of the pivotal role played by the gut microbiome within the Diet-Microbiota-Immunity (DMI) tripartite, aiming to enhance anti-cancer immunotherapy efficacy. While revolutionizing cancer treatment, resistance to immunotherapy and immune-related adverse events (irAEs) remain challenges. The tumor microenvironment (TME), shaped by cancer cells, influences immunotherapy resistance. The gut microbiome, influenced by genetics, environment, diet, and interventions, emerges as a critical player in TME reshaping, thereby modulating immune responses and treatment outcomes. Dietary patterns like the Mediterranean diet, caloric restriction modifications, and specific nutritional components show promise in influencing the tumor microenvironment and gut microbiome for better treatment outcomes. Antibiotics, disrupting gut microbiota diversity, may compromise immunotherapy efficacy. This review emphasizes the need for tailored nutritional strategies to manipulate microbial communities, enhance immune regulation, and improve immunotherapy accessibility while minimizing side effects. Ongoing studies investigate the impact of dietary interventions on cancer immunotherapy, pointing towards promising developments in personalized cancer care. This narrative review synthesizes existing knowledge and charts a course for future investigations, presenting a holistic perspective on the dynamic interplay between dietary interventions, the gut microbiome, and cancer immunotherapy within the DMI tripartite.

Telomeres – special DNA-protein structures at the ends of linear eukaryotic chromosomes define the proliferation potential of cells. Extremely short telomeres promote DNA damage response and cell death to eliminate cells potentially accumulated mutations after multiple divisions. However, telomere elongation is associated with increased proliferative potential of special types of cells, such as stem and germ cells, permanently, and is activated temporally in processes of activation of immune response, regeneration processes. Activation of mechanisms of telomere lengthening coupled with increased proliferation and with requirements of cells in energy and building resourses. To obtain necessary nutrients cells stimulate metabolism by switching of oxidative phosphorylation program to glycolysis. In this review we focused on the interconnection of metabolism program and telomere lengthening mechanisms known for the situation of the programmed activation of proliferation such as germ cells maturation, early embryonic development program and immune response activation. Here, we propose that it is possible to reprogram metabolism in order to regulate the telomere length, proliferative activity of cells that may be important for the development of approaches to regeneration, immune response modulation and cancer therapy and further investigations in this area are necessary to improve the understanding and manipulating of molecular mechanisms used for regulation of proliferation.

Background: Cutaneous melanoma arises from skin melanocytes and has a high risk of metastatic spread. Despite better prevention, earlier detection, and the development of innovative therapies melanoma incidence and mortality increase annually. Major clinical risk factors for melanoma include fair skin, an increased number of nevi, the presence of dysplastic nevi, and a family history of melanoma. However, several external inducers seem to be associated with melanoma susceptibility such as environmental exposure, primarily unprotected sun experience, alcohol consumption, and heavy metals. In recent years, epidemiological studies have highlighted a potential risk of β-hexachlorocyclohexane (β-HCH), the most studied organochlorine pesticide, on cancer induction including melanoma. Methods: We evaluated in vitro the impact of this pollutant on epidermal and dermal cells, attempting to describe mechanisms that could render cutaneous cells more prone to oncogenic transformation. Results: We demonstrated that β-HCH impacts melanocyte biology with a highly cell-type specific signature that involves perturbation of AKT/mTOR and Wnt/β-catenin signaling, and AMPK activation that converges in lowering energy reserve, cell proliferation, and pigment production. Conclusion: In conclusion, long-term exposure to persistent organic pollutants damages melanocyte metabolism in the function of the melanin content with a consequent reduction of melanogenesis indicating a potential augmented skin cancer risk.

Excessive nitrogen application has become a hidden danger threatening the sustainable development of agriculture. Exploring the potential genes will help to improve the nitrogen availability of wheat through molecular breeding. We therefore conducted wheat transcriptomics and proteomics researches under complete culture medium without nitrogen (N0) and complete culture medium with nitrogen (N1). The results showed that, the nitrogen deficit decreased the fresh weight, N content and net photosynthetic rate of winter wheat. 3949 and 2675 differentially expressed genes (DEGs) were identified in the shoot and root, respectively, while 164 and 129 differentially expressed proteins (DEPs) were identified in the shoot and root respectively. 9 genes in shoot and 26 genes in root showed the same trends in RNA and protein levels. 5 genes in shoot and 4 genes in root showed the opposite trends in RNA and protein levels. Pathway enrichment of wheat transcriptome and proteome under nitrogen deficit proposed 3 candidate genes related to photosynthesis in shoot, 4 candidate genes related to carbon metabolism in shoot, and 12 candidate genes related to carbon metabolism in root. Meanwhile, the chromosomal and subcellular localization of these genes were listed, which will provide reference for improving nitrogen availability through molecular breeding.

Primulina serrulata is a valuable ornamental herb with rosette leaves and vibrant flowers. Some leaves exhibit a bright and distinct white color along the upper veins, enhancing their ornamental value, while others are less white or entirely green. This variation is observed among adult leaves in natural habitats and among young leaves from seedlings grown in the laboratory. TMT-labeled proteomic technology was employed to study the protein-level biogenesis of white-veined (WV) leaves of P. serrulata. The chlorophyll (Chl) content was significantly lower in the WV group than in the control group. A total of 6,261 proteins were identified, revealing 69 differentially expressed proteins (DEPs), with 44 down-regulated and 25 up-regulated in WV plants. Some DEPs associated with chloroplasts and Chl biosynthesis were down-regulated, leading to the absence of green coloration. Concurrently, gene ontology enrichment analysis further underscored an insufficiency of magnesium , the key element in Chl biosynthesis. Many DEPs associated with abiotic or biotic stresses were down-regulated, suggesting an overall weakening of stress resistance with certain compensatory mechanisms in place. Similarly, many DEPs related to biomacromolecule modification were down-regulated, possibly influenced by the decrease in proteins involved in photosynthesis and stress resistance. Some DEPs containing iron were up-regulated, indicating that iron was mainly used to synthesize heme and ferritin instead of Chl. Additionally, several DEPs related to sulfur or sulfate were up-regulated, implying strengthened respiration. Expansin-A4 and pectinesterase displayed up-regulation, coinciding with the emergence of a rough and bright surface in the white area, indicative of the elongation and gelation processes in cell walls. These findings provide new insights that could be utilized by future studies to explore the mechanism of color formation in WV leaves.

Nicotinamide riboside (NR) is an NAD+ precursor capable of regulating mammalian cellular metabolism. Phycocyanin oligopeptide (PC), a phytonutrient found in blue-green algae, has antioxidant and anti-inflammatory properties. This study explored the effects of NR, PC, and their combination on telomere length, inflammatory and antioxidant status in rats under chronic stressed conditions (CS). Forty-nine rats were allocated into seven groups: Control, chronic stress (CS), CS with NR (26.44 mg/kg), a low dose of 2.64 mg/kg of PC (PC-LD), or a high dose of 26.44 mg/kg PC (PC-HD), NR+PC-LD and NR+PC-HF. Rats were given daily corticosterone injections (40 mg/kg) to induce stressed conditions, or NR and PC were orally administered for 21 days. NR and PC supplementation, particularly NR plus PC, increased the serum antioxidant enzyme activities, hepatic nicotinamide adenine (NAD+) content, and telomere length (P&lt;0.001 for all) compared with the CS group. The levels of serum malondialdehyde (MDA), liver interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), IL-1β, and IL-8 were reduced under CS condition (P&lt;0.001). In addition, CS decreased the levels of hepatic telomere-related proteins and sirtuin1 (SIRT1-3), while supplementation of NR and PC alone or in combination increased the levels of telomere-related proteins (e.g., POT1b, TRF1, and TRF2), and SIRT3, NAMPT P&lt;0.05. In conclusion, NR and PC, especially their combination, can alleviate metabolic abnormalities by enhancing hepatic cytokines, SIRT3, NAMPT, and NAD+ levels in CS-exposed rats. More research is needed to elucidate further the potential health effects of the combination of NR and PC in humans.

In the recent decades, per- and polyfluoroalkyl substances (PFAS) have garnered widespread public attention due to their persistence in the environment and detrimental effects on the health of living organisms, spurring the generation of several transcriptome-centered investigations to understand the biological basis of their mechanism. In this study, we collected 2144 publicly available samples from 7 distinct animal species to examine the molecular responses to PFAS exposure and to determine if there are conserved responses. Our comparative transcriptional analysis revealed that exposure to PFAS is conserved across different tissues, molecules and species. We identified and reported several genes exhibiting consistent and evolutionarily conserved transcriptional response to PFAS, such as ESR1, HADHA and ID1, as well as several pathways including lipid metabolism, immune response and hormone pathways. This study provides the first evidence that distinct PFAS molecules induce comparable transcriptional changes and affect the same metabolic processes across inter-species borders. Our findings have significant implications for understanding the impact of PFAS exposure on living organisms and the environment. We believe that this study offers a novel perspective on the molecular responses to PFAS exposure and provides a foundation for future research into developing strategies for mitigating the detrimental effects of these substances in the ecosystem.

Introduction Currently, the increase in the percentage of obese people observed along with the development of civilization, reaching the level of a global pandemic, has forced the search for methods of effective and permanent obesity treatment. Obesity is a multifactorial disease, it coexists with many disease entities and requires multidisciplinary treatment. Obesity leads to metabolic changes in the form of metabolic syndrome, which includes, among others, atherogenic dyslipidemia. The proven relationship between dyslipidemia and cardiovascular risk enforces the need to effectively improve the lipid profile of obese patients. Laparoscopic sleeve gastrectomy is a method of surgical treatment of morbid obesity which improves bariatric and metabolic parameters. The aim of the study was to assess the effectiveness of laparoscopic sleeve gastrectomy (LSG) in improving lipid profile parameters in 1-year follow-up. Material and Methods Bariatric parameters of 196 patients who underwent laparoscopic sleeve gastrectomy as well as lipid profile of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-NDL, and triglycerides (TG) in 1-year observation were analyzed. Results Improvements in bariatric parameters were observed in patients after LSG. Total cholesterol, low-density lipoprotein (LDL), triglycerides and non-HDL levels decrease were observed along with the increase of high-density lipoprotein (HDL) cholesterol level. Conclusions Sleeve gastrectomy is an effective method of treating obesity and improving the lipid profile in obese patients.

Altered metabolism is a common feature of many cancers and in some cases is a consequence of mutation in metabolic genes, such as the ones involved in Krebs cycle. Isocitrate dehydrogenase (IDH) gene is mutated in many gliomas and other cancers. Physiologically IDH converts isocitrate to αketoglutarate (αKG), but when mutated, IDH reduces αKG to D2-hydroxyglutarate (D2-HG). D2-HG accumulates at high levels in IDH mutant cancers, and in the last decade, a massive effort has been done to develop small inhibitors targeting mutant IDH. In this review, we summarize current knowledge about the cellular and molecular consequences of IDH mutations, and the therapeutic approached developed to target IDH mutant tumours, with a focus on gliomas.

Adipocytes play a critical role in maintaining a healthy systemic metabolism by storing and releasing energy in the form of fat and helping to regulate glucose and lipid levels in the body. Adipogenesis is the process through which pre-adipocytes are differentiated into mature adipocytes. It is a complex process involving various transcription factors and signaling pathways. Dysregulation of adipogenesis has been implicated in the development of obesity and metabolic disorders. Therefore, understanding the mechanisms that regulate adipogenesis and the factors that contribute to its dysregulation may provide insights into the prevention and treatment of these conditions. RNA Binding Motif Single Stranded Interacting Protein 1 (RBMS1) is a protein that binds to RNA and plays a critical role in various cellular processes such as alternative splicing, mRNA stability, and translation. The RBMS1 polymorphism has been shown to be associated with obesity and Type 2 diabetes, but the role of RBMS1 in adipose metabolism and adipogenesis is not known. We show that RBMS1 is highly expressed during the early phase of differentiation of the murine adipocyte cell line 3T3-L1 and is significantly upregulated in adipose tissue depots and adipocytes of high-fat-fed mice, implying a possible role in adipogenesis and adipose metabolism. Knockdown of RBMS1 in pre-adipocytes impacted the differentiation process and reduced the expression of some of the key adipogenic markers. Transcriptomic and proteomic analysis indicated that RBMS1 depletion affected the expression of several genes involved in major metabolic processes, including carbohydrate and lipid metabolism. Our findings imply that RBMS1 plays an important role in adipocyte metabolism and may offer novel therapeutic opportunity for metabolic disorders such as obesity and type 2 diabetes.

White adipose tissue (WAT) represents an endocrinologically and immunologically active tissue that’s primary role is energy storage and homeostasis. Breast WAT is involved in the secretion of hormones and proinflammatory molecules that are associated with breast cancer development and progression. The role of adiposity and systemic inflammation in immune responses and resistance to anti-cancer treatment in breast cancer (BC) patients is still not clear. This review aims to evaluate the emerging evidence on the crosstalk between adiposity and the immune-tumour microenvironment in BC, its progression and treatment resistance. Adiposity, and by extension subclinical inflammation, are associated with metabolic dysfunction and changes in the immune-tumour microenvironment in BC. In oestrogen receptor positive (ER+) breast tumours, it is proposed that these changes are mediated via a paracrine interaction between macrophages and preadipocytes leading to elevated aromatase expression and secretion of pro-inflammatory cytokines and adipokines in the breast tissue in patients who are obese or overweight. In HER2+ breast tumours, WAT inflammation has been shown to be associated with resistance to trastuzumab mediated via MAPK or PI3K pathways. Furthermore, adipose tissue in patients with obesity is associated with upregulation of immune checkpoints on T-cells that is partially mediated via immunomodulatory effects of leptin and has been paradoxically associated with improved responses to immunotherapy in several cancers. In conclusion, evidence suggests that body composition and metabolic status are associated with patient outcomes. To optimise patient stratification and personalisation of treatment, prospective studies are required to evaluate the role of body composition and metabolic parameters in metabolic immune reprogramming with and without immunotherapy in patients with BC.

Abstract: Changes in sugar composition occur continuously in plants tissues, at different develop-mental stages. Tuber dormancy induction, stability, and breaking are very critical developmental transitions in yam crop production. Prolonged tuber dormancy after physiological maturity has constituted a great challenge in yam genetic improvement and productivity. In the present study, biochemical profiling of non-structural sugar in yam tuber during dormancy was performed to determine the role of non-structural sugar in yam tuber dormancy regulation. Two genotypes of white yam specie; one local genotype (Obiaoturugo) and (TDr1100873) were used for this study. Tubers were sampled at (42, 56, 87, 101, 115, and 143) days after physiological maturity (DAPM). Obiaoturugo exhibited a short dormant phenotype and sprouted at 101DAPM, whereas TDr1100873 exhibited a long-dormant phenotype, and sprouted at 143DAPM. Significant metabolic changes were observed in non-structural sugar parameters, dry matter, and moisture content in Obiaoturugo from 56DAPM, whereas, in TDr1100873 significant metabolic changes were observed from 101DAPM. It was observed that the onset of these metabolic changes occurred at a point when the tubers of both genotypes exhibited dry matter content of 60%, indicating that dry matter content of 60% might be a critical threshold for white yam tuber sprouting. Nonreducing sugars increased by 9-10-fold during sprouting in both genotypes which indicates its key role in tuber dormancy regulation in white yam. This result implies that some key sugar metabolites can be targeted for dormancy manipulation of yam crop.

The prevalence of overweight and obesity is increasing worldwide not only in Western countries but also in Asian countries. Among Asian countries, South Asian countries experience the rapid increase of overweight and obesity that co-exist with the rapid increase of obesity-related non communicable diseases such as diabetes, dyslipidemia and cardiovascular. The phenomena in South Asian countries are triggered by growth in population size, population aging, urbanization and changes in lifestyle including increases in energy intake and reductions in physical activity. The imbalance between energy intake and energy expenditure leads to the development of positive energy balance, which over the time acumulate in a higher body fat. South Asians were reported to have a more unfavorable body composition with a higher body fat percentage as compared to BMI-matched Caucasians. The differences in body composition between South Asians and Caucasians contribute to differences in resting energy expenditure, in which South Asians have a lower resting energy expenditure as compared to BMI-matched Caucasians. Resting energy expenditure is the largest component of daily total energy expenditure, and therefore play an important role in determining the energy balance between energy intake and expenditure.

Background and Aims: Dyslipidemia and cardiovascular diseases (CAD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 cluster, has been associated CAD, but its impact on metabolic traits and liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 have HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC) and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n=125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p<0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The G allele was associated with higher risk of HCC and advanced tumor stage (p<0.05) in the Overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p<0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p<0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p<0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p<0.05). Conclusions: In sum, the rs599839 A>G variant improves dyslipidemia thus protecting against CAD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively

Archaea are an essential class of gut microorganisms in humans and animals. Despite the substantial progress in gut microbiome research in the last decade, most studies have focused on bacteria, and little is known about archaea in mammals. In this study, we investigated the composition, diversity, and functional potential of gut archaeal communities in pigs by re-analyzing a published metagenomic dataset including a total of 276 fecal samples from three countries: China (n=76), Denmark (n=100), and France (n=100). For alpha diversity (Shannon Index) of the archaeal communities, Chinese pigs were less diverse than Danish and French pigs (P<0.001). Consistently, Chinese pigs also possessed different archaeal community structures from the other two groups based on the Bray-Curtis distance matrix. Methanobrevibacter was the most dominant archaeal genus in Chinese pigs (44.94%) and French pigs (15.41%), while Candidatus Methanomethylophilus was the most predominant in Danish pigs (15.71%). At the species level, the relative abundance of Candidatus Methanomethylophilus alvus, Natrialbaceae archaeon XQ INN 246, and Methanobrevibacter gottschalkii were greatest in Danish, French, and Chinese pigs with a relative abundance of 14.32%, 11.67%, and 16.28%, respectively. In terms of metabolic potential, the top three pathways in the archaeal communities included the MetaCyc pathway related to the biosynthesis of L-valine, L-isoleucine, and isobutanol. Interestingly, the pathway related to hydrogen consumption (METHANOGENESIS-PWY) was only observed in archaeal reads, while the pathways participating in hydrogen production (FERMENTATION-PWY and PWY4LZ-257) were only detected in bacterial reads. Archaeal communities also possessed CAZyme gene families, with the top five being: AA3, GH43, GT2, AA6, and CE9. In terms of antibiotic resistance genes (ARGs), the class of multidrug resistance was the most abundant ARG, accounting for 87.41% of archaeal ARG hits. Our study reveals the diverse composition and metabolic functions of archaea in pigs, suggesting that archaea might play important roles in swine nutrition and metabolism.

Coral reefs are declining worldwide due to global changes in the marine environment. The increasing frequency of massive bleaching events in the tropics is highlighting the need to better understand the stages of coral physiological responses to extreme conditions. Moreover, like many other coastal regions, coral reef ecosystems are facing additional localized anthropogenic issues such as nutrient loading, increased turbidity, and coastal development. Different strategies have been developed to measure the health status of a damaged reef, ranging from the resolution of individual polyps to an entire coral community, but techniques for measuring coral physiology in situ are not yet widely implemented. For instance, while there are many studies of the coral holobiont response in single or limited-number multiple stressor experiments, they provide only partial insights to metabolic performance under more complex temporally and spatially variable natural conditions. Here, we discuss the current status of coral reefs and their global and local stressors in the context of experimental techniques that measure core processes in coral metabolism (respiration, photosynthesis, and biocalcification) in situ, and their role in indicating the health status of colonies and communities. We highlight the need to improve the capability of in situ studies in order to better understand the resilience and stress response of corals under multiple global and local scale stressors.

A growing body of evidence indicates that aging of the brain is strictly related to the decline of energy metabolism. In particular, in older adults, the neuronal metabolism of glucose declines steadily resulting in a growing deficit of ATP production. The decline is evoked by deficient NAD recovery in the salvage pathway and subsequent impairment of the Krebs cycle. NAD deficit impairs also the activity of NAD-dependent enzymes. All these open vicious circles of neurodegeneration and neuronal death. Some brain structures are particularly prone to aging and neurodegeneration. These are pathological foci of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. This review article summarizes the impacts and mutual relationships between metabolic processes both on neuronal and brain levels. It also provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.

It has been long recognized that under hypoxia conditions cancer cells reprogram their metabolism through shift from oxidative phosphorylation (OXPHOS) to glycolysis to meet elevated requirements in energy and nutrients for proliferation, migration and survival. However, data accumulated over the last years increasingly evidence that cancer cells can revert from glycolysis to OXPHOS and maintain both reprogrammed and oxidative metabolism even in the same tumor. The phenomenon denoted as cancer cell metabolic plasticity or hybrid metabolism depends on a tumor micro-environment, which is highly heterogeneous and influenced by intensity of vasculature and blood flow, oxygen concentration, nutrient and energy supply, and requires regulatory interplay between multiple oncogenes, transcription factors, growth factors, reactive oxygen species (ROS), etc. Hypoxia-inducible factor-1 (HIF-1) and AMP-activated protein kinase (AMPK) represent key modulators of switch between reprogrammed and oxidative metabolism. The present review focuses on cross-talks between HIF-1, GLUTs, and AMPK and other regulatory proteins including oncogenes such as c-Myc, p53 and KRAS, growth factor-initiated PKB/Akt, PI3K and mTOR signaling pathways and tumor suppressors such as LKB1 and TSC1 in controlling cancer cell metabolism. The multiple switches between metabolic pathways can underlie chemo-resistance to conventional anti-cancer therapy and should be taken into account in choosing molecular targets to discovery novel anti-cancer drugs.

We previously reported how the loss of CHIP expression (Carboxyl terminus of Hsc70-Interacting Protein) during pressure overload resulted in robust cardiac dysfunction, accompanied by a failure to maintain ATP levels in the face of increased energy demand. In this study, we analyzed the cardiac metabolome after seven days of pressure overload and found an increase in long- and medium-chain fatty acid metabolites in wild-type hearts, a response that was attenuated in mice that lack expression of CHIP (CHIP^-/-). These findings suggest that CHIP may play an essential role in regulating oxidative metabolism, pathways that are regulated in part by the nuclear receptor PPARα (Peroxisome Proliferator-Activated Receptor alpha). Next, we challenged CHIP^-/- mice with the PPARα agonist, fenofibrate. Surprisingly, treating CHIP^-/- mice with fenofibrate for five weeks under non-pressure overload conditions resulted in a loss of skeletal muscle mass and a marked increase in cardiac fibrosis, accompanied by a decrease in cardiac function. Isolated CHIP^-/- cardiac fibroblasts treated with fenofibrate did not increase synthesis of collagen or TGFβ, suggesting that the fibrosis observed in CHIP^-/- hearts likely depends on signaling from other cell types or circulating factors. In conclusion, in the absence of functional CHIP expression, fenofibrate results in unexpected cardiac pathologies. These findings are particularly relevant to patients harboring loss-of-function mutations in CHIP and are consistent with a prominent role for CHIP in regulating cardiac metabolism.

Background: The control of energy metabolism is fundamental for cell growth and function, and anomalies are implicated in complex diseases and ageing. It is important for cells to carefully tune metabolic pathways to optimize their function in response to different nutrient or physiological conditions. Metabolism in yeast cells can be easily manipulated by supplying different carbon sources: on glucose yeast rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. The growth medium and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in key energy metabolism pathways were coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that the acetyl-CoA synthase, rather than the citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: These systematic and targeted analyses provide a rich framework of the genetic and regulatory basis of fundamental metabolic states to guide future studies on energy metabolism in fission yeast and beyond. Our study pinpoints weaknesses of commonly used auxotroph mutants for investigating energy metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.

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.

Ti-aluminosilicate gels were used as supports for immobilization of Fe, Co and Ni oxides (5%) by impregnation, and synthesis of efficient photocatalysts in degradation of β-lactam antibiotic from water. Titanium oxide (1 and 2%) was incorporated into zeolite network by modifying the gel during the zeolitation process. The formation of the zeolite Y structure and its microporous structure were evidenced by X-ray diffraction and N2 physisorption. The structure, composition, reduction and optical properties were studied by X-ray difraction, H2-TPR, XPS, Raman, photoluminiscence and UV-Vis spectroscopy. The obtained results indicated a zeolite Y structure for all photocatalysts with tetra-coordinate Ti4+ sites. The immobilized metals from group VIII are both in the form of metal oxides such as Fe2O3, Fe3O4, CoO, Co3O4 , NiO and also in the me-tallic state (Fe0, Co0, and Ni0). A red shift of the absorption edge was observed in UV-Vis spectra of photocatalysts upon addition of Fe, Co or Ni species. The photocatalytic performances were evaluated in degradation of cefuroxime from water under visible light irradiation. The best results were obtained for iron immobilized photocatalysts. Scavenger experiments explained the photocatalytic results and their mechanisms. A different contribution of the active species to the photocatalytic reactions was evidenced.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

Globally, cancer is an important health problem worldwide, and has become one modern medicine’s most serious problems to prevent, diagnose, and treat. Many types of cancers still have non-negligible mortality rates, and new treatments need to be developed for them. This study aimed to elucidate cancer mechanisms and facilitate cancer treatment and prevention. The ideal temperature for cancer growth is 35°C; however, conditions were not consistent with chromosomal instability, loss of alleles of tumor-suppressor genes, abnormal DNA methylation, and collagen phagocytosis, which are known causes of cancer. In addition, when cancer develops, white blood cells attack the cancer tissue and remove it; however, as the decrease in body temperature drops, leads to a reduction in the immune potential of the white blood cells. Based on previous papers, this study focused on aimed to determine the effects of the low-temperature environment of 35°C, the temperature at which cancer is most likely to proliferate, and changes in adenosine triphosphate (ATP) levels. The study revealed that Therefore, the causes of cancer is caused by include chromosome fusion that occurs occurring due to the impaired DNA topoisomerase IIα proliferation and primary cilia rotation due to resulting from decreased intercellular adhesion.

Objectives: Metabolic interactions amongst mutated genes in myelodysplastic syndrome (MDS) offer promising avenues for novel anticancer treatments. Our comprehensive study delves into these mutational and transcriptomic landscapes, pinpointing hallmark gene mutations and deregulated gene expression that could influence MDS patients’ metabolomes. Methods: The study utilized a retrospective, cross-sectional approach, employing mutational data on the cBio Cancer Genomics Portal conducted and reported by the University of Tokyo in 2011 and multi-center MDS cohorts regulated by Wellcome Trust Sanger Institute, United Kingdom, all in 2020. For transcriptomic data, we selected three publicly accessible independent cohorts on the Gene Expression Omnibus (GEO) database (GSE114922 in Wellcome Trust Centre for Human Genetics, United Kingdome, GSE63569 in University of Oxford, United Kingdome, and GSE183328 in CIMA, Spain) held in 2015, 2018, and 2022, respectively. To compile clinical, mutational, and transcriptomic data on MDS patients from multiple datasets and studies. This meta-analysis included genomic data derived from cellular genomics sources to assess mutations in specific genes, alongside an examination of transcriptomic data from three separate datasets that have been previously published. Results: DNMT3A presented a 20% mutation frequency, playing a pivotal role in MDS metabolomics. The DNMT3A gene mutations displayed significant mutual exclusivity with the SRSF2, ASXL1, JAK2, and TP53 genes. The mutational analysis also showed that the gene expression landscape in MDS is associated with alterations to DNA methylation pathways. Conclusion: This analysis suggests a potential therapeutic niche. Identifying signature genes in MDS that have metabolic and methylation affiliations could illuminate the disease's intricate biology and inspire novel treatments.