Changes In Metabolic Activity Research Articles

Energetic Costs of Stress in Developing Fishes: Quantifying Allostasis and Allostatic Load.

Stress exerts negative effects on fish health through stimulation of the hypothalamic-pituitary-interrenal (HPI) axis and autonomic nervous system (ANS), resulting in heightened neural and neuroendocrine responses. Energetic investment and physiological adaptation are then required to re-establish homeostatic stability or reach a new allostatic state. The cost of the energetic investment is referred to as allostatic load (AL). While determining the sources of stress and assessing their consequences have resulted in estimates of AL, most of this work has been conducted in adult mammals and humans; no ALs exist for developing fish. From a series of experiments on a model species, zebrafish (Danio rerio) which yolk-sac larvae were exposed to two chronic stressors (high-temperature and hypoxia) ALs were quantified based on biomarkers of ontogenetic changes in growth, morphometrics, and metabolic activities. Results showed that for zebrafish yolk-sac larvae, chronic stress imposed high AL and, thus, high total allostatic energetic costs, (Rt (AL)), because of prolonged energy demand in the face of limited resources (e.g., yolk). Under severe chronic stress, energetic costs were sufficiently large that energy-limited developing fish may not be able to fully compensate, resulting in maladaptive responses from allostatic overload, leading either to death or to novel allostatic states, possibly more resilient to environmental change.

Estimating Enzyme Expression and Metabolic Pathway Activity in Borreliella-Infected and Uninfected Mice.

Evaluating changes in metabolic pathway activity is essential for studying disease mechanisms and developing new treatments, with significant benefits extending to human health. Here, we propose EMPathways2, a maximum likelihood pipeline that is based on the expectation-maximization algorithm, which is capable of evaluating enzyme expression and metabolic pathway activity level. We first estimate enzyme expression from RNA-seq data that is used for simultaneous estimation of pathway activity levels using enzyme participation levels in each pathway. We implement the novel pipeline to RNA-seq data from several groups of mice, which provides a deeper look at the biochemical changes occurring as a result of bacterial infection, disease, and immune response. Our results show that estimated enzyme expression, pathway activity levels, and enzyme participation levels in each pathway are robust and stable across all samples. Estimated activity levels of a significant number of metabolic pathways strongly correlate with the infected and uninfected status of the respective rodent types.

Effects of natural flood management woody dams on benthic macroinvertebrates and benthic metabolism in upland streams: Importance of wood‐induced geomorphic changes

AbstractNatural Flood Management (NFM) aims to reduce flood hazard by working with nature and is gaining prominence worldwide. One particular NFM technique involves the use of channel‐spanning woody dams that maintain a clearance height above baseflow. These dams function by increasing channel roughness during high flows and by forcing excessive water onto the floodplain. Whether these dams provide additional benefits to nature remains unclear. While there are many existing studies on natural in‐stream wood structures, very few have documented the impact of NFM woody dams in particular. This study adopted a multidisciplinary approach and a Before–After Control–Impact (BACI) research design to assess whether NFM woody dams installed in a small upland catchment had driven changes in benthic macroinvertebrate assemblages and benthic metabolic activities through the geomorphic changes that they had created. Statistical results indicate that macroinvertebrate density, richness, and diversity did not show any difference between stream reaches with and without NFM woody dams. The metrics were generally not related to grain‐size parameters and volumes of sediments eroded or deposited. However, individual genera such as Baetis and Rhithrogena became more dominant in the control reach towards the end of the study period, likely due to the higher flow velocities and coarser sediments there resulting from the lack of flow resistance in the absence of NFM woody dams. Rates of benthic respiration (but not rates of photosynthesis) were consistently significantly higher in woody dam reaches than in control reaches, likely due to the presence of patches of finer sediments in the former.

Phenotypic and proteomic differences in biofilm formation of two Lactiplantibacillus plantarum strains in static and dynamic flow environments

Lactiplantibacillus plantarum is a Gram-positive non-motile bacterium capable of producing biofilms that contribute to the colonization of surfaces in a range of different environments. In this study, we compared two strains, WCFS1 and CIP104448, in their ability to produce biofilms in static and dynamic (flow) environments using an in-house designed flow setup. This flow setup enables us to impose a non-uniform flow velocity profile across the well. Biofilm formation occurred at the bottom of the well for both strains, under static and flow conditions, where in the latter condition, CIP104448 also showed increased biofilm formation at the walls of the well in line with the higher hydrophobicity of the cells and the increased initial attachment efficacy compared to WCFS1. Fluorescence and scanning electron microscopy showed open 3D structured biofilms formed under flow conditions, containing live cells and ∼30 % damaged/dead cells for CIP104448, whereas the WCFS1 biofilm showed live cells closely packed together. Comparative proteome analysis revealed minimal changes between planktonic and static biofilm cells of the respective strains suggesting that biofilm formation within 24 h is merely a passive process. Notably, observed proteome changes in WCFS1 and CIP104448 flow biofilm cells indicated similar and unique responses including changes in metabolic activity, redox/electron transfer and cell division proteins for both strains, and myo-inositol production for WCFS1 and oxidative stress response and DNA damage repair for CIP104448 uniquely. Exposure to DNase and protease treatments as well as lethal concentrations of peracetic acid showed highest resistance of flow biofilms. For the latter, CIP104448 flow biofilm even maintained its high disinfectant resistance after dispersal from the bottom and from the walls of the well. Combining all results highlights that L. plantarum biofilm structure and matrix, and physiological state and stress resistance of cells is strain dependent and strongly affected under flow conditions. It is concluded that consideration of effects of flow on biofilm formation is essential to better understand biofilm formation in different settings, including food processing environments.

Molecular mechanisms of cytochrome P450-mediated detoxification of tetraniliprole, spinetoram, and emamectin benzoate in the fall armyworm, Spodoptera frugiperda (J.E. Smith).

The fall armyworm (FAW) Spodoptera frugiperda (J.E. Smith) is a highly damaging invasive omnivorous pest that has developed varying degrees of resistance to commonly used insecticides. To investigate the molecular mechanisms of tolerance to tetraniliprole, spinetoram, and emamectin benzoate, the enzyme activity, synergistic effect, and RNA interference were implemented in S. frugiperda. The functions of cytochrome P450 monooxygenase (P450) in the tolerance to tetraniliprole, spinetoram, and emamectin benzoate in S. frugiperda was determined by analysing changes in detoxification metabolic enzyme activity and the effects of enzyme inhibitors on susceptibility to the three insecticides. 102 P450 genes were screened via transcriptome and genome, of which 67 P450 genes were differentially expressed in response to tetraniliprole, spinetoram, and emamectin benzoate and validated by quantitative real-time PCR. The expression patterns of CYP9A75, CYP340AA4, CYP340AX8v2, CYP340L16, CYP341B15v2, and CYP341B17v2 were analysed in different tissues and at different developmental stages in S. frugiperda. Silencing CYP340L16 significantly increased the susceptibility of S. frugiperda to tetraniliprole, spinetoram, and emamectin benzoate. Furthermore, knockdown of CYP340AX8v2, CYP9A75, and CYP341B17v2 significantly increased the sensitivity of S. frugiperda to tetraniliprole. Knockdown of CYP340AX8v2 and CYP340AA4 significantly increased mortality of S. frugiperda to spinetoram. Knockdown of CYP9A75 and CYP341B15v2 significantly increased the susceptibility of S. frugiperda to emamectin benzoate. These results may help to elucidate the mechanisms of tolerance to tetraniliprole, spinetoram and emamectin benzoate in S. frugiperda.

Labile assembly of a tardigrade protein induces biostasis.

Tardigrades are microscopic animals that survive desiccation by inducing biostasis. To survive drying tardigrades rely on intrinsically disordered CAHS proteins, which also function to prevent perturbations induced by drying in vitro and in heterologous systems. CAHS proteins have been shown to form gels both in vitro and in vivo, which has been speculated to be linked to their protective capacity. However, the sequence features and mechanisms underlying gel formation and the necessity of gelation for protection have not been demonstrated. Here we report a mechanism of fibrillization and gelation for CAHS D similar to that of intermediate filament assembly. We show that in vitro, gelation restricts molecular motion, immobilizing and protecting labile material from the harmful effects of drying. In vivo, we observe that CAHS D forms fibrillar networks during osmotic stress. Fibrillar networking of CAHS D improves survival of osmotically shocked cells. We observe two emergent properties associated with fibrillization; (i) prevention of cell volume change and (ii) reduction of metabolic activity during osmotic shock. We find that there is no significant correlation between maintenance of cell volume and survival, while there is a significant correlation between reduced metabolism and survival. Importantly, CAHS D's fibrillar network formation is reversible and metabolic rates return to control levels after CAHS fibers are resolved. This work provides insights into how tardigrades induce reversible biostasis through the self-assembly of labile CAHS gels.

Analysis of pharmacokinetic profile and ecotoxicological character of cefepime and its photodegradation products

An important problem is the impact of photodegradation on product toxicity in biological tests, which may be complex and context-dependent. Previous studies have described the pharmacology of cefepime, but the toxicological effects of its photodegradation products remain largely unknown. Therefore, photodegradation studies were undertaken in conditions similar to those occurring in biological systems insilico, in vitro, in vivo and ecotoxicological experiments. The structures of four cefepime photodegradation products were determined by UPLC-MS/MS method. The calculated in silico ADMET profile indicates that carcinogenic potential is expected for compounds CP-1, cefepime, CP-2 and CP-3. The Cell Line Cytomotovity Predictor 2.0 tool was used to predict the cytotoxic effects of cefepime and related compounds in non-transformed and cancer cell lines. The results indicate that possible actions include: non-small cell lung cancer, breast adenocarcinoma, prostate cancer and papillary renal cell carcinoma. OPERA models were used to predict absorption, distribution, metabolism and excretion (ADME) endpoints, and potential bioactivity of CP-2, cefepime and CP-4. The results obtained in silico show that after 96h of exposure, cefepime, CP-1, CP-2, and CP-3 are moderately toxic in the zebrafish model, while CP-4 is highly toxic. On the contrary, cefepime is more toxic to T. platyurus (highly toxic) compared to the zebrafish model, similar to products CP-4, CP-3 and CP-2. In vitro cytotoxicity studies were performed by MTT assay and in vivo acute embryo toxicity studies using Danio rerio embryos and larvae. In vitro showed an increase in the cytotoxicity of products with the longest exposure period i.e. for 8 h. Additionally, at a concentration of 200 μg/mL, statistically significant changes in metabolic activity were observed depending on the irradiation time. In vivo studies conducted with Zebrafish showed that both cefepime and its photodegradation products have only low toxicity. Assessment of potential ecotoxicity included Microbiotests on invertebrates (Thamnotoxkit F and Daphtoxkit F), and luminescence inhibition tests (LumiMara). The observed toxicity of the tested solutions towards both Thamnocephalus platyurus and Daphnia magna indicates that the parent substance (unexposed) has lower toxicity, which increases during irradiation. The acute toxicity (Lumi Mara) of nonirradiated cefepime solution is low for all tested strains (<10%), but mixtures of cefepime and its photoproducts showed growth inhibition against all tested strains (except #6, Photobacterium phoreum). Generally, it can be concluded that after UV–Vis irradiation, the mixture of cefepime phototransformation products shows a significant increase in toxicity.

Research on the Application and Mechanisms of Electroactive Microorganisms in Toxicants Monitoring: A Review.

A biological treatment is the core process for removing organic pollutants from industrial wastewater. However, industrial wastewater often contains large amounts of toxic and harmful pollutants, which can inhibit the activity of microorganisms in a treatment system, precipitate the deterioration of effluent quality, and threaten water ecological security from time to time. In most of the existing anaerobic biological treatment processes, toxic effects on microorganisms are determined according to the amounts of end-products of the biochemical reactions, and the evaluation results are relatively lacking. When microorganisms contact toxic substances, changes in biological metabolic activity precede the accumulation of reaction products. As sensitive units, electroactive microorganisms can generate electrical signals, a change in which can directly reflect the toxicity level. The applications of electroactive microorganisms for the toxicity monitoring of wastewater are very promising. Further attention needs to be paid to considering the appropriate evaluation index, the influence of the environment on test results, mechanisms, and other aspects. Therefore, we reviewed the literature regarding the above aspects in order to provide a research foundation for the practical application of electroactive microorganisms in toxicant monitoring.

The maturity, humus content, and microbial metabolic function of sheep manure compost on the Qinghai-Tibet Plateau can be significantly improved by reducing the moisture content.

The Qinghai-Tibet Plateau (QTP) is characterized by an extreme hypoxia, which may lead to lack of sufficient oxygen for compost production, and thus seriously affecting the compost quality. The moisture content (MC) has a direct effect on the oxygen content of composting pile. At present, the research on the optimum moisture content of compost production on the QTP is still lacking. This study aimed to investigate the influences of MC on fermentation quality of sheep manure composting on the QTP and to further analyze the changes of microbial metabolic function and enzyme activity under different MC. Composting experiment with low MC (45%) and conventional MC (60%) was conducted in both summer and autumn. The results showed that the composting efficiency of 45% MC was better than 60% in both seasons, which was mainly manifested as longer high-temperature period (summer:16d vs 14d, autumn: 7d vs 2d), higher germination index (summer:136.1% vs 128.6%, autumn:103.5% vs 81.2%), and more humus synthesis (summer:159.8g/kg vs 151.2g/kg, autumn:136.1k/kg vs 115.5k/kg). The 45% MC can improve microbial metabolism, including increasing the abundance of functional genes involved in carbohydrate metabolism, amino acid metabolism, and nucleotide metabolism and improving the activities of cellulase, β-glucosidase, protease, polyphenol oxidase, and peroxidase. In conclusion, 45% MC can improve the fermentation efficiency and products quality of sheep manure compost on QTP.

Monitoring drug metabolic pathways through extracellular vesicles in mouse plasma.

The ability to monitor the response of metabolic enzymes to drug exposure in individuals is highly appealing and critical to personalized medicine. Although pharmacogenomics assesses genotypic differences, it does not report changes in metabolic enzyme activities due to environmental factors such as drug interactions. Here, we report a quantitative proteomics strategy to monitor drug metabolic pathways by profiling metabolic enzymes in circulating extracellular vesicles (EVs) upon drug exposure. Mass spectrometry (MS)-based measurement revealed that changes in metabolic enzyme abundance in EVs paralleled those in hepatic cells isolated from liver tissue. Coupling with multiplexed isotopic labeling, we temporally quantified 34 proteins involved in drug absorption, distribution, metabolism, and excretion (ADME) pathways. Out of 44 known ADME proteins in plasma EVs, previously annotated mouse cytochrome P450 3A11 (Cyp3a11), homolog to human CYP3A4, and uridine 5'-diphospho (UDP) glucuronosyltransferase 2A3 (Ugt2a3), increased upon daily rifampicin dosage. Dasatinib, a tyrosine kinase inhibitor to treat leukemia, also elevated Cyp3a11 levels in plasma EVs, but to a lesser extent. Altogether, this study demonstrates that measuring drug enzymes in circulating EVs as an effective surrogate is highly feasible and may transform today's drug discovery and development for personalized medicine.

Revving the engine: PKB/AKT as a key regulator of cellular glucose metabolism.

Glucose metabolism is of critical importance for cell growth and proliferation, the disorders of which have been widely implicated in cancer progression. Glucose uptake is achieved differently by normal cells and cancer cells. Even in an aerobic environment, cancer cells tend to undergo metabolism through glycolysis rather than the oxidative phosphorylation pathway. Disordered metabolic syndrome is characterized by elevated levels of metabolites that can cause changes in the tumor microenvironment, thereby promoting tumor recurrence and metastasis. The activation of glycolysis-related proteins and transcription factors is involved in the regulation of cellular glucose metabolism. Changes in glucose metabolism activity are closely related to activation of protein kinase B (PKB/AKT). This review discusses recent findings on the regulation of glucose metabolism by AKT in tumors. Furthermore, the review summarizes the potential importance of AKT in the regulation of each process throughout glucose metabolism to provide a theoretical basis for AKT as a target for cancers.

The Potential Transcriptomic and Metabolomic Mechanisms of ATO and ATRA in Treatment of FLT3-ITD Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) with Fms-like tyrosine kinase 3 gene internal tandem duplication (FLT3-ITD) mutations has a poor prognosis. The combination of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) has a synergistic killing effect on leukemia cells with FLT3-ITD mutation. However, the mechanism, especially the changes of gene expression and metabolic activity remain unclear. Here we explore the transcriptome and metabolomics changes of FLT3-ITD AML cells treated with ATO/ATRA. RNA-seq was used to identify differential expressed genes (DEGs), and ultra-high performance liquid chromatography-quadrupole electrostatic field orbital trap mass spectrometry (UHPLC-QE-MS) nontargeted metabolomics method was used to screen out the differential metabolites in FLT3-ITD mutant cell lines treated with ATRA and ATO. KEGG pathway database was utilized for pathway exploration and Seahorse XF24 was used to detect extracellular acidification rate (ECAR). Metabolic polymerase chain reaction (PCR) array and real-time quantitative PCR (RT-qPCR) were used to detect mRNA levels of key metabolic genes of glycolysis and fatty acid after drug treatment. A total of 3873 DEGs were identified and enriched in 281 Gene Ontology (GO) terms, among which 210 were related to biological processes, 43 were related to cellular components, and 28 were related to molecular functions. Besides, 1794 and 927 differential metabolites were screened in positive and negative ion mode separately, and 59 different metabolic pathways were involved, including alanine-aspartate-glutamate metabolic pathway, arginine, and proline metabolic pathway, glycerophospholipid metabolic pathways, etc. According to KEGG Pathway analysis of transcriptome combined with metabolome, glycolysis/gluconeogenesis pathway and fatty acid metabolism pathway were significantly founded enriched. ATRA + ATO may inhibit the glycolysis of FLT3-ITD AML cells by inhibiting FLT3 and its downstream AKT/HK2-VDAC1 signaling pathway. The gene transcription profile and metabolites of FLT3-ITD mutant cells changes significantly after treatment, which might be related to the anti-FLT3-ITD AML effect. The screened DEGs, differential metabolites pathway are helpful in studying the mechanism of anti-leukemia effects and drug targets.

Evidence of the Beneficial Impact of Three Probiotic-Based Food Supplements on the Composition and Metabolic Activity of the Intestinal Microbiota in Healthy Individuals: An Ex Vivo Study.

Scientific evidence has increasingly supported the beneficial effects of probiotic-based food supplements on human intestinal health. This ex vivo study investigated the effects on the composition and metabolic activity of the intestinal microbiota of three probiotic-based food supplements, containing, respectively, (1) Bifidobacterium longum ES1, (2) Lactobacillus acidophilus NCFM®, and (3) a combination of L. acidophilus NCFM®, Lactobacillus paracasei Lpc-37™, Bifidobacterium lactis Bi-07™, and Bifidobacterium lactis Bl-04™. This study employed fecal samples from six healthy donors, inoculated in a Colon-on-a-plate® system. After 48 h of exposure or non-exposure to the food supplements, the effects were measured on the overall microbial fermentation (pH), changes in microbial metabolic activity through the production of short-chain and branched-chain fatty acids (SCFAs and BCFAs), ammonium, lactate, and microbial composition. The strongest effect on the fermentation process was observed for the combined formulation probiotics, characterized by the significant stimulation of butyrate production, a significant reduction in BCFAs and ammonium in all donors, and a significant stimulatory effect on bifidobacteria and lactobacilli growth. Our findings suggest that the combined formulation probiotics significantly impact the intestinal microbiome of the healthy individuals, showing changes in metabolic activity and microbial abundance as the health benefit endpoint.

Aged tendons lack adaptive response to acute compressive injury.

Rotator cuff tendinopathy has a multifactorial etiology, with both aging and external compression found to influence disease progression. However, tendon's response to these factors is still poorly understood and in vivo animal models make it difficult to decouple these effects. Therefore, we developed an explant culture model that allows us to directly apply compression to tendons and then observe their biological responses. Using this model, we applied a single acute compressive injury to C57BL/6J flexor digitorum longus tendon explants and observed changes in viability, metabolic activity, matrix composition, matrix biosynthesis, matrix structure, gene expression, and mechanical properties. We hypothesized that a single acute compressive load would result in an injury response in tendon and that this effect would be amplified in aged tendons. We found that young tendons had increased matrix turnover with a decrease in small leucine-rich proteoglycans, increase in compression-resistant proteoglycan aggrecan, increase in collagen synthesis, and an upregulation of collagen-degrading MMP-9. Aged tendons lacked any of these adaptive responses and instead had decreased metabolic activity and collagen synthesis. This implies that aged tendons lack the adaptation mechanisms required to return to homeostasis, and therefore are at greater risk for compression-induced injury. Overall, we present a novel compressive injury model that demonstrates lasting age-dependent changes and has the potential to examine the long-term response of tendon to a variety of compressive loading conditions.

Rapid intestinal and systemic metabolic reprogramming in an immunosuppressed environment

Intrinsic metabolism shapes the immune environment associated with immune suppression and tolerance in settings such as organ transplantation and cancer. However, little is known about the metabolic activities in an immunosuppressive environment. In this study, we employed metagenomic, metabolomic, and immunological approaches to profile the early effects of the immunosuppressant drug tacrolimus, antibiotics, or both in gut lumen and circulation using a murine model. Tacrolimus induced rapid and profound alterations in metabolic activities within two days of treatment, prior to alterations in gut microbiota composition and structure. The metabolic profile and gut microbiome after seven days of treatment was distinct from that after two days of treatment, indicating continuous drug effects on both gut microbial ecosystem and host metabolism. The most affected taxonomic groups are Clostriales and Verrucomicrobiae (i.e., Akkermansia muciniphila), and the most affected metabolic pathways included a group of interconnected amino acids, bile acid conjugation, glucose homeostasis, and energy production. Highly correlated metabolic changes were observed between lumen and serum metabolism, supporting their significant interactions. Despite a small sample size, this study explored the largely uncharacterized microbial and metabolic events in an immunosuppressed environment and demonstrated that early changes in metabolic activities can have significant implications that may serve as antecedent biomarkers of immune activation or quiescence. To understand the intricate relationships among gut microbiome, metabolic activities, and immune cells in an immune suppressed environment is a prerequisite for developing strategies to monitor and optimize alloimmune responses that determine transplant outcomes.

Changes in attachment and metabolic activity of rat neonatal cardiomyocytes and nonmyocytes caused by Macrovipera lebetina obtusa venom

The Caucasian viper Macrovipera lebetina obtusa (MLO) is one of the most prevalent and venomous snakes in the Caucasus and the surrounding regions, yet the effects of MLO venom on cardiac function remain largely unknown. We examined the influence of MLO venom (crude and with inhibited metalloproteinases and phospholipase A2) on attachment and metabolic activity of rat neonatal cardiomyocytes (CM) and nonmyocytes (nCM), assessed at 1 and 24 h. After exposing both CM and nCM to varying concentrations of MLO venom, we observed immediate cytotoxic effects at a concentration of 100 μg/ml, causing detachment from the culture substrate. At lower MLO venom concentrations both cell types detached in a dose-dependent manner. Inhibition of MLO venom metalloproteinases significantly improved CM and nCM attachment after 1-hour exposure. At 24-hour exposure to metalloproteinases inhibited venom statistically significant enhancement was observed only in nCM attachment. However, metabolic activity of CM and nCM did not decrease upon exposure to the lower dose of the venom. Moreover, we demonstrated that metalloproteinases and phospholipases A2 are not the components of the MLO venom that change metabolic activity of both CM and nCM. These results provide a valuable platform to study the impact of MLO venom on prey cardiac function. They also call for further exploration of individual venom components for pharmaceutical purposes.

Diurnal cycles drive rhythmic physiology and promote survival in facultative phototrophic bacteria

Bacteria have evolved many strategies to spare energy when nutrients become scarce. One widespread such strategy is facultative phototrophy, which helps heterotrophs supplement their energy supply using light. Our knowledge of the impact that such behaviors have on bacterial fitness and physiology is, however, still limited. Here, we study how a representative of the genus Porphyrobacter, in which aerobic anoxygenic phototrophy is ancestral, responds to different light regimes under nutrient limitation. We show that bacterial survival in stationary phase relies on functional reaction centers and varies depending on the light regime. Under dark-light alternance, our bacterial model presents a diphasic life history dependent on phototrophy: during dark phases, the cells inhibit DNA replication and part of the population lyses and releases nutrients, while subsequent light phases allow for the recovery and renewed growth of the surviving cells. We correlate these cyclic variations with a pervasive pattern of rhythmic transcription which reflects global changes in diurnal metabolic activity. Finally, we demonstrate that, compared to either a phototrophy mutant or a bacteriochlorophyll a overproducer, the wild type strain is better adapted to natural environments, where regular dark-light cycles are interspersed with additional accidental dark episodes. Overall, our results highlight the importance of light-induced biological rhythms in a new model of aerobic anoxygenic phototroph representative of an ecologically important group of environmental bacteria.

UVA Hyperspectral Light-Sheet Microscopy for Volumetric Metabolic Imaging: Application to Preimplantation Embryo Development.

Cellular metabolism is a key regulator of energetics, cell growth, regeneration, and homeostasis. Spatially mapping the heterogeneity of cellular metabolic activity is of great importance for unraveling the overall cell and tissue health. In this regard, imaging the endogenous metabolic cofactors, nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD), with subcellular resolution and in a noninvasive manner would be useful to determine tissue and cell viability in a clinical environment, but practical use is limited by current imaging techniques. In this paper, we demonstrate the use of phasor-based hyperspectral light-sheet (HS-LS) microscopy using a single UVA excitation wavelength as a route to mapping metabolism in three dimensions. We show that excitation solely at a UVA wavelength of 375 nm can simultaneously excite NAD(P)H and FAD autofluorescence, while their relative contributions can be readily quantified using a hardware-based spectral phasor analysis. We demonstrate the potential of our HS-LS system by capturing dynamic changes in metabolic activity during preimplantation embryo development. To validate our approach, we delineate metabolic changes during preimplantation embryo development from volumetric maps of metabolic activity. Importantly, our approach overcomes the need for multiple excitation wavelengths, two-photon imaging, or significant postprocessing of data, paving the way toward clinical translation, such as in situ, noninvasive assessment of embryo viability.

The mechanisms of action of mitochondrial targeting agents in cancer: inhibiting oxidative phosphorylation and inducing apoptosis.

The tumor microenvironment affects the structure and metabolic function of mitochondria in tumor cells. This process involves changes in metabolic activity, an increase in the amount of reactive oxygen species (ROS) in tumor cells compared to normal cells, the production of more intracellular free radicals, and the activation of oxidative pathways. From a practical perspective, it is advantageous to develop drugs that target mitochondria for the treatment of malignant tumors. Such drugs can enhance the selectivity of treatments for specific cell groups, minimize toxic effects on normal tissues, and improve combinational treatments. Mitochondrial targeting agents typically rely on small molecule medications (such as synthetic small molecules agents, active ingredients of plants, mitochondrial inhibitors or autophagy inhibitors, and others), modified mitochondrial delivery system agents (such as lipophilic cation modification or combining other molecules to form targeted mitochondrial agents), and a few mitochondrial complex inhibitors. This article will review these compounds in three main areas: oxidative phosphorylation (OXPHOS), changes in ROS levels, and endogenous oxidative and apoptotic processes.

Enhanced Antibacterial Ability of Electrospun PCL Scaffolds Incorporating ZnO Nanowires.

The infection of implanted biomaterial scaffolds presents a major challenge. Existing therapeutic solutions, such as antibiotic treatment and silver nanoparticle-containing scaffolds are becoming increasingly impractical because of the growth of antibiotic resistance and the toxicity of silver nanoparticles. We present here a novel concept to overcome these limitations, an electrospun polycaprolactone (PCL) scaffold functionalised with zinc oxide nanowires (ZnO NWs). This study assessed the antibacterial capabilities and biocompatibility of PCL/ZnO scaffolds. The fabricated scaffolds were characterised by SEM and EDX, which showed that the ZnO NWs were successfully incorporated and distributed in the electrospun PCL scaffolds. The antibacterial properties were investigated by co-culturing PCL/ZnO scaffolds with Staphylococcus aureus. Bacterial colonisation was reduced to 51.3% compared to a PCL-only scaffold. The biocompatibility of the PCL/ZnO scaffolds was assessed by culturing them with HaCaT cells. The PCL scaffolds exhibited no changes in cell metabolic activity with the addition of the ZnO nanowires. The antibacterial and biocompatibility properties make PCL/ZnO a good choice for implanted scaffolds, and this work lays a foundation for ZnO NWs-infused PCL scaffolds in the potential clinical application of tissue engineering.