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UV irradiation of the human skin downregulates lipid synthesis and adipokine production in subcutaneous fat. Recent evidence has suggested that UV exposure limits body weight gain in mouse models of obesity. However, the relationship between norepinephrine and UV irradiation has not been previously reported. Chronic UV exposure stimulated food intake but prevented body weight gain. Leptin, an appetite-suppressing hormone, was significantly reduced in the serum of the UV-irradiated mice. In contrast, UV irradiation induced browning of subcutaneous white adipose tissues without increasing physical activity. Notably, UV irradiation significantly increased norepinephrine levels, and the inhibition of norepinephrine production reversed the effects of chronic UV irradiation on food intake and body weight gain. In conclusion, chronic UV irradiation induces norepinephrine release, resulting in the stimulation of food intake due to the downregulation of leptin levels, but it prevents weight gain by inducing the browning process and elevating energy expenditure., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In recent years exposure of living beings to radiofrequency radiation (RFR) emitted from wireless equipment has increased. In this study, we investigated the effects of 3.5-GHz RFR on hormones that regulate energy metabolism in the body. Twenty-eight rats were divided into four groups: healthy sham (n = 7), healthy RFR (n = 7), diabetic sham (n = 7), and diabetic RFR (n = 7). Over a month, each group spent 2 h/day in a Plexiglas carousel. The rats in the experimental group were exposed to RFR, but the sham groups were not. At the end of the experiment, blood and adipose tissues were collected from euthanized rats. Total antioxidant, total oxidant, hydrogen peroxide, ghrelin, nesfatin-1, and irisin were determined. Insulin expression in pancreatic tissues was examined by immunohistochemical analysis. Whole body specific absorption rate was 37 mW/kg. For the parameters analyzed in blood and fat, the estimated effect size varied within the ranges of 0.215-0.929 and 0.503-0.839, respectively. The blood and adipose nesfatin-1 (p = 0.002), blood and pancreatic insulin are decreased, (p = 0.001), gherelin (p = 0.020), irisin (p = 0.020), and blood glucose (p = 0.040) are increased in healthy and diabetic rats exposed to RFR. While nesfatin-1 are negatively correlated with oxidative stress, hyperglycemia and insulin, ghrelin and irisin are positively correlated with oxidative stress and hyperglycemia. Thus, RFR may have deleterious effects on energy metabolism, particularly in the presence of diabetes., (© 2024 Bioelectromagnetics Society.)

Aims: This study proposes to investigate the effects of microwave radiation and its thermal effects, compared to thermal effects alone, on the bioenergetics of mitochondria isolated from mouse liver., Methods: The main parameters investigated in this study are mitochondrial respiration (coupled states: S3 and S4; uncoupled state), using a high-resolution respirometer, and swelling, using a spectrophotometer., Results: Mitochondria irradiated at 2.45 GHz microwave with doses 0.085, 0.113 and 0.141 kJ/g, presented a decrease in S3 and uncoupled state, but an increase in S4. Conversely, mitochondria thermally treated at 40, 44 and 50 °C presented an increasing in S3 and S4, while uncoupled state was unaltered. Mitochondrial swelling increases as a function of the dose or temperature, indicating membrane damages in both cases., Conclusion: Microwave radiation and thermal effect alone indicated different bioenergetics mitochondria response. These results imply that the effects due to microwave in medical treatment are not exclusively due to the increase in temperature, but a combination of electromagnetic and thermal effects.

Obesity and mobile phone usage have simultaneously spread worldwide. Radio frequency-modulated electromagnetic fields (RF-EMFs) emitted by mobile phones are largely absorbed by the head of the user, influence cerebral glucose metabolism, and modulate neuronal excitability. Body weight adjustment, in turn, is one of the main brain functions as food intake behavior and appetite perception underlie hypothalamic regulation. Against this background, we questioned if mobile phone radiation and food intake may be related. In a single-blind, sham-controlled, randomized crossover comparison, 15 normal-weight young men (23.47 ± 0.68 years) were exposed to 25 min of RF-EMFs emitted by two different mobile phone types vs. sham radiation under fasting conditions. Spontaneous food intake was assessed by an ad libitum standard buffet test and cerebral energy homeostasis was monitored by 31 phosphorus-magnetic resonance spectroscopy measurements. Exposure to both mobile phones strikingly increased overall caloric intake by 22-27% compared with the sham condition. Differential analyses of macronutrient ingestion revealed that higher calorie consumption was mainly due to enhanced carbohydrate intake. Measurements of the cerebral energy content, i.e., adenosine triphosphate and phosphocreatine ratios to inorganic phosphate, displayed an increase upon mobile phone radiation. Our results identify RF-EMFs as a potential contributing factor to overeating, which underlies the obesity epidemic. Beyond that, the observed RF-EMFs-induced alterations of the brain energy homeostasis may put our data into a broader context because a balanced brain energy homeostasis is of fundamental importance for all brain functions. Potential disturbances by electromagnetic fields may therefore exert some generalized neurobiological effects, which are not yet foreseeable.

DAF-16-dependent activation of a dauer-associated genetic program in the C. elegans insulin/IGF-1 daf-2(e1370) mutant leads to accumulation of large amounts of glycogen with concomitant upregulation of glycogen synthase, GSY-1. Glycogen is a major storage sugar in C. elegans that can be used as a short-term energy source for survival, and possibly as a reservoir for synthesis of a chemical chaperone trehalose. Its role in mitigating anoxia, osmotic and oxidative stress has been demonstrated previously. Furthermore, daf-2 mutants show increased abundance of the group 3 late embryogenesis abundant protein LEA-1, which has been found to act in synergy with trehalose to exert its protective role against desiccation and heat stress in vitro, and to be essential for desiccation tolerance in C. elegans dauer larvae. Here we demonstrate that accumulated glycogen is not required for daf-2 longevity, but specifically protects against hyperosmotic stress, and serves as an important energy source during starvation. Similarly, lea-1 does not act to support daf-2 longevity. Instead, it contributes to increased resistance of daf-2 mutants to heat, osmotic, and UV stress. In summary, our experimental results suggest that longevity and stress resistance can be uncoupled in IIS longevity mutants.

Thoracic radiotherapy increases the risk of radiation‑induced heart damage (RIHD); however, the molecular mechanisms underlying these changes are not fully understood. The aim of the present study was to investigate the effects of radiation on the mouse heart using high‑throughput proteomics. Male C57BL/6J mice were used to establish a model of RIHD by exposing the entire heart to 16 Gy high‑energy X‑rays, and cardiac injuries were verified using a cardiac echocardiogram, as well as by measuring serum brain natriuretic peptide levels and conducting H&E and Masson staining 5 months after irradiation. Proteomics experiments were performed using the heart apex of 5‑month irradiated mice and control mice that underwent sham‑irradiation. The most significantly differentially expressed proteins were enriched in 'cardiac fibrosis' and 'energy metabolism'. Next, the cardiac fibrosis and changes to energy metabolism were confirmed using immunohistochemistry staining and western blotting. Extracellular matrix proteins, such as collagen type 1 α 1 chain, collagen type III α 1 chain, vimentin and CCCTC‑binding factor, along with metabolism‑related proteins, such as fatty acid synthase and solute carrier family 25 member 1, exhibited upregulated expression following exposure to ionizing radiation. Additionally, the myocardial mitochondria inner membranes were injured, along with a decrease in ATP levels and the accumulation of lactic acid in the irradiated heart tissues. These results suggest that the high doses of ionizing radiation used lead to structural remodeling, functional injury and fibrotic alterations in the mouse heart. Radiation‑induced mitochondrial damage and metabolic alterations of the cardiac tissue may thus be a pathogenic mechanism of RIHD.

Background/aim: Carbon-ion radiotherapy has strong antitumor effects in X-ray-resistant tumors. However, the mechanisms underlying the strong antitumor effect, especially on metabolic alterations, are not fully elucidated. This study aimed to determine the effect of therapeutic carbon ions on metabolic alterations in cancer cells., Materials and Methods: Five human cancer cell lines were used in this study. The change in 333 metabolite levels in response to carbon ions was analyzed using gas chromatography-mass spectrometry., Results: Fifty-two metabolites were commonly detected in all cell lines. The levels of five metabolites significantly changed in four or more cell lines. Three of the five metabolites (i.e., 2-ketoglutaric acid, fumaric acid and 2-hydroxyglutaric acid) were associated with the TCA cycle. TCA cycle intermediates and the downstream oncometabolite 2-hydroxyglutaric acid were up-regulated by carbon ions., Conclusion: We demonstrated for the first time that TCA cycle intermediates and 2-hydroxyglutaric acid are up-regulated after carbon-ion irradiation., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Problem: Excess caloric intake and irregular circadian rhythm could severely impair female reproductive, metabolic, and immune function. However, the similarities and differences between their individual and combined effects and mechanisms have not been fully elucidated. Due to limitations and confounding factors in clinical research, we used these two kinds of unhealthy factors to intervene the mice singly or in combination to explore their effects on individuals., Method of Study: We used a high-calorie diet (HCD), constant light exposure (CLE), and a high-calorie diet combined with constant light exposure (HCD + CLE) to build three different mouse models. During the 9 weeks modeling period, the estrous cycles were monitored, and after modeling, the indicators of glycolipid metabolism, inflammation, and reproductive endocrine function were tested., Results: We found that both HCD and CLE alone could induce ovulatory disorders, obesity, and chronic low-grade inflammation and inhibit melatonin secretion. The difference was that HCD significantly reduced the serum luteinizing hormone (LH) and testosterone (T) levels, inhibited the expression of FSH β and LH β in pituitary, increased cytochrome P450 enzymes and LH receptor expression in ovary, as well causing impaired glucose tolerance and hyperlipidemia, and significantly promoted the secretion of leptin and inhibited the secretion of adiponectin. However, CLE significantly increased blood LH and T, prompted the expression of kisspeptin in hypothalamus and LH β in pituitary, and had no effect on glycolipid metabolic indexes or the secretion of leptin or adiponectin. The phenotype of HCD + CLE model was basically the same as that of HCD model, associated with more severe visceral obesity and chronic inflammation., Conclusions: In conclusion, we found that unhealthy lifestyle determines the phenotype of reproductive endocrine, immune, and metabolic disorders. These findings can provide theoretical support for the subsequent study of PCOS-like features., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Exposure to acute, damaging radiation may occur through a variety of events from cancer therapy and industrial accidents to terrorist attacks and military actions. Our understanding of how to protect individuals and mitigate the effects of radiation injury or Acute Radiation Syndrome (ARS) is still limited. There are only a few Food and Drug Administration-approved therapies for ARS; whereas, amifostine is limited to treating low dose (0.7-6 Gy) radiation poisoning arising from cancer radiotherapy. An early intervention is critical to treat ARS, which necessitates identifying diagnostic biomarkers to quickly characterize radiation exposure. Towards this end, a multiplatform metabolomics study was performed to comprehensively characterize the temporal changes in metabolite levels from mice and non-human primate serum samples following γ-irradiation. The metabolomic signature of amifostine was also evaluated in mice as a model for radioprotection. The NMR and mass spectrometry metabolomics analysis identified 23 dysregulated pathways resulting from the radiation exposure. These metabolomic alterations exhibited distinct trajectories within glucose metabolism, phospholipid biosynthesis, and nucleotide metabolism. A return to baseline levels with amifostine treatment occurred for these pathways within a week of radiation exposure. Together, our data suggests a unique physiological change that is independent of radiation dose or species. Furthermore, a metabolic signature of radioprotection was observed through the use of amifostine prophylaxis of ARS.

Diagnostic imaging has significantly grown over the last thirty years as indispensable support for diagnostic, prognostic, therapeutic and monitoring procedures of human diseases. This study explored the effects of low-dose X-ray medical diagnostics exposure on female fertility. To aim this, cumulus-oocyte complexes (COCs) recovered from the ovaries of juvenile sheep and human ovaries were used as complementary models for in vitro studies. In the sheep model, the effects of low-dose X-rays on oocyte viability and developmental competence were evaluated. In human ovaries originated from two age group (21-25 and 33-36 years old) subjects with gender dysphoria, X-rays effects on tissue morphology, follicular density and expression of apoptosis-related (NOXA, PUMA, Bcl2, Bak, γH2AX) and cell cycle-related genes (p21 and ki67) were investigated. It was noted that in sheep, the minimum dose of 10 mGy did not influence most of examined parameters at oocyte and embryo levels, whereas 50 and 100 mGy X-ray exposure reduced oocyte bioenergetic/oxidative activity but without any visible effects on oocyte and embryo development. In addition, blastocyst bioenergetic/oxidative status was reduced with all used doses. Overall data on human ovaries showed that low-dose X-rays, similarly as in sheep, did not alter any of examined parameters. However, in women belonging to the 33-36 year group, significantly reduced follicular density was observed after exposure to 50 and 100 mGy, and increased NOXA and Bax expression after exposure at 50 mGy. In conclusion, used low-doses of X-ray exposure, which resemble doses used in medical diagnostics, produce weak damaging effects on female fertility with increased susceptibility in advanced age., Competing Interests: The authors have declared that no competing interests exist.

Artificial systems capable of self-sustained movement with self-sufficient energy are of high interest with respect to the development of many challenging applications, including medical treatments, but also technical applications. The bottom-up assembly of such systems in the context of synthetic biology is still a challenging task. In this work, we demonstrate the biocompatibility and efficiency of an artificial light-driven energy module and a motility functional unit by integrating light-switchable photosynthetic vesicles with demembranated flagella. The flagellar propulsion is coupled to the beating frequency, and dynamic ATP synthesis in response to illumination allows us to control beating frequency of flagella in a light-dependent manner. In addition, we verified the functionality of light-powered synthetic vesicles in in vitro motility assays by encapsulating microtubules assembled with force-generating kinesin-1 motors and the energy module to investigate the dynamics of a contractile filamentous network in cell-like compartments by optical stimulation. Integration of this photosynthetic system with various biological building blocks such as cytoskeletal filaments and molecular motors may contribute to the bottom-up synthesis of artificial cells that are able to undergo motor-driven morphological deformations and exhibit directional motion in a light-controllable fashion.

The objective of this study was to evaluate effects of photobiomodulation therapy (PBMT) on the 3000 m running performance (primary outcome), running economy (RE), metabolic cost and ratings of perceived exertion during running (secondary outcomes). Twenty male endurance athletes performed 4-min treadmill rectangular test at 12 km.h-1 monitored by a gas analyser. After that, PBMT or placebo in each lower limb was applied, followed performed a maximum test of 3000 m. Immediately after 3000 m test, the athletes repeated the treadmill test. Another application of PBMT/placebo was done after the treadmill test, and athletes went back to the laboratory 24 h later to repeat the treadmill test. After a 72 h interval, athletes repeated all procedures with another treatment intervention (PBMT/placebo). Athletes performed the 3000 m running test ~7s faster when treated with PBMT with similar effort score compared placebo condition. The RE remains unchanged immediately post 3000 m running test, nonetheless RE measured post-24 h improved by 5% with PBMT application without changes in metabolic cost. The PBMT pre- and post-conditioning enhanced the 3000 m running performance and improved RE 24 h following the 3000 m test. However, no changes on ratings of perceived exertion and metabolic cost with the application of PBMT.

In the present study, we investigated the correlation between histopathological, metabolic, and volumetric changes in the brain and plasma under experimental conditions. Adult male Wistar rats received fractionated whole-brain irradiation (fWBI) with a total dose of 32 Gy delivered in 4 fractions (dose 8 Gy per fraction) once a week on the same day for 4 consecutive weeks. Proton magnetic resonance spectroscopy ( 1 H MRS) and imaging were used to detect metabolic and volumetric changes in the brain and plasma. Histopathological changes in the brain were determined by image analysis of immunofluorescent stained sections. Metabolic changes in the brain measured by 1 H MRS before, 48 h, and 9 weeks after the end of fWBI showed a significant decrease in the ratio of total N-acetylaspartate to total creatine (tNAA/tCr) in the corpus striatum. We found a significant decrease in glutamine + glutamate/tCr (Glx/tCr) and, conversely, an increase in gamma-aminobutyric acid to tCr (GABA/tCr) in olfactory bulb (OB). The ratio of astrocyte marker myoinositol/tCr (mIns/tCr) significantly increased in almost all evaluated areas. Magnetic resonance imaging (MRI)-based brain volumetry showed a significant increase in volume, and a concomitant increase in the T 2 relaxation time of the hippocampus. Proton nuclear magnetic resonance ( 1 H NMR) plasma metabolomics displayed a significant decrease in the level of glucose and glycolytic intermediates and an increase in ketone bodies. The histomorphological analysis showed a decrease to elimination of neuroblasts, increased astrocyte proliferation, and a mild microglia response. The results of the study clearly reflect early subacute changes 9-11 weeks after fWBI with strong manifestations of brain edema, astrogliosis, and ongoing ketosis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: By taking advantage of 18F-FDG PET imaging and tissue nuclear magnetic resonance (NMR) metabolomics, we examined the dynamic metabolic alterations induced by liver irradiation in a mouse model for hepatocellular carcinoma (HCC)., Methods: After orthotopic implantation with the mouse liver cancer BNL cells in the right hepatic lobe, animals were divided into two experimental groups. The first received irradiation (RT) at 15 Gy, while the second (no-RT) did not. Intergroup comparisons over time were performed, in terms of 18F-FDG PET findings, NMR metabolomics results, and the expression of genes involved in inflammation and glucose metabolism., Results: As of day one post-irradiation, mice in the RT group showed an increased 18F-FDG uptake in the right liver parenchyma compared with the no-RT group. However, the difference reached statistical significance only on the third post-irradiation day. NMR metabolomics revealed that glucose concentrations peaked on day one post-irradiation both, in the right and left lobes-the latter reflecting a bystander effect. Increased pyruvate and glutamate levels were also evident in the right liver on the third post-irradiation day. The expression levels of the glucose-6-phosphatase (G6PC) and fructose-1, 6-bisphosphatase 1 (FBP1) genes were down-regulated on the first and third post-irradiation days, respectively. Therefore, liver irradiation was associated with a metabolic shift from an impaired gluconeogenesis to an enhanced glycolysis from the first to the third post-irradiation day., Conclusion: Radiation-induced metabolic alterations in the liver parenchyma occur as early as the first post-irradiation day and show dynamic changes over time.

Eukaryotic phytoplankton have a small global biomass but play major roles in primary production and climate. Despite improved understanding of phytoplankton diversity and evolution, we largely ignore the cellular bases of their environmental plasticity. By comparative 3D morphometric analysis across seven distant phytoplankton taxa, we observe constant volume occupancy by the main organelles and preserved volumetric ratios between plastids and mitochondria. We hypothesise that phytoplankton subcellular topology is modulated by energy-management constraints. Consistent with this, shifting the diatom Phaeodactylum from low to high light enhances photosynthesis and respiration, increases cell-volume occupancy by mitochondria and the plastid CO 2 -fixing pyrenoid, and boosts plastid-mitochondria contacts. Changes in organelle architectures and interactions also accompany Nannochloropsis acclimation to different trophic lifestyles, along with respiratory and photosynthetic responses. By revealing evolutionarily-conserved topologies of energy-managing organelles, and their role in phytoplankton acclimation, this work deciphers phytoplankton responses at subcellular scales.

The efficient production of energy via oxidative phosphorylation is essential to the growth, survival, and reproduction of eukaryotes. The behavior (position of, and communication between, mitochondria) and morphology of mitochondria play key roles in efficient energy production and are influenced by oxidative stressors such as ultraviolet (UV) radiation. We tested the hypothesis that mitochondria change their behavior and morphology to meet energetic demands of responding to changes in oxidative stress. Specifically, we predicted that UV irradiation would increase the density of inner mitochondrial membrane and proportion of inter-mitochondrial junctions to influence whole-animal metabolic rate. Using transmission electron microscopy, we found that both three and six hours of UV-A/B irradiation (0.5 W/m 2 ) increased the proportion of inter-mitochondrial junctions (with increasing mitochondrial aspect ratio) and the density of inner mitochondrial membrane in myocytes of Tigriopus californicus copepods. Mitochondrial density increased following both irradiation treatments, but mitochondrial size decreased under the six hour treatment. Metabolic rate was maintained under three hours of irradiation but decreased following six hours of exposure. These observations demonstrate that the density of inner mitochondrial membrane and proportion of inter-mitochondrial junctions can play formative roles in maintaining whole-animal metabolic rate, and ultimately organismal performance, under exposure to an oxidative stressor., (Copyright © 2020 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Photobiomodulation (PBM) by far-red (FR) to near-infrared (NIR) light has been demonstrated to restore the function of damaged mitochondria, increase the production of cytoprotective factors and prevent cell death. Our laboratory has shown that FR PBM improves functional and structural outcomes in animal models of retinal injury and retinal degenerative disease. The current study tested the hypothesis that a brief course of NIR (830 nm) PBM would preserve mitochondrial metabolic state and attenuate photoreceptor loss in a model of retinitis pigmentosa, the P23H transgenic rat. P23H rat pups were treated with 830 nm light (180 s; 25 mW/cm 2 ; 4.5 J/cm 2 ) using a light-emitting diode array (Quantum Devices, Barneveld, WI) from postnatal day (p) 10 to p25. Sham-treated rats were restrained, but not treated with 830 nm light. Retinal metabolic state, function and morphology were assessed at p30 by measurement of mitochondrial redox (NADH/FAD) state by 3D optical cryo-imaging, electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), and histomorphometry. PBM preserved retinal metabolic state, retinal function, and retinal morphology in PBM-treated animals compared to the sham-treated group. PBM protected against the disruption of the oxidation state of the mitochondrial respiratory chain observed in sham-treated animals. Scotopic ERG responses over a range of flash intensities were significantly greater in PBM-treated rats compared to sham controls. SD-OCT studies and histological assessment showed that PBM preserved the structural integrity of the retina. These findings demonstrate for the first time a direct effect of NIR PBM on retinal mitochondrial redox status in a well-established model of retinal disease. They show that chronic proteotoxic stress disrupts retinal bioenergetics resulting in mitochondrial dysfunction, and retinal degeneration and that therapies normalizing mitochondrial metabolism have considerable potential for the treatment of retinal degenerative disease.

Aquaporin 9 (AQP9) is an aquaglyceroporin that can transport lactate. Accumulating evidence suggests that astrocyte-to-neuron lactate shuttle (ANLS) plays a critical role in energy metabolism in neurons, including retinal ganglion cells (RGCs). To test the hypothesis that AQP9, in concert with monocarboxylate transporters (MCTs), participates in ANLS to maintain function and survival of RGCs, Aqp9-null mice and wild-type (WT) littermates were subjected to optic nerve crush (ONC) with or without intravitreal injection of an MCT2 inhibitor. RGC density was similar between the Aqp9-null mice and WT mice without ONC, while ONC resulted in significantly more RGC density reduction in the Aqp9-null mice than in the WT mice at day 7. Positive scotopic threshold response (pSTR) amplitude values were similar between the two groups without ONC, but were significantly more reduced in the Aqp9-null mice than in the WT mice 7days after ONC. MCT2 inhibitor injection accelerated RGC death and pSTR amplitude reduction only in the WT mice with ONC. Immunolabeling revealed that both RGCs and astrocytes expressed AQP9, that ONC predominantly reduced astrocytic AQP9 expression, and that MCTs 1, 2, and 4 were co-localized with AQP9 at the ganglion cell layer. These retinal MCTs were also co-immunoprecipitated with AQP9 in the WT mice. ONC decreased the co-immunoprecipitation of MCTs 1 and 4, but did not impact co-immunoprecipitation of MCT2. Retinal glucose transporter 1 expression was increased in Aqp9-null mice. Aqp9 gene deletion reduced and increased the intraretinal L-lactate and D-glucose concentrations, respectively. Results suggest that AQP9 acts as the ANLS to maintain function and survival of RGCs.

Vine cuttings with six to eight unfolded leaves are utilized as is conventional in sweetpotato (Ipomoea batatas (L.) Lam.) seedling production. However, most vine cuttings wilt after transplanting into the field. Moreover, few researchers have examined the influence of photon flux density (PFD) provided by white or white plus red light-emitting diodes (LEDs) on sweetpotato plantlets. In this study, hydroponic sweetpotato (cv. Beniharuka) seedlings using single-node cutting were grown under 20 combinations of five levels of PFDs of 150, 200, 250, 300, and 350 μmol m -2 d -1 and four light qualities: white LEDs with a red light to blue light ratio (R:B ratio) of 0.9, white plus red LEDs with R:B ratios of 1.2 and 2.2, respectively, and fluorescent lamp with an R:B ratio of 1.8 as control, for 20 days under a controlled enviroment. Results showed that the number of newly developed leaves on hydroponic sweetpotato seedlings increased with time in a quadratic function, regardless of light quality. Fluorescent lamps led to greater numbers of new leaves on hydroponic sweetpotato seedlings compared with those grown under LEDs. Plant height, leaf area, and fresh and dry weights increased initially and then decreased with increasing daily light integral (DLI) in quadratic funcitons with a highest value under a PFD of 250 μmol m -2 d -1 . However, no significant differences were observed in fresh and dry weights of hydroponic sweetpotato seedlings grown under PFDs of 200 and 250 μmol m -2 s -1 . The quantum yield of photosystem II (ФPSII) decreased linearly as DLI increased from 8.6-20.2 mol m -2 d -1 . Power consumptions based on fresh and dry weights were lowest in sweetpotato seedlings grown under a PFD of 200 μmol m -2 s -1 provided by white LEDs with an R:B ratio of 0.9. White LEDs also showed higher light energy use efficiency than white plus red LEDs. In summary, it is recommended that a PFD of 200 μmol m -2 s -1 with DLI at 11.5 mol m -2 d -1 provided by white LEDs with an R:B ratio of 0.9 is suitable for hydroponic sweetpotato (cv. Beniharuka) seedling production under a controlled environment., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

The role of mitochondria in cancer formation and progression has been studied extensively, but much remains to be understood about this complex relationship. Mitochondria regulate many processes that are known to be altered in cancer cells, from metabolism to oxidative stress to apoptosis. Here, we review the evolving understanding of the role of mitochondria in cancer cells, and highlight key evidence supporting the role of mitochondria in cancer immune evasion and the effects of mitochondria-targeted antitumor therapy. Also considered is how knowledge of the role of mitochondria in cancer can be used to design and improve cancer therapies, particularly immunotherapy and radiation therapy. We further offer critical insights into the mechanisms by which mitochondria influence tumor immune responses, not only in cancer cells but also in immune cells. Given the central role of mitochondria in the complex interactions between cancer and the immune system, high priority should be placed on developing rational strategies to address mitochondria as potential targets in future preclinical and clinical studies. We believe that targeting mitochondria may provide additional opportunities in the development of novel antitumor therapeutics., (Copyright © 2020 Klein, He, Younes, Barsoumian, Chen, Ozgen, Mosaffa, Patel, Gu, Novaes, Narayanan, Cortez and Welsh.)

Glucose, as the main consuming nutrient of the body, faces different destinies in cancer cells. Glycolysis, oxidative phosphorylation, and pentose phosphate pathways produce different glucose-derived metabolites and thus affect cells' bioenergetics differently. Tumor cells' dependency to aerobic glycolysis and other cancer-specific metabolism changes are known as the cancer hallmarks, distinct cancer cells from normal cells. Therefore, these tumor-specific characteristics receive the limelight as targets for cancer therapy. Glutamine, serine, and fatty acid oxidation together with 5-lipoxygenase are main pathways that have attracted lots of attention for cancer therapy. In this review, we not only discuss different tumor metabolism aspects but also discuss the metabolism roles in the promotion of cancer cells at different stages and their difference with normal cells. Besides, we dissect the inhibitors potential in blocking the main metabolic pathways to introduce the effective and non-effective inhibitors in the field.

Scientific and reasonable treatment of dredged silt can not only protect the ecological environment but also play an essential role in the utilization of silt resources. Due to high water content, low permeability and high organic matter content of the silt, a large amount of bacteria and harmful gases are often produced during the process of silt sedimentation. Thermal drying has been taken as a technically attractive method for harmless treatment of contaminated dredged silt. In this study, ultrasound technology is introduced to shorten the time needed for silt drying. A preliminary laboratory study is carried out to assess the effectiveness of ultrasound on thermal drying. A series of thermal drying tests, with and without ultrasound, were conducted on kaolin soil specimens that were prepared by settling and self-weight consolidation. The test results show that the length of drying time can be shortened by increasing temperature and ultrasound power. The drying time plays a dominant role in the determination of the total energy consumption. This is because reduction of drying time leads to significant decrease in energy consumption for thermal drying, and the energy consumption for additional ultrasound is relatively marginal. For thermal drying at temperatures 60 and 100°C, when combined with 100 W ultrasound, the length of drying time was shortened by 44.19% and 45.16%, and the energy consumption was saved by 30.07% and 38.16%, respectively; when combined with 60 W ultrasound, the length of drying time was shortened by 4.65% and 6.45%, but the energy consumption was increased by 9.79% and 0.48%, respectively. The combination of thermal drying and 100 W ultrasound is found to be optimal in terms of drying rate and energy consumption for silt drying., Competing Interests: No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously. All the authors listed have approved the manuscript that is enclosed.

Patients with mutated TP53 have been identified as having comparatively poor outcomes compared to those retaining wild-type p53 in many cancers, including squamous cell carcinomas of the head and neck (SCCHN). We have examined the role of p53 in regulation of metabolism in SCCHN cells and find that loss of p53 function determines the Warburg effect in these cells. Moreover, this metabolic adaptation to loss of p53 function creates an Achilles' heel for tumour cells that can be exploited for potential therapeutic benefit. Specifically, cells lacking normal wild-type p53 function, whether through mutation or RNAi-mediated downregulation, display a lack of metabolic flexibility, becoming more dependent on glycolysis and losing the ability to increase energy production from oxidative phosphorylation. Thus, cells that have compromised p53 function can be sensitised to ionizing radiation by pre-treatment with a glycolytic inhibitor. These results demonstrate the deterministic role of p53 in regulating energy metabolism and provide proof of principle evidence for an opportunity for patient stratification based on p53 status that can be exploited therapeutically using current standard of care treatment with ionising radiation., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest to declare., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Accumulation of high-value products in microalgae is not conducive with rapid cell growth, which is the potential conflict in microalgal production. Overcoming such conflict faces numerous challenges in comprehensively understanding cell behavior and metabolism. Here, we show a fully integrated interaction between cell behavior, carbon partitioning, carbon availability and path rate of central carbon metabolism, and have practically overcome the production conflict of Chromochloris zofingiensis. We demonstrate that elevated carbon availability and active path rate of precursors are determinants for product biosynthesis, and the former exhibits a superior potential. As protein content reaches a threshold value to confer survival advantages, carbon availability becomes the major limiting factor for product biosynthesis and cell reproduction. Based on integrated interaction, regulating the C/N balance by feeding carbon source under excess light increases content of high-value products without inhibiting cell growth. Our findings provide a new orientation to achieve great productivity improvements in microalgal production.

Cold stimuli and the subsequent activation of β-adrenergic receptor (β-AR) potently stimulate adipose tissue thermogenesis and increase whole-body energy expenditure. However, systemic activation of the β3-AR pathway inevitably increases blood pressure, a significant risk factor for cardiovascular disease, and, thus, limits its application for the treatment of obesity. To activate fat thermogenesis under tight spatiotemporal control without external stimuli, here, we report an implantable wireless optogenetic device that bypasses the β-AR pathway and triggers Ca 2+ cycling selectively in adipocytes. The wireless optogenetics stimulation in the subcutaneous adipose tissue potently activates Ca 2+ cycling fat thermogenesis and increases whole-body energy expenditure without cold stimuli. Significantly, the light-induced fat thermogenesis was sufficient to protect mice from diet-induced body-weight gain. The present study provides the first proof-of-concept that fat-specific cold mimetics via activating non-canonical thermogenesis protect against obesity.

Advanced cancer patients exhibit cachexia, a condition characterized by a significant reduction in the body weight predominantly from loss of skeletal muscle and adipose tissue. Cachexia is one of the major causes of morbidity and mortality in cancer patients. Decreased food intake and multi-organ energy imbalance in cancer patients worsen the cachexia syndrome. Cachectic cancer patients have a low tolerance for chemo- and radiation therapies and also have a reduced quality of life. The presence of tumors and the current treatment options for cancer further exacerbate the cachexia condition, which remains an unmet medical need. The onset of cachexia involves crosstalk between different organs leading to muscle wasting. Recent advancements in understanding the molecular mechanisms of skeletal muscle atrophy/hypertrophy and adipose tissue wasting/browning provide a platform for the development of new targeted therapies. Therefore, a better understanding of this multifactorial disorder will help to improve the quality of life of cachectic patients. In this review, we summarize the metabolic mediators of cachexia, their molecular functions, affected organs especially with respect to muscle atrophy and adipose browning and then discuss advanced therapeutic approaches to cancer cachexia., Competing Interests: Declaration of competing interest SKB is one of the co-founders of Sanguine Diagnostics and Therapeutics, Inc. The other authors declare no competing interests. The authors have declared that the submitted manuscript is original, is not under consideration by another journal, and has not been published previously in any form. Every author is aware of and has agreed to the content of this paper., (Copyright © 2020. Published by Elsevier B.V.)

Background: Metabolic complications are highly prevalent in cancer survivors treated with irradiation but the underlying mechanisms remain unknown., Methods: Chow or high fat-fed C57Bl/6J mice were irradiated (6Gy) before investigating the impact on whole-body or skeletal muscle metabolism and profiling their lipidomic signature. Using a transgenic mouse model (Tg:Pax7-nGFP), we isolated muscle progenitor cells (satellite cells) and characterised their metabolic functions. We recruited childhood cancer survivors, grouped them based on the use of total body irradiation during their treatment and established their lipidomic profile., Results: In mice, irradiation delayed body weight gain and impaired fat pads and muscle weights. These changes were associated with impaired whole-body fat oxidation in chow-fed mice and altered ex vivo skeletal muscle fatty acid oxidation, potentially due to a reduction in oxidative fibres and reduced mitochondrial enzyme activity. Irradiation led to fasting hyperglycaemia and impaired glucose uptake in isolated skeletal muscles. Cultured satellite cells from irradiated mice showed decreased fatty acid oxidation and reduced glucose uptake, recapitulating the host metabolic phenotype. Irradiation resulted in a remodelling of lipid species in skeletal muscles, with the extensor digitorum longus muscle being particularly affected. A large number of lipid species were reduced, with several of these species showing a positive correlation with mitochondrial enzymes activity. In cancer survivors exposed to irradiation, we found a similar decrease in systemic levels of most lipid species, and lipid species that increased were positively correlated with insulin resistance (HOMA-IR)., Conclusion: Irradiation leads to long-term alterations in body composition, and lipid and carbohydrate metabolism in skeletal muscle, and affects muscle progenitor cells. Such changes result in persistent impairment of metabolic functions, providing a new mechanism for the increased prevalence of metabolic diseases reported in irradiated individuals. In this context, changes in the lipidomic signature in response to irradiation could be of diagnostic value., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A major challenge of cancer immunotherapy is the potential for undesirable effects on bystander cells and tumor-associated immune cells. Fundamentally, we need to understand what effect targeting tumor metabolism has upon the metabolism and phenotype of tumor-associated leukocytes, whose function can be critical for effective cancer therapeutic strategies. Undesirable effects of cancer therapeutics are a major reason for drug-associated toxicity, which confounds drug dosing and efficacy. As with any chemotherapeutic agent, drugs targeting tumor metabolism will exert potent effects on host stromal cells and tumor-associated leukocytes. Any drug targeting glycolysis, for example, could metabolically starve tumor-infiltrating T cells, inhibit their effector function and enable tumor progression. The targeting of oxidative phosphorylation in tumors will have complex effects on the polarization and function of tumor-associated macrophages. In short, we need to improve our understanding of tumor and immune cell metabolism and devise ways to specifically target tumors without compromising necessary host metabolism. Exploiting cell-specific metabolic pathways to directly target tumor cells may minimize detrimental effects on tumor-associated leukocytes.

Almost all life forms can detect and decode light information for adaptive advantage. Examples include the visual system, in which photoreceptor signals are processed into virtual images, and the circadian system, in which light entrains a physiological clock. Here we describe a light response pathway in mice that employs encephalopsin (OPN3, a 480 nm, blue-light-responsive opsin) to regulate the function of adipocytes. Germline null and adipocyte-specific conditional null mice show a light- and Opn3-dependent deficit in thermogenesis and become hypothermic upon cold exposure. We show that stimulating mouse adipocytes with blue light enhances the lipolysis response and, in particular, phosphorylation of hormone-sensitive lipase. This response is Opn3 dependent. These data establish a key mechanism in which light-dependent, local regulation of the lipolysis response in white adipocytes regulates energy metabolism., Competing Interests: Declaration of Interests R.J.S. receives research support from Novo Nordisk, Zafgen, Kallyope, Pfizer, and Ironwood Pharmaceuticals., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite increased understanding of the genetic events underlying pediatric high-grade gliomas (pHGGs), therapeutic progress is static, with poor understanding of nongenomic drivers. We therefore investigated the role of alterations in mitochondrial function and developed an effective combination therapy against pHGGs., Methods: Mitochondrial DNA (mtDNA) copy number was measured in a cohort of 60 pHGGs. The implication of mtDNA alteration in pHGG tumorigenesis was studied and followed by an efficacy investigation using patient-derived cultures and orthotopic xenografts., Results: Average mtDNA content was significantly lower in tumors versus normal brains. Decreasing mtDNA copy number in normal human astrocytes led to a markedly increased tumorigenicity in vivo. Depletion of mtDNA in pHGG cells promoted cell migration and invasion and therapeutic resistance. Shifting glucose metabolism from glycolysis to mitochondrial oxidation with the adenosine monophosphate-activated protein kinase activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) or the pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA) significantly inhibited pHGG viability. Using DCA to shift glucose metabolism to mitochondrial oxidation and then metformin to simultaneously target mitochondrial function disrupted energy homeostasis of tumor cells, increasing DNA damage and apoptosis. The triple combination with radiation therapy, DCA and metformin led to a more potent therapeutic effect in vitro and in vivo., Conclusions: Our results suggest metabolic alterations as an onco-requisite factor of pHGG tumorigenesis. Targeting reduced mtDNA quantity represents a promising therapeutic strategy for pHGG., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. For commercial re-use, please contact journals.permissions@oup.com.)

Background : Involuntary body weight loss in head and neck cancer is common. Fundamental for weight loss is an energy imbalance where total energy expenditure exceeds energy intake. Aim : To map energy intake and parameters of energy expenditure at the start of and after radiotherapy, and their relation to weight change, body mass index, and immune markers in patients with head and neck cancer. Materials and Methods : Data from 20 patients on energy intake (24-hour dietary intake recalls), total energy expenditure (SenseWear Armband Pro3), resting energy expenditure (indirect calorimetry), body weight, body mass index, and immune markers in serum (C-reactive protein and Interleukin-6) were collected at the start of and after radiotherapy (median 8 mo, range 5-13). Results : No statistical significance was shown between the two measurement points for energy intake or for the different parameters of energy expenditure. Median values for energy balance were 0.93 and 0.96 for the start of treatment and follow-up, respectively. Twelve and 13 patients had a negative energy balance at the start of radiotherapy and at follow-up, respectively. Conclusion: A negative energy balance was seen for the majority of patients, which stresses the importance of nutritional treatment at the start of and after radiotherapy.

To examine the processing characteristics and high quality of an improved microwave vacuum drying system, litchi fruits were dried using intermittent microwave volumetric heating while microwave vacuum drying at 2 W/g was carried out for comparison; the intermittent microwave heating profiles were set as (1) 5 min drying-on, 5 min drying-off; (2) 5 min drying-on, 10 min drying-off; and (3) 5 min drying-on, 15 min drying-off. Energy consumption during drying was determined, and physicochemical properties such as moisture content, vitamin C, total phenolics, color, and sensory evaluation of dried products were assessed. In microwave vacuum drying, intermittent microwave volumetric heating was found to be energy-efficient (about 32 KJ/g to 45 KJ/g) and saved at least 31% of energy consumption compared with microwave vacuum drying as well as decreasing product browning. In addition, microwave volumetric heating had no substantial effects on sugar and protein contents, while antioxidants were affected significantly ( p ≤ 0.05). Moreover, sensory evaluation showed that intermittent microwave-assisted vacuum drying (IMVD) increased the acceptance of the dried product compared with microwave vacuum drying (MVD).

We report a 100-million atom-scale model of an entire cell organelle, a photosynthetic chromatophore vesicle from a purple bacterium, that reveals the cascade of energy conversion steps culminating in the generation of ATP from sunlight. Molecular dynamics simulations of this vesicle elucidate how the integral membrane complexes influence local curvature to tune photoexcitation of pigments. Brownian dynamics of small molecules within the chromatophore probe the mechanisms of directional charge transport under various pH and salinity conditions. Reproducing phenotypic properties from atomistic details, a kinetic model evinces that low-light adaptations of the bacterium emerge as a spontaneous outcome of optimizing the balance between the chromatophore's structural integrity and robust energy conversion. Parallels are drawn with the more universal mitochondrial bioenergetic machinery, from whence molecular-scale insights into the mechanism of cellular aging are inferred. Together, our integrative method and spectroscopic experiments pave the way to first-principles modeling of whole living cells., (Published by Elsevier Inc.)

Ramlibacter tataouinensis TTB310, a non-photosynthetic betaproteobacterium isolated from a semi-arid region of southern Tunisia, forms both rods and cysts. Cysts are resistant to desiccation and divide when water and nutrients are available. Rods are motile and capable of dissemination. Due to the strong correlation between sunlight and desiccation, light is probably an important external signal for anticipating desiccating conditions. Six genes encoding potential light sensors were identified in strain TTB310. Two genes encode for bacteriophytochromes, while the four remaining genes encode for putative blue light receptors. We determined the spectral and photochemical properties of the two recombinant bacteriophytochromes RtBphP1 and RtBphP2. In both cases, they act as sensitive red light detectors. Cyst divisions and a complete cyst-rod-cyst cycle are the main processes in darkness, whereas rod divisions predominate in red or far-red light. Mutant phenotypes caused by the inactivation of genes encoding bacteriophytochromes or heme oxygenase clearly show that both bacteriophytochromes are involved in regulating the rod-rod division. This process could favor rapid rod divisions at sunrise, after dew formation but before the progressive onset of desiccation. Our study provides the first evidence of a light-based strategy evolved in a non-photosynthetic bacterium to exploit scarse water in a desert environment.

Chitosan, being one of the most promising biological macromolecules, has an immense scope in agriculture to boost crop growth and defense responses. In this study, chitosan was exposed to gamma rays in order to obtain a low molecular weight derivative. Viscometric characterization showed a sharp decrease in molecular weight and FTIR based analysis confirmed retention of structural integrity of the polymer upon gamma irradiation. Assessments of various physiological and biochemical attributes were carried out on sugarcane plantlets that were subjected to progressive water deficit stress. The irradiated chitosan was found to differentially ameliorate water deficit stress tolerance against that of normal chitosan through positive modulation of various gas exchange parameters alongside significant improvement in relative tissue water content, SOD activity, soluble sugars and adenine energetics. Furthermore, application of irradiated chitosan significantly reduced cell membrane damage, lipid peroxidation, H 2 O 2 and free-proline accumulations. This is the first report on the use of gamma irradiated chitosan to alleviate water deficit stress tolerance in sugarcane. Overall comparative assessments showed that differential plant responses were triggered upon foliar application of normal and gamma irradiated chitosan in sugarcane plants grown under water deficit stress conditions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Short-term abiotic stress treatment before harvest can enhance the quality of horticultural crops cultivated in controlled environments. Here, we investigated the effects of combined chilling and UV-A treatment on the accumulation of phenolic compounds in kale ( Brassica oleracea var. acephala ). Five-week-old plants were subjected to combined treatments (10 °C plus UV-A LED radiation at 30.3 W/m 2 ) for 3-days, as well as single treatments (4 °C, 10 °C, or UV-A LED radiation). The growth parameters and photosynthetic rates of plants under the combined treatment were similar to those of the control, whereas UV-A treatment alone significantly increased these parameters. Maximum quantum yield ( Fv/Fm ) decreased and H 2 O 2 increased in response to UV-A and combined treatments, implying that these treatments induced stress in kale. The total phenolic contents after 2- and 3-days of combined treatment and 1-day of recovery were 40%, 60%, and 50% higher than those of the control, respectively, and the phenylalanine ammonia-lyase activity also increased. Principal component analysis suggested that stress type and period determine the changes in secondary metabolites. Three days of combined stress treatment followed by 2-days of recovery increased the contents of quercetin derivatives. Therefore, combined chilling and UV-A treatment could improve the phenolic contents of leafy vegetables such as kale, without growth inhibition.

Background/objectives: Inadequate sleep increases obesity and environmental noise contributes to poor sleep. However, women may be more vulnerable to noise and hence more susceptible to sleep disruption-induced weight gain than men. In male rats, exposure to environmental (i.e. ambient) noise disrupts sleep and increases feeding and weight gain. However, the effects of environmental noise on sleep and weight gain in female rats are unknown. Thus, this study was designed to determine whether noise exposure would disturb sleep, increase feeding and weight gain and alter the length of the estrous cycle in female rats., Subjects/methods: Female rats (12 weeks old) were exposed to noise for 17d (8 h/d during the light period) to determine the effects of noise on weight gain and food intake. In a separate set of females, estrous cycle phase and length, EEG, EMG, spontaneous physical activity and energy expenditure were recorded continuously for 27d during baseline (control, 9d), noise exposure (8 h/d, 9d) and recovery (9d) from sleep disruption., Results: Noise exposure significantly increased weight gain and food intake compared to females that slept undisturbed. Noise also significantly increased wakefulness, reduced sleep and resulted in rebound sleep during the recovery period. Total energy expenditure was significantly lower during both noise exposure and recovery due to lower energy expenditure during spontaneous physical activity and sleep. Notably, noise did not alter the estrous cycle length., Conclusions: As previously observed in male rats, noise exposure disrupted sleep and increased weight gain in females but did not alter the length of the estrous cycle. This is the first demonstration of weight gain in female rats during sleep disruption. We conclude that the sleep disruption caused by exposure to environmental noise is a significant tool for determining how sleep loss contributes to obesity in females.

Light is involved in many critical physiological or biochemical processes of human beings, such as visual sensing and the production of vitamin D. Recent studies have showed that the lights of different wavelengths have a profound influence in life activities. For example, blue light promotes alertness, whereas green light (GL) induces sleep in mice. On the other hand, metabolic homeostasis is regulated by a variety of factors, including dietary habits and light exposure. Our study aims to study whether certain wavelength of light would affect metabolic status of mice. Mice were divided into normal diet-fed group and high-fat diet (HFD)-fed group, and then exposed to various colors of the light. Physiological parameters, such as body weight, food intake and water drinking were regularly measured. Glucose tolerance test and pyruvate tolerance test were simultaneously performed. After mice were humanely sacrificed, liver histology and serologic analysis were performed for detecting lipid levels. We found that GL group showed obvious glucose intolerance and increased levels of serum and liver lipid contents compared to white light group. Meanwhile, the expression levels of lipid metabolism-related genes were almost down-regulated in liver. Furthermore, melatonin receptor-1b and thyroid hormone receptor-β expression levels were significantly lowered in liver of GL-treated obese mice, suggesting that these hormone pathways may mediate the changes of lipid metabolism. Our data indicate that GL has a detrimental effect on the energy metabolism and aggravates HFD-induced obesity in mice. In addition to malnutrition, the colors of the lights also have a profound influence in the metabolic homeostasis and should be taken into consideration in the therapy of metabolic disorders., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Key aspects of leaf mitochondrial metabolism in the light remain unresolved. For example, there is debate about the relative importance of exporting reducing equivalents from mitochondria for the peroxisomal steps of photorespiration versus oxidation of NADH to generate ATP by oxidative phosphorylation. Here, we address this and explore energetic coupling between organelles in the light using a diel flux balance analysis model. The model included more than 600 reactions of central metabolism with full stoichiometric accounting of energy production and consumption. Different scenarios of energy availability (light intensity) and demand (source leaf versus a growing leaf) were considered, and the model was constrained by the nonlinear relationship between light and CO 2 assimilation rate. The analysis demonstrated that the chloroplast can theoretically generate sufficient ATP to satisfy the energy requirements of the rest of the cell in addition to its own. However, this requires unrealistic high light use efficiency and, in practice, the availability of chloroplast-derived ATP is limited by chloroplast energy dissipation systems, such as nonphotochemical quenching, and the capacity of the chloroplast ATP export shuttles. Given these limitations, substantial mitochondrial ATP synthesis is required to fulfill cytosolic ATP requirements, with only minimal, or zero, export of mitochondrial reducing equivalents. The analysis also revealed the importance of exporting reducing equivalents from chloroplasts to sustain photorespiration. Hence, the chloroplast malate valve and triose phosphate-3-phosphoglycerate shuttle are predicted to have important metabolic roles, in addition to their more commonly discussed contribution to the avoidance of photooxidative stress., (© 2019 The author(s). All Rights Reserved.)

The transition from G 1 to S phase and subsequent nuclear DNA replication in the cells of many species of eukaryotic algae occur predominantly during the evening and night in the absence of photosynthesis; however, little is known about how day/night changes in energy metabolism and cell cycle progression are coordinated and about the advantage conferred by the restriction of S phase to the night. Using a synchronous culture of the unicellular red alga Cyanidioschyzon merolae , we found that the levels of photosynthetic and respiratory activities peak during the morning and then decrease toward the evening and night, whereas the pathways for anaerobic consumption of pyruvate, produced by glycolysis, are upregulated during the evening and night as reported recently in the green alga Chlamydomonas reinhardtii Inhibition of photosynthesis by 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) largely reduced respiratory activity and the amplitude of the day/night rhythm of respiration, suggesting that the respiratory rhythm depends largely on photosynthetic activity. Even when the timing of G 1 /S-phase transition was uncoupled from the day/night rhythm by depletion of retinoblastoma-related (RBR) protein, the same patterns of photosynthesis and respiration were observed, suggesting that cell cycle progression and energy metabolism are regulated independently. Progression of the S phase under conditions of photosynthesis elevated the frequency of nuclear DNA double-strand breaks (DSB). These results suggest that the temporal separation of oxygenic energy metabolism, which causes oxidative stress, from nuclear DNA replication reduces the risk of DSB during cell proliferation in C. merolae IMPORTANCE Eukaryotes acquired chloroplasts through an endosymbiotic event in which a cyanobacterium or a unicellular eukaryotic alga was integrated into a previously nonphotosynthetic eukaryotic cell. Photosynthesis by chloroplasts enabled algae to expand their habitats and led to further evolution of land plants. However, photosynthesis causes greater oxidative stress than mitochondrion-based respiration. In seed plants, cell division is restricted to nonphotosynthetic meristematic tissues and populations of photosynthetic cells expand without cell division. Thus, seemingly, photosynthesis is spatially sequestrated from cell proliferation. In contrast, eukaryotic algae possess photosynthetic chloroplasts throughout their life cycle. Here we show that oxygenic energy conversion (daytime) and nuclear DNA replication (night time) are temporally sequestrated in C. merolae This sequestration enables "safe" proliferation of cells and allows coexistence of chloroplasts and the eukaryotic host cell, as shown in yeast, where mitochondrial respiration and nuclear DNA replication are temporally sequestrated to reduce the mutation rate., (Copyright © 2019 Miyagishima et al.)

The effect of extremely low-frequency electromagnetic fields (ELF-EMFs) on human health has become a worldwide concern, and no molecule/factor has been established as a measurable indicator of this effect. Diseases related to ELF-EMF are generally accompanied with energy metabolic dysfunction, and the energy in metabolism often flows in terms of electrons in all living cells. Hence, this study specifically investigated the relationship between metabolic current and ELF-EMF. By applying 0-128 Gauss ELF-EMFs to Geobacter sulfurreducens-inoculated bioelectrochemical systems, we found that metabolic current was increased and oscillated in ELF-EMF-exposed G. sulfurreducens. All effects were exposure dose dependent. Moreover, the oscillation amplitude varied linearly with the ELF-EMF strength. These results reveal that metabolic current can be used as a dosimetric indicator of the effect of ELF-EMF on living organisms, including human beings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Rapid assessment of radiation signatures in noninvasive biofluids may aid in assigning proper medical treatments for acute radiation syndrome (ARS) and delegating limited resources after a nuclear disaster. Metabolomic platforms allow for rapid screening of biofluid signatures and show promise in differentiating radiation quality and time postexposure. Here, we use global metabolomics to differentiate temporal effects (1-60 d) found in nonhuman primate (NHP) urine and serum small molecule signatures after a 4 Gy total body irradiation. Random Forests analysis differentially classifies biofluid signatures according to days post 4 Gy exposure. Eight compounds involved in protein metabolism, fatty acid β oxidation, DNA base deamination, and general energy metabolism were identified in each urine and serum sample and validated through tandem MS. The greatest perturbations were seen at 1 d in urine and 1-21 d in serum. Furthermore, we developed a targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM) method to quantify a six compound panel (hypoxanthine, carnitine, acetylcarnitine, proline, taurine, and citrulline) identified in a previous training cohort at 7 d after a 4 Gy exposure. The highest sensitivity and specificity for classifying exposure at 7 d after a 4 Gy exposure included carnitine and acetylcarnitine in urine and taurine, carnitine, and hypoxanthine in serum. Receiver operator characteristic (ROC) curve analysis using combined compounds show excellent sensitivity and specificity in urine (area under the curve [AUC] = 0.99) and serum (AUC = 0.95). These results highlight the utility of MS platforms to differentiate time postexposure and acquire reliable quantitative biomarker panels for classifying exposed individuals.

The association between light pollution and disruption of daily rhythms, metabolic and hormonal disorders, as well as cancer progression is well-recognized. These adverse effects could be due to nocturnal melatonin suppression. The signaling pathway by which light pollution affects metabolism and endocrine responses is unclear. We studied the effects of artificial light at night (ALAN 1 ) on body mass, food and water intake, daily rhythms of body temperature, serum glucose and insulin in male rats. Daily rhythms of urine production and urinary 6-sulfatoxymelatonin (6-SMT 2 ), as well as global DNA methylation in pancreas and liver tissues were also assessed. Mass gain was higher in ALAN rats compared with controls. Food intake, water consumption, glucose, insulin, and 6-SMT levels markedly lessened in response to ALAN. Conversely, urine production and body temperature were elevated in ALAN rats compared with controls. Significant 24-h rhythms were detected for all variables that were altered in mesor, amplitude, and acrophase occurrences under ALAN conditions. DNA hypo-methylation was detected in ALAN pancreatic tissue compared with controls, but not in hepatic tissue. Overall, ALAN affects metabolic and hormonal physiology in different levels in which flexible crosstalk between melatonin and both epigenetics and metabolic levels expressed as body temperature rhythm, is suggested to mediate the environmental exposure at the molecular level and subsequently physiology is altered. The flexibility of epigenetic modifications provides a potential therapeutic target for rectifying ALAN adverse effects by epigenetic markers such as melatonin and behavioral lifestyle interventions for confining ALAN exposures as much as possible., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Attempts to construct an artificial cell have widened our understanding of living organisms. Many intracellular systems have been reconstructed by assembling molecules, however the mechanism to synthesize its own constituents by self-sufficient energy has to the best of our knowledge not been developed. Here, we combine a cell-free protein synthesis system and small proteoliposomes, which consist of purified ATP synthase and bacteriorhodopsin, inside a giant unilamellar vesicle to synthesize protein by the production of ATP by light. The photo-synthesized ATP is consumed as a substrate for transcription and as an energy for translation, eventually driving the synthesis of bacteriorhodopsin or constituent proteins of ATP synthase, the original essential components of the proteoliposome. The de novo photosynthesized bacteriorhodopsin and the parts of ATP synthase integrate into the artificial photosynthetic organelle and enhance its ATP photosynthetic activity through the positive feedback of the products. Our artificial photosynthetic cell system paves the way to construct an energetically independent artificial cell.

We studied the effects of different radiation treatments on the physiology and UV-absorbing compounds of the model liverwort Marchantia polymorpha subsp. ruderalis. Starting from gemmae, samples were exposed to five radiation treatments: low photosynthetically active radiation (PAR), low PAR+ UV-A, low PAR + UV-B, low PAR + UV-A + UV-B, and high PAR. After 35 days, the maximum quantum yield of photosystem II was similar between treatments, which suggested comparable photoinhibition and physiological vitality, also supported by results showing an unchanged chlorophyll a/b ratio and only slight changes in growth. However, the total contents of both chlorophylls and carotenoids decreased in the UV radiation treatments and, more strongly, in the high-PAR samples, suggesting mainly PAR-dependent damage to the photosynthetic pigments. The xanthophyll index (antheraxanthin + zeaxanthin)/(violaxanthin + antheraxanthin + zeaxanthin) was only increased in the high-PAR samples, indicating an increase in photoprotection through nonphotochemical dissipation of the excess energy. The sclerophylly index (the ratio between the thallus dry mass and surface area) was increased in the UV-B-exposed samples, suggesting a UV-induced structural protection. Only the UV-B-exposed samples showed DNA damage. Several apigenin and luteolin derivatives were found in the methanol-soluble vacuolar fraction of the liverwort and p-coumaric and ferulic acids in the methanol-insoluble cell wall-bound fraction. Most individual soluble compounds, the bulk level of soluble compounds, and chalcone synthase expression increased in UV-B-exposed samples, whereas individual insoluble compounds increased in the samples exposed to only PAR. Principal components analysis summarized these responses, showing the strong influence of both UV-B and PAR levels on the physiology and UV protection of the samples.

Over the past few years, three photorespiratory bypasses have been introduced into plants, two of which led to observable increases in photosynthesis and biomass yield. However, most of the experiments were carried out using Arabidopsis under controlled environmental conditions, and the increases were only observed under low-light and short-day conditions. In this study, we designed a new photorespiratory bypass (called GOC bypass), characterized by no reducing equivalents being produced during a complete oxidation of glycolate into CO 2  catalyzed by three rice-self-originating enzymes, i.e., glycolate oxidase, oxalate oxidase, and catalase. We successfully established this bypass in rice chloroplasts using a multi-gene assembly and transformation system. Transgenic rice plants carrying GOC bypass (GOC plants) showed significant increases in photosynthesis efficiency, biomass yield, and nitrogen content, as well as several other CO 2 -enriched phenotypes under both greenhouse and field conditions. Grain yield of GOC plants varied depending on seeding season and was increased significantly in the spring. We further demonstrated that GOC plants had significant advantages under high-light conditions and that the improvements in GOC plants resulted primarily from a photosynthetic CO 2 -concentrating effect rather than from improved energy balance. Taken together, our results reveal that engineering a newly designed chloroplastic photorespiratory bypass could increase photosynthetic efficiency and yield of rice plants grown in field conditions, particularly under high light., (Copyright © 2018 The Author. Published by Elsevier Inc. All rights reserved.)

Inflammation and bone erosion are central in rheumatoid arthritis (RA). Even though effective medications for control and treatment of RA are available, remission is only seen in a subset of patients. Treatment with low-dose radiotherapy (LD-RT) which has been already successfully used for amelioration of symptoms in benign diseases should be a promising approach to reduce pain, inflammation, and particularly bone erosion in patients with RA. Even though anti-inflammatory effects of LD-RT are already described with non-linear dose response relationships, and pain-reducing effects have been clinically observed, the underlying mechanisms are widely unknown. Besides immune cells many other cell types, such as fibroblast-like synoviocytes (FLS), osteoclasts, and osteoblast are present in the affected joint and might be modulated by LD-RT. For this study, these cell types were obtained from human tumor necrosis factor-α transgenic (h TNF- α tg) mice and were consecutively exposed to different doses of ionizing radiation (0.1, 0.5, 1.0, and 2.0 Gy, respectively) in vitro . In order to study the in vivo effects of LD-RT within the arthritic joint, hind paws of arthritic h TNF- α tg mice were locally irradiated with 0.5 Gy, a single dose per fraction that is known for good clinical responses. Starting at a dose of 0.5 Gy, proliferation of FLS was reduced and apoptosis significantly enhanced with no changes in necrosis. Further, expression of RANK-L was slightly reduced following irradiation with particularly 0.5 Gy. Starting from 0.5 Gy, the numbers of differentiated osteoclasts were significantly reduced, and a lower bone resorbing activity of treated osteoclasts was also observed, as monitored via pit formation and Cross Laps presence. LD-RT had further a positive effect on osteoblast-induced mineralization in a discontinuous dose response relationship with 0.5 Gy being most efficient. An increase of the gene expression ratio of OPG/RANK-L at 0.1 and 0.5 Gy and of production of OPG at 0.5 and 1.0 Gy was observed. In vivo , LD-RT resulted in less severe arthritis in arthritic h TNF- α tg mice and in significant reduction of inflammatory and erosive area with reduced osteoclasts and neutrophils. Locally applied LD-RT can, therefore, induce a beneficial micro-environment within arthritic joints by predominantly positively impacting on bone metabolism.

Leptin has a central role in the maintenance of energy homeostasis, and its sensitivity is influenced by both the photoperiod and dietary polyphenols. The aim of this study was to investigate the effect of seasonal consumption of polyphenol-rich fruits on the hypothalamic leptin signaling system in non-obese and obese animals placed under different photoperiods. Non-obese and diet-induced obese male Fischer 344 rats were placed under either a short-day (SD) or long-day (LD) photoperiod and were supplemented with either 100 mg/kg of lyophilized red grapes or cherries. In non-obese animals, both fruits reduced energy balance independent of the photoperiod to which they were placed. However, the hypothalamic gene expression of Pomc was significantly up-regulated only in the SD photoperiod. In contrast, in obese animals only cherry significantly decreased the energy balance, although both fruits were able to counteract the diet-induced increase in hypothalamic AgRP mRNA levels when consumed during the SD photoperiod. In conclusion, the consumption of rich-polyphenol fruits may increase leptin sensitivity through the modulation of the hypothalamic leptin signal pathway mainly when consumed in the SD photoperiod. Therefore, fruit seasonality should be considered, as it can influence energy homeostasis and obesity.

Exposure to light at night is a disruptive condition for the adult circadian system, leading to arrhythmicity in nocturnal rodents. Circadian disruption is a risk factor for developing physiological and behavioral alterations, including weight gain and metabolic disease. During early stages of development, the circadian system undergoes a critical period of adjustment, and it is especially vulnerable to altered lighting conditions that may program its function, leading to long-term effects. We hypothesized that during lactation a disrupted light-dark cycle due to light at night may disrupt the circadian system and in the long term induce metabolic disorders. Here we explored in pups, short- and long-term effects of constant light (LL) during lactation. In the short term, LL caused a loss of rhythmicity and a reduction in the immunopositive cells of VIP, AVP, and PER1 in the suprachiasmatic nucleus (SCN). In the short term, the affection on the circadian clock in the pups resulted in body weight gain, loss of daily rhythms in general activity, plasma glucose and triglycerides (TG). Importantly, the DD conditions during development also induced altered daily rhythms in general activity and in the SCN. Exposure to LD conditions after lactation did not restore rhythmicity in the SCN, and the number of immunopositve cells to VIP, AVP, and PER1 remained reduced. In the long term, daily rhythmicity in general activity was restored; however, daily rhythms in glucose and TG remained disrupted, and daily mean levels of TG were significantly increased. Present results point out the programming role played by the LD cycle during early development in the function of the circadian system and on metabolism. This study points out the risk represented by exposure to an altered light-dark cycle during early stages of development., Abbreviations: AVP: arginine vasopressin peptide; CRY: cryptochrome; DD: constant darkness; DM: dorsomedial; LD: light-dark cycle; LL: constant light; NICUs: neonatal intensive care units; P: postnatal days; PER: period; S.E.M.: standard error of the mean; SCN: suprachiasmatic nucleus; TG: triglycerides; VIP: vasointestinal peptide; VL: ventrolateral; ZT: zeitgeber time.

Although growing evidence indicates that bioenergetic metabolism plays an important role in the progression of tumorigenesis, little information is available on the contribution of reprogramming of energy metabolism in cancer initiation. By applying a quantitative proteomic approach and targeted metabolomics, we find that specific metabolic modifications precede primary skin tumor formation. Using a multistage model of ultraviolet B (UVB) radiation-induced skin cancer, we show that glycolysis, tricarboxylic acid (TCA) cycle, and fatty acid β-oxidation are decreased at a very early stage of photocarcinogenesis, while the distal part of the electron transport chain (ETC) is upregulated. Reductive glutamine metabolism and the activity of dihydroorotate dehydrogenase (DHODH) are both necessary for maintaining high ETC. Mice with decreased DHODH activity or impaired ETC failed to develop pre-malignant and malignant lesions. DHODH activity represents a major link between DNA repair efficiency and bioenergetic patterning during skin carcinogenesis., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)