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Advancements in the field of reintroduction biology are needed, but understanding of how to effectively conduct translocations, particularly with snakes, is lacking. We conducted a systematic review of snake translocation studies to identify potential tactics for reducing postrelease effects. We included studies on intentional, human-mediated, wild-wild, or captive-wild translocations to any location, regardless of motive or number of snakes translocated. Only studies that presented results for at least 1 of 4 outcomes (movement behavior, site fidelity, survival, or population establishment) were included. We systematically searched 4 databases for published studies and used 5 methods to search the gray literature. Our search and screening criteria yielded 121 data sources, representing 130 translocation cases. We quantified the association between 15 translocation tactics and short-term translocation outcomes by calculating odds ratios and used forest plots to display results. Snake translocations involved 47 species (from mainly 2 families), and most were motivated by research, were monitored for at least 6 months, occurred in North America, and took place from the 1990s onward. The odds of a positive snake translocation outcome were highest with release of captive reared or juvenile snakes, release of social groups together, delayed release, provision of environmental enrichment or social housing before release, or minimization of distance translocated. The odds of a positive outcome were lowest when snakes were released early in their active season. Our results do not demonstrate causation, but outcomes of snake translocation were associated with 8 tactics (4 of which were strongly correlated). In addition to targeted comparative studies, we recommend practitioners consider the possible influence of these tactics when planning snake translocations.La biología de la reintroducción requiere de avances; sin embargo, hay muy poco conocimiento sobre cómo realizar efectivamente las reubicaciones, particularmente las de las serpientes. Revisamos sistemáticamente los estudios sobre reubicación de serpientes para identificar las potenciales maniobras de reducción del estrés postliberación. Incluimos estudios sobre las reubicaciones a cualquier localidad que hayan sido intencionales, mediadas por humanos, de ambiente silvestre a ambiente silvestre o de cautiverio a ambiente silvestre sin importar el motivo o el número de serpientes reubicadas. Sólo incluimos estudios que presentaran resultados para al menos 1 de los cuatro resultados posibles: conducta de movimiento, fidelidad al sitio, supervivencia o establecimiento poblacional. Buscamos sistemáticamente en cuatro bases de datos de estudios publicados y usamos cinco métodos para buscar en la literatura gris. Nuestros criterios de búsqueda y revisión resultaron en 121 fuentes de datos, las cuales representaron 130 casos de reubicación. Cuantificamos la asociación entre 15 maniobras de reubicación y los resultados a corto plazo de las reubicaciones mediante el cálculo de la razón de probabilidades y usamos diagramas de efecto para mostrar los resultados. La reubicación de serpientes incluyó a 47 especies (principalmente de dos familias) y la mayoría estuvo motivada por la investigación, fue monitoreada durante seis meses (al menos), se ubicó en América del Norte y ocurrieron a partir de la década de 1990. La probabilidad de que la reubicación de serpientes tuviera un resultado positivo fueron mayores con la liberación de serpientes criadas o juveniles, la liberación de grupos sociales en conjunto, la liberación retardada, el suministro de enriquecimiento ambiental o alojamiento previo a la liberación o la reducción de la distancia de reubicación. Esta misma probabilidad fue menor cuando las serpientes fueron liberadas tempranamente durante su temporada activa. Nuestros resultados no demuestran causalidad, pero los resultados de la reubicación de serpientes estuvieron asociados con ocho maniobras (cuatro de las cuales contaban con una correlación sólida). Además de los estudios comparativos focalizados, recomendamos que los practicantes consideren la posible influencia de estas maniobras cuando se planifiquen la reubicación de serpientes.重引入领域需要进一步发展, 但如何有效进行生物迁移仍存在知识空缺, 特别是对蛇类的迁移。我们对蛇类迁地研究进行了系统性综述, 以确定减少释放后影响的潜在策略。我们收集了所有地区有意的、人类介导的、野生-野生及圈养-野生的迁地研究, 无论动机或蛇的数量。只有包含四个结果(运动行为、位点保守性、存活率、种群建立情况)中至少一个的研究才被纳入分析。我们系统地搜索了四个数据库中已发表的研究, 并用五种方法搜索了灰色文献, 最终获得121个数据源, 代表了130个迁地案例。我们通过计算优势比量化了15种迁地策略和短期迁地结果之间的关联, 并用森林图展示了结果。我们发现, 蛇类的迁移涉及47个物种(主要来自2个科), 大多数发生在北美、在20世纪90年代以后、出于研究的动机, 且监测了至少6个月。在释放人工饲养的蛇或亚成体蛇、同时释放社会群体、延迟释放、在释放前提供环境丰容或遮蔽物, 以及尽量减少迁移距离的情况下, 产生积极结果的几率最高。当在蛇的活动季节早期释放, 产生积极结果的几率最低。我们的结果并不能证明因果关系, 但发现蛇类迁移结果与8种策略有关(其中4种强相关)。除了有针对性的比较研究外, 我们还建议保护实践者在规划蛇类迁地项目时考虑这些策略可能产生的影响。【翻译:胡怡思;审校:聂永刚】.

The main aim of this study is trying to contribute to a better understanding of the role of surface roughness basal planes on toppling-related instability phenomena. In this way, the authors focus on the stability against toppling of a single block resting on a regular rough surface. To do that they have first artificially created sample rock blocks with a regular rough base and tested them against toppling in a tilt-test machine. The authors have also developed analytical formulations to theoretically estimate toppling instability under these circumstances and have carried out simple numerical DEM models to reproduce the corresponding tests. The comparison between obtained analytical and numerical results and the physical model response indicated good representativeness of both numerical and analytical approaches. Geometry characteristics of the saw cut artificially created blocks did affect results, so the numerical and analytical models were adapted by including an equivalent curvature radius in the corner of the cut block around which the overturning phenomenon takes place to account for this geometrical effect. Further research will extend these results to the case of blocks with natural irregular rough surfaces.

Quantum key distribution (QKD) provides in principle unconditional security of key sharing based on the laws of physics only. In the last decade, several experimental and commercial QKD networks have been built and operated worldwide. Demonstrational applications of QKD in financial institutions, government networks, and critical infrastructures such as the power grid have been initially explored. However, large-scale deployment and full-scale commercialization of QKD networks still faces some technological and standardisation challenges. In this paper, recent developments and in-field deployments of QKD networks are reviewed and advancements in QKD standardisation are also discussed.

The metrology of the QKD devices and systems grows increasingly important in recent years not only because of the needs for conformance and performance testing in the standardization, but more importantly, imperfect implementation of the devices and systems or deviations from the theoretical models, which could be exploited by eavesdropper, should be carefully characterised to avoid the so-called side channel attack. In this paper, we review the recent advances in many aspects of the QKD metrology in both fibre based QKD and free space QKD systems, including a cutting edge metrology facility development and application, traceable calibration methods, and practical device characterising technologies, all of which have been contributed by the metrology communities and relative institutions.

We report on experimental observation of non-laminar proton acceleration modulated by a strong magnetic field in laser irradiating micrometer aluminum targets. The results illustrate the coexistence of ring-like and filamentation structures. We implement the knife edge method into the radiochromic film detector to map the accelerated beams, measuring a source size of 30–110 μm for protons of more than 5 MeV. The diagnosis reveals that the ring-like profile originates from low-energy protons far off the axis whereas the filamentation is from the near-axis high-energy protons, exhibiting non-laminar features. Particle-in-cell simulations reproduced the experimental results, showing that the short-term magnetic turbulence via Weibel instability and the long-term quasi-static annular magnetic field by the streaming electric current account for the measured beam profile. Our work provides direct mapping of laser-driven proton sources in the space-energy domain and reveals the non-laminar beam evolution at featured time scales.

IntroductionAllergic rhinitis has a severe impact on patients’ life quality, and the incidence rate keeps increasing. Moxibustion is widely used for treating allergic rhinitis, and quantity is the basis of moxibustion efficacy. The purpose of this study is to evaluate the relationship between the different quantities of moxibustion and the efficacy of moxibustion in the treatment of allergic rhinitis. This study may be conductive to the standardization of moxibustion and furnish the mechanism of dose-effect relationship of moxibustion with data and new ideas.Methods and analysisThis randomized, placebo-controlled clinical trial will include 33 patients with allergic rhinitis who will be randomly assigned into three groups in a 1:1:1 ratio: high-dose moxibustion group, low-dose moxibustion group and sham moxibustion control group. All groups will be treated once every other day, 20 days for one treatment course. And the patients will receive treatment for 2 courses with an interval of 2 days between courses. We will conduct a follow-up 30 days later after completion of treatments. The primary outcome measure is Total Nasal Symptom Score, carried out at baseline, 3, 6 and 10 weeks. Secondary outcome measure is Rhino Conjunctivitis Quality of Life Questionnaire, carried out at baseline, 6 and 10 weeks.Ethics and disseminationThis trail has been approved by the IRB of Shanghai TCM-Integrated Hospital, Shanghai University of TCM. The results of the trial will be disseminated in peer-reviewed journals.Trial registration numberChiCTR2100050373; Pre-results.Strengths and limitations of this studyA randomised, placebo-controlled and parallel clinical trial will be conducted to test if ginger interposed moxibustion would have curative effect on allergic rhinitis and reveal the preliminary dose-effect relationship of moxibustion.This study will set high-dose moxibustion group and low-dose moxibustion group to test if more quantities of ginger interposed moxibustion would achieve better therapeutic effects on allergic rhinitis.Further study should be carried out to test if the curative effect of ginger interposed moxibustion would be positively correlated with the quantities.

The dynamic buckling of an elastic cylindrical shell with a general boundary condition (composed of stiffness and damping) under an axial impact by a rigid body is considered. A dynamic equation is derived to obtain the axial stress and radial displacement of the shell. Then, by substituting the results into the energy equation, the critical condition for the dynamic buckling of the shell is obtained. The influence of the general boundary condition on the critical velocity of the impactor is analyzed. The results reveal that the boundary condition exerts no effect on the dynamic buckling of the shell before the stress wave becomes reflected from the fixed end face of the shell. After reflection, the critical velocity decreases with increasing impactor mass and stiffness, but increases with increasing damping. At times smaller than the instant when the stress wave reaches the fixed end face of the shell, the dynamic buckling occurs earlier at greater values of damping and stiffness. After stress wave reflection, the earlier dynamic buckling is observed at smaller values of damping and stiffness.

BackgroundDespite the constant updating of rheumatoid arthritis (RA) treatment strategies, whether poor prognostic factors (PPFs) can guide RA treatment is still controversial. There are limited data about the presence of PPFs in Chinese RA patients.ObjectivesTo describe the profile of PPFs based on European League Against Rheumatism (EULAR) recommendations in Chinese RA patients, and explore the significance of these factors in adjusting treatment therapy.MethodsIn this real-world study, RA patients were enrolled from 2012 to 2020. The baseline characteristics and prognostic factors based on EULAR recommendations include acute-phase reactant levels, rheumatoid factor (RF), anti-cyclic citrullinate peptide (anti-CCP antibody), swollen joint counts (SJC), early bone erosions, and responses to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) at month 3 or month 6 were collected. Disease activity was assessed by disease activity score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR), DAS28-C-reactive protein (DAS28-CRP), simple disease activity index (SDAI), and clinical disease activity index (CDAI). The association of different factors was represented by a Venn diagram. The number of patients presenting with different combinations of prognostic factors was graphically displayed by UpSetR. Correlation between binary variables was analyzed by the Chi-square test.Results1252 registered RA patients were enrolled. 901/1252 (72.0%) patients had elevated ESR or CRP and 1027/1164 (88.2%) patients had positive RF or anti-CCP antibody. 397/1252 (31.7%) patients had ors was graphicas. 166/444 (37.0%) patients had early bone erosions, which usually coexisted with other PPFs. 394 (34.4%) of the 1105 patients who received csDMARD therapy as prescribed had persistent moderate or high disease activity (MDA/HDA). Failure of two or more csDMARDs was found in 245 (22.2%) patients. 99% of RA patients had at least one PPF. Patients with MDA/HDA usually coexisted with other PPF. MDA/HDA was significantly correlated with elevated ESR/CRP or high SJC and is not correlated with positive RF/anti-CCP antibody or early bone erosion.ConclusionPPFs are prevalent in RA patients in real-world data. It is inappropriate to guide treatment strategies just based on the presence or absence of PPFs. The categories of PPFs should be simplified and the role of different combinations of PPFs in guiding treatment therapies remains to be explored.References[1]Hu, H., et al., Burden of rheumatoid arthritis from a societal perspective: A prevalence-based study on the cost of this illness for patients in China. International journal of rheumatic diseases, 2018. 21(8): p. 1572-1580.[2]Muñoz-Fernández, S., et al., Use of prognostic factors of rheumatoid arthritis in clinical practice and perception of their predictive capacity before and after exposure to evidence. Rheumatology international, 2018. 38(12): p. 2289-2296.[3]Koga, T., et al., Prognostic Factors Toward Clinically Relevant Radiographic Progression in Patients With Rheumatoid Arthritis in Clinical Practice: A Japanese Multicenter, Prospective Longitudinal Cohort Study for Achieving a Treat-to-Target Strategy. Medicine, 2016. 95(17): p. e3476.[4]Smolen, J.S., et al., EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Annals of the rheumatic diseases, 2020. 79(6): p. 685-699.[5]Fraenkel, L., et al., 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis care & research, 2021. 73(7): p. 924-939.Figure 1.Coexistence of 6 PPFs including positive RF/anti-CCP antibody, elevated ESR/CRP, high SJC, persistent MDA/HDA, failure of two or more csDMARDs, and early bone erosion.AcknowledgementsThis study was based on the contributions of all colleagues in our department during the outpatient visits over the past decade.Disclosure of InterestsNone declared

Cathode materials are important in determining the performance of a capacitive deionization cell. In this work activated carbon cloth (ACC) grafted with tungsten oxide was employed as cathode, which was first grown on ACC with a flaky morphology by a self-anodization method. The oxide was uniformly distributed over the surface of the ACC. The desalination capacity of the obtained material is deduced from electrochemical characterization, based on the preliminary stage, in the static 1 M NaCl aqueous solution over a potential range from −1 V to 0.2 V. The modified ACC attained an enhanced ion removal ability, which gives promising potential in the further application on removing heavy ions from the wastewater of industries.

Plant height and lodging resistance can affect rice yield significantly, but these traits have always conflicted in crop cultivation and breeding. The current study aimed to establish a rapid and accurate plant type evaluation mechanism to provide a basis for breeding tall but lodging-resistant super rice varieties. A comprehensive approach integrating plant anatomy and histochemistry was used to investigate variations in flexural strength (a material property, defined as the stress in a material just before it yields in a flexure test) of the rice stem and the lodging index of 15 rice accessions at different growth stages to understand trends in these parameters and the potential factors influencing them. Rice stem anatomical structure was observed and the lignin content the cell wall was determined at different developmental stages. Three rice lodging evaluation models were established using correlation analysis, multivariate regression and artificial radial basis function (RBF) neural network analysis, and the results were compared to identify the most suitable model for predicting optimal rice plant types. Among the three evaluation methods, the mean residual and relative prediction errors were lowest using the RBF network, indicating that it was highly accurate and robust and could be used to establish a mathematical model of the morphological characteristics and lodging resistance of rice to identify optimal varieties.

The structural evolution of the oxide films at 25–450 °C on nanocrystalline (NC) and coarse crystalline (CC) 304 stainless steels (SS) was investigated. The structure of the oxide film on both NC and CC SSs was observed to undergo transient processes from a bi-layer to a single-layer and then back to a bi-layer when the temperature changed from the low range (25–150 °C) to the medium range (150–300 °C) and subsequently to the high range (300–450 °C), respectively. These formation mechanisms of the oxide films on SS were attributed to the different diffusion properties of Cr and Fe in the three temperature ranges. The thickness of the oxide films was similar between the NC and CC SSs below 300 °C due to their similar Cr ox /Fe ox concentration ratios in their oxide films at this temperature. Above 300 °C, Cr diffusion enhancement in the NC matrix led to a higher Cr ox /Fe ox ratio and better compactness of the oxide film, which resulted in a slower atomic diffusion rate in the oxide film and a thinner oxide film. Therefore, the temperature of 300 °C was concluded to be the critical temperature of the detectable Cr diffusion enhancement in the NC SS compared to the CC SS.

AIM To investigate the role of suppressor of cytokine signaling 1 (SOCS1) in regulating MET-mediated invasive potential of hepatocellular carcinoma (HCC) cells. METHODS Stable derivatives of mouse (Hepa1-6) and human (hep3B, HepG2) HCC cell lines expressing SOCS1 or control vector were evaluated for their ability to migrate towards hepatocyte growth factor (HGF) in the transwell migration assay, invade extracellular matrix in response to HGF stimulation in a 3-D invasion assay by confocal microscopy, and to undergo anchorage-independent proliferation in semisolid agar. Following intravenous and intrasplenic inoculation into NOD.scid.gamma mice, the ability of Hepa cells to form othotopic tumors was evaluated. Following HGF stimulation of Hepa and Hep3B cells, expression of proteins implicated in epithelial-to-mesenchymal transition was evaluated by western blot and qRT-PCR. RESULTS SOCS1 expression in mouse and human HCC cells inhibited HGF-induced migration through matrigel. In the 3-D invasion assay, HGF stimulation induced invasion of HCC cells across type-I collagen matrix, and SOCS1 expression significantly reduced the depth of invasion. SOCS1 expression also reduced the number and size of colonies formed by anchorage-independent growth in semisolid agar. Following intravenous inoculation, control Hepa cell formed large tumor nodules that obliterated the liver whereas the SOCS1-expressing Hepa cells formed significantly smaller nodules. Tumors formed by SOCS1-expressing cells showed reduced phosphorylation of STAT3 and ERK that was accompanied by reduced levels of MET protein expression. HGF stimulated Hepa cells expressing SOCS1 showed increased expression of E-cadherin and decreased expression of EGR1, SNAI1 and ZEB1. Comparable results were obtained with Hep3B cells. SOCS1 expressing HCC cells also showed reduced levels of EGR1 and SNAI1 transcripts. CONCLUSION Our findings indicate that loss of SOCS1-dependent control over epithelial-to-mesenchymal transition may contribute to MET-mediated migration, invasion and metastatic growth of HCC.

Introduction The study was to investigate trajectories of infant sleep duration and associations with trajectories of maternal depression status during 3 years post-partum. Methods Data were from the Child Health Promotion Project in Shanghai (CHPPS). Mothers were recruited at the third trimester of pregnancy and followed up together with the infants until 36 months postpartum. Between 2012 and 2013, 262 women (Mage=29.5, SDage=3.2, range: 22-39 years old) were recruited and were followed from June 2012 to August 2015. Sleep duration of the children was assessed using Brief Infant Sleep Questionnaire (BISQ) at 42 days, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, and 36 months postpartum. Center for Epidemiological Survey-Depression Scale (CESD), Edinburgh Postnatal Depression Scale (EPDS), and the Profile of Mood States (POMS) were used to measure the mother’s depression status at late pregnancy, 42 days postpartum, and 12-36 months postpartum, respectively. The group-based trajectory models (GBTM) were used to estimate patterns of infant sleep duration development and maternal depression status. Results Two trajectories of infant day sleep duration were identified, defined as “initial short sleepers” (54.8%) and “initial long sleepers” (45.2%). Three trajectories of infant night sleep duration were identified, labeled as “increasing” (8.5%), “stable” (61.7%), and “mild declining” (29.8%). Two trajectories infant total sleep duration were identified, defined as “initial short sleepers” (51.5%) and “initial long sleepers” (48.5%). Two trajectories of maternal depression status were identified, labeled as “low” (74.2%) and “high” (25.8%). After controlling for covariates, women who have higher depression status had infants of shorter day sleep duration. There was no significant association with infant night sleep duration. Conclusion Our study suggests that maternal postpartum depression is associated with short infant day sleep duration, but not with infant night sleep duration. Support Supported by the Chinese National Natural Science Foundation of China (81773443, 81728017, 81602870, 81601162, 81602868)

Due to excessive anthropogenic emissions, heavy aerosol pollution episodes (HPEs) often occur during winter in the Beijing–Tianjin–Hebei (BTH) area of the North China Plain. Extensive observational studies have been carried out to understand the causes of HPEs; however, few measurements of vertical aerosol fluxes exist, despite them being the key to understanding vertical aerosol mixing, specifically during weak turbulence stages in HPEs. In the winter of 2016 and the spring of 2017 aerosol vertical mass fluxes were measured by combining large aperture scintillometer (LAS) observations, surface PM2.5 and PM10 mass concentrations, and meteorological observations, including temperature, relative humidity (RH), and visibility, at a rural site in Gucheng (GC), Hebei Province, and an urban site at the Chinese Academy of Meteorological Sciences (CAMS) in Beijing located 100 km to the northeast. These are based on the light propagation theory and surface-layer similarity theory. The near-ground aerosol mass flux was generally lower in winter than in spring and weaker in rural GC than in urban Beijing. This finding provides direct observational evidence for a weakened turbulence intensity and low vertical aerosol fluxes in winter and polluted areas such as GC. The HPEs included a transport stage (TS), an accumulative stage (AS), and a removal stage (RS). During the HPEs from 25 to 31 January 2017, in Beijing, the mean mass flux decreased by 51 % from 0.0049 mg m−2 s−1 in RSs to 0.0024 mg m−2 s−1 in the TSs. During the ASs, the mean mass flux decreased further to 0.00087 mg m−2 s−1, accounting for approximately one-third of the flux in the TSs. A similar reduction from the TSs to ASs was observed in the HPE from 16 to 22 December 2016 in GC. It can be seen that from the TS to the AS, the aerosol vertical turbulent flux decreased, but the aerosol particle concentration within the surface layer increased, and it is inferred that in addition to the contribution of regional transport from upwind areas during the TS, suppression of vertical turbulence mixing confining aerosols to a shallow boundary layer increased accumulation.

Cancer cell metabolism is heavily influenced by microenvironmental factors, including nutrient availability. Therefore, knowledge of microenvironmental nutrient levels is essential to understand tumor metabolism. To measure the extracellular nutrient levels available to tumors, we utilized quantitative metabolomics methods to measure the absolute concentrations of >118 metabolites in plasma and tumor interstitial fluid, the extracellular fluid that perfuses tumors. Comparison of nutrient levels in tumor interstitial fluid and plasma revealed that the nutrients available to tumors differ from those present in circulation. Further, by comparing interstitial fluid nutrient levels between autochthonous and transplant models of murine pancreatic and lung adenocarcinoma, we found that tumor type, anatomical location and animal diet affect local nutrient availability. These data provide a comprehensive characterization of the nutrients present in the tumor microenvironment of widely used models of lung and pancreatic cancer and identify factors that influence metabolite levels in tumors., eLife digest In the body, cancer cells can rely on different nutrients than normal cells, and they can use these nutrients in a different way. What cancer cells consume also depends on what is available in their immediate environment. In a tumor, cells grab nutrients from the ‘interstitial’ fluid that surrounds them, but what is present in this liquid may vary within tumors arising in different locations. Understanding what nutrients are ‘on the menu’ in specific tumors would help to target diseased cells while sparing healthy ones, but this knowledge has been difficult to obtain. To investigate this, Sullivan et al. used a technique called mass spectrometry to measure the amounts of 120 nutrients present in the interstitial fluid of mouse pancreas and lung tumors. Different levels of nutrients were found in the two types of tumors, and analyses showed that what was present in the interstitial fluid depended on the type of cancer cells, where the tumor was located, and what the animals ate. This suggests that cancer cells may have different needs because they are limited in what they have access to. It remains to be seen whether the nutrients levels found in mouse tumors are the same as those in humans. Armed with this knowledge, it may then be possible to feed cancer cells grown in the laboratory with the nutrient menu that they would have access to in the body. This could help identify new cancer treatments.

Aerobic glycolysis, or preferential fermentation of glucose-derived pyruvate to lactate despite available oxygen, is a hallmark of proliferative metabolism that is observed across many organisms and conditions. To better understand why aerobic glycolysis is associated with cell proliferation, we examined the metabolic consequence of activating the pyruvate dehydrogenase complex (PDH) to increase mitochondrial pyruvate oxidation at the expense of fermentation. We find that increasing PDH activity impairs cell proliferation by reducing the nicotinamide adenine dinucleotide cofactor ratio (NAD+/NADH). This change in NAD+/NADH ratio is caused by an increase in mitochondrial membrane potential that impairs mitochondrial electron transport and NAD+ regeneration. Uncoupling mitochondrial respiration from ATP synthesis or increasing ATP hydrolysis restores NAD+/NADH homeostasis and proliferation even when glucose oxidation is increased. These data suggest that when the demand for NAD+ to support oxidation reactions exceeds the demand for ATP consumption in cells, NAD+ regeneration by mitochondrial respiration becomes constrained, promoting fermentation despite available oxygen. This argues that cells engage in aerobic glycolysis when the cellular demand for NAD+ is in excess of the cellular demand for ATP.

A lack of understanding regarding the feeding biology of post-settlement mussels has considerably constrained the hatchery culture of many commercially important mussel species, including the Greenshell™ mussel, Perna canaliculus . Therefore, we evaluated how particles of different size (MySpat artificial diet full particle size range 2–60 μm, sieved MySpat diet with a size range of 2–15 μm; polystyrene beads, 3–15 μm, and microalgae, 4–6.5 μm) affected the retention and capture efficiency in post-settlement juveniles (PSJ). The response of PSJ of various sizes (PSJ-I: 0.3 mm shell length, PSJ-II: 1.0 mm, and PSJ-III: 7.0 mm) was different. Overall, smaller mussels (PSJ-I and PSJ-II) were unable to selectively capture particles by their size on all diets, conversely larger juveniles actively captured smaller particles between 2 and 8 μm. Independently of the PSJ size, the full particle size range MySpat artificial diet had a negative effect on the feeding activity of the mussels, with particles blocking the pallial organs in the non-selective PSJ-I and PSJ-II, and completely inhibiting the feeding activity in the more selective PSJ-III. These results provide useful information to understand the feeding biology and ecology of PSJ of this species that can be used for the improvement of hatchery feeding methods. Artificial and live food particle size can be chosen in order to avoid larger harmful particles (> 15 μm), and the exclusive use of smaller food particles should be considered for PSJ Statement of relevance This article provides information to better understand particle capture process in post-settlement juvenile mussel in order to improve hatchery/nursery feeding practices. The results of this research will allow making informed decisions regarding selection of food particle size in relation to the size of the juvenile mussels and their ability to deal with particles of different sizes. Furthermore will also help to decide the adequate size of transfer for grow-out as well as being useful for the development of suitable artificial diets.

We study two classes of sets of real numbers related to Luroth expansions and obtain their Hausdorff dimensions. One is determined by prescribed group frequencies of digits in their Luroth expansions. It is proved that the Hausdorff dimension of such a set is equal to the supremum of the Hausdorff dimensions for sets of real numbers with prescribed digit frequencies in their Luroth expansion. The other is determined by randomly selecting the digits in their Luroth expansion from a finite number of given digit sets.

Cultured cells convert glucose to lactate, and glutamine is the major source of tricarboxylic acid (TCA)-cycle carbon, but whether the same metabolic phenotype is found in tumors is less studied. We infused mice with lung cancers with isotope-labeled glucose or glutamine and compared the fate of these nutrients in tumor and normal tissue. As expected, lung tumors exhibit increased lactate production from glucose. However, glutamine utilization by both lung tumors and normal lung was minimal, with lung tumors showing increased glucose contribution to the TCA cycle relative to normal lung tissue. Deletion of enzymes involved in glucose oxidation demonstrates that glucose carbon contribution to the TCA cycle is required for tumor formation. These data suggest that understanding nutrient utilization by tumors can predict metabolic dependencies of cancers in vivo. Furthermore, these data argue that the in vivo environment is an important determinant of the metabolic phenotype of cancer cells., National Science Foundation (U.S.) (Grant T32GM007287)

Despite the commercial aquaculture importance of the Greenshell™ mussel, Perna canaliculus , the morphological development of gill structure (ctenidial filaments) in relation to potential particle feeding abilities have not been described. Scanning electron microscopy (SEM) and light microscopy were used to examine the ontogenetic changes across five size classes of mussels from post-settlement larvae to adults ranging from 300 μm to > 100 mm in shell height. Key morphological characteristics were measured including filament width, the eulatero-frontal cirri (ELF) length, interfilamentary space (IFS) and the mean distance between adjacent ELF, d ELF . Overall the development of the ctenidial filaments in P. canaliculus , shared some similarities to other homorhabdic filibranch bivalves with differences in the timing of development. Filament width and ELF length followed sigmoidal growth curves in relation to increasing shell height of mussels. The morphological changes of the ctenidia, reflected in changes in the ELF/IFS ratios, together with the development of cilia in the ELF may help explain the differences in the capture efficiency of small particles between small individuals ( Statement of relevance –This article provides information regarding the gill ontogenetic development of the commercially important Greenshell™ mussel, Perna canaliculus . –The information given will help improve hatchery practices, especially regarding the selection of adequate particle size for feeding post-settlement P. canaliculus . –Considering that mussel aquaculture is a global phenomenon, these results could be used worldwide in order to help the industry find economically feasible alternatives for mussel juvenile supply. The New Zealand Greenshell™ industry has recently invested $20 M to build a large scale hatchery/nursery to address an on-going shortage with seed supply which has been constraining the growth of the industry. Shortages of mussel seed, caused by poor feeding and starvation, have resulted in seed shortages in the industry for the last three years, shaving off almost 20% production of the entire industry, in the order of $30 M lost production a year. Hence there is intense interest in better understanding the feeding biology of juvenile mussels and using this knowledge to resolve the major production issues faced by this aquaculture industry. From our international contacts, we understand that other countries with significant mussel farming industries face similar issues, such as Chile. Therefore, we believe that there is strong reader interest and value in the publication of this fundamental research.

The structure and compactness of the passive films on nanocrystalline (NC) and coarse crystalline (CC) 304 stainless steels (SSs) are investigated. A bi-layer passive film composed of an inner Cr2O3-rich layer and an outer Fe2O3-rich layer is obtained on both NC and CC 304SSs. The lower oxide formation potential Uox(Cr) of chromium causes the Cr2O3-rich inner layer to form initially, and when the surface potential of the passive film increases due to Cr2O3 formation, Fe2O3 with a higher formation potential Uox(Fe) forms and predominates in the outer layer as a result of the higher diffusion rate of Fe than that of Cr across the inner layer. Compared with the CC-304SS, the inner layer of the passive film on the NC-304SS possesses a higher Cr2O3 content, which is attributed to the greater nucleation sites and faster growth rate of Cr2O3 in NC-304SS and is believed to be responsible for the higher compactness of the passive film on NC-304SS.

Transition metal phosphides (TMPs) are prospective anode materials for lithium-ion batteries (LIBs) due to their high theoretical capacities and low redox voltages. Herein, we report a template directing method to develop a tube-sheath hybrid composing of cobalt phosphide particles encapsulated in metal organic frameworks (MOFs) derived N-doped carbon sheaths (CoxP@NC). The utilization of directing template leads to a homogenous distribution of the subsequently formed cobalt phosphide particles, restrains the aggregation of cobalt phosphides, and thus results in the superb rate capability and cyclability. Contributable to the integrated merits of the interior downsized cobalt phosphide particles and the outer ZIF-67 derived porous carbon sheath, the volume expansion during cycling is effectively suppressed. The CoxP@NC hybrid shows superb electrochemical performance as anode material for LIB, with good reversible capacity of 928 mAh·g−1 after 100 cycles at 0.1 A g−1, and high stability of 526 mAh·g−1 after 600 cycles at 1.0 A g−1. This work provides a route for rational design of MOF derived carbon-based anode material for LIB, which could also be applied as a promising platform in diverse field.

Background:Early diagnosis and treat-to-target strategies in RA improve clinical and radiographic outcomes. 14-3-3η is a soluble diagnostic biomarker that is involved in the pathogenesis of RA (1) including the potent activation of key signalling cascades such as the JAK-STAT pathway and whose initial expression coincides with a transition to synovitis. In undifferentiated arthralgia, 14-3-3η independently predicts the development of RA. In confirmed RA, 14-3-3η levels decrease with treatment response (2) and those changes are associated with clinical and radiographic outcomes, including the prediction of joint damage progression in patients who have achieved clinical remission. Upadacitinib (UPA), an oral JAK1-selective inhibitor, demonstrated significant and clinically meaningful improvements in RA vs. methotrexate (MTX) in the SELECT-EARLY phase 3 study (3).Objectives:To determine the impact of treatment with UPA monotherapy 15 mg QD on the levels of plasma 14-3-3η and to explore its relationship with clinical measures in early MTX-naïve RA patients.Methods:Patients from the SELECT-EARLY study were randomly selected (UPA n = 100; MTX n = 100) from the pool of patients with available plasma samples. 14-3-3η tests were performed at Augurex according to standard operating procedures. Concentrations (ng/mL) were log-transformed for analysis. Non-parametric correlations between biomarker data and clinical end points were derived using the Spearman method. Changes in 14-3-3η over time were compared using a Repeated Measure Mixed Linear Model. All statistical analyses were conducted in JMP 14.1 (SAS Institute).Results:At baseline, 79% of patients were 14-3-3η positive (≥ 0.19 ng/mL) with similar levels in both arms. Baseline levels of 14-3-3η correlated significantly with baseline disease activity measures (CDAI ρ = 0.164, p = 0.042; DASCRP ρ = 0.222, p = 0.004; and SDAI ρ = 0.177, p = 0.028) but not with baseline mTSS (ρ =-0.021, p = 0.787); of note baseline mTSS were relatively low in this subset of early RA patients (median = 2, IQR [0 – 9.5]). Over time, 14-3-3η levels tended to be lower in both the UPA and MTX groups. However, only treatment with UPA for 24 weeks resulted in a significant decrease in circulating 14-3-3η (p = 0.0002) (Figure 1). In addition, at week 24 in the UPA arm, changes in 14-3-3η levels correlated significantly with changes in concurrent disease activity measures (Δ CDAI ρ = 0.264, p = 0.030; Δ DASCRP ρ = 0.267, p = 0.021; and Δ SDAI ρ = 0.267, p = 0.028) but not with change in mTSS (ρ =-0.186, p = 0.111). In contrast to UPA, the relatively small changes in 14-3-3η induced by MTX did not correlate with any clinical measures.Figure1Conclusion:This study demonstrates that treatment with UPA 15 mg QD monotherapy for 24 weeks significantly reduces the levels of circulating 14-3-3η in MTX-naïve RA patients and that these changes correlate with clinical measures of disease activity. Although we were not able to detect a clear relationship between changes in 14-3-3η and rate of structural damage progression, we would like to hypothesize that the superior clinical activity of UPA over MTX on joint damage may be related to the significant reduction in 14-3-3η induced by UPA; this hypothesis should be tested in a larger RA cohort with a larger proportion of joint damage progressors.References:[1]Maksymowych WP et al. Arthritis Res Ther. 2014;16(2):R99.[2]Hirata S et al. Arthritis Res Ther. 2015;17(1):280.[3]van Vollenhoven R et al. Arthritis Rheumatol.;2018 (Suppl 10; vol.70).Disclosure of Interests:Thierry Sornasse Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Simran Chahal Shareholder of: Augurex Life Science Corp, Employee of: Augurex Life Science Corp, Yuan Gui Shareholder of: Augurex Life Science Corp, Employee of: Augurex Life Science Corp, Neeraja Nagarajan Employee of: Augurex Life Science Corp, Alan Friedman Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Norma Biln Shareholder of: Augurex Life Science Corp, AbbVie Inc, Employee of: Augurex Life Science Corp

An oblique detonation wave stabilized over a body has been studied due to the ongoing development of high-speed propulsion systems, such as oblique detonation wave engines and ram accelerators. Standing window of oblique detonation wave reflects the degree of standing difficulty. Firstly, Shock relations coupled with chemical equilibrium are solved to draw detonation polar diagrams between oblique detonation angle and wedge angle by iterative algorithm. In these diagrams, the wedge angle detaching from the wedge nose is referred as the maximum wedge angle θιηॉκ and forming CJ detonation in the direction normal to the oblique detonation wave is referred as the minimum wedge angle θख़τ. The region between the two wedge angles is regarded as the standing windows. G. Emanuel holds that Taylor waves follow the oblique detonation wave as the wedge angle is smaller than θख़τ. Based on reactive Euler equation, wedge-induced oblique detonation is simulated in this paper. For the case of the wedge angle below θख़τ, Taylor waves change post-detonation wave flow field to maintain standing oblique detonation wave. Therefore, the standing window becomes wider.

The role of pyruvate kinase M2 (PKM2) in cell proliferation is controversial. A unique function of PKM2 proposed to be important for the proliferation of some cancer cells involves the direct activity of this enzyme as a protein kinase; however, a detailed biochemical characterization of this activity is lacking. Using [32P]-phosphoenolpyruvate (PEP) we examine the direct substrates of PKM2 using recombinant enzyme and in vitro systems where PKM2 is genetically deleted. Labeling of some protein species from [32P]-PEP can be observed; however, most were dependent on the presence of ADP, and none were dependent on the presence of PKM2. In addition, we also failed to observe PKM2-dependent transfer of phosphate from ATP directly to protein. These findings argue against a role for PKM2 as a protein kinase., Howard Hughes Medical Institute (International Student Research Fellowship), Vertex Pharmaceuticals Incorporated. Vertex Scholars Program, Massachusetts Institute of Technology. Department of Biology (Grant T32GM007287), David H. Koch Institute for Integrative Cancer Research at MIT (Graduate Student Fellowship), National Cancer Institute (U.S.) (Grants R01CA168653 and P30CA14051), Burroughs Wellcome Fund

SummaryMitochondrial respiration is important for cell proliferation; however, the specific metabolic requirements fulfilled by respiration to support proliferation have not been defined. Here, we show that a major role of respiration in proliferating cells is to provide electron acceptors for aspartate synthesis. This finding is consistent with the observation that cells lacking a functional respiratory chain are auxotrophic for pyruvate, which serves as an exogenous electron acceptor. Further, the pyruvate requirement can be fulfilled with an alternative electron acceptor, alpha-ketobutyrate, which provides cells neither carbon nor ATP. Alpha-ketobutyrate restores proliferation when respiration is inhibited, suggesting that an alternative electron acceptor can substitute for respiration to support proliferation. We find that electron acceptors are limiting for producing aspartate, and supplying aspartate enables proliferation of respiration deficient cells in the absence of exogenous electron acceptors. Together, these data argue a major function of respiration in proliferating cells is to support aspartate synthesis.

Suppressor of cytokine signaling 1 (SOCS1) is considered as a tumor suppressor protein in hepatocellular carcinoma (HCC), but the underlying mechanisms remain unclear. Previously, we have shown that SOCS1-deficient hepatocytes displayed increased responsiveness to hepatocyte growth factor (HGF) due to enhanced signaling via the MET receptor tyrosine kinase. As aberrant MET activation occurs in many tumors including HCC, here we elucidated the mechanisms of SOCS1-mediated regulation. SOCS1 attenuated HGF-induced proliferation of human and mouse HCC cell lines and their growth as tumors in NOD.scid.gamma mice. Tumors formed by SOCS1 expressing HCC cells showed significantly reduced MET expression, indicating that SOCS1 not only attenuates MET signaling but also regulates MET expression. Mechanistically, SOCS1 interacted with MET via the Src homology 2 domain and this interaction was promoted by MET tyrosine kinase activity. The SOCS1-mediated reduction in MET expression does not require the juxtamembrane Y1003 residue implicated in Cbl-mediated downmodulation. Moreover, the proteasome inhibitor MG-132, but not the inhibitors of lysosomal degradation bafilomycin and chloroquine, reversed the SOCS1-mediated reduction in MET expression, indicating that this process is distinct from Cbl-mediated downmodulation. Accordingly, SOCS1 promoted polyubiquitination of MET via K48-dependent but not K63-mediated ubiquitin chain elongation. Furthermore, siRNA-mediated downmodulation of Cbl did not abolish SOCS1-mediated reduction in MET expression in HCC cells. SOCS1-dependent ubiquitination of endogenous MET receptor occurred rapidly following HGF stimulation in HCC cells, leading to proteasomal degradation of phosphorylated MET receptor. These findings indicate that SOCS1 mediates its tumor suppressor functions, at least partly, by binding to MET and interfering with downstream signaling pathways as well as by promoting the turnover of the activated MET receptor. We propose that loss of this control mechanism due to epigenetic repression of SOCS1 could contribute to oncogenic MET signaling in HCC and other cancers, and that MET inhibitors might be useful in treating these patients.

Many mammalian cancer cell lines depend on glutamine as a major tri-carboxylic acid (TCA) cycle anaplerotic substrate to support proliferation. However, some cell lines that depend on glutamine anaplerosis in culture rely less on glutamine catabolism to proliferate in vivo. We sought to understand the environmental differences that cause differential dependence on glutamine for anaplerosis. We find that cells cultured in adult bovine serum, which better reflects nutrients available to cells in vivo, exhibit decreased glutamine catabolism and reduced reliance on glutamine anaplerosis compared to cells cultured in standard tissue culture conditions. We find that levels of a single nutrient, cystine, accounts for the differential dependence on glutamine in these different environmental contexts. Further, we show that cystine levels dictate glutamine dependence via the cystine/glutamate antiporter xCT/SLC7A11. Thus, xCT/SLC7A11 expression, in conjunction with environmental cystine, is necessary and sufficient to increase glutamine catabolism, defining important determinants of glutamine anaplerosis and glutaminase dependence in cancer., eLife digest Cancer cells need to consume certain nutrients in order to grow, and some cancer drugs work by affecting the ability of the cells to use these nutrients. For decades researchers have grown cancer cells in petri dishes with standard nutrient formulations (also known as tissue culture), but the nutrients available to cancer cells in tissue culture are not the same as those found in the body. Cancer cells growing in tissue culture consume large amounts of a nutrient called glutamine. These cells die when exposed to a class of drugs called glutaminase inhibitors that prevent them from processing glutamine. However, when these same cancer cells grow as tumors in animals, they process less glutamine and are not affected by glutaminase inhibitors. So what differences are there between growing cancer cells in tumors and tissue culture that explain this different reliance on glutamine? Muir et al. reasoned that changing the levels of nutrients available to cancer cells might change what these cells consume, and so grew human cancer cells in cow serum (which has a similar nutrient content to blood in humans and other mammals). Indeed, these cells consumed less glutamine and responded to glutaminase inhibitors in a way that is similar to how tumors in the body respond to these drugs. Comparing the nutrient content of cow serum and typical tissue culture formulations revealed that high levels of the nutrient cystine cause the cells to rely more on glutamine. The results presented by Muir et al. suggest that cancer cells in tumors could be made to consume more glutamine and that this would make them sensitive to glutaminase inhibitors – a possibility that will be studied in future work. Exposing cultured cancer cells to nutrient levels closer to those found in the body may also better predict how tumor cells use nutrients and respond to some treatments.

Background The soluble biomarker sub-committee of OMERACT has published validation criteria for biomarkers reflecting structural damage end-points. Within these, categories of Discrimination and Feasibility relate to assay reproducibility and performance. 14–3-3eta (η) is a joint-derived biomarker that drives joint damage processes and informs radiographic progression independently of acute phase reactants. As an ELISA assay, 14–3-3η is currently available for clinical use as a laboratory developed test (LDT) in the United States (US) and as an in-vitro diagnostic (IVD) in Canada. The ELISA is (CE) marked for Europe and is Therapeutics Good Administration (TGA) approved for Australia. Previous studies have described 14–3-3eta assay equivalence at independent laboratories in the US and Canada. Objectives The purpose of this study was to demonstrate the reproducibility of 14–3-3eta measurements at two independent laboratories in Japan and one in Canada. Methods A total of 212 samples from the University of Occupational and Environmental Health were provided for this study. Serum 14–3-3eta measurements were performed using the 14–3-3eta ELISA provided by Augurex. Testing in Canada occurred in August 2015; these 14–3-3eta values were set as the “standard”. The 212 samples were shipped from Canada to Japan in January 2016 with testing being performed in February 2016. Testing at MBL was performed on a blinded-basis. Upon completion of testing, results were sent to the investigators at which point in time, MBL was unblinded. 14–3-3eta positivity was defined at ≥0.19ng/ml. Contigency and Spearman analyses were performed to assess the strength of the results between the two testing centres. Values above the linear range of the assay i.e. ≥20ng/ml were excluded for the Spearman analyses and determination of the median (IQR). A p-value of Results In Canada, of the 212 samples tested, 146 (68.8%) were 14–3-3eta positive and in Japan, 147 (69.3%) were positive. In Canada, 187 patients had reportable values in the linear range and in Japan 186 did. Median 14–3-3eta levels in Canada were 0.51 ng/ml (IQR: 0.11–2.09) and in Japan they were 0.58 ng/ml (IQR: 0.02–2.68), respectively. Spearman correlation analysis revealed a highly significant correlation between the two testing sites, r=0.92; p Conclusions As defined by the soluble biomarker sub-committee of OMERACT, reliability and standardization of biomarker assessments in routine clinical practice across the globe and in clinical studies is of high importance. The results presented herein demonstrate that the 14–3-3eta assay is highly reliable, that testing/delivery of results can be standardized between two independent laboratories, and that it is very stable over time and when shipped between continents. Disclosure of Interest S. Hirata: None declared, M. Kaneda Employee of: Medical & Biological Laboratories, T. Isayama Employee of: Medical & Biological Laboratories, Y. Gui Employee of: Augurex Life Sciences Corp., A. Marotta Employee of: Augurex Life Sciences Corp., W. Maksymowych Consultant for: Augurex Life Sciences Corp, Y. Tanaka: None declared

Background 14–3-3η is a joint-derived serum protein that up-regulates pro-inflammatory factors. We have previously reported that baseline 14–3-3η levels ≥0.50 ng/ml (HIGH 14–3-3η) were predictive of radiographic progression over 5 years. Objectives Our objective was to verify if the persistence of HIGH 14–3-3η at 18 months in recent-onset polyarthritis patients in REMISSION predicts more rapid radiographic progression over the following years, up to 42 months. Methods Serum 14–3-3η titres were assessed at baseline and at 18 months into disease, a median of 14 months after diagnosis and initiation of treatment. Three definitions of “clinical remission” at 18 months were used: Swollen Joint Count (SJC) =0; SJC + Tender Joint Count (TJC) =0; ACR/EULAR Boolean definition. The progression of radiographic damage (Erosion and Total Sharp/van der Heijde (SvH) scores) in patients with LOW ( Results Out of 331 patients, 36.0% of which had HIGH 14–3-3η at Baseline, 308 had complete data up to 5 years. Median age was 60 years, 62% women. Depending on the stringency of the definition used, variable numbers of patients reached remission at 18 months: 162 (53%) had SJC=0; 108 (35%) SJC+TJC=0; and 56 (18%) Boolean. Remission at 18 months was negatively associated with persistence of HIGH 14–3-3η since HIGH 14–3-3η were then present in 32/162 (19.7%) SJC=0 patients; 22/108 (20.4%) SJC+TJC=0 and 13/56 (23.2%) Boolean. Compared to patients in remission with LOW 14–3-3η, patients in remission with HIGH 14–3-3η at 18 months had numerically faster subsequent progression with all definitions. For example, in patients with Boolean remission, mean (SD) erosion progression over 42 months was 7.2±13.1 vs 1.5±3.3 and mean (SD) progression of Total score 9.2±14.5 vs 2.8±4.4 units (Figure). However, due to low numbers and limited power, differences in progression were statistically significant only for the less strict definitions of remission and only over the following year: Erosions (SJC=0, p=0.0042, SJC+TJC=0, p=0.0236), Total score (SJC=0, p=0.0146; with a trend for SJC+TJC=0, p=0.077). None of the comparisons over 42 months or of those involving Boolean reached significance. Conclusions The persistence of 14–3-3η levels ≥0.50 ng/ml appears to be associated with a lower probability of reaching remission in polyarthritis patients. 14–3-3η levels ≥0.50 ng/ml in patients in clinical remission appear to be associated with more rapid radiographic (especially erosive) progression over the following year. A larger study is required to validate these findings, especially with the most stringent criterion of Boolean remission. Disclosure of Interest N. Carrier: None declared, M.-P. Garant: None declared, A. Marotta Employee of: Augurex Life Sciences Corp., A. De Brum Fernandes Grant/research support from: AJdBF is part of the Centre de Recherche Clinique from the CHUS, which received a team grant from the Fonds de Recherche en Sante-Quebec, P. Liang: None declared, A. Masetto: None declared, Y. Gui Employee of: Augurex Life Sciences Corp., J. Savill Employee of: Augurex Life Sciences Corp., S. Michienzi Employee of: Augurex Life Sciences Corp., W. Maksymowych Consultant for: Augurex Life Sciences Corp., G. Boire Grant/research support from: GB is part of the Centre de Recherche Clinique from the CHUS, which received a team grant from the FRSQ. GB is the recipient of CIHR grant MOP-110959. Since 2007, the Sherbrooke EUPA cohort has also received financial support from the Canadian ArTritis CoHort (CATCH), a study designed and implemented by investigators and financially supported via unrestricted research grants initially by Amgen Canada Inc

Metabolic reprogramming contributes to tumor development and introduces metabolic liabilities that can be exploited to treat cancer. Chemotherapies targeting metabolism have been effective cancer treatments for decades, and the success of these therapies demonstrates that a therapeutic window exists to target malignant metabolism. New insights into the differential metabolic dependencies of tumors have provided novel therapeutic strategies to exploit altered metabolism, some of which are being evaluated in pre-clinical models or clinical trials. Here, we review our current understanding of cancer metabolism and discuss how this might guide treatments targeting the metabolic requirements of tumor cells.

Many cancer cell lines depend on extracellular glutamine as a major tri-carboxylic acid (TCA) cycle anaplerotic substrate to support proliferationin vitro. However, recent studies have suggested that some cells that depend on glutamine anaplerosis in culture rely much less on glutamine catabolism to proliferatein vivo, with environmental differences between tumors and cell culture influencing the extent of glutamine catabolism. Here we sought to better understand the environmental differences that cause differential dependence on glutamine for TCA cycle anaplerosis. We find that cells cultured in adult bovine serum, a condition that more closely reflects the nutrients available to cellsin vivo, leads to decreased glutamine catabolism and reliance on glutamine anaplerosis compared to standard tissue culture conditions. By analyzing the nutrient differences between bovine serum and media, we find that levels of a single nutrient, cystine, can account for the differential dependence on glutamine in these different environmental contexts. Further, we show that cystine levels dictate glutamine dependence via the cystine/glutamate antiporter xCT/SLC7A11, and that environmental cystine levels in conjunction withxCT/SLC7A11expression is necessary and sufficient to drive increased glutamine anaplerosis, defining important determinants of glutamine anaplerosis and glutaminase dependence in cancer cells.

Prospective, randomized and controlled study.The aim of the study was to investigate the effect of intermittent normobaric hyperoxia (InHO) for treatment of neuropathic pain in patients with spinal cord injury (SCI).The First Affiliated Hospital of Nanhua University, Hengyang, Hunan Province, China.Patients with SCI from Hunan Province were recruited from the First Affiliated Hospital of Nanhua University. History, duration, localization and characteristics of pain were recorded. Visual analog scale (VAS), the Patient Global Impression of Change (PGIC) and Short Form-36 walk-wheel (SF-36ww) was used to investigate the effect of InHO. Patients were randomly assigned to study and control groups. In study group, patients were exposed to pure oxygen via non-rebreathing reservoir mask, which increased the provided oxygen at a rate of 7 l minA total of 62 SCI patients with neuropathic pain were included in the study. The mean age of the patients was 36.85±10.71 years. Out of 62 patients, 21 were tetraplegic and 41 were paraplegic. Overall, 14 patients had complete SCI while 48 patients had incomplete injuries. Three groups were similar with respect to age, gender, duration, smoker or not, level and severity of injury. In the 4 h per day InHO groups, a statistically significant reduction of the VAS values was observed (P0.05). Significant difference was also found in SF-36ww pain scores and PGIC (P0.05). However, such an effect was not evident in the control group.This study revealed that in treatment of neuropathic pain of SCI patients, InHO may be effective.This article presents InHO may effectively complement pharmacological treatment in patients with SCI and neuropathic pain.

The fine microstructure of the passive films on nanocrystalline (NC) and coarse crystalline (CC) 304 stainless steels (SSs) in 0.5 M H2SO4 were investigated by electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). The results indicate that the passive film on both CC and NC SSs exhibits a two-layer microstructure consisting of a compact inner layer and a porous outer layer. Some hydrated compounds (HC) were present in the porous outer layer of NC SS but not CC SS in 0.5 M H2SO4 solution. The pores in the outer layer of the NC SS were observed to be in the nanoscale by AFM. HC filling of the pores in the passive film on NC SS may occur due to capillary forces endowed by the nanosize pores. XPS analysis of the passive films on both CC and NC SSs, however, does not show such a composition difference which is attributed to dehydration occurring in the XPS vacuum chamber. Both the inner and outer layers of the NC SS were determined by EIS analysis to be more compact and protective than the corresponding films on CC SS as evidenced by the lower Q value, higher n, and much higher R value in the corresponding layer.