Mycobacterium tuberculosis (Mtb) adapt to various host environments and utilize a variety of sugars and lipids as carbon sources. Among these sugars, maltose and trehalose, also play crucial role in ...bacterial physiology and virulence. However, some key enzymes involved in trehalose and maltose metabolism in Mtb are not yet known. Here we structurally and functionally characterized a conserved hypothetical gene Rv3400. We determined the crystal structure of Rv3400 at 1.7 Å resolution. The crystal structure revealed that Rv3400 adopts Rossmann fold and shares high structural similarity with haloacid dehalogenase family of proteins. Our comparative structural analysis suggested that Rv3400 could perform either phosphatase or pyrophosphatase or β‐phosphoglucomutase (β‐PGM) activity. Using biochemical studies, we further confirmed that Rv3400 performs β‐PGM activity and hence, Rv3400 encodes for β‐PGM in Mtb. Our data also confirm that Mtb β‐PGM is a metal dependent enzyme having broad specificity for divalent metal ions. β‐PGM converts β‐D‐glucose‐1‐phosphate to β‐D‐glucose‐6‐phosphate which is required for the generation of ATP and NADPH through glycolysis and pentose phosphate pathway, respectively. Using site directed mutagenesis followed by biochemical studies, we show that two Asp residues in the highly conserved DxD motif, D29 and D31, are crucial for enzyme activity. While D29A, D31A, D29E, D31E and D29N mutants lost complete activity, D31N mutant retained about 30% activity. This study further helps in understanding the role of β‐PGM in the physiology of Mtb.
The synthesis of carbonaceous CO2 adsorbents doped with nitrogen were carried out via a hydrothermal reaction of biomass d-glucose, followed by urea treatment and K2CO3 activation. These carbons ...display high uptake of CO2 at 1 bar and 25 and 0 °C, up to 3.92 and 6.23 mmol g–1, respectively. Additionally, the as-synthesized materials exhibit superior reusability, high CO2/N2 selectivity, fast CO2 adsorption kinetics, and excellent dynamic capture capacity at the experimental conditions used. The synthetic effect of the nitrogen content and narrow microporosity decide the capture capacity for CO2 at 1 bar and 25 °C for these N-enriched carbonaceous adsorbents. This study provides a viable method to prepare high-performance CO2 carbonaceous sorbents without using caustic KOH. In addition, this work gives further insights into the CO2 adsorption mechanism for nitrogen-doped porous carbon sorbents and, hence, inspires ways to synthesize novel carbonaceous materials for removing CO2 from combustion exhaust gases.
Objectives/Hypothesis
The study aimed to investigate the prognostic effects of interim 18fluoro‐2‐deoxy‐D‐glucose positron emission tomography/computed tomography (PET/CT) during definitive ...radiotherapy (RT) or chemoradiotherapy (CRT) in patients with head and neck cancer.
Study Design
This is a prospectively treatment study.
Methods
The pretreatment and interim PET/CT images of 51 patients with advanced pharyngeal cancers receiving definitive RT/CRT were evaluated prospectively. The interim PET/CT images were taken at a cumulative RT dose ranging from 41.4 to 46.8 Gy. The maximum standardized uptake value (SUVm) of the interim PET/CT and the reduction ratio of the SUVm (SRR) between the two images were measured. The differences between patients with or without local failures were examined using the Mann‐Whitney test. Overall survival (OS), disease‐free survival (DFS), and primary and nodal relapse‐free survival rates were calculated using the Kaplan‐Meier method. Independent prognosticators were identified using Cox regression analysis.
Results
After a median follow‐up duration of 23 months, a higher interim SUVm was associated with local failures. Conducting a multivariate analysis revealed that a SUVmax reduction ratio of primary tumor (SRR‐P) < 0.64 was associated with the inferior OS (hazard ratio 2.64; P =0.035) and DFS (hazard ratio 2.33; P = 0.045). Patients who had tumors with an SRR‐P < 0.64 had a considerably lower 2‐year OS and DFS compared with those who had SRR‐P ≥ 0.64 (47% vs. 66%; 41% vs. 64%).
Conclusion
A higher interim SUVm was associated with local recurrence. In addition, patients with a lower SRR‐P should be considered to be at risk of primary failure.
Level of Evidence
4. Laryngoscope, 124:2732–2738, 2014
Glucose metabolism is a crucial biological pathway maintaining the activation of extra- and intracellular signaling pathways involved in the immune response. Immune cell stimulation via various ...environmental factors results in their activation and metabolic reprogramming to aerobic glycolysis. Different immune cells exhibit cell-type-specific metabolic patterns when performing their biological functions. Numerous published studies have shed more light on the importance of metabolic reprogramming in the immune system. Moreover, this knowledge is crucial for revealing new ways to target inflammatory pathologic states, such as autoimmunity and hyperinflammation. Here, we discuss the role of glycolysis in immune cell activity in physiological and pathological conditions, and the potential use of inhibitors of glycolysis for disease treatment.
The notorious growth of lithium (Li) dendrites and the instability of the solid electrolyte interface (SEI) during cycling make Li metal anodes unsuitable for use in commercial Li‐ion batteries. ...Herein, the use of simple sugar coating (α‐d‐glucose) is demonstrated on top of Li metal to halt the growth of Li dendrites and stabilize the SEI. The α‐d‐glucose layer possesses high surface and adhesive energies toward Li, which promote the homogenous stripping and plating of Li ions on top of the Li metal. Density functional theory reveals that Li‐ion diffusion within the α‐d‐glucose layer is governed by hopping around the bare sides of the O atoms and along the apparent passages formed by the glucose molecules. Stable cycling performance is achieved when combining α‐d‐glucose–coated Li (G|Li) anodes with sulfur‐ and LiFePO4‐based cathodes in both LiTFSI (ether) and LiPF6 (carbonate) electrolyte systems. A G|Li–based symmetrical cell operates at a current density of 1 mA cm−2 and areal capacity of 1 mAh cm−2 displays a stable overpotential profile for over 9 months (7000 h) of continuous charge/discharge cycling.
Inhibition of lithium dendrites is achieved by a simple strategy of coating an α‐d‐glucose layer on top of lithium metal. The α‐d‐glucose possessing high surface and adhesive energy with lithium can promote uniform deposition and stripping of Li‐ions and significantly enhance the cycle life of symmetrical and full cells in both ether and carbonate‐based electrolyte systems.
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•Ca2+ signals are key triggers of augmented aerobic glycolysis in astrocytes.•cAMP aids to Ca2+-driven increase in aerobic glycolysis in astrocytes.•Aerobic glycolysis in astrocytes ...depends on extracellular d-glucose.•Aerobic glycolysis in astrocytes depends on glycogen shunt activity.
Astroglial aerobic glycolysis, a process during which d-glucose is converted to l-lactate, a brain fuel and signal, is regulated by the plasmalemmal receptors, including adrenergic receptors (ARs) and purinergic receptors (PRs), modulating intracellular Ca2+ and cAMP signals. However, the extent to which the two signals regulate astroglial aerobic glycolysis is poorly understood. By using agonists to stimulate intracellular α1-/β-AR-mediated Ca2+/cAMP signals, β-AR-mediated cAMP and P2R-mediated Ca2+ signals and genetically encoded fluorescence resonance energy transfer-based glucose and lactate nanosensors in combination with real-time microscopy, we show that intracellular Ca2+, but not cAMP, initiates a robust increase in the concentration of intracellular free d-glucose (glci) and l-lactate (laci), both depending on extracellular d-glucose, suggesting Ca2+-triggered glucose uptake and aerobic glycolysis in astrocytes. When the glycogen shunt, a process of glycogen remodelling, was inhibited, the α1-/β-AR-mediated increases in glci and laci were reduced by ∼65 % and ∼30 %, respectively, indicating that at least ∼30 % of the utilization of d-glucose is linked to glycogen remodelling and aerobic glycolysis. Additional activation of β-AR/cAMP signals aided to α1-/β-AR-triggered laci increase, whereas the glci increase was unaltered. Taken together, an increase in intracellular Ca2+ is the prime mechanism of augmented aerobic glycolysis in astrocytes, while cAMP has only a moderate role. The results provide novel information on the signals regulating brain metabolism and open new avenues to explore whether astroglial Ca2+ signals are dysregulated and contribute to neuropathologies with impaired brain metabolism.
•A new polysaccharide pFSP was isolated from Bletilla striata fibrous roots.•pFSP mainly consisted of mannose, galactose and glucose with Mw of 9.1 × 104 Da.•Structure of the pFSP was established by ...1D and 2D NMR and chemical approaches.•pFSP exhibited stronger antioxidant abilities than polysaccharide from tuber.
A new polysaccharide (pFSP) was first isolated from the originally discarded fibrous roots part of Chinese traditional herb, Bletilla striata. pFSP was composed of D-glucose, D-galactose and D-mannose in a molar ratio of 1: 2.03: 3.45 with molecular weight of 9.1 × 104 Da. It could effectively scavenge DPPH and superoxide radicals with inhibition rate of 64.47% and 72.27% at 5.0 mg/ml, higher than that of polysaccharide from Bletilla striata tuber. Structural investigations of the periodate oxidation studies and Smith-degradation as well as the FT-IR spectroscopy were performed, and combined with 1D and 2D NMR spectroscopy, the repeating unit of pFSP contained (1→4)-linked-α-D-Glcp, (1→4)-linked-β-D-Manp and (1→3,6)-linked-β-D-Manp units, together with the branches of (1→6)-linked-β-D-Galp and terminated with (1→)-linked-β-D-Manp residue.
The porous carbon aerogel activated persulfate through a non-radical pathway in the Rhodamine B removal.
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•Carbon aerogel (CA) was an excellent catalyst for degrading rhodamine B ...(RhB).•CA could activate persulfate (PS) to degrade RhB in a non-radical mechanism.•CA behaved best on the catalytic removal of RhB among several catalysts.•CA exhibited high reproducibility for activating PS after several runs.
In this study, porous carbon aerogel (CA) was synthesized with D-glucose, ammonium persulfate and aniline by a hydrothermal carbonization method. It was reported for the first time as an excellent catalyst for activating persulfate (PS) to degrade rhodamine B (RhB). The morphology of CA was characterized, exhibiting microporous and mesoporous structures. The solution pH of 3, 5, 7 and 9 showed slight impact on the degradation of RhB; however, when the pH increased to 11, the removal of RhB decreased. The PS concentration and CA dosage played a key role in the RhB degradation, and the activation energy was calculated to be 22.11 kJ/mol. Electron paramagnetic resonance (EPR) spectra suggested that neither sulfate radical (SO4−) nor hydroxyl radical (OH) was generated from the PS activation. The radical quenching experiments also confirmed that CA activated PS in a non-radical pathway. It was indicated that PS bonded with CC in the sp2 hybridized system could directly degrade RhB. The defective edges at the boundary of CA also facilitated the RhB removal. This work presented a green material with both excellent catalytic performance and high regeneration possibility in the heterogeneous metal-free PS activation, providing a new strategy in water treatment.
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