Comparative studies with EPR and MRI on the in vivo tissue redox status estimation using redox-sensitive nitroxyl probes: influence of the choice of the region of interest

In vivo decay rates of a nitroxyl contrast agent were estimated by a MR redox imaging (MRRI) technique and compared with the decay rates obtained by the electron paramagnetic resonance spectroscopy (EPRS) and imaging (EPRI). MRRI is a dynamic imaging technique employing T₁-weighted pulse sequence, which can visualise a nitroxyl-induced enhancement of signal intensity by T₁-weighted contrast. EPR techniques can directly measure the paramagnetic nitroxyl radical. Both the squamous cell carcinoma (SCC) tumour-bearing and normal legs of a female C3H mouse were scanned by T₁-weighted SPGR sequence at 4.7 T with the nitroxyl radical, carbamoyl-proxyl (CmP), as the contrast agent. Similarly, the time course of CmP in normal muscle and tumour tissues was obtained using a 700-MHz EPR spectrometer with a surface coil. The time course imaging of CmP was also performed by 300?MHz CW EPR imager. EPRS and EPRI gave slower decay rates of CmP compared to the MRRI. Relatively slow decay rate at peripheral region of the tumour tissues, which was found in the image obtained by MRRI, may contribute to the slower decay rates observed by EPRS and/or the EPRI measurements. To reliably determine the tissue redox status from the reduction rates of nitroxyls such as CmP, heterogenic structure in the tumour tissue must be considered. The high spatial and temporal resolution of T₁-weighted MRI and the T₁-enhancing capabilities of nitroxyls support the use of this method to map tissue redox status which can be a useful biomarker to guide appropriate treatments based on the tumour microenvironment.     

Integrated continuous biomanufacturing platform with ATF perfusion and one column chromatography operation for optimum resin utilization and productivity

A new integrated continuous biomanufacturing platform for continuous production of antibodies at fixed cell volumes and cell concentrations for extended periods with immediate capture is presented. Upstream antibody production has reached technological maturity, however, the bottleneck for continuous biomanufacturing remains the efficient and cost-effective capture of therapeutic antibodies in an initial chromatography step. In this study, the first successful attempt at using one-column continuous chromatography (OCC) for the continuous capture of therapeutic antibodies produced through alternating tangential flow perfusion is presented. By performing upstream media optimizations, the upstream perfusion rate was reduced to one vessel volume per day (vv/d), increasing antibody titer and reducing the volume of perfusate. In addition, process improvements were performed to increase productivity by 80% over previously reported values. In addition, a real-time method for evaluating column performance to make column switching decisions was developed. This improved productivity coupled with the use of a single-column improved process monitoring and control in OCC compared to multi-column systems. This approach is the first report on using a single column for the implementation of an integrated continuous biomanufacturing platform and offers a cost-effective and flexible platform process for the manufacture of therapeutic proteins.     

Low‐Defect and Low‐Porosity Hard Carbon with High Coulombic Efficiency and High Capacity for Practical Sodium Ion Battery Anode

Hard carbon is regarded as the most promising anode material for commercialization of Na ion batteries because of its high capacity and low cost. At present, the practical utilization of hard carbon anodes is largely limited by the low initial Coulombic efficiency (ICE). Na ions have been found to adopt an adsorption–insertion storage mechanism. In this paper a systematic way to control the defect concentration and porosity of hard carbon with similar overall architectures is shown. This study elucidates that the defects in the graphite layers are directly related to the ICE as they would trap Na ions and create a repulsive electric field for other Na ions so as to shorten the low‐voltage intercalation capacity. The obtained low defect and porosity hard carbon electrode has achieved the highest ICE of 86.1% (94.5% for pure hard carbon material by subtracting that of the conductive carbon black), reversible capacity of 361 mA h g^?1, and excellent cycle stability (93.4% of capacity retention over 100 cycles). This result sheds light on feasible design principles for high performance Na storage hard carbon: suitable carbon layer distance and defect free graphitic layers.     

KVOPO4: A New High Capacity Multielectron Na‐Ion Battery Cathode

Sodium ion batteries have attracted much attention in recent years, due to the higher abundance and lower cost of sodium, as an alternative to lithium ion batteries. However, a major challenge is their lower energy density. In this work, we report a novel multi‐electron cathode material, KVOPO₄, for sodium ion batteries. Due to the unique polyhedral framework, the V³⁺ ? V⁴⁺ ? V⁵⁺ redox couple was for the first time fully activated by sodium ions in a vanadyl phosphate phase. The KVOPO₄ based cathode delivered reversible multiple sodium (i.e. maximum 1.66 Na⁺ per formula unit) storage capability, which leads to a high specific capacity of 235 Ah kg^?1. Combining an average voltage of 2.56 V vs. Na/Na⁺, a high practical energy density of over 600 Wh kg^?1 was achieved, the highest yet reported for any sodium cathode material. The cathode exhibits a very small volume change upon cycling (1.4% for 0.64 sodium and 8.0% for 1.66 sodium ions). Density functional theory (DFT) calculations indicate that the KVOPO₄ framework is a 3D ionic conductor with a reasonably, low Na⁺ migration energy barrier of ≈450 meV, in line with the good rate capability obtained.     

3D,Mutually Embedded MOF@Carbon Nanotube Hybrid Networks for High‐Performance Lithium‐Sulfur Batteries

Metal‐organic frameworks (MOFs) hybridized with a conductive matrix could potentially serve as a sulfur host for lithium‐sulfur (Li‐S) battery electrodes; so far most of the previously studied hybrid structures are in the powder form or thin compact films. This study reports 3D porous MOF@carbon nanotube (CNT) networks by grafting MOFs with tailored particle size uniformly throughout a CNT sponge skeleton. Growing larger‐size MOF particles to entrap the conductive CNT network yields a mutually embedded structure with high stability, and after sulfur encapsulation, it shows an initial discharge capacity of ≈1380 mA h g^?1 (at 0.1 C) and excellent cycling stability with a very low fading rate. Furthermore, owing to the 3D porous network that is suitable for enhanced sulfur loading, a remarkable areal capacity of ≈11 mA h cm^?2 (at 0.1 C) is obtained, which is much higher than other MOF‐based hybrid electrodes. The mutually embedded MOF@CNTs with simultaneously high specific capacity, areal capacity, and cycling stability represent an advanced candidate for developing high‐performance Li‐S batteries and other energy storage systems.     

丁苯酞软胶囊对急性脑梗死患者ROS、T-AOC、炎症因子及神经功能的影响

目的:探讨丁苯酞软胶囊对急性脑梗死患者活性氧(reactive oxygen species,ROS)、总抗氧化能力(total antioxidant capacity,T-AOC)、炎症因子及神经功能的影响。方法:将2016年7月至2017年7月我院收治的急性脑梗死患者100例随机分为对照组(n=50)和观察组(n=50)。对照组患者给予常规对症治疗,观察组患者在对照组的基础上加用丁苯酞软胶囊。两组连续治疗14天后,比较治疗前后两组血清ROS、T-AOC、炎症因子水平及神经功能的变化及治疗后两组的临床疗效。结果:治疗前,两组血清ROS、T-AOC、高敏C反应蛋白(high sensitive C reaction protein,hs-CRP)、肿瘤坏死因子-α(tumor necrosis factor,TNF-α)、白细胞介素-6(interleukin-6,IL-6)水平、美国国立卫生研究院卒中量表(National Institute of Health stroke scale)评分比较差异均无统计学意义(P0.05)。与本组治疗前比较,两组治疗后血清T-AOC水平显著升高,且观察组显著高于对照组(P0.05);对照组治疗后血清ROS水平显著高于治疗前(P0.05),观察组患者治疗前后的血清ROS水平相比差异无统计学意义(P0.05),且观察组治疗后ROS水平显著低于对照组(P0.05);两组血清hs-CRP、TNF-α、IL-6水平、NHISS评分均显著低于治疗前(P0.05),且观察组以上指标均显著低于对照组(P0.05);观察组总有效率为82%,明显优于对照组的52%(P0.05)。结论:在常规治疗的基础上加用丁苯酞软胶囊可有效降低急性脑梗死患者血清炎症因子水平,提高机体总抗氧化能力,促进神经功能的修复,提高临床治疗效果     

蓝莓浓缩汁对小鼠疲劳的改善作用及机制初探

目的:对蓝莓浓缩汁进行抗疲劳功效评价,并对其所涉及的作用机制进行初步探究。方法:小鼠通过预筛选和强制游泳预处理后,以生理盐水为对照组,蓝莓浓缩汁高、低剂量和VC分别作为实验组。经给药及游泳处理后,观察各组小鼠的行为学特征,测定力竭游泳时间,检测血浆和脑组织匀浆中T-SOD活力、MDA含量、LDH活性及血浆中BUN含量的变化,并经HE染色察看小鼠组织病变状况。结果:与S对照组相比,高剂量蓝莓浓缩汁可明显改善疲劳小鼠的行为学特征,延长力竭游泳时间;在血浆和脑组织匀浆中,可增加T-SOD活性((136.92±10.39)%,(50.31±7.26)%),降低MDA含量((58.32±2.91)%,(50.89±2.91)%),提高LDH活性((72.79±19.11)%,(65.11±6.55)%),并减少血浆中BUN((46.92±3.36)%)的产生,(P0.01);还可防止细胞病变间隙的发生。低剂量蓝莓浓缩汁和VC处理组的改善效果不如高剂量组明显。结论:蓝莓浓缩汁有明显抗疲劳功效,所涉及的机制可能与其增强抗氧化酶活性,提高机体有氧代谢能力及改善机体物质代谢等有关。     

Hydrogen-rich water mediates redox regulation of the antioxidant system,mycelial regeneration and fruiting body development in Hypsizygus marmoreus

Hypsizygus marmoreus is an important industrialized mushroom, yet the lack of basic research on this fungus has hindered further development of its economic value. In this study, mycelia injured by scratching were treated with hydrogen-rich water (HRW) to investigate the involvement of the redox system in fruiting body development. Compared to the control group, damaged mycelia treated with HRW regenerated earlier and showed significantly enhanced fruiting body production. Antioxidant capacity increased significantly in damaged mycelia after HRW treatment, as indicated by higher antioxidant enzyme activities and antioxidant contents; the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were also reduced at the mycelial regeneration stage after treatment with HRW. Furthermore, genes involved in ROS, Ca²⁺, MAPK and oxylipin signaling pathways were up-regulated by HRW treatment. In addition, laccase and manganese peroxidase activities and mycelial biomass were higher after HRW treatment, suggesting that HRW might enhance the substrate-degradation rate to provide more carbon sources for fruiting body production.     

Mutations in algal and cyanobacterial Photosystem I that independently affect the yield of initial charge separation in the two electron transfer cofactor branches

In Photosystem I, light-induced electron transfer can occur in either of two symmetry-related branches of cofactors, each of which is composed of a pair of chlorophylls (ec2_A/ec3_A or ec2_B/ec3_B) and a phylloquinone (PhQ_A or PhQ_B). The axial ligand to the central Mg^2 + of the ec2_A and ec2_B chlorophylls is a water molecule that is also H-bonded to a nearby Asn residue. Here, we investigate the importance of this interaction for charge separation by converting each of the Asn residues to a Leu in the green alga, Chlamydomonas reinhardtii, and the cyanobacterium, Synechocystis sp. PCC6803, and studying the energy and electron transfer using time-resolved optical and EPR spectroscopy. Nanosecond transient absorbance measurements of the PhQ to F_X electron transfer show that in both species, the PsaA-N604L mutation (near ec2_B) results in a ~ 50% reduction in the amount of electron transfer in the B-branch, while the PsaB-N591L mutation (near ec2_A) results in a ~ 70% reduction in the amount of electron transfer in the A-branch. A diminished quantum yield of P₇₀₀⁺ PhQ^? is also observed in ultrafast optical experiments, but the lower yield does not appear to be a consequence of charge recombination in the nanosecond or microsecond timescales. The most significant finding is that the yield of electron transfer in the unaffected branch did not increase to compensate for the lower yield in the affected branch. Hence, each branch of the reaction center appears to operate independently of the other in carrying out light-induced charge separation.     

Bacteria and archaea as the sources of traits for enhanced plant phenotypes

Rising global demand for food and population increases are driving the need for improved crop productivity over the next 30 years. Plants have inherent metabolic limitations on productivity such as inefficiencies in carbon fixation and sensitivity to environmental conditions. Bacteria and archaea inhabit some of the most inhospitable environments on the planet and possess unique metabolic pathways and genes to cope with these conditions. Microbial genes involved in carbon fixation, abiotic stress tolerance, and nutrient acquisition have been utilized in plants to enhance plant phenotypes by increasing yield, photosynthesis, and abiotic stress tolerance. Transgenic plants expressing bacterial and archaeal genes will be discussed along with emerging strategies and tools to increase plant growth and yield.