ATP metabolism is controlled mainly by ATP synthase (ATP ase ) and creatine kinase (CK) reactions that regulate cerebral ATP production, transportation, and utilization. These coupled reactions constitute a chemical exchange metabolic network of PCr7ATP7Pi characterized by two forward and two reverse reaction fluxes, which can be studied noninvasively by in vivo 31 P MRS combined with magnetization transfer (MT). However, it is still debated whether current MT approaches can precisely determine all of these fluxes. We developed and tested a modified in vivo 31 P MT approach based on a multiple single-site saturation (MSS) technique to study the entire PCr7ATP7Pi network in human occipital lobe at 7T. Our results reveal that 1) the MSS MT approach can explicitly determine all four reaction fluxes with a minimal number of The primary functions of brain cells are excitation and conduction, which are reflected by constant electrophysiological activity in the brain. The cerebral bioenergetics that support sustained electrophysiological activity are ultimately driven by a variety of biochemical processes that maintain the normal function and structural integrity of the brain (1). Of these processes, the most fundamental for supporting various cellular activities is adenosine triphosphate (ATP) metabolism in living cells (2). The majority of ATP is formed from adenosine diphosphate (ADP) and inorganic phosphate (Pi) in the mitochondria through oxidative phosphorylation catalyzed by the ATP synthase (ATP ase ) enzyme, as illustrated by Fig. 1a (3,4). The highly demanding biochemical processes involving ATP production and utilization in the brain cause rapid chemical cycling among ATP, ADP, and Pi (see Fig. 1a). These processes are also accompanied by another important chemical reaction involving phosphocreatine (PCr) and creatine kinase (CK). PCr acts as an ATP reservoir and carrier, and transfers energy from the mitochondria to sites of ATP utilization in the cytosol through reversible CK reactions, ultimately maintaining a stable cellular ATP level (4,5). These two chemical exchange reactions (i.e., PCr7ATP and Pi7ATP) play central roles in regulating ATP metabolism and maintaining normal ATP functionality, both of which are crucial for cerebral bioenergetics and brain function in the healthy brain as well as in neurodegenerative diseases. Moreover, the ATP ase and CK reactions are tightly coupled together, leading to a complex three-31 P-spin chemical exchange kinetic network (i.e., PCr7ATP7Pi) as depicted in Fig. 1b. Thus, it is essential to develop a noninvasive, reliable technique that is capable of assessing the entire kinetic network of PCr7ATP7Pi and associated ATP metabolic fluxes in situ, particularly in the human brain.Measuring all kinetic parameters involved in the PCr7ATP7Pi network requires extensive information, including three steady-state phosphate metabolite concentrations (i.e., [ATP], [PCr], and [Pi]) and four pseudo-firstorder chemical reaction rate constants (forward and reverse rate constants fo...

Despite the essential role of the brain energy generated from ATP hydrolysis in supporting cortical neuronal activity and brain function, it is challenging to noninvasively image and directly quantify the energy expenditure in the human brain. In this study, we applied an advanced in vivo 31P MRS imaging approach to obtain regional cerebral metabolic rates of high-energy phosphate reactions catalyzed by ATPase (CMRATPase) and creatine kinase (CMRCK), and to determine CMRATPase and CMRCK in pure grey mater (GM) and white mater (WM), respectively. It was found that both ATPase and CK rates are three times higher in GM than WM; and CMRCK is seven times higher than CMRATPase in GM and WM. Among the total brain ATP consumption in the human cortical GM and WM, 77% of them are used by GM in which approximately 96% is by neurons. A single cortical neuron utilizes approximately 4.7 billion ATPs per second in a resting human brain. This study demonstrates the unique utility of in vivo 31P MRS imaging modality for direct imaging of brain energy generated from ATP hydrolysis, and provides new insights into the human brain energetics and its role in supporting neuronal activity and brain function.

The primary goal of this study was to establish a rigorous approach for determining and comparing the NMR detection sensitivity of in vivo 31P MRS at different field strengths (B0). This was done by calculating the signal-to-noise ratio (SNR) achieved within a unit sampling time at a given field strength. In vivo 31P spectra of human occipital lobe were acquired at 4 and 7 T under similar experimental conditions. They were used to measure the improvement of the human brain 31P MRS when the field strength increases from 4 to 7 T. The relaxation times and line widths of the phosphocreatine (PCr) resonance peak and the RF coil quality factors (Q) were also measured at these two field strengths. Their relative contributions to SNR at a given field strength were analyzed and discussed. The results show that in vivo 31P sensitivity was significantly improved at 7 T as compared with 4 T. Moreover, the line-width of the PCr resonance peak showed less than a linear increase with increased B0, which leads to a significant improvement in 31P spectral resolution. These findings indicate the advantage of high-field strength to improve in vivo 31P MRS quality in both sensitivity and spectral resolution. This advantage should improve the reliability and applicability of in vivo 31P MRS in studying high-energy phosphate metabolism, phospholipid metabolism and cerebral biogenetics in the human at both normal and diseased states noninvasively. Finally, the approach used in this study for calculating in vivo 31P MRS sensitivity provides a general tool in estimating the relative NMR detection sensitivity for any nuclear spin at a given field strength.

To engineer low-cost, high-efficiency, and stable oxygen evolution reaction (OER) catalysts, structure effects should be primarily understood. Focusing on this, we systematically investigated the relationship between structures of materials and their OER performances by taking four 2D α-Ni(OH) as model materials, including layer-stacked bud-like Ni(OH)-NB, flower-like Ni(OH)-NF, and petal-like Ni(OH)-NP as well as the ultralarge sheet-like Ni(OH)-NS. For the first three (layer-stacking) catalysts, with the decrease of stacked layers, their accessible surface areas, abilities to adsorb OH, diffusion properties, and the intrinsic activities of active sites increase, which accounts for their steadily enhanced activity. As expected, Ni(OH)-NP shows the lowest overpotential (260 mV at 10 mA cm) and Tafel slope (78.6 mV dec) with a robust stability over 10 h among the samples, which also outperforms the benchmark IrO (360 mV and 115.8 mV dec) catalyst. Interestingly, Ni(OH)-NS relative to Ni(OH)-NP exhibits even faster substance diffusion due to the sheet-like structure, but shows inferior OER activity, which is mainly because the Ni(OH)-NP with a smaller size possesses more active boundary sites (higher reactivity of active sites) than Ni(OH)-NS, considering the adsorption properties and accessible surface areas of the two samples are quite similar. By comparing the different structures and their OER behaviors of four α-Ni(OH) samples, our work may shed some light on the structure effect of 2D materials and accelerate the development of efficient OER catalysts.