Non-linear ICA Analysis of Resting-State fMRI in Mild Cognitive Impairment

Compared to linear independent component analysis (ICA), non-linear ICA is more suitable for the decomposition of mixed components. Existing studies of functional magnetic resonance imaging (fMRI) data by using linear ICA assume that the brain's mixed signals, which are caused by the activity of brain, are formed through the linear combination of source signals. But the application of the non-linear combination of source signals is more suitable for the mixed signals of brain. For this reason, we investigated statistical differences in resting state networks (RSNs) on 32 healthy controls (HC) and 38 mild cognitive impairment (MCI) patients using post-nonlinear ICA. Post-nonlinear ICA is one of the non-linear ICA methods. Firstly, the fMRI data of all subjects was preprocessed. The second step was to extract independent components (ICs) of fMRI data of all subjects. In the third step, we calculated the correlation coefficient between ICs and RSN templates, and selected ICs of the largest spatial correlation coefficient. The ICs represent the corresponding RSNs. After finding out the eight RSNs of MCI group and HC group, one sample t-tests were performed. Finally, in order to compare the differences of RSNs between MCI and HC groups, the two-sample t-tests were carried out. We found that the functional connectivity (FC) of RSNs in MCI patients was abnormal. Compared with HC, MCI patients showed the increased and decreased FC in default mode network (DMN), central executive network (CEN), dorsal attention network (DAN), somato-motor network (SMN), visual network(VN), MCI patients displayed the specifically decreased FC in auditory network (AN), self-referential network (SRN). The FC of core network (CN) did not reveal significant group difference. The results indicate that the abnormal FC in RSNs is selective in MCI patients

Knockout of Myostatin by Zinc-finger Nuclease in Sheep Fibroblasts and Embryos

Myostatin (MSTN) can negatively regulate the growth and development of skeletal muscle, and natural mutations can cause “double-muscling” trait in animals. In order to block the inhibiting effect of MSTN on muscle growth, we transferred zinc-finger nucleases (ZFN) which targeted sheep MSTN gene into cultured fibroblasts. Gene targeted colonies were isolated from transfected fibroblasts by serial dilution culture and screened by sequencing. Two colonies were identified with mono-allele mutation and one colony with bi-allelic deletion. Further, we introduced the MSTN-ZFN mRNA into sheep embryos by microinjection. Thirteen of thirty-seven parthenogenetic embryos were targeted by ZFN, with the efficiency of 35%. Our work established the technical foundation for generation of MSTN gene editing sheep by somatic cloning and microinjection ZFN into embryos

Design of B/N Co-doped micro/meso porous carbon electrodes from CNF/BNNS/ZIF-8 nanocomposites for advanced supercapacitors

Boron (B) and nitrogen (N) co-doped 3D hierarchical micro/meso porous carbon (BNPC) were successfully fabricated from cellulose nanofiber (CNF)/ boron nitride nanosheets (BNNS)/ zinc-methylimidazolate framework-8 (ZIF-8) nanocomposites prepared by 2D BNNS, ZIF-8 nanoparticles, and wheat straw based CNFs. Herein, CNF/ZIF-8 acts as versatile skeleton and imparts partial N dopant into porous carbon structure, while the introduced BNNS can help strengthen the hierarchical porous superstructure and endow abundant B/N co-dopants within BNPC matrix. The obtained BNPC electrode possesses a high specific surface area of 505.4 m2/g, high B/N co-doping content, and desirable hydrophilicity. Supercapacitors assembled with BNPC-2 (B/N co-doped porous carbon with a CNF/BNNS mass ratio of 1꞉2) electrodes exhibited exceptional electrochemical performance, demonstrating high capacitance stability even after 5 000 charge-discharge cycles. The devices exhibited outstanding energy density and power density, as well as the highest specific capacitance of 433.4 F/g at 1.0 A/g, when compared with other similar reports. This study proposes a facile and sustainable strategy for efficiently fabrication of rich B/N co-doped hierarchical micro/meso porous carbon electrodes from agricultural waste biomass for advanced supercapacitor performance

A steel slag–derived Boudouard reaction catalyst for improved performance of direct carbon solid oxide fuel cells

Solid oxide fuel cells (SOFCs) can directly utilize solid carbon as fuel by integrating with the reverse Boudouard reaction in the anode chamber. Efficiency of the Boudouard gasification of solid carbon fuel is one of the crucial factors influencing the performance of direct carbon SOFCs (DC-SOFCs). In this paper, a novel Boudouard reaction catalyst derived from steel slag was first introduced into DC-SOFCs for improving the electrochemical performance. The catalytic activity of the steel slag was activated using the molten alkali method to decompose the inert mineral phases of the raw material. The steel slag–derived catalyst was loaded on the activated charcoal by a wet ball milling method. This kind of catalyst can match up to the readily available solid carbon fuels in cost. Promoted by this highly active Boudouard reaction catalyst, the initial Boudouard gasification temperature of the carbon fuel decreased by 99°C, and the producing rate of carbon monoxide doubled. Furthermore, the power outputs of the fuel cells increased from 91 to 159 mW cm, and the fuel utilization increased from 17.10% to 46.43% at 825°C. This study demonstrates that the steel slag–derived catalyst is a promising material for the performance improvement of DC-SOFCs and may make a valuable contribution to their commercial application

Genetic Deletion of the Adenosine A2A Receptor Confers Postnatal Development of Relative Myopia in Mice

The reduced collagen fibril diameter in the sclera of the A2AR KO mouse and increased expression of collagen expression in the sclera fibroblasts suggest that adenosine A2A receptor modulates vision-induced ocular growth and the development of myopia through modulation of collagen synthesis in the sclera

Oxidative Stress-Mediated Blood-Brain Barrier (BBB) Disruption in Neurological Diseases

The blood-brain barrier (BBB), as a crucial gate of brain-blood molecular exchange, is involved in the pathogenesis of multiple neurological diseases. Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and the scavenger system. Since oxidative stress plays a significant role in the production and maintenance of the BBB, the cerebrovascular system is especially vulnerable to it. The pathways that initiate BBB dysfunction include, but are not limited to, mitochondrial dysfunction, excitotoxicity, iron metabolism, cytokines, pyroptosis, and necroptosis, all converging on the generation of ROS. Interestingly, ROS also provide common triggers that directly regulate BBB damage, parameters including tight junction (TJ) modifications, transporters, matrix metalloproteinase (MMP) activation, inflammatory responses, and autophagy. We will discuss the role of oxidative stress-mediated BBB disruption in neurological diseases, such as hemorrhagic stroke, ischemic stroke (IS), Alzheimer’s disease (AD), Parkinson’s disease (PD), traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and cerebral small vessel disease (CSVD). This review will also discuss the latest clinical evidence of potential biomarkers and antioxidant drugs towards oxidative stress in neurological diseases. A deeper understanding of how oxidative stress damages BBB may open up more therapeutic options for the treatment of neurological diseases

Breaking of Inversion Symmetry and Interlayer Electronic Coupling in Bilayer Graphene Heterostructure by Structural Implementation of High Electric Displacement Fields

Controlling the interlayer coupling in two-dimensional (2D) materials generates novel electronic and topological phases. Its effective implementation is commonly done with a transverse electric field. However, phases generated by high displacement fields are elusive in this standard approach. Here, we introduce an exceptionally large displacement field by structural modification of a model system: AB-stacked bilayer graphene (BLG) on a SiC(0001) surface. We show that upon intercalation of gadolinium, electronic states in the top graphene layers exhibit a significant difference in the on-site potential energy, which effectively breaks the interlayer coupling between them. As a result, for energies close to the corresponding Dirac points, the BLG system behaves like two electronically isolated single graphene layers. This is proven by local scanning tunneling microscopy (STM)/spectroscopy, corroborated by density functional theory, tight binding, and multiprobe STM transport. The work presents metal intercalation as a promising approach for the synthesis of 2D graphene heterostructures with electronic phases generated by giant displacement fields.This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication as Kolmer, Marek, Wonhee Ko, Joseph Hall, Shen Chen, Jianhua Zhang, Haijun Zhao, Liqin Ke, Cai-Zhuang Wang, An-Ping Li, and Michael C. Tringides. "Breaking of Inversion Symmetry and Interlayer Electronic Coupling in Bilayer Graphene Heterostructure by Structural Implementation of High Electric Displacement Fields." The Journal of Physical Chemistry Letters 13 (2022): 11571-11580. Copyright 2022 American Chemical Society after peer review. To access the final edited and published work see DOI: 10.1021/acs.jpclett.2c02407. Posted with permission. DOE Contract Number(s): AC02-07CH1135

Bone morphogenetic protein 4 (BMP4) promotes hepatic glycogen accumulation and reduces glucose level in hepatocytes through mTORC2 signaling pathway

Liver is an important organ for regulating glucose and lipid metabolism. Recent studies have shown that bone morphogenetic proteins (BMPs) may play important roles in regulating glucose and lipid metabolism. In our previous studies, we demonstrated that BMP4 significantly inhibits hepatic steatosis and lowers serum triglycerides, playing a protective role against the progression of non-alcoholic fatty liver disease (NAFLD). However, the direct impact of BMP4 on hepatic glucose metabolism is poorly understood. Here, we investigated the regulatory roles of BMP4 in hepatic glucose metabolism. Through a comprehensive analysis of the 14 types of BMPs, we found that BMP4 was one of the most potent BMPs in promoting hepatic glycogen accumulation, reducing the level of glucose in hepatocytes and effecting the expression of genes related to glucose metabolism. Mechanistically, we demonstrated that BMP4 reduced the hepatic glucose levels through the activation of mTORC2 signaling pathway in vitro and in vivo. Collectively, our findings strongly suggest that BMP4 may play an essential role in regulating hepatic glucose metabolism. This knowledge should aid us to understand the molecular pathogenesis of NAFLD, and may lead to the development of novel therapeutics by exploiting the inhibitory effects of BMPs on hepatic glucose and lipid metabolism

Breaking of Inversion Symmetry and Interlayer Electronic Coupling in Bilayer Graphene Heterostructure by Structural Implementation of High Electric Displacement Fields

Controlling the interlayer coupling in two-dimensional (2D) materials generates novel electronic and topological phases. Its effective implementation is commonly done with a transverse electric field. However, phases generated by high displacement fields are elusive in this standard approach. Here, we introduce an exceptionally large displacement field by structural modification of a model system: AB-stacked bilayer graphene (BLG) on a SiC(0001) surface. We show that upon intercalation of gadolinium, electronic states in the top graphene layers exhibit a significant difference in the on-site potential energy, which effectively breaks the interlayer coupling between them. As a result, for energies close to the corresponding Dirac points, the BLG system behaves like two electronically isolated single graphene layers. This is proven by local scanning tunneling microscopy (STM)/spectroscopy, corroborated by density functional theory, tight binding, and multiprobe STM transport. The work presents metal intercalation as a promising approach for the synthesis of 2D graphene heterostructures with electronic phases generated by giant displacement fields