Conjugated Coordination Polymer Aerogels with Increased Accessibility of Well-Defined Single-Atom Metal Sites as a New Paradigm of Electrocatalysts.

Developing high-performance single-atom catalysts (SACs) with maximum metal utilization efficiency is of significance, which presents enormous potentials to be extensively applied. It is desired yet challenging to elaborately tailor the coordination structures of active sites in SACs and simultaneously enable sufficient accessibility of these active sites to reactants. Here, a facile and general strategy to prepare conjugated coordination polymer aerogels (CCPA) with porous architectures that can markedly increase the accessibility of their elaborately-tailored active sites, which as a new electrocatalyst paradigm can fully present both the structural advantages of SACs and aerogel materials, is reported.

Dysbiosis and extraintestinal cancers.

The gut microbiota plays a crucial role in safeguarding host health and driving the progression of intestinal diseases. Despite recent advances in the remarkable correlation between dysbiosis and extraintestinal cancers, the underlying mechanisms are yet to be fully elucidated. Pathogenic microbiota, along with their metabolites, can undermine the integrity of the gut barrier through inflammatory or metabolic pathways, leading to increased permeability and the translocation of pathogens.

EEG-Informed fMRI Analysis Reveals Neurovascular Coupling in Motor Execution and Imagery.

The complementary strengths of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have driven extensive research into integrating these two noninvasive modalities to better understand the neural mechanisms underlying cognitive, sensory, and motor functions. However, the precise neural patterns associated with motor functions, especially imagined movements, remain unclear. Specifically, the correlations between electrophysiological responses and hemodynamic activations during executed and imagined movements have not been fully elucidated at a whole-brain level.

From inflammation to bone formation: the intricate role of neutrophils in skeletal muscle injury and traumatic heterotopic ossification.

Neutrophils are emerging as an important player in skeletal muscle injury and repair. Neutrophils accumulate in injured tissue, thus releasing inflammatory factors, proteases and neutrophil extracellular traps (NETs) to clear muscle debris and pathogens when skeletal muscle is damaged. During the process of muscle repair, neutrophils can promote self-renewal and angiogenesis in satellite cells.

Recent developments in the use of nanocrystals to improve bioavailability of APIs.

Nanocrystals refer to materials with at least one dimension smaller than 100 nm, composing of atoms arranged in single crystals or polycrystals. Nanocrystals have significant research value as they offer unique advantages over conventional pharmaceutical formulations, such as high bioavailability, enhanced targeting selectivity and controlled release ability and are therefore suitable for the delivery of a wide range of drugs such as insoluble drugs, antitumor drugs and genetic drugs with broad application prospects. In recent years, research on nanocrystals has been progressively refined and new products have been launched or entered the clinical phase of studies.

A Calibration-Free Hybrid Approach Combining SSVEP and EOG for Continuous Control.

While SSVEP-BCI has been widely developed to control external devices, most of them rely on the discrete control strategy. The continuous SSVEP-BCI enables users to continuously deliver commands and receive real-time feedback from the devices, but it suffers from the transition state problem, a period the erroneous recognition, when users shift their gazes between targets. To resolve this issue, we proposed a novel calibration-free Bayesian approach by hybridizing SSVEP and electrooculography (EOG).

Integrating Simultaneous Motor Imagery and Spatial Attention for EEG-BCI Control.

Objective: EEG-based brain-computer interfaces (BCI) are non-invasive approaches for replacing or restoring motor functions in impaired patients, and direct brain-to-device communication in the general population. Motor imagery (MI) is one of the most used BCI paradigms, but its performance varies across individuals and certain users require substantial training to develop control. In this study, we propose to integrate a MI paradigm simultaneously with a recently proposed Overt Spatial Attention (OSA) paradigm, to accomplish BCI control.

Direct and indirect effects of pathogenic bacteria on the integrity of intestinal barrier.

Bacterial translocation is a pathological process involving migration of pathogenic bacteria across the intestinal barrier to enter the systemic circulation and gain access to distant organs. This phenomenon has been linked to a diverse range of diseases including inflammatory bowel disease, pancreatitis, and cancer. The intestinal barrier is an innate structure that maintains intestinal homeostasis.

Integrating simultaneous motor imagery and spatial attention for EEG-BCI control.

Objective: EEG-based brain-computer interfaces (BCI) are non-invasive approaches for replacing or restoring motor functions in impaired patients, and direct brain-to-device communication in the general population. Motor imagery (MI) is one of the most used BCI paradigms, but its performance varies across individuals and certain users require substantial training to develop control. In this study, we propose to integrate a MI paradigm simultaneously with a recently proposed Overt Spatial Attention (OSA) paradigm, to accomplish BCI control.

Transcriptional regulation of CYP3A4 by nuclear receptors in human hepatocytes under hypoxia.

The human hepatic cytochrome P-450 3A4 (CYP3A4), recognized as a multifunctional enzyme, has a wide range of substrates including commonly used drugs. Previous investigations demonstrated that the expression of CYP3A4 in human hepatocytes could be regulated by some nuclear receptors (NRs) at transcriptional level under diverse situations. The significance of oxygen on CYP3A4-mediated metabolism seems notable while the regulatory mode of CYP3A4 in the particular case still remains elusive.

[Research progress on the effects of plateau hypoxia on blood-brain barrier structure and drug permeability].

Drugs for the treatment of central nervous system diseases need to enter the brain tissue through the blood-brain barrier to function. In high altitude hypoxic environment, there are changes in tight junction proteins of blood-brain barrier tissue structure, transporters in astrocytes and endothelial cells and ATP in endothelial cells; at the same time the permeability of the blood-brain barrier is increased. These changes are an important reference for rational drug use in patients with central nervous system disease in the plateau region.

[Effects of acute hypoxia on expression of pregnane X receptor in liver tissues of rats exposed to high altitude].

Objective: To investigate the effects of high-altitude hypoxic environment on the expression of pregnane X receptor (PXR) in rat liver and related mechanism.

Methods: Wistar rats were randomly divided into five groups with 8 rats in each group, the rats were exposed to high-plateau hypoxia for 0 (control group), 12, 24, 36 and 48 h, respectively. Abdominal aortic blood samples were collected for blood gas analysis.

Potential Regulation Mechanisms of P-gp in the Blood-Brain Barrier in Hypoxia.

The blood-brain barrier (BBB) is a barrier of the central nervous system (CNS), which can restrict the free exchange of substances, such as toxins and drugs, between cerebral interstitial fluid and blood, keeping the relative physiological stabilization. The brain capillary endothelial cells, one of the structures of the BBB, have a variety of ATP-binding cassette transporters (ABC transporters), among which the most widely investigated is Pglycoprotein (P-gp) that can efflux numerous substances out of the brain. The expression and activity of P-gp are regulated by various signal pathways, including tumor necrosis factor-α (TNF-α)/protein kinase C-β (PKC- β)/sphingosine-1-phosphate receptor 1 (S1P), vascular endothelial growth factor (VEGF)/Src kinase, etc.

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma.

Increased lipid droplet number and fatty acid synthesis allow glioblastoma multiforme, the most common and aggressive type of brain cancer, to withstand accelerated metabolic rates and resist therapeutic treatments. Lipid droplets are postulated to sequester hydrophobic therapeutic agents, thereby reducing drug effectiveness. We hypothesized that the inhibition of lipid droplet accumulation in glioblastoma cells using pyrrolidine-2, a cytoplasmic phospholipase A2 alpha inhibitor, can sensitize cancer cells to the killing effect of curcumin, a promising anticancer agent isolated from the turmeric spice.

Ratiometric biosensors based on dimerization-dependent fluorescent protein exchange.

We have developed a versatile new class of genetically encoded fluorescent biosensor based on reversible exchange of the heterodimeric partners of green and red dimerization-dependent fluorescent proteins. We demonstrate the use of this strategy to construct both intermolecular and intramolecular ratiometric biosensors for qualitative imaging of caspase activity, Ca(2+) concentration dynamics and other second-messenger signaling activities.

An engineered monomeric Zoanthus sp. yellow fluorescent protein.

Protein engineering has created a palette of monomeric fluorescent proteins (FPs), but there remains an ~30 nm spectral gap between the most red-shifted useful Aequorea victoria green FP (GFP) variants and the most blue-shifted useful Discosoma sp. red FP (RFP) variants. To fill this gap, we have engineered a monomeric version of the yellow FP (YFP) from Zoanthus sp.

Dimerization-dependent green and yellow fluorescent proteins.

Dimerization-dependent fluorescent proteins (ddFP) are a recently introduced class of genetically encoded reporters that can be used for the detection of protein interactions in live cells. The progenitor of this class of tools was a red fluorescent ddFP (ddRFP) derived from a homodimeric variant of Discosoma red fluorescent protein. Here, we describe the engineering and application of an expanded palette of ddFPs, which includes green (ddGFP) and yellow (ddYFP) variants.

A fluorogenic red fluorescent protein heterodimer.

The expanding repertoire of genetically encoded biosensors constructed from variants of Aequorea victoria green fluorescent protein (GFP) enable the imaging of a variety of intracellular biochemical processes. To facilitate the imaging of multiple biosensors in a single cell, we undertook the development of a dimerization-dependent red fluorescent protein (ddRFP) that provides an alternative strategy for biosensor construction. An extensive process of rational engineering and directed protein evolution led to the discovery of a ddRFP with a K(d) of 33 μM and a 10-fold increase in fluorescence upon heterodimer formation.

Förster resonance energy transfer-based biosensors for multiparameter ratiometric imaging of Ca2+ dynamics and caspase-3 activity in single cells.

As one of the principal cytoplasmic second messengers, the calcium ion (Ca(2+)) is central to a variety of intracellular signal transduction pathways. Accordingly, there is a sustained interest in methods for spatially- and temporally resolved imaging of the concentration of Ca(2+) in live cells using noninvasive methods such as genetically encoded biosensors based on Förster resonance energy transfer (FRET) between fluorescent proteins (FPs). In recent years, protein-engineering efforts have provided the research community with FRET-based Ca(2+) biosensors that are dramatically improved in terms of enhanced emission ratio change and optimized Ca(2+) affinity for various applications.

A bacteria colony-based screen for optimal linker combinations in genetically encoded biosensors.

Background: Fluorescent protein (FP)-based biosensors based on the principle of intramolecular Förster resonance energy transfer (FRET) enable the visualization of a variety of biochemical events in living cells. The construction of these biosensors requires the genetic insertion of a judiciously chosen molecular recognition element between two distinct hues of FP. When the molecular recognition element interacts with the analyte of interest and undergoes a conformational change, the ratiometric emission of the construct is altered due to a change in the FRET efficiency.