Periodic cyclic cohomology of group rings

We generalize previous results ([2], [3], [4], etc.) relative to the cyclic homology and cohomology of the group algebra of G. In many cases, we express them in terms of the (co)homology of the discrete groups(u) = Z (u)/C (u), where 〈u〉 runs through the set of conjugacy classes of G and where Z(u) (resp. C(u)) denotes the centralizer of u (resp. the cyclic group generated by u).     

Longitudinal stability of resting-state networks in normal aging,mild cognitive impairment,and Alzheimer's disease

Test–retest reliability is essential for using resting-state functional magnetic resonance imaging (rs-fMRI) as a potential biomarker for Alzheimer's disease (AD), especially when monitoring longitudinal changes and treatment effects. In addition, test–retest variability itself might represent a feature of AD. Using 3.0 T rs-fMRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we examined the long-term (1-year) test–retest reliability of resting-state networks (RSNs) in 31 healthy elderly subjects, 63 patients with mild cognitive impairment (MCI), and 17 patients with AD by applying temporal concatenation group independent component analysis and dual regression. The intraclass correlation coefficient estimates of RSN amplitudes ranged from 0.44 to 0.77 in healthy elderly subjects, from 0.31 to 0.62 in patients with MCI, and from −0.06 to 0.44 in patients with AD. The overall test–retest reliability of RSNs was lower in patients with MCI than in healthy elderly subjects, and was lower in patients with AD than in patients with MCI. The differences in the test–retest reliabilities were due to the RSN amplitudes rather than the RSN shapes. Head motion was not significantly different among the three groups of subjects. The results indicate that the test–retest stability of RSNs generally declines with progression to MCI and AD, mainly due to the RSN amplitudes rather than the RSN shapes. The test–retest instability in MCI and AD may reflect progressive neurofunctional alterations related to the pathology of AD.     

Meta-analysis of gene expression for development and validation of a diagnostic biomarker panel for Oral Squamous Cell Carcinoma

We use a newly developed feature extraction and classification method to analyze previously published gene expression data sets in Oral Squamous Cell Carcinoma and in healthy oral mucosa in order to find a gene set sufficient for diagnoses. The feature selection technology is based on the relative dichotomy power concept published by us earlier. The resulting biomarker panel has 100% sensitivity and 95% specificity, is enriched in genes associated with oncogenesis and invasive tumor growth, and, unlike marker panels devised in earlier studies, shows concordance with previously published marker genes.     

Identifying cancer specific signaling pathways based on the dysregulation between genes

A large collection of studies has shown that the occurrence of cancer is related to the functional dysfunction of the pathways. Identification of cancer-related pathways could help researchers understand the mechanisms of complex diseases well. Whereas, most current signaling pathway analysis methods take no account of the gene interaction variations within pathways. Furthermore, considering that some pathways have connection with two or more cancer types, while some are likely to be cancer-type specific pathways. Identifying cancer-type specific pathways contributes to interpreting the different mechanisms of different cancer types. In this study, we first proposed a pathway analysis method named Pathway Analysis of Intergenic Regulation (PAIGR) to identify pathways with dysregulation between genes and compared the performance of this method with four existing methods on four colorectal cancer (CRC) datasets. The results showed that PAIGR could find cancer-related pathways more accurately. Moreover, in order to explore the relationship between the identified pathways and the cancer type, we constructed a pathway interaction network, in which nodes and edges represented pathways and interactions between pathways respectively. Highly connected pathways were considered to play a central role in an extensive range of biological processes, while sparsely connected pathways are considered to have certain specificity. Our results showed that pathways identified by PAIGR had a low nodal degree (i.e., a few numbers of interactions), which suggested that most of these pathways were cancer-type specific.     

Sensitization of nerve cells to ultrasound stimulation through Piezo1-targeted microbubbles

Neuromodulation by ultrasound (US) has recently drawn considerable attention due to its great advantages in noninvasiveness, high penetrability across the skull and highly focusable acoustic energy. However, the mechanisms and safety from US irradiation still remain less understood. Recently, documents revealed Piezo1, a mechanosensitive cation channel, plays key role in converting mechanical stimuli from US through its trimeric propeller-like structure. Here, we developed a Piezo1-targeted microbubble (PTMB) which can bind to the extracellular domains of Piezo1 channel. Due to the higher responsiveness of bubbles to mechanical stimuli from US, significantly lower US energy for these PTMB-binding cells may be needed to open these mechanosensitive channels. Our results showed US energy at 0.03 MPa of peak negative pressure can achieve an equivalent level of cytoplasmic Ca²⁺ transients which generally needs 0.17 MPa US intensity for the control cells. Cytoplasmic Ca²⁺ elevations were greatly reduced by chelating extracellular calcium ions or using the cationic ion channel inhibitors, confirming that US-mediated calcium influx are dependent on the Piezo1 channels. No bubble destruction and obvious temperature increase were observed during the US exposure, indicating cavitation and heating effects hardly participate in the process of Ca²⁺ transients. In conclusion, our study provides a novel strategy to sensitize the response of nerve cells to US stimulation, which makes it safer application for US-mediated neuromodulation in the future.     

A novel vanadium complex VO(p-dmada) inhibits neuroinflammation induced by lipopolysaccharide

Uncontrolled microglial activation is decisively involved in the neuroinflammatory pathogenesis of brain diseases. Consequently, suppression of microglial overactivation appears to be a strategy for the prevention of nerve injury. In this paper, a novel vanadium complex, vanadyl N-(p-N,N-dimethylaminophenylcarbamoylmethyl)iminodiacetate (VO(p-dmada)), was synthesized from vanadyl sulfate and N,N-dimethyl-p-phenylenediamine, which was structurally characterized by Fourier transform infrared spectrum and ESI-MS analysis. The effect of VO(p-dmada) on neuroinflammation was investigated by using the models of lipopolysaccharide (LPS)-induced BV2 microglial cells and BALB/c mice. Our data demonstrated that VO(p-dmada) significantly suppressed microglial activation by downregulating inflammatory mediators and associated proteins, and inactivating nuclear factor-κB (NF-κB) signaling pathway. VO(p-dmada) also upregulated peroxisome proliferator activated receptor gamma (PPARγ) by reducing transglutaminase 2 and heat shock protein 60 expression. Co-treatment with PPARγ antagonist GW9662 significantly impeded the inhibitory effect of VO(p-dmada) on LPS-induced neuroinflammation. These cumulative findings demonstrated that VO(p-dmada) is a potential new drug for the treatment of neuroinflammation-related neurodegenerative diseases.     

Codon phylogenetic distance

We develop here an analytical evolution model based on a trinucleotide mutation matrix 64x64 with nine substitution parameters associated with the three types of substitutions in the three trinucleotide sites and with non-zero elements on its main diagonal. It generalizes the previous models based on the nucleotide mutation matrices 4x4 and the trinucleotide mutation matrices 64x64 with zero elements on its main diagonal. It determines at some time t the exact occurrence probabilities of trinucleotides mutating randomly according to these nine substitution parameters. Furthermore, applications of this model allow to generalize an evolutionary analytical solution of the common circular code of eukaryotes and prokaryotes and also to derive a codon phylogenetic distance.     

Photo-responsive NIR-II biomimetic nanomedicine for efficient cancer-targeted theranostics

In pancreatic cancer, the special barrier system formed by a large number of stromal cells severely hinders drug penetration in deep tumor tissues, resulting in low treatment efficiency. Cell membrane protein-camouflaged liposomal nanomedicines have cancer cell targeting abilities, whereas near-infrared two-zone (NIR-II) fluorescence imaging can achieve deep tissue penetration due to its long light wavelength (1,000–1,700 nm). To combine the cell membrane-based biomimetic technology with NIR-II fluorescence imaging, we constructed a biomimetic nanomedicine (BLIPO-I/D) by camouflaging indocyanine green-doxorubicin (ICG-DOX) liposomes with SW1990 pancreatic cancer cell membrane. The nanomedicine exhibited light-controlled DOX release and high pancreatic cancer treatment efficiency in vitro and in vivo. BLIPO-I/D showed the ability of targeted delivery of a large number of liposomes to pancreatic tumor tissues through homologous targeting of SW1990 cell membranes, which increased the NIR-II fluorescence imaging intensity. Irradiation of the liposomes taken up by pancreatic tumor tissues with near-infrared light (808 nm) triggered the rapid release of DOX from the liposomes, induced the photothermal and photodynamic effects of ICG, which exerted anti-tumor effects. Therefore, the fabricated biomimetic liposomal nanomedicine BLIPO-I/D is expected to achieve precise theranostics of pancreatic cancer.     

Design and construction of an interchangeable RF coil system for rodent spinal cord MR imaging at 9.4 T

Rodent models of spinal cord injury (SCI) have been widely used in pre-clinical studies. Injuries may occur at different levels of the lumbar and thoracic cord, and the number of segments injured and their depths may vary along the spine. It is thereby challenging to build one universal RF coil that exhibits optimal performance for all spinal cord imaging applications, especially in an animal scanner with small in-bore space and limited hardware configurations. We developed an interchangeable RF coil system for a 9.4 T small animal MRI scanner, in which the users can select an optimal coil specialized for imaging specific parts of a rat spine. We also developed the associated animal management device for immobilization and positioning. The whole system allows ease of RF coil exchange, animal fixation, and positioning, and thus reduces the animal preparation time before the MRI scan significantly. Compared to a commercial general-purpose 2-cm-diameter coil that was used in our previous studies, the specialized coil optimized for Sprague-Dawley rat lumbar spinal cord imaging exhibits up to 2.4 times SNR improvement.