Fluorescent Molecular Rotors for Viscosity Sensors.

Fluorescent molecular rotors (FMRs) can act as viscosity sensors in various media including subcellular organelles and microfluidic channels. In FMRs, the rotation of rotators connected to a fluorescent π-conjugated bridge is suppressed by increasing environmental viscosity, resulting in increasing fluorescence (FL) intensity. In this minireview, we describe recently developed FMRs including push-pull type π-conjugated chromophores, meso-phenyl (borondipyrromethene) (BODIPY) derivatives, dioxaborine derivatives, cyanine derivatives, and porphyrin derivatives whose FL mechanism is viscosity-responsive. In addition, FMR design strategies for addressing various issues (e.g., obtaining high FL contrast, internal FL references, and FL intensity-contrast trade-off) and their biological and microfluidic applications are also discussed.

Programmed Death 1 and Cytotoxic T-Lymphocyte-Associated Protein 4 Gene Expression in Peripheral Blood Mononuclear Cells Can Serve as Prognostic Biomarkers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly aggressive form of liver cancer with poor prognosis. The lack of reliable biomarkers for early detection and accurate diagnosis and prognosis poses a significant challenge to its effective clinical management. In this study, we investigated the diagnostic and prognostic potential of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in peripheral blood mononuclear cells (PBMCs) in HCC. PD-1 and CTLA-4 gene expression was analyzed comparatively using PBMCs collected from HCC patients and healthy individuals. The results revealed higher PD-1 gene expression levels in patients with multifocal tumors, lymphatic invasion, or distant metastasis than those in their control counterparts. However, conventional serum biomarkers of liver function do not exhibit similar correlations. In conclusion, PD-1 gene expression is associated with OS and PFS and CTLA-4 gene expression is associated with OS, whereas the serum biomarkers analyzed in this study show no significant correlation with survival in HCC. Hence, PD-1 and CTLA-4 expressed in PBMCs are considered potential prognostic biomarkers for patients with HCC that can facilitate prediction of malignancy, response to currently available HCC treatments, and overall survival.

Mathematical Modeling and Analyses of Interspike-Intervals of Spontaneous Activity in Afferent Neurons of the Zebrafish Lateral Line.

Without stimuli, hair cells spontaneously release neurotransmitter leading to spontaneous generation of action potentials (spikes) in innervating afferent neurons. We analyzed spontaneous spike patterns recorded from the lateral line of zebrafish and found that distributions of interspike intervals (ISIs) either have an exponential shape or an "L" shape that is characterized by a sharp decay but wide tail. ISI data were fitted to renewal-process models that accounted for the neuron refractory periods and hair-cell synaptic release. Modeling the timing of synaptic release using a mixture of two exponential distributions yielded the best fit for our ISI data. Additionally, lateral line ISIs displayed positive serial correlation and appeared to exhibit switching between faster and slower modes of spike generation. This pattern contrasts with previous findings from the auditory system where ISIs tended to have negative serial correlation due to synaptic depletion. We propose that afferent neuron innervation with multiple and heterogenous hair-cells synapses, each influenced by changes in calcium domains, can serve as a mechanism for the random switching behavior. Overall, our analyses provide evidence of how physiological similarities and differences between synapses and innervation patterns in the auditory, vestibular, and lateral line systems can lead to variations in spontaneous activity.

The relationship between microstructural alterations of the brain and clinical measurements in children and adolescents with hair pulling disorder.

Several studies have evaluated gray matter abnormalities and white matter integrity in adults with hair pulling disorder (HPD). However, no prior studies have defined the relationship between neuroimaging parameters and clinical measurements in children and adolescents with HPD. The purposes of this study were to determine the correlation between magnetic resonance imaging (MRI) indices and clinical measurements in children and adolescents with HPD, and to compare HPD patients with age- and sex- matched healthy controls (HC). Pediatric HPD patients (n = 9) and HC subjects (n = 10), aged 9-17 years, were recruited. Three-dimensional T1-weighted structural MRI (3D T1W) and diffusion-tensor imaging (DTI) scans were obtained for each subject. Gray matter and white matter volumes were calculated from 3D T1W. Fractional anisotropy (FA) and average diffusion coefficients (Dav) were mapped from DTI. Voxel-based and region-of-interest correlations between MRI indices and clinical measurements were analyzed. In addition, two-sample t-tests were used to compare voxel-based tissue volumes, FA, and Dav maps between the two groups. Alterations in both brain tissue volume and white matter integrity were associated with symptom severity, especially in the precuneus, anterior cingulate, temporal cortex, and frontal cortex regions. FA values in HPD patients were significantly higher than those observed in HC subjects, particularly in the cerebellum and cuneus regions. Alterations of brain tissue volumes and microstructural changes are associated with severity of clinical symptoms in children and adolescents with HPD. Fractional anisotropy is the most sensitive method to distinguish pediatric HPD patients from healthy children. The results of this study can facilitate use of MRI indices to follow the transition from pediatric HPD to adult HPD.

Serum C-reactive protein levels in normal-weight polycystic ovary syndrome.

BACKGROUND/AIMS: Serum levels of highly sensitive C-reactive protein (hsCRP), a vascular inflammatory marker, may predict the development of cardiovascular disease (CVD) and type 2 diabetes. Women with polycystic ovary syndrome (PCOS) are at greater risk for type 2 diabetes and CVD. The aim of this study was to compare hsCRP levels between normal weight women with PCOS and controls with a normal menstrual cycle and to determine the factors associated with serum hsCRP levels. METHODS: Thirty-nine lean PCOS patients and 24 healthy, regular cycling women were enrolled in this study. We performed anthropometric measurements, fat computed tomography (CT), and blood sampling to determine blood chemistry and levels of hsCRP, gonadotropins, testosterone, and sex-hormone binding globulin. We also conducted 75-g oral glucose-tolerance test and euglycemic hyperinsulinemic clamp to assess insulin sensitivity. RESULTS: Serum hsCRP concentrations were higher in women with PCOS than in women with regular mensturation. However, this difference was no longer significant after adjusting for body mass index (BMI). hsCRP levels were correlated with waist circumference (r=0.46, p<0.01), BMI (r=0.46, p<0.01), visceral fat area (r=0.45, p<0.01), and systolic (r=0.42, p<0.05) and diastolic blood pressure (r=0.39, p<0.05). hsCRP also tended to be negatively associated with insulin-mediated glucose uptake (IMGU) (r=-0.31, p=0.07). A multiple regression analysis revealed that BMI (beta=0.29, p<0.05), systolic blood pressure (beta=0.39, p<0.01), and IMGU (beta=-0.31, p<0.05) predicted serum hsCRP levels in women with PCOS. CONCLUSIONS: PCOS by itself does not seem to be associated with increased hsCRP levels, whereas known CVD risk factors affect serum hsCRP levels in PCOS.

Crystallization and preliminary X-ray crystallographic analysis of a putative agmatinase from Deinococcus radiodurans.

Agmatine, which results from the decarboxylation of arginine by arginine decarboxylase, is a metabolic intermediate in the biosynthesis of putresine and higher polyamines. The enzyme agmatinase catalyses the hydrolysis of agmatine to putresine and urea. Recent studies indicate that agmatinase plays important roles in mammals. Human mitochondrial agmatinase shows a considerable level of sequence similarity to bacterial agmatinases, including a putative agmatinase from Deinococcus radiodurans. The putative agmatinase from D. radiodurans has been overexpressed in Escherichia coli and crystallized at 297 K using polyethylene glycol 3000 as a precipitant. X-ray diffraction data were collected to 1.80 A from a crystal grown in the presence of Mn2+ and 1,6-hexanediamine. The crystals are orthorhombic, belonging to the space group P2(1)2(1)2(1), with unit-cell parameters a = 81.77, b = 131.44, c = 168.85 A, alpha = beta = gamma = 90 degrees. A hexameric molecule is likely to be present in the asymmetric unit, giving a crystal volume per protein weight (VM) of 2.15 A3 Da(-1) and a solvent content of 41.8%.