Zinc-α2-glycoprotein 1 (AZGP1) plays important roles in metabolism-related diseases. The underlying molecular mechanisms and therapeutic effects of AZGP1 remain unknown in non-alcoholic fatty liver disease (NAFLD).

Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC.

DNA mutational analysis of pancreatic cystic fluid (CF) is a useful adjunct to the evaluation of pancreatic cysts. KRAS/GNAS or RAF/PTPRD/CTNNB1/RNF43 mutations are highly specific to precancerous or advanced neoplasia. Several studies recently demonstrated the ability of next-generation sequencing (NGS) analysis to detect DNA mutations in pancreatic CF, but few studies have performed a systematic comparative analysis between pancreatic CF and neoplastic surgical tissue (NT). The value of CF-NGS analysis indicators for determining surgical resection necessitates evaluation.

Small-for-size grafts (SFSGs) in living donor liver transplantation (LDLT) could optimize donor postoperative outcomes and also expand the potential donor pool. Evidence on whether SFSGs would affect medium-term and long-term recipient graft survival is lacking.

Nanoparticles (NPs) can be toxic due to their nano-range sizes. Zinc oxide (ZnO) has good biocompatibility and is commercially used in cosmetics. Moreover, ZnO NPs have potential biomedical uses, but their safety remains unclear.

Nanogels (NGs) are promising drug delivery tools but are typically limited to hydrophilic drugs. Many potential new drugs are hydrophobic. Our study systematically investigates amphiphilic NGs with varying hydrophobicity, but similar colloidal features to ensure comparability. The amphiphilic NGs used in this experiment consist of a hydrophilic polymer network with randomly distributed hydrophobic groups. For the synthesis we used a new synthetic platform approach. Their amphiphilic character allows the encapsulation of hydrophobic drugs. Importantly, the hydrophilic/hydrophobic balance determines drug loading and biological interactions. In particular, protein adsorption to NG surfaces is dependent on hydrophobicity and critically determines circulation time. Our study investigates how network hydrophobicity influences protein binding, biocompatibility and cellular uptake.

Hepatocellular carcinoma is a common malignant cancer and the second most common cause of cancer-related deaths worldwide. Collagen triple helix repeat containing 1 (CTHRC1) has been increasingly reported to be involved in tumorigenesis and/or tumor progression. However, limited data are available regarding the role of CTHRC1 in hepatocellular carcinoma.

To explore if bexarotene (BEX) synergistically enhances docetaxel (DTX) cytotoxicity in castration-resistant prostate cancer cell lines.

Autophagy plays various roles in non-small-cell lung cancer (NSCLC). MCOLN1, a reactive oxygen species sensor, can regulate autophagy via lysosomal Ca(2+); however, the role of MCOLN1 in NSCLC is largely unknown. This study aimed to explore the effects of MCOLN1 on proliferation, invasion and migration in NSCLC and the underling mechanisms.

Heavy use of cannabis (marijuana) has been associated with decreased semen quality, which may reflect disruption of the endocannabinoid system (ECS) in the male reproductive tract by exogenous cannabinoids. Components of ECS have been previously described in human spermatozoa and in the rodent testis but there is little information on the ECS expression within the human testis. In this study we characterised the main components of the ECS by immunohistochemistry (IHC) on archived testis tissue samples from 15 patients, and by in silico analysis of existing transcriptome datasets from testicular cell populations. The presence of 2-arachidonoylglycerol (2-AG) in the human testis was confirmed by matrix-assisted laser desorption ionization imaging analysis. Endocannabinoid-synthesising enzymes; diacylglycerol lipase (DAGL) and N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), were detected in germ cells and somatic cells, respectively. The cannabinoid receptors, CNR1 and CNR2 were detected at a low level in post-meiotic germ cells and Leydig- and peritubular cells. Different transcripts encoding distinct receptor isoforms (CB1, CB1A, CB1B and CB2A) were also differentially distributed, mainly in germ cells. The cannabinoid-metabolising enzymes were abundantly present; the α/β-hydrolase domain-containing protein 2 (ABHD2) in all germ cell types, except early spermatocytes, the monoacylglycerol lipase (MGLL) in Sertoli cells, and the fatty acid amide hydrolase (FAAH) in late spermatocytes and post-meiotic germ cells. Our findings are consistent with a direct involvement of the ECS in regulation of human testicular physiology, including spermatogenesis and Leydig cell function. The study provides new evidence supporting observations that recreational cannabis can have possible deleterious effects on human testicular function.

We present a novel biometric authentication system enabled by ratiometric analysis of impedance of fingers. In comparison to the traditional biometrics that relies on acquired images of structural information of physiological characteristics, our biological impedance approach not only eliminates any practical means of making fake copies of the relevant physiological traits but also provides reliable features of biometrics using the ratiometric impedance of fingers. This study shows that the ratiometric features of the impedance of fingers in 10 different pairs using 5 electrodes at the fingertips can reduce the variation due to undesirable factors such as temperature and day-to-day physiological variations. By calculating the ratio of impedances, the difference between individual subjects was amplified and the spectral patterns were diversified. Overall, our ratiometric analysis of impedance improved the classification accuracy of 41 subjects and reduced the error rate of classification from 29.32% to 5.86% (by a factor of 5).

Overexpression of the epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC) is considered to cause increased EGFR activity, which adds to tumorigenicity and therapy resistance. Since it is still unclear, whether EGFR expression is indeed associated with increased activity in HNSCC, we analyzed the relationship between EGFR expression and auto-phosphorylation as a surrogate marker for activity. We used a tissue micro array, fresh frozen HNSCC tumor and corresponding normal tissue samples and a large panel of HNSCC cell lines. While we observed substantial overexpression only in approximately 20% of HNSCC, we also observed strong discrepancies between EGFR protein expression and auto-phosphorylation in HNSCC cell lines as well as in tumor specimens using Western blot and SH2-profiling; for the majority of HNSCC EGFR expression therefore seems not to be correlated with EGFR auto-phosphorylation. Blocking of EGFR activity by cetuximab and erlotinib points to increased EGFR activity in samples with increased basal auto-phosphorylation. However, we could also identify cells with low basal phosphorylation but relevant EGFR activity. In summary, our data demonstrate that EGFR expression and activity are not well correlated. Therefore EGFR positivity is no reliable surrogate marker for EGFR activity, arguing the need for alternative biomarkers or functional predictive tests.

Ample evidence indicates that loneliness in old age is associated with poor bodily and mental health. However, little is known about structural cerebral correlates of loneliness in healthy older adults. We examined such correlates in a magnetic resonance imaging (MRI) subsample of 319 older adults aged 61 to 82 years drawn from the Berlin Aging Study II. Using voxel-based morphometry (VBM) and structural equation modeling (SEM), latent hierarchical regression analyses were performed to examine associations of (i) loneliness, (ii) a range of covariates, and (iii) loneliness by covariate interactions with latent brain volume estimates of brain structures known to be involved in processing, expressing, and regulating emotions. Results from whole-brain VBM analyses showed that individuals with higher loneliness scores tended to have smaller gray matter volumes in three clusters comprising (i) the left amygdala/anterior hippocampus, (ii) the left posterior parahippocampus and (iii) the left cerebellum. Significant associations and interactions between loneliness and latent factors for the amygdala and the hippocampus were confirmed with a region-of-interest (ROI)-based approach. These findings suggest that individual differences in loneliness among older adults are correlated with individual differences in the volumes of brain regions that are central to cognitive processing and emotional regulation, also after correcting for confounders such as social network size. We discuss possible mechanisms underlying these associations and their implications.

Despite being the fourth largest island in the Mediterranean basin, the genetic variation of Corsica has not been explored as exhaustively as Sardinia, which is situated only 11 km South. However, it is likely that the populations of the two islands shared, at least in part, similar demographic histories. Moreover, the relative small size of the Corsica may have caused genetic isolation, which, in turn, might be relevant under medical and translational perspectives. Here we analysed genome wide data of 16 Corsicans, and integrated with newly (33 individuals) and previously generated samples from West Eurasia and North Africa. Allele frequency, haplotype-based, and ancient genome analyses suggest that although Sardinia and Corsica may have witnessed similar isolation and migration events, the latter is genetically closer to populations from continental Europe, such as Northern and Central Italians.

Acoustic illusion devices present a novel approach for defeating detection systems such as sonar by misrepresenting information about the target. These devices are currently designed for a predetermined illusion using metamaterials. We present the first active acoustic illusion utilizing monopole control sources and error sensors arranged circumferentially around a rigid object to generate the desired illusion in the global acoustic field. We also utilize control sources and error sensors in a line array to generate an illusion in the forward-scatter region of the object. Multiple types of illusions are achieved for a given control configuration.

Several cellular processes depend on networks of proteins assembled at specific sites near the plasma membrane. Scaffold proteins assemble these networks by recruiting relevant molecules. The scaffold protein ERC1/ELKS and its partners promote cell migration and invasion, and assemble into dynamic networks at the protruding edge of cells. Here by electron microscopy and single molecule analysis we identify ERC1 as an extended flexible dimer. We found that ERC1 scaffolds form cytoplasmic condensates with a behavior that is consistent with liquid phases that are modulated by a predicted disordered region of ERC1. These condensates specifically host partners of a network relevant to cell motility, including liprin-α1, which was unnecessary for the formation of condensates, but influenced their dynamic behavior. Phase separation at specific sites of the cell periphery may represent an elegant mechanism to control the assembly and turnover of dynamic scaffolds needed for the spatial localization and processing of molecules.

Previous studies have proposed that altered reward processing and elevated cognitive control underlie the etiology of anorexia nervosa (AN). A newly debated notion suggests altered habit learning and an overreliance on habits may contribute to the persistence of AN. In weight-recovered AN patients, we previously found neuroimaging-based evidence for unaltered reward processing, but elevated cognitive control. In order to differentiate between state versus trait factors, we here contrast the aforementioned hypotheses in a sample of acutely underweight AN (acAN) patients. 37 acAN patients and 37 closely matched healthy controls (HC) underwent a functional MRI while performing an established instrumental motivation task. We found no group differences with respect to neural responses during the anticipation or receipt of reward. However, the behavioral response data showed a bimodal distribution, indicative for a goal-directed (gAN) and a habit-driven (hAN) patient subgroup. Additional analyses revealed decreased mOFC activation during reward anticipation in hAN, which would be in line with a habit-driven response. These findings provide a new perspective on the debate regarding the notion of increased goal-directed versus habitual behavior in AN. If replicable, the observed dissociation between gAN and hAN might help to tailor therapeutic approaches to individual patient characteristics.

Photopharmacology has yielded compounds that have potential to restore impaired visual responses resulting from outer retinal degeneration diseases such as retinitis pigmentosa. Here we evaluate two photoswitchable azobenzene ion channel blockers, DAQ and DAA for vision restoration. DAQ exerts its effect primarily on RGCs, whereas DAA induces light-dependent spiking primarily through amacrine cell activation. Degeneration-induced local field potentials remain a major challenge common to all vision restoration approaches. These 5-10 Hz rhythmic potentials increase the background firing rate of retinal ganglion cells (RGCs) and overlay the stimulated response, thereby reducing signal-to-noise ratio. Along with the bipolar cell-selective photoswitch DAD and second-generation RGC-targeting photoswitch PhENAQ, we investigated the effects of DAA and DAQ on rhythmic local field potentials (LFPs) occurring in the degenerating retina. We found that photoswitches targeting neurons upstream of RGCs, DAA (amacrine cells) and DAD (bipolar cells) suppress the frequency of LFPs, while DAQ and PhENAQ (RGCs) had negligible effects on frequency or spectral power of LFPs. Taken together, these results demonstrate remarkable diversity of cell-type specificity of photoswitchable channel blockers in the retina and suggest that specific compounds may counter rhythmic LFPs to produce superior signal-to-noise characteristics in vision restoration.

Members of the genus Penicillium are commonly isolated from various terrestrial and marine environments, and play an important ecological role as a decomposer. To gain insight into the ecological role of Penicillium in intertidal zones, we investigated the Penicillium diversity and community structure using a culture-dependent technique and a culture independent metagenomic approach using ITS (ITS-NGS) and partial β-tubulin (BenA-NGS) as targets. The obtained isolates were tested for halotolerance, enzyme activity, and polycyclic aromatic hydrocarbons (PAHs) degradation. A total of 96 Penicillium species were identified from the investigated intertidal zones. Although the BenA-NGS method was efficient for detecting Penicillium, some species were only detected using conventional isolation and/or the ITS-NGS method. The Penicillium community displayed a significant degree of variation relative to season (summer and winter) and seaside (western and southern coast). Many Penicillium species isolated in this study exhibited cellulase and protease activity, and/or degradation of PAHs. These findings support the important role of Penicillium in the intertidal zone for nutrient recycling and pollutant degradation.

Atypical parkinsonian disorders (APDs) comprise a group of neurodegenerative diseases with heterogeneous clinical and pathological features. Most APDs are sporadic, but rare familial forms have also been reported. Epidemiological and post-mortem studies associated APDs with oxidative stress and cellular protein aggregates. Identifying molecular mechanisms that translate stress into toxic protein aggregation and neurodegeneration in APDs is an active area of research. Recently, ribonucleic acid (RNA) stress granule (SG) pathways were discussed to be pathogenically relevant in several neurodegenerative disorders including APDs. Using whole genome sequencing, mRNA expression analysis, transfection assays and cell imaging, we investigated the genetic and molecular basis of a familial neurodegenerative atypical parkinsonian disorder. We investigated a family with six living members in two generations exhibiting clinical symptoms consistent with atypical parkinsonism. Two affected family members suffered from parkinsonism that was associated with ataxia. Magnetic resonance imaging (MRI) of these patients showed brainstem and cerebellar atrophy. Whole genome sequencing identified a heterozygous stop-gain variant (c.C811T; p.R271X) in the Poly(A) binding protein, cytoplasmic 4-like (PABPC4L) gene, which co-segregated with the disease in the family. In situ hybridization showed that the murine pabpc4l is expressed in several brain regions and in particular in the cerebellum and brainstem. To determine the functional impact of the stop-gain variant in the PABPC4L gene, we investigated the subcellular localization of PABPC4L in heterologous cells. Wild-type PABPC4L protein localized predominantly to the cell nucleus, in contrast to the truncated protein encoded by the stop-gain variant p.R271X, which was found homogeneously throughout the cell. Interestingly, the wild-type, but not the truncated protein localized to RasGAP SH3 domain Binding Protein (G3BP)-labeled cytoplasmic granules in response to oxidative stress induction. This suggests that the PABPC4L variant alters intracellular distribution and possibly the stress granule associated function of the protein, which may underlie APD in this family. In conclusion, we present genetic and molecular evidence supporting the role of a stop-gain PABPC4L variant in a rare familial APD. Our data shows that the variant results in cellular mislocalization and inability of the protein to associate with stress granules.