Long noncoding RNA HULC is highly up-regulation in human hepatocellular carcinoma (HCC). However, the functions of HULC in hepatocarcinogenesis remains unclear.

In this study, live weight, live weight gain, plasma GPx, GR, LDH, ALT activities, triglyceride, total protein, albumin and LPO levels, also liver and brain SOD and GPx activities were investigated after administration of boron (0.10, 0.20 and 0.30 mg/day) into male mice with drinking water for 60 days. Blood albumin and triglyceride levels were not affected with boron (p > 0.05) where triglyceride levels, with increasing amounts of boron, displayed a slight decrease within the normal ranges. From the antioxidant-oxidant balance parameters, LPO and GR levels were not affected from boron, where GPx activity was increased significantly (p < 0.001) comparing the groups of boron and control. LDH and ALT activities were affected significantly (p < 0.001) with decreased ALT and increased LDH levels with increasing amounts of boron. In regards of liver and brain GPx and SOD activities, significant increases were determined. Liver GPx and SOD activities were increased within the groups with the increasing amount of boron, where in brain, SOD (p < 0.05) was affected significantly but GPx (p > 0.05) displayed a gradual insignificant increase. As regards live weight gain, a gradual increase was determined during experimental period, but only the 45th day, the increase was statistically significant (p < 0.05). It is suggested that, new studies on the effects of different doses and compounds of boron in laboratory animals in regards of antioxidant and metabolic effects may be helpful for the understanding of the subject.

Online discussion forums allow those in addiction recovery to seek help through text-based messages, including when facing triggers to drink or use drugs. Trained staff (or "moderators") may participate within these forums to offer guidance and support when participants are struggling but must expend considerable effort to continually review new content. Demands on moderators limit the scalability of evidence-based digital health interventions.

Hydrocephalus, a disorder of impaired cerebrospinal fluid (CSF) homeostasis, often results from an imbalance between CSF production and reabsorption. Rarely, hydrocephalus is the consequence of CSF hypersecretion in the context of diffuse villous hyperplasia of the choroid plexus (DVHCP). The limited genetic information in previously reported cases suggests a high prevalence of gains of Chromosome 9p in this disease, although the critical genes involved in DVHCP pathogenesis have not been identified. Here, we report a patient with syndromic hydrocephalus with DVHCP associated with a novel 9p24.3-11.2 triplication and 15q13.2-q13.3 microdeletion. We review the clinical, radiological, and pathological features of DVHCP, as well as its surgical management. A better understanding of the genetic basis of DVHCP could spur the development of rational, targeted nonsurgical hydrocephalus treatments.

Sudden cardiac arrest (CA) often results in severe injury to the brain, and neuroprotection after CA has proved to be difficult to achieve. Herein, we sought to investigate the effects of metformin pretreatment on brain injury secondary to CA and cardiopulmonary resuscitation.

Persistence is a reversible and low-frequency phenomenon allowing a subpopulation of a clonal bacterial population to survive antibiotic treatments. Upon removal of the antibiotic, persister cells resume growth and give rise to viable progeny. Type II toxin-antitoxin (TA) systems were assumed to play a key role in the formation of persister cells in Escherichia coli based on the observation that successive deletions of TA systems decreased persistence frequency. In addition, the model proposed that stochastic fluctuations of (p)ppGpp levels are the basis for triggering activation of TA systems. Cells in which TA systems are activated are thought to enter a dormancy state and therefore survive the antibiotic treatment. Using independently constructed strains and newly designed fluorescent reporters, we reassessed the roles of TA modules in persistence both at the population and single-cell levels. Our data confirm that the deletion of 10 TA systems does not affect persistence to ofloxacin or ampicillin. Moreover, microfluidic experiments performed with a strain reporting the induction of the yefM-yoeB TA system allowed the observation of a small number of type II persister cells that resume growth after removal of ampicillin. However, we were unable to establish a correlation between high fluorescence and persistence, since the fluorescence of persister cells was comparable to that of the bulk of the population and none of the cells showing high fluorescence were able to resume growth upon removal of the antibiotic. Altogether, these data show that there is no direct link between induction of TA systems and persistence to antibiotics.IMPORTANCE Within a growing bacterial population, a small subpopulation of cells is able to survive antibiotic treatment by entering a transient state of dormancy referred to as persistence. Persistence is thought to be the cause of relapsing bacterial infections and is a major public health concern. Type II toxin-antitoxin systems are small modules composed of a toxic protein and an antitoxin protein counteracting the toxin activity. These systems were thought to be pivotal players in persistence until recent developments in the field. Our results demonstrate that previous influential reports had technical flaws and that there is no direct link between induction of TA systems and persistence to antibiotics.

Members of the genus Rickettsiella are bacterial pathogens of insects and other arthropods. Recently, a novel facultative endosymbiont, "Candidatus Rickettsiella viridis," was described in the pea aphid Acyrthosiphon pisum, whose infection causes a striking host phenotype: red and green genetic color morphs exist in aphid populations, and upon infection with the symbiont, red aphids become green due to increased production of green polycyclic quinone pigments. Here we determined the complete genome sequence of the symbiont. The 1.6-Mb circular genome, harboring some 1,400 protein-coding genes, was similar to the genome of entomopathogenic Rickettsiella grylli (1.6 Mb) but was smaller than the genomes of phylogenetically allied human pathogens Coxiella burnetii (2.0 Mb) and Legionella pneumophila (3.4 Mb). The symbiont's metabolic pathways exhibited little complementarity to those of the coexisting primary symbiont Buchnera aphidicola, reflecting the facultative nature of the symbiont. The symbiont genome harbored neither polyketide synthase genes nor the evolutionarily allied fatty acid synthase genes that are suspected to catalyze the polycyclic quinone synthesis, indicating that the green pigments are produced not by the symbiont but by the host aphid. The symbiont genome retained many type IV secretion system genes and presumable effector protein genes, whose homologues in L. pneumophila were reported to modulate a variety of the host's cellular processes for facilitating infection and virulence. These results suggest the possibility that the symbiont is involved in the green pigment production by affecting the host's metabolism using the secretion machineries for delivering the effector molecules into the host cells.IMPORTANCE Insect body color is relevant to a variety of biological aspects such as species recognition, sexual selection, mimicry, aposematism, and crypsis. Hence, the bacterial endosymbiont "Candidatus Rickettsiella viridis," which alters aphid body color from red to green, is of ecological interest, given that different predators preferentially exploit either red- or green-colored aphids. Here we determined the complete 1.6-Mb genome of the symbiont and uncovered that, although the red-green color transition was ascribed to upregulated production of green polycyclic quinone pigments, the symbiont genome harbored few genes involved in the polycyclic quinone biosynthesis. Meanwhile, the symbiont genome contained type IV secretion system genes and presumable effector protein genes, whose homologues modulate eukaryotic cellular processes for facilitating infection and virulence in the pathogen Legionella pneumophila We propose the hypothesis that the symbiont may upregulate the host's production of polycyclic quinone pigments via cooption of secretion machineries and effector molecules for pathogenicity.

To identify and compare emollient formularies across all clinical commissioning groups (CCGs) and local health boards (LHBs) in England and Wales.

Dysregulation of nuclear envelope (NE) assembly results in various cancers; for example, renal and some lung carcinomas ensue due to NE malformation. The NE is a dynamic membrane compartment and its completion during mitosis is a highly regulated process, but the detailed mechanism still remains incompletely understood. Previous studies have found that isolated diacylglycerol (DAG)-containing vesicles are essential for completing the fusion of the NE in nonsomatic cells. We investigated the impact of DAG depletion from the cis-Golgi in mammalian cells on NE reassembly. Using advanced electron microscopy, we observed an enriched DAG population of vesicles at the vicinity of the NE gaps of telophase mammalian cells. We applied a mini singlet oxygen generator-C1-domain tag that localized DAG-enriched vesicles at the perinuclear region, which suggested the existence of NE fusogenic vesicles. We quantified the impact of Golgi-DAG depletion by measuring the in situ NE rim curvature of the reforming NE. The rim curvature in these cells was significantly reduced compared with controls, which indicated a localized defect in NE morphology. Our novel results demonstrate the significance of the role of DAG from the cis-Golgi for the regulation of NE assembly.

Wastewater treatment plants (WWTPs) are designed to eliminate organic matter and pathogens but most WWTPs discharges antimicrobial resistance pathogens into aquatic milieu. The study aimed to examine the antibiotics resistant patterns and the presence of some resistance genes among E. coli isolates from WWTPs effluents. Water were collected from WWTPs final effluents, filtered through nitrocellulose membrane and the filter papers were placed on chromogenic agar plates, incubated for 24 h at 37 °C. Presumptive E. coli isolates (173) were obtained from the culture method. From the presumptive E. coli isolates screened by polymerase chain reaction (PCR), 111 isolates were positive and the positive isolates were further screened for six diarrheagenic E. coli pathotypes (EPEC, ETEC, EHEC, DAEC, EIEC, and EAEC) and from the pathotypes screened, nine isolates harboured daaE gene. The phenotypic susceptibility patterns of the 111 isolates to 12 antibiotics were determined by Kirby-Bauer disk diffusion technique. All the isolates were resistant to erythromycin and clindamycin. From the resistance genes screened, 31 isolates harboured mcr-1 gene and nine isolates harboured ermA gene. The study reveals that water samples recovered from the final effluents of WWTPs may likely be one of the major sources of antibiotic-resistant in Escherichia coli.

Certain endophytic fungi belonging to the Hypoxylon genus have recently been found to produce volatile organic compounds (VOCs) that have potential relevance as hydrocarbon fuels. Here, a recently discovered Hypoxylon sp. (BS15) was demonstrated to also produce VOCs, but with diminished VOC production after an extended period of in vitro growth. Restoring VOC production was partially achieved by growing BS15 in growth media containing finely ground woody tissue from the original host plant (Taxodium distichum). In an effort to isolate VOC production modulators, extracts from this woody tissue were made by sequentially extracting with dichloromethane, methanol, and water. Both the dichloromethane and water extracts were found to modulate VOC production, while the methanol extract had no effect. Surprisingly, the woody tissue remaining after exhaustive extraction was also shown to act as a VOC production modulator when included in the growth media, with changes observed in the production of four compounds. This woody tissue also induced production of two compounds not observed in the original BS15 extract. Filter paper had the same modulating effect as exhaustively extracted woody tissue, suggesting the modulation was perhaps due to cellulose degradation products. Overall, this study demonstrated that VOC production in BS15 can be influenced by multiple compounds in the woody tissue rather than a single modulator.

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly with less effective treatment, especially for dry AMD (90% of AMD). Although the etiology of this disease is not well elucidated, increasing evidences indicate that excessive reactive oxygen species (ROS) impairing the physiological functions of retinal pigment epithelium (RPE) cells may be one of the main causes. Therefore, it could be a great strategy to find some drugs that can effectively protect RPE cells from oxidative damage which is desired to treat and slow the process of AMD. In the present study, a well-known traditional Chinese medicine berberine (BBR) was found to suppress hydrogen peroxide (H₂O₂)-induced oxidative damage in D407 cells, a human RPE cell line. Pre-treatment of D407 cells with BBR significantly suppressed H₂O₂-induced cell apoptosis by restoring abnormal changes in nuclear morphology, preventing the decline of mitochondrial membrane potential, reducing lactate dehydrogenase release and inhibiting caspase 3/7 activities induced by H₂O₂. Western blot analysis showed that BBR was able to stimulate the phosphorylation/activation of AMPK in a time- and dose-dependent manner in D407 cells, while treatment of cells with AMPK pathway inhibitor Compound C, or knockdown of the AMPK by specific siRNA blocked the effect of BBR. Similar results were obtained in primary cultured human RPE cells. Taken together, these results demonstrated that BBR was able to protect RPE cells against oxidative stress via the activation of AMPK pathway. Our findings also indicate the potential application of BBR in AMD treatment.

Regulatory B cells (Bregs) participate in auto-tolerance maintenance and immune homeostasis. Despite their impact on many diseases and due to the difficulty to define them, knowledge about their origin and their physiological inducers is still unclear. The incomplete understanding about the generation of Bregs and their limited numbers in periphery make it difficult to develop Breg-based therapy. Therefore, identifying factors that promote their development would allow their ex-vivo production in order to create new immunotherapy. This project aims to test the capacity of several cytokines (Interleukin 1-beta (IL-1β), Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF), and Cluster of differentiation 40 ligand (CD40L)) and bacteria-derived oligodeoxynucleotides (CpG-ODN), alone or in combination, to generate B cells with regulatory phenotype and function. We have demonstrated that the Breg-associated phenotypes were heterogeneous between one and other stimulation conditions. However, the expression of other markers related to Bregs such as IL-10, CD80, CD86, CD71, Programmed cell death-1 (PD-1), and Programmed death-ligand 1 (PD-L1) was increased when cells were stimulated with CpG alone or in combination. Moreover, stimulated B cells presented a suppressive function on autologous activated peripheral blood mononuclear cells (PBMC) proliferation. Therefore, this work is the first step to demonstrate the feasibility to induce functional Breg-like cells in vitro and will then facilitate the way to produce Breg-like cells as a potential future cellular therapy.

Cardiovascular disorders (CVD) and major depressive disorder (MDD) are the most frequent diseases worldwide responsible for premature death and disability. Behavioral and immunological variables influence the pathophysiology of both disorders. We therefore determined frequency and severity of MDD in CVD and studied whether MDD without CVD or other somatic diseases influences classical and inflammatory biomarkers of cardiovascular risk. In addition, we investigated the influence of proinflammatory cytokines on antidepressant treatment outcome.

There is continuing need for new and improved drugs to tackle malaria, which remains a major public health problem, especially in tropical and subtropical regions of the world. Natural products represent credible sources of new antiplasmodial agents for antimalarial drug development. Endophytes that widely colonize healthy tissues of plants have been shown to synthesize a great variety of secondary metabolites that might possess antiplasmodial benefits. The present study was carried out to evaluate the antiplasmodial potential of extracts from endophytic fungi isolated from Symphonia globulifera against a chloroquine-resistant strain of Plasmodium falciparum (PfINDO). Sixty-one fungal isolates with infection frequency of 67.77% were obtained from the bark of S. globulifera. Twelve selected isolates were classified into six different genera including Fusarium, Paecilomyces, Penicillium, Aspergillus, Mucor, and Bipolaris. Extracts from the 12 isolates were tested against PfINDO, and nine showed good activity (IC50 < 10 μg·mL−1) with three fungi including Paecilomyces lilacinus (IC50 = 0.44 μg·mL−1), Penicillium janthinellum (IC50 = 0.2 μg·mL−1), and Paecilomyces sp. (IC50 = 0.55 μg·mL−1) showing the highest promise. These three isolates were found to be less cytotoxic against the HEK293T cell line with selectivity indices ranging from 24.52 to 70.56. Results from this study indicate that endophytic fungi from Symphonia globulifera are promising sources of hit compounds that might be further investigated as novel drugs against malaria. The chemical investigation of active extracts is ongoing.

Horn flies, Haematobia irritans, a major cattle pest in the USA, cause substantial economic losses and current control methods rely heavily on insecticides. Three horn fly populations were evaluated for insecticide susceptibility to permethrin, β-cyfluthrin, and diazinon. Susceptibility was variable by population, with the greatest resistance exhibited by a 66-fold resistance ratio (RR) to permethrin and >14-fold RR to diazinon. Mechanisms of resistance were determined using molecular techniques and enzymatic assays. The knockdown resistance (kdr) genotype (L150F) associated with pyrethroid resistance, and a G262A mutation in acetylcholinesterase, previously associated with organophosphate resistance, were found in all field populations evaluated. Insensitivity of diazoxon at the acetylcholinesterase (AChE) target site was significantly different in horn flies from one of the field sites. For metabolic detoxifying enzymes, cytochrome P450 nor general esterases showed a significant difference between field strains and a laboratory susceptible strain. Pyrethroid resistance was likely due to the presence of the L150F mutation in the population. In vitro studies targeting the AChE enzyme did not support the notion that the G262A mutation was the sole cause of resistance to organophosphates, and, therefore, the exact resistance mechanism to diazinon was not able to be confirmed.

In this paper, a novel feature selection and fusion framework is proposed to enhance the discrimination ability of gas sensor arrays for odor identification. Firstly, we put forward an efficient feature selection method based on the separability and the dissimilarity to determine the feature selection order for each type of feature when increasing the dimension of selected feature subsets. Secondly, the K-nearest neighbor (KNN) classifier is applied to determine the dimensions of the optimal feature subsets for different types of features. Finally, in the process of establishing features fusion, we come up with a classification dominance feature fusion strategy which conducts an effective basic feature. Experimental results on two datasets show that the recognition rates of Database I and Database II achieve 97.5% and 80.11%, respectively, when k = 1 for KNN classifier and the distance metric is correlation distance (COR), which demonstrates the superiority of the proposed feature selection and fusion framework in representing signal features. The novel feature selection method proposed in this paper can effectively select feature subsets that are conducive to the classification, while the feature fusion framework can fuse various features which describe the different characteristics of sensor signals, for enhancing the discrimination ability of gas sensors and, to a certain extent, suppressing drift effect.

Chicken serum albumin (CSA) is a hen's egg yolk allergen causing IgE-mediated allergy. The objective of this study was to produce a recombinant version of CSA and compare its IgE reactivity to natural CSA (nCSA). CSA was cloned and expressed as a soluble fraction in the yeast Kluyveromyces lactis (K. lactis) protein expression system. The gene encoding CSA was amplified with a C-terminal hemagglutinin epitope tag by polymerase chain reaction (PCR) and cloned into the pKLAC2 expression vector prior to transforming into K. lactis. Recombinant CSA (rCSA) was purified by immunoprecipitation. Twenty-one patients allergic to hen's egg white were examined for sensitisation against nCSA. 38% of patients were found to be sensitised to CSA based on Western immunoassay. Immunoglobulin E (IgE) binding capacity of rCSA and nCSA was analysed by ELISA using sera from patients sensitised to CSA. Levels of IgE-binding were similar for both the recombinant and the natural CSA, indicating the existence of similar epitopes. rCSA produced in this study is a potential candidate to be used in component-resolved diagnosis (CRD) of egg yolk allergy. The usefulness of rCSA in CRD of egg yolk allergy warrants further characterisation using sera from patients with allergy to hen's egg yolk in future studies.

In this paper, the selective interactions of synthetic derivatives of two natural compounds, berberine and palmatine, with DNA G-quadruplex structures were reported. In particular, the previous works on this subject concerning berberine were further presented and discussed, whereas the results concerning palmatine are presented here for the first time. In detail, these palmatine derivatives were developed by inserting seven different small peptide basic chains, giving several new compounds that have never been reported before. The preliminary studies of the interactions of these compounds with various G-quadruplex-forming sequences were carried out by means of various structural and biochemical techniques, which showed that the presence of suitable side chains is very useful for improving the interaction of the ligands with G-quadruplex structures. Thus, these new palmatine derivatives might act as potential anticancer drugs.

Seven new triterpenoid saponins (1⁻7), together with three known ones (8⁻10), were isolated from Ilex pubescens. Elucidation of their structures was performed based on high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS), infrared spectra (IR), and nuclear magnetic resonance (NMR) spectroscopic data. The anti-inflammatory activity of the isolates toward lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages was investigated. The results demonstrated that compounds 3, 5, and 6 inhibited the expression of inducible nitric oxide synthase (iNOS) protein in comparison with LPS stimulation in RAW264.7 cells.