Background

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Although much is known about both the cellular changes that lead to HCC and the etiological agents responsible for the majority of HCC cases, the molecule pathogenesis of HCC is still not well understood. We aimed to determine the effect of c-Myc gene expression on the proliferative, invasive, and migrative capabilities of hepatocellular carcinoma HepG2 cells.

Methods

A plasmid- based polymerase III promoter system was used to deliver and express short interfering RNA targeting c-Myc to reduce its expression in HepG2 cells. Western blot analysis was used to measure the protein level of c-Myc in HepG2 cells. The effects of c-Myc silencing on the invasion, motility, and proliferation of HepG2 cells were assessed using a Transwell chamber cell migration assay system and a growth curve assay, respectively.

Results

The data showed that plasmids expressing siRNA against c-Myc significantly decreased its expression in HepG2 cells by up to 85%. Importantly, pSilencer-c-Myc transfected cells showed a significantly reduced potential in migration, invasion, and proliferation.

Conclusion

C-Myc plays an important role in the development of hepatocellular carcinoma. The data show that down-regulating the c-Myc protein level in HepG2 cells by RNAi could significantly inhibit migration, invasion and proliferation of HepG2 cells. Thus, c-Myc might be a potential therapeutic target for hepatocellular carcinoma.

BACKGROUND

Soluble ST2 (sST2) is a cardiac biomarker whose concentration rises in response to myocardial strain. Increased sST2 concentrations may predict adverse outcomes in patients with heart failure and myocardial infarction. Because sST2 was largely undetectable with first-generation assays in ambulatory individuals, there are few data regarding its distribution and correlates in community-based populations.

METHODS

We measured sST2 using a highly sensitive ELISA in 3450 Framingham Heart Study participants who attended a routine examination. We used multivariable linear regression models to identify covariates associated with sST2 in the general sample. We obtained a reference sample (n = 1136) by excluding individuals with prevalent coronary disease, heart failure, atrial fibrillation, diabetes, hypertension, obesity, valvular disease, left ventricular systolic dysfunction, and pulmonary and renal dysfunction. We used empiric and quantile regression techniques to estimate the 2.5th, 50th, 97.5th, and 99th quantiles.

RESULTS

In the general sample (mean age 59 years, 55% women), systolic blood pressure (P = 0.006), antihypertensive medication use (P = 0.03), and diabetes (P < 0.001) were associated with sST2 concentrations. In the reference sample (mean age 55, 59% women), male sex (P < 0.0001) and older age (P = 0.004) were predictive of higher sST2 concentrations. Quantile and empirical methods were used to define the reference intervals. Using the empirical approach, upper 99% percentile values in different age groups ranged from 46.6 to 64.4 μg/L in men and 36.7 to 53.0 μg/L in women.

CONCLUSIONS

In a well-characterized, community-based cohort, values for sST2 differ between men and women, increase with age, and are associated with diabetes and hypertension.

New template-based self-propelled gold/nickel/polyaniline/platinum (Au/Ni/PANI/Pt) microtubular engines, functionalized with the Concanavalin A (ConA) lectin bioreceptor, are shown to be extremely useful for the rapid, real-time isolation of Escherichia coli (E. coli) bacteria from fuel-enhanced environmental, food and clinical samples. These multifunctional microtube engines combine the selective capture of E. coli with the uptake of polymeric drug-carrier particles to provide an attractive motion-based theranostics strategy. Triggered release of the captured bacteria is demonstrated by movement through a low-pH glycine-based dissociation solution. The smaller size of the new polymer-metal microengines offers convenient, direct and label-free optical visualization of the captured bacteria and discrimination against non-target cells.

Previous research has shown that the geographical distribution patterns of freshwater fishes and amphibians have been influenced by past climatic oscillations in China resulting from Pleistocene glacial activity. However, it remains unknown how these past changes have impacted the present-day distribution of Chinese freshwater crabs. This work describes the diversity and endemism of freshwater crabs belonging to Sinopotamon, a highly speciose genus endemic to China, and evaluates its distribution in terms of topography and past climatic fluctuations. Species diversity within Sinopotamon was found to be concentrated in an area from the northeastern edge of the Yunnan-Guizhou Plateau to the Jiangnan Hills, and three areas of endemism were identified. Multiple regression analysis between current climatic variables and Sinopotamon diversity suggested that regional annual precipitation, minimum temperature in the coldest month, and annual temperature range significantly influenced species diversity and may explain the diversity patterns of Sinopotamon. A comparison of ecological niche models (ENMs) between current conditions and the last glacial maximum (LGM) showed that suitable habitat for Sinopotamon in China severely contracted during the LGM. The coincidence of ENMs and the areas of endemism indicated that southeast of the Daba Mountains, and central and southeastern China, are potential Pleistocene refuges for Sinopotamon. The presence of multiple Pleistocene refuges within the range of this genus could further promote inter- and intraspecific differentiations, and may have led to high Sinopotamon species diversity, a high endemism rate and widespread distribution.

Porcine hemagglutinating encephalomyelitis (PHE) is caused by the coronavirus hemagglutinating encephalomyelitis virus (PHE-CoV), and the recent, rapid spread of PHE-CoV in piglets from many countries emphasizes the urgent need for a PHE-CoV vaccine. Here we use a murine model for evaluation of the induction of humoral and cellular immune responses by inactivated and PHE-CoV DNA vaccines in order to define the immune correlates for protection against PHE-CoV. The inactivated vaccine was composed of purified PHE-CoV and aluminum hydroxide gel (alum), which was chosen as an adjuvant because of its long history of safety for human use. The PHE-CoV DNA vaccine was constructed by subcloning the S1 gene of PHE-CoV into the pVAX1 vector to create the recombinant plasmid pV-S1. Our results showed that the inactivated PHE-CoV vaccine (IPV) elicited a high level of humoral immunity, resulting in good protection efficacy against PHE-CoV challenge. The IPV induced the IgG1 subclass of serum antibodies and expression of the cytokine interleukin-4 (IL-4), suggesting that the IPV generated a predominantly Th2-type immune response. The DNA vaccine was found to mediate primarily a cellular immune response with high levels of IgG2a and the cytokines IL-2 and gamma interferon (IFN-γ). However, mice that were vaccinated twice with the DNA vaccine and boosted with the IPV could mount a sufficient neutralizing antibody response against live PHE-CoV, with little variation in IgG1 and IgG2a levels, and showed high levels of IL-2 and IL-4. This response may activate both B and T cells to mount a specific humoral and cellular immune response that could, in turn, elicit a phagocyte-mediated defense against PHE-CoV infections to achieve viral clearance.

Recombinant calcineurin B-like protein 1 from Ammopiptanthus mongolicus (AmCBL1) was overexpressed, purified and crystallized.

Calcineurin B-like protein 1 (CBL1) is a calcium sensor in plants. It transmits the calcium signal through the downstream protein CBL-interacting protein kinase (CIPK). CBL1 and CIPK play crucial roles in the response to environmental stresses such as low K+, osmotic shock, high salt, cold and drought. Recombinant CBL1 from Ammopiptanthus mongolicus (AmCBL1) was overexpressed, purified and crystallized. However, the crystal did not diffract well. A mutant prepared using the surface-entropy method and crystallized using the hanging-drop method at 298 K with PEG 2000 MME as a precipitant diffracted to 2.90 Å resolution. The crystal belonged to space group P21212, with unit-cell parameters a = 99.87, b = 114.42, c = 63.80 Å, α = β = γ = 90.00° and three molecules per asymmetric unit.

GLP-1 is an insulinotropic hormone that synergistically with glucose gives rise to an increased insulin response. Its secretion is increased following a meal and it is thus of interest to describe the secretion of this hormone following an oral glucose tolerance test (OGTT). The aim of this study was to build a mechanism-based population model that describes the time course of total GLP-1 and provides indices for capability of secretion in each subject. The goal was thus to model the secretion of GLP-1, and not its effect on insulin production. Single 75 g doses of glucose were administered orally to a mixed group of subjects ranging from healthy volunteers to patients with type 2 diabetes (T2D). Glucose, insulin, and total GLP-1 concentrations were measured. Prior population data analysis on measurements of glucose and insulin were performed in order to estimate the glucose absorption rate. The individual estimates of absorption rate constants were used in the model for GLP-1 secretion. Estimation of parameters was performed using the FOCE method with interaction implemented in NONMEM VI. The final transit/indirect-response model obtained for GLP-1 production following an OGTT included two stimulation components (fast, slow) for the zero-order production rate. The fast stimulation was estimated to be faster than the glucose absorption rate, supporting the presence of a proximal–distal loop for fast secretion from L-cells. The fast component (st3 = 8.64·10−5 [mg−1]) was estimated to peak around 25 min after glucose ingestion, whereas the slower component (st4 = 26.2·10−5 [mg−1]) was estimated to peak around 100 min. Elimination of total GLP-1 was characterised by a first-order loss. The individual values of the early phase GLP-1 secretion parameter (st3) were correlated (r = 0.52) with the AUC(0–60 min.) for GLP-1. A mechanistic population model was successfully developed to describe total GLP-1 concentrations over time observed after an OGTT. The model provides indices related to different mechanisms of subject abilities to secrete GLP-1. The model provides a good basis to study influence of different demographic factors on these components, presented mainly by indices of the fast- and slow phases of GLP-1 response.

The variation in mutations in exons 3, 6, 7, 11 and 12 of the phenylalanine hydroxylase (PAH) gene was investigated in 59 children with phenylketonuria (PKU) and 100 normal children. Three single nucleotide polymorphisms were detected by sequence analysis. The mutational frequencies of cDNA 696, cDNA 735 and cDNA 1155 in patients were 96.2%, 76.1% and 7.6%, respectively, whereas in healthy children the corresponding frequencies were 97.0%, 77.3% and 8.3%. In addition, 81 mutations accounted for 61.0% of the mutant alleles. R111X, H64 > TfsX9 and S70 del accounted for 5.1%, 0.8% and 0.8% mutation of alleles in exon 3, whereas EX6-96A > G accounted for 10.2% mutation of alleles in exon 6. R243Q had the highest incidence in exon 7 (12.7%), followed by Ivs7 + 2 T > A (5.1%) and T278I (2.5%). G247V, R252Q, L255S, R261Q and E280K accounted for 0.8% while Y356X and V399V accounted for 5.9% and 5.1%, respectively, in exon 11. R413P and A434D accounted for 5.9% and 2.5%, respectively, in exon 12. Seventy-two variant alleles accounted for the 16 mutations observed here. The mutation characteristics and distributions demonstrated that EX6-96A > G and R243Q were the hot regions for mutations in the PAH gene in Shanxi patients with PKU.

Aims

Fascin-1, ezrin and paxillin, cytoskeleton-associated proteins, have been implicated in several human cancers, but their role in laryngeal squamous cell carcinoma (LSCC) is unknown. We investigated the association of their expression and clinicopathologic factors and their prognostic value in LSCC.

Materials and Methods

Quantitative RT-PCR and western blot analyses were used to examine mRNA and protein levels in 10 fresh LSCC specimens and 10 corresponding adjacent normal margin (ANM) tissues from patients undergoing surgery in 2012. We used immunohistochemistry to retrospectively study 216 paraffin blocks of LSCC samples from patients (193 men) who had undergone surgery between 2000 and 2006 and had not received special treatment before the diagnosis. Univariate analysis of patient survival involved the Kaplan–Meier method. Multivariate analyses involved the Cox proportional hazards model.

Results

The relative mRNA and protein levels of fascin-1, ezrin and paxillin were significantly greater in LSCC than ANM tissue (P<0.05). The high expression of fascin-1, ezrin or paxillin was positively correlated with poor tumor differentiation, cervical lymph node metastasis (N+), and advanced clinical stage (III+IV) (P<0.05) but not sex or metastasis. In addition, a high expression of fascin-1 (P = 0.007) or ezrin (P = 0.047) was associated with advanced tumor stage (T3+T4). The expression of fascin-1 was higher in smokers than non-smokers (P = 0.019). A high expression of fascin-1, ezrin or paxillin was associated with poor prognosis.

Conclusions

Fascin-1, ezrin and paxillin may be prognostic of poor outcome with LSCC after surgery. Our study may lead to establishing new molecular therapeutic targets and/or prognostic biomarkers in LSCC.

Non-specific low back pain (NLBP) is an increasing health problem for athletes. This randomized controlled trial was designed to investigate the effects of Chinese massage combined with herbal ointment for NLBP. 110 athletes with NLBP were randomly assigned to experimental group with Chinese massage combined with herbal ointment or control group with simple massage therapy. The primary outcome was pain by Chinese Short Form McGill Pain Questionnaire (C-SFMPQ). The secondary outcome was local muscle stiffness by Myotonometer. After 4 weeks, the experimental group experienced significant improvements in C-SFMPQ and in local muscle stiffness compared with control group (between-group difference in mean change from baseline, −1.24 points, P = 0.005 in sensory scores; −3.14 points, P < 0.001 in affective scores; −4.39 points, P < 0.001 in total scores; −0.64 points, P = 0.002 in VAS; −1.04 points, P = 0.005 in local muscle stiffness during relaxation state). The difference remained at one month followup, but it was only significant in affective scores (−2.83 points, P < 0.001) at three months followup. No adverse events were observed. These findings suggest that Chinese massage combined with herbal ointment may be a beneficial complementary and alternative therapy for athletes with NLBP.

Background

Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes.

Methods

We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3–5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders.

Findings

Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05–1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores.

Interpretation

The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention.

It is known that the conservation of protein-coding genes is associated with their sequences both various species, such as animals and plants. However, the association between microRNA (miRNA) conservation and their sequences in various species remains unexplored. Here we report the association of miRNA conservation with its sequence features, such as base content and cleavage sites, suggesting that miRNA sequences contain the fingerprints for miRNA conservation. More interestingly, different species show different and even opposite patterns between miRNA conservation and sequence features. For example, mammalian miRNAs show a positive/negative correlation between conservation and AU/GC content, whereas plant miRNAs show a negative/positive correlation between conservation and AU/GC content. Further analysis puts forward the hypothesis that the introns of protein-coding genes may be a main driving force for the origin and evolution of mammalian miRNAs. At the 5′ end, conserved miRNAs have a preference for base U, while less-conserved miRNAs have a preference for a non-U base in mammals. This difference does not exist in insects and plants, in which both conserved miRNAs and less-conserved miRNAs have a preference for base U at the 5′ end. We further revealed that the non-U preference at the 5′ end of less-conserved mammalian miRNAs is associated with miRNA function diversity, which may have evolved from the pressure of a highly sophisticated environmental stimulus the mammals encountered during evolution. These results indicated that miRNA sequences contain the fingerprints for conservation, and these fingerprints vary according to species. More importantly, the results suggest that although species share common mechanisms by which miRNAs originate and evolve, mammals may develop a novel mechanism for miRNA origin and evolution. In addition, the fingerprint found in this study can be predictor of miRNA conservation, and the findings are helpful in achieving a clearer understanding of miRNA function and evolution.

Background

Streptococcus pneumoniae is the main pathogen that causes respiratory infections in children younger than five years. The increasing incidence of macrolide- and tetracycline-resistant pneumococci among children has been a serious problem in China for many years. The molecular characteristics of erythromycin-resistant pneumococcal isolates that were collected from pediatric patients younger than five years in Beijing in 2010 were analyzed in this study.

Results

A total of 140 pneumococcal isolates were collected. The resistance rates of all isolates to erythromycin and tetracycline were 96.4% and 79.3%, respectively. Of the 135 erythromycin-resistant pneumococci, 91.1% were non-susceptible to tetracycline. In addition, 30.4% of the erythromycin-resistant isolates expressed both the ermB and mef genes, whereas 69.6% expressed the ermB gene but not the mef gene. Up to 98.5% of the resistant isolates exhibited the cMLSB phenotype, and Tn6002 was the most common transposon present in approximately 56.3% of the resistant isolates, followed by Tn2010, with a proportion of 28.9%. The dominant sequence types (STs) in all erythromycin-resistant S. pneumoniae were ST271 (11.9%), ST81 (8.9%), ST876 (8.9%), and ST320 (6.7%), whereas the prevailing serotypes were 19F (19.3%), 23F (9.6%), 14 (9.6%), 15 (8.9%), and 6A (7.4%). The 7-valent pneumococcal conjugate vaccine (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) coverage of the erythromycin-resistant pneumococci among the children younger than five years were 45.2% and 62.2%, respectively. ST320 and serotype 19A pneumococci were common in children aged 0 to 2 years. CC271 was the most frequent clonal complex (CC), which accounts for 24.4% of all erythromycin-resistant isolates.

Conclusions

The non-invasive S. pneumoniae in children younger than five years in Beijing presented high and significant resistance rates to erythromycin and tetracycline. The expressions of ermB and tetM genes were the main factors that influence pneumococcal resistance to erythromycin and tetracycline, respectively. Majority of the erythromycin-resistant non-invasive isolates exhibited the cMLSB phenotype and carried the ermB, tetM, xis, and int genes, suggesting the spread of the transposons of the Tn916 family. PCV13 provided higher serotype coverage in the childhood pneumococcal diseases caused by the erythromycin-resistant isolates better than PCV7. Further long-term surveys are required to monitor the molecular characteristics of the erythromycin-resistant S. pneumoniae in children.

The matrix metalloproteinase (MMP) family of proteins degrades extracellular matrix (ECM) components as well as processes cytokines and growth factors. MMPs are involved in regulating ECM homeostasis in both normal physiology and disease pathophysiology. Here, we report the critical roles of mmp23b in normal zebrafish liver development. Mmp23b was initially identified as a gene linked to the genomic locus of an enhancer trap transgenic zebrafish line in which GFP expression was restricted to the developing liver. Follow-up analysis of mmp23b mRNA expression confirmed its liver-specific expression pattern. Morpholino (MO) knockdown of mmp23b resulted in defective hepatocyte proliferation, causing a reduction in liver size while maintaining relatively normal pancreas and gut development. Genetically, we showed that mmp23b functions through the tumor necrosis factor (TNF) signaling pathway. Antisense knockdown of tnfa or tnfb in zebrafish caused similar reductions of liver size whereas overexpression of tnfa or tnfb rescued liver defects in mmp23b morphants but not vice versa. Biochemically, MMP23B, the human ortholog of Mmp23b, directly interacts with TNF and mediates its release from the cell membrane in a cell culture system. Since mmp23b/MMP23B is highly conserved, our findings in zebrafish warrant further investigation of its role in regulating liver development in mammals.

Background

Breathlessness is a common and distressing symptom affecting many patients with advanced disease both from malignant and non-malignant origin. A combination of pharmacological and non-pharmacological measures is necessary to treat this symptom successfully. Breathlessness services in various compositions aim to provide comprehensive care for patients and their carers by a multiprofessional team but their effectiveness and cost-effectiveness have not yet been proven. The Breathlessness Support Service (BSS) is a newly created multiprofessional and interdisciplinary outpatient service at a large university hospital in South East London. The aim of this study is to develop and evaluate the effectiveness and cost effectiveness of this multidisciplinary out–patient BSS for the palliation of breathlessness, in advanced malignant and non-malignant disease.

Methods

The BSS was modelled based on the results of qualitative and quantitative studies, and systematic literature reviews. A randomised controlled fast track trial (RCT) comprising two groups: 1) intervention (immediate access to BSS in addition to standard care); 2) control group (standard best practice and access to BSS after a waiting time of six weeks). Patients are included if suffering from breathlessness on exertion or at rest due to advanced disease such as cancer, chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), interstitial lung disease (ILD) or motor neurone disease (MND) that is refractory to maximal optimised medical management. Both quantitative and qualitative outcomes are assessed in face to-face interviews at baseline, after 6 and 12 weeks. The primary outcome is patients' improvement of mastery of breathlessness after six weeks assessed on the Chronic Respiratory Disease Questionnaire (CRQ). Secondary outcomes for patients include breathlessness severity, symptom burden, palliative care needs, service use, and respiratory measures (spirometry). For analyses, the primary outcome, mastery of breathlessness after six weeks, will be analysed using ANCOVA. Selection of covariates will depend on baseline differences between the groups. Analyses of secondary outcomes will include patients’ symptom burden other than breathlessness, physiological measures (lung function, six minute walk distance), and caregiver burden.

Discussion

Breathlessness services aim to meet the needs of patients suffering from this complex and burdensome symptom and their carers. The newly created BSS is different to other current services as it is run in close collaboration of palliative medicine and respiratory medicine to optimise medical care of patients. It also involves professionals from various medical, nursing, physiotherapy, occupational therapy and social work background.

Trial registration

ClinicalTrials.gov (NCT01165034)

NMDA receptors (NMDARs) are glutamate-gated ion channels present at most excitatory mammalian synapses. The four GluN2 subunits (GluN2A–D) contribute to four diheteromeric NMDAR subtypes that play divergent physiological and pathological roles. Channel properties fundamental to NMDAR function vary among subtypes. We investigated the amino acid residues responsible for variations in channel properties by creating and examining NMDARs containing mutant GluN2 subunits. Unexpectedly, we found that the NMDAR subtype specificity of three crucial channel properties, Mg2+ block, selective permeability to Ca2+, and single-channel conductance, all are controlled primarily by the residue at a single GluN2 site in the M3 transmembrane region. Mutant cycle analysis guided by molecular modeling revealed that a GluN2-GluN1 subunit interaction mediates the site’s effects. We conclude that a single GluN2 subunit residue couples with the pore-forming loop of the GluN1 subunit to create naturally-occurring variations in NMDAR properties that are critical to synaptic plasticity and learning.

Background

The incidence of PHE among pigs in many countries is on the rise, and it has caused great economic losses to the pig industry. Therefore, the development of a sensitive, specific, and easily-performed assay is crucial for the rapid detection and surveillance of PHE-CoV infection and transmission.

Results

An immunochromatographic strip was developed for the detection of PHE-CoV. The colloidal gold-labeled MAb 4D4 was used as the detection reagent, and the MAb 1E2 and goat anti-mouse IgG coated the strip's test and control lines, respectively. The immunochromatographic strip was capable of specifically detecting PHE-CoV with a HA unit of 2 within 10 min. Storage of the strips at room temperature for 6 months or at 4°C for 12 months did not change their sensitivity or specificity. Using RT-PCR as a reference test, the relative specificity and sensitivity of the immunochromatographic strip were determined to be 100% and 97.78%, respectively. There was an excellent agreement between the results obtained by RT-PCR and the immunochromatographic strips (kappa = 0.976). Additionally, there was a strong agreement between the sandwich enzyme-linked immunosorbent assay (ELISA) and immunochromatographic strips (Kappa = 0.976). When the immunochromatographic strips were used for diagnosing PHE-CoV infection in the Jilin Province, the PHE-CoV-positive rate ranged from 61.54% in the Jilin district to 17.95% in the Songyuan district.

Conclusions

Based on its high specificity, sensitivity, and stability, the immunochromatographic strip would be suitable for on-site detection of PHE-CoV for surveillance and epidemiological purposes.

If the components of a battery, including electrodes, separator, electrolyte and the current collectors can be designed as paints and applied sequentially to build a complete battery, on any arbitrary surface, it would have significant impact on the design, implementation and integration of energy storage devices. Here, we establish a paradigm change in battery assembly by fabricating rechargeable Li-ion batteries solely by multi-step spray painting of its components on a variety of materials such as metals, glass, glazed ceramics and flexible polymer substrates. We also demonstrate the possibility of interconnected modular spray painted battery units to be coupled to energy conversion devices such as solar cells, with possibilities of building standalone energy capture-storage hybrid devices in different configurations.

In the title compound, C14H10BrN5S, the dihedral angle between the triazole ring and the pyridine and bromo­benzene rings are 26.42 (13) and 6.28 (13)°, respectively. The molecule exists as a thione in the solid state. In the crystal, mol­ecules are linked by N—H⋯N hydrogen bonds, generating [010] C(8) chains.

We used longitudinal magnetic resonance imaging (MRI) data to determine whether there are any gender differences in grey matter atrophy patterns over time in 197 individuals with probable Alzheimer’s disease (AD) and 266 with amnestic mild cognitive impairment (aMCI), compared with 224 healthy controls participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). While previous research has differentiated probable AD and aMCI groups from controls in brain atrophy, it is unclear whether and how sex plays a role in patterns of change over time. Using regional volumetric maps, we fit longitudinal models to the grey matter data collected at repeated occasions, seeking differences in patterns of volume change over time by sex and diagnostic group in a voxel-wise analysis. Additionally, using a region-of-interest approach, we fit longitudinal models to the global volumetric data of predetermined brain regions to determine whether this more conventional approach is sufficient for determining sex and group differences in atrophy. Our longitudinal analyses revealed that, of the various grey matter regions investigated, males and females in the AD group and the aMCI group showed different patterns of decline over time compared to controls in the bilateral precuneus, bilateral caudate nucleus, right entorhinal gyrus, bilateral thalamus, bilateral middle temporal gyrus, left insula, and right amygdala. As one of the first investigation to model more than two time points of structural MRI data over time, our findings add insight into how AD and aMCI males and females differ from controls and from each other over time.

In the title hydrate, C4H7N3O2·H2O, all the non-H atoms lie on a crystallographic mirror plane. The H atoms of both methyl groups are disordered over two sets of sites. In the crystal, N—H⋯Ow and Ow—H⋯Ok (w = water and k = ketone) hydrogen bonds link the components into (010) sheets.

AIM: To investigate the diagnostic value of glypican-3 (GPC3) and its relationship with hepatocellular carcinoma (HCC) recurrence after liver transplantation.

METHODS: HCC tissue samples (n = 31) obtained from patients who had undergone liver transplantation were analyzed. GPC3 mRNA and protein expression were analyzed by TaqMan real-time reverse transcription-polymerase chain reaction and immunohistochemistry. Correlation between the GPC3 expression and clinicopathological features was analyzed. The potential prognostic value of GPC3 was investigated by comparing recurrence-free survival between HCC patients with and without GPC3 expression.

RESULTS: Using a cutoff value of 3.5 × 10-2, 20 of 31 cancerous tissues had expression values of > 3.5 × 10-2, whereas 3 of 31 adjacent non-neoplastic parenchyma and 0 of 20 control liver tissues had expression values of > 3.5 × 10-2 (P < 0.001). GPC3 protein was immunoexpressed in 68% of cancerous tissues, but not in adjacent non-neoplastic parenchyma and control liver tissues. Vascular invasion was significantly related to GPC3 expression (P < 0.05). Recurrence-free survival was significantly longer for patients without GPC3 mRNA overexpression (> 3.5 × 10-2) and those without vascular invasion (P < 0.05 for both).

CONCLUSION: GPC3 expression may serve as a valuable diagnostic marker for HCC. GPC3 mRNA overexpression may be an adverse indicator for HCC patients after liver transplantation.

Background

Traditional Chinese medicine uses various herbs for the treatment of various diseases for thousands of years and it is now time to assess the characteristics and effectiveness of these medicinal plants based on modern genetic and molecular tools. The herb Flos Lonicerae Japonicae (FLJ or Lonicera japonica Thunb.) is used as an anti-inflammatory agent but the chemical quality of FLJ and its medicinal efficacy has not been consistent. Here, we analyzed the transcriptomes and metabolic pathways to evaluate the active medicinal compounds in FLJ and hope that this approach can be used for a variety of medicinal herbs in the future.

Results

We assess transcriptomic differences between FLJ and L. japonica Thunb. var. chinensis (Watts) (rFLJ), which may explain the variable medicinal effects. We acquired transcriptomic data (over 100 million reads) from the two herbs, using RNA-seq method and the Illumina GAII platform. The transcriptomic profiles contain over 6,000 expressed sequence tags (ESTs) for each of the three flower development stages from FLJ, as well as comparable amount of ESTs from the rFLJ flower bud. To elucidate enzymatic divergence on biosynthetic pathways between the two varieties, we correlated genes and their expression profiles to known metabolic activities involving the relevant active compounds, including phenolic acids, flavonoids, terpenoids, and fatty acids. We also analyzed the diversification of genes that process the active compounds to distinguish orthologs and paralogs together with the pathways concerning biosynthesis of phenolic acid and its connections with other related pathways.

Conclusions

Our study provides both an initial description of gene expression profiles in flowers of FLJ and its counterfeit rFLJ and the enzyme pool that can be used to evaluate FLJ quality. Detailed molecular-level analyses allow us to decipher the relationship between metabolic pathways involved in processing active medicinal compounds and gene expressions of their processing enzymes. Our evolutionary analysis revealed specific functional divergence of orthologs and paralogs, which lead to variation in gene functions that govern the profile of active compounds.

The complete mol­ecule of the title compound, C8H12N4, is generated by a crystallographic inversion centre. The piperazine ring adopts a chair conformation with the N-bonded substituents in equatorial positions. In the crystal, mol­ecules are linked by C—H⋯Nc (c = cyanide) hydrogen bonds.

Background

Hyperlipidemia plays a crucial role in the development and progression of coronary artery disease (CAD). Recent studies have identified that microRNAs (miRNAs) are important regulators of lipid metabolism, but little is known about the circulating levels of lipometabolism-related miRNAs and their relationship with the presence of CAD in patients with hyperlipidemia.

Methods

In the present study, we enrolled a total of 255 hyperlipidemia patients with or without CAD and 100 controls with normal blood lipids. The plasma levels of four known lipometabolism-related miRNAs, miR-122, miR-370, miR-33a, and miR-33b were quantified by real-time quantitative PCR. Blood levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol were determined. Furthermore, the severity of CAD was assessed with the Gensini score system based on the degree of luminal narrowing and its geographic importance.

Results

Our results revealed for the first time that plasma levels of miR-122 and miR-370 were significantly increased in hyperlipidemia patients compared with controls, and the levels of miR-122 and miR-370 were positively correlated with TC, TG, and LDL-C levels in both hyperlipidemia patients and controls. Multiple logistic regression analysis demonstrated that the increased levels of miR-122 and miR-370 were associated with CAD presence, even after adjustment for other cardiovascular risk factors. Furthermore, miR-122 and miR-370 levels were positively correlated with the severity of CAD quantified by the Gensini score. However, both miR-33a and miR-33b were undetectable in plasma.

Conclusions

Our results suggest that increased plasma levels of miR-122 and miR-370 might be associated with the presence as well as the severity of CAD in hyperlipidemia patients.