Label-free detection of fibrillar collagen deposition associated with vascular elements in glioblastoma multiforme by using multiphoton microscopy.

Glioblastoma multiforme (GBM-WHO grade IV) is the most common and the most aggressive form of brain tumors in adults with the median survival of 10-12 months. The diagnostic detection of extracellular matrix (ECM) component in the tumour microenvironment is of prognostic value. In this paper, the fibrillar collagen deposition associated with vascular elements in GBM were investigated in the fresh specimens and unstained histological slices by using multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Our study revealed the existence of fibrillar collagen deposition in the adventitia of remodelled large blood vessels and in glomeruloid vascular structures in GBM. The degree of fibrillar collagen deposition can be quantitatively evaluated by measuring the adventitial thickness of blood vessels or calculating the ratio of SHG pixel to the whole pixel of glomeruloid vascular structure in MPM images. These results indicated that MPM can not only be employed to perform a retrospective study in unstained histological slices but also has the potential to apply for in vivo brain imaging to understand correlations between malignancy of gliomas and fibrillar collagen deposition.

Population structure analysis and association mapping of blast resistance in indica rice (Oryza sativa L.) landraces.

Rice blast caused by Magnaporthe oryzae is one of the most devastating rice diseases worldwide. To understand the genetic diversity of indica landrace accessions and identify simple sequence repeat (SSR) markers that are associated with blast resistance, a population of 276 indica landraces from across the world was constructed. This population was then used to evaluate the blast-resistance phenotype through artificial inoculation under controlled conditions in 2012 and 2013. The genetic diversity and association of the population with resistance were analyzed by examining the phenotype for 160 SSR markers distributed on 12 rice chromosomes. The 276 accessions were classified into seven groups using model- and distance-based cluster analyses. Associations between SSR markers and blast resistance showed that 26 SSR markers were significantly associated with blast resistance in 2012 and 2013 (P < 0.01) and that the phenotypic variation ranged from 2.68 to 13.11%. Nineteen of the markers associated with blast resistance were located in regions where genes or quantitative trait loci (QTLs) have been previously reported, and seven were newly identified in this study. These results indicate that marker-trait association has potential advantages over classical linkage analysis and QTL mapping, and that these markers could be used for marker-assisted selection in rice blast-resistance-breeding programs.

Effects of AFP gene silencing on Survivin mRNA expression inhibition in HepG2 cells.

We investigated the effects of alpha-fetoprotein (AFP) gene silencing on Survivin expression in HepG2 cells. Small interfering RNA technology was used to downregulate AFP expression in HepG2 cells. An enzyme-linked immunosorbent assay was used to measure AFP concentration in the supernatant before and after transfection. An MTT assay was used to detect cell proliferation activity before and after transfection. We performed flow cytometric analysis to detect the cell apoptosis rate, and reverse transcription-polymerase chain reaction to detect Survivin mRNA levels before and after transfection. Forty-eight hours after transfection, AFP concentration in the supernatant of the experimental group significantly decreased, hepatocellular carcinoma cell growth was inhibited by 43.1%, and the apoptosis rate increased by 24.3%. Survivin mRNA expression was reduced by 78.0% in HepG2 cells. These indicators in the control group and in the blank group did not change significantly. Silencing of AFP expression in HepG2 cells can effectively inhibit the growth of hepatoma cells and promote apoptosis, which may be useful for reducing intracellular Survivin mRNA levels.

Room-temperature quantum emission from interface excitons in mixed-dimensional heterostructures.

The development of van der Waals heterostructures has introduced unconventional phenomena that emerge at atomically precise interfaces. For example, interlayer excitons in two-dimensional transition metal dichalcogenides show intriguing optical properties at low temperatures. Here we report on room-temperature observation of interface excitons in mixed-dimensional heterostructures consisting of two-dimensional tungsten diselenide and one-dimensional carbon nanotubes. Bright emission peaks originating from the interface are identified, spanning a broad energy range within the telecommunication wavelengths. The effect of band alignment is investigated by systematically varying the nanotube bandgap, and we assign the new peaks to interface excitons as they only appear in type-II heterostructures. Room-temperature localization of low-energy interface excitons is indicated by extended lifetimes as well as small excitation saturation powers, and photon correlation measurements confirm antibunching. With mixed-dimensional van der Waals heterostructures where band alignment can be engineered, new opportunities for quantum photonics are envisioned.

Interaction of a contact resonance of microspheres with surface acoustic waves.

We study the interaction of surface acoustic waves (SAWs) with a contact-based vibrational resonance of 1 µm silica microspheres forming a two-dimensional granular crystal adhered to a substrate. The laser-induced transient grating technique is used to excite SAWs and measure their dispersion. The measured dispersion curves exhibit "avoided crossing" behavior due to the hybridization of the SAWs with the microsphere resonance. We compare the measured dispersion curves with those predicted by our analytical model and find excellent agreement. The approach presented can be used to study the contact mechanics and adhesion of micro- and nanoparticles as well as the dynamics of microscale granular crystals.

Silicon nanowires with controlled sidewall profile and roughness fabricated by thin-film dewetting and metal-assisted chemical etching.

This paper presents a non-lithographic approach to generate wafer-scale single crystal silicon nanowires (SiNWs) with controlled sidewall profile and surface morphology. The approach begins with silver (Ag) thin-film thermal dewetting, gold (Au) deposition and lift-off to generate a large-scale Au mesh on Si substrates. This is followed by metal-assisted chemical etching (MacEtch), where the Au mesh serves as a catalyst to produce arrays of smooth Si nanowires with tunable taper up to 13°. The mean diameter of the thus fabricated SiNWs can be controlled to range from 62 to 300 nm with standard deviations as small as 13.6 nm, and the areal coverage of the wire arrays can be up to 46%. Control of the mean wire diameter is achieved by controlling the pore diameter of the metallic mesh which is, in turn, controlled by adjusting the initial thin-film thickness and deposition rate. To control the wire surface morphology, a post-fabrication roughening step is added to the approach. This step uses Au nanoparticles and slow-rate MacEtch to produce rms surface roughness up to 3.6 nm.

Failure to protect against myocardial ischemia-reperfusion injury with sevoflurane postconditioning in old rats in vivo.

BACKGROUND: Sevoflurane post-conditioning (SpostC) protects young hearts against ischemia-reperfusion injury. It is unknown whether the infarct-limiting effect is also maintained in aged cohorts and whether there are age-associated differences in the underlying mechanisms. METHODS: Young or old rats were randomly subjected to 30-min myocardial ischemia, followed by 120-min reperfusion in vivo, with or without SpostC in the presence or absence of phosphatidylinositol 3-kinase (PI3K) or mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor. Western blotting was used to determine the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2). Myocardial nicotinamide adenine dinucleotide (NAD(+) ) level was measured to indicate mitochondrial permeability transition pore (mPTP) opening. RESULTS: SpostC significantly decreased infarct size in young (35 ± 4% vs. 56 ± 3%, P < 0.05) but not old rats (45 ± 3% vs. 47 ± 4%, P > 0.05) compared with each control group. SpostC substantially augmented phosphorylation of Akt (0.74 ± 0.03 arbitrary units vs. 0.27 ± 0.03 arbitrary units, P < 0.05) or ERK1/2 (0.85 ± 0.04 arbitrary units vs. 0.29 ± 0.04 arbitrary units, P < 0.05) compared with control group, which was abolished by PI3K or MEK1/2 inhibitor in young rats, respectively, but failed to activate Akt and ERK1/2 in old rats. NAD(+) level (nmol/g tissue) was higher in SpostC group in young (118.57 ± 9.27 vs. 46.78 ± 4.54, P < 0.05) but not old rats (58.50 ± 7.16 vs. 61.15 ± 5.50, P > 0.05) compared with each control group. PI3K or MEK1/2 inhibitor abrogated the infarct-sparing effect and inhibition of loss of NAD(+) induced by SpostC in young rats, respectively. CONCLUSION: SpostC-mediated cardioprotection in young rats is not effective in senescent rats, which may at least be the consequence of failure to activate Akt and ERK1/2, and resultant failure to inhibit mPTP opening.

Resonant exciton transfer in mixed-dimensional heterostructures for overcoming dimensional restrictions in optical processes.

Nanomaterials exhibit unique optical phenomena, in particular excitonic quantum processes occurring at room temperature. The low dimensionality, however, imposes strict requirements for conventional optical excitation, and an approach for bypassing such restrictions is desirable. Here we report on exciton transfer in carbon-nanotube/tungsten-diselenide heterostructures, where band alignment can be systematically varied. The mixed-dimensional heterostructures display a pronounced exciton reservoir effect where the longer-lifetime excitons within the two-dimensional semiconductor are funneled into carbon nanotubes through diffusion. This new excitation pathway presents several advantages, including larger absorption areas, broadband spectral response, and polarization-independent efficiency. When band alignment is resonant, we observe substantially more efficient excitation via tungsten diselenide compared to direct excitation of the nanotube. We further demonstrate simultaneous bright emission from an array of carbon nanotubes with varied chiralities and orientations. Our findings show the potential of mixed-dimensional heterostructures and band alignment engineering for energy harvesting and quantum applications through exciton manipulation.

Gamma-glutamyltransferase levels and risk of metabolic syndrome: a meta-analysis of prospective cohort studies.

AIMS: Several epidemiological studies suggested that gamma-glutamyltransferase (GGT) levels may be associated with risk of Metabolic Syndrome (MetS). However, the exact association between them is still not fully clear. We therefore conducted a meta-analysis of prospective cohort studies to comprehensively evaluate the exact association between GGT and risk of MetS. METHODS: The Pubmed, Embase, Science Citation Index (ISI Web of Science) databases were searched to collect all prospective cohort studies on the association between GGT and MetS. Then, the association between GGT and MetS was analysed in qualitative and quantitative manners. RESULTS: Nine prospective cohort studies involving 47,499 participants and 5009 cases of MetS were included. When comparing the risk of MetS between the highest versus the lowest category of GGT levels, the pooled RR of MetS was 1.63 (95% CI: 1.43-1.82; p < 0.000). The second dose-response analysis of GGT levels per 5 U/l increment with risk of MetS showed that the summary RR of MetS was 1.09 (95% CI: 1.06-1.13; p < 0.000). Subgroup analysis suggested that number of adjusted confounding factors may be a potential source of heterogeneity. Sensitivity analyses showed that no single study significantly influenced the pooled RRs. CONCLUSIONS: Our results show that GGT levels are positively associated with risk of MetS independently of alcohol intake. GGT may be a promising marker for predicting MetS. Further studies are needed to confirm our findings and elucidate the underlying mechanisms in future.

Direct metal nano-imprinting using an embossed solid electrolyte stamp.

In this paper, we report direct patterning of metal nanostructures using an embossed solid electrochemical stamp. Microforming of solid superionic stamps using Si templates--analogous to polymer patterning in nano-imprint lithography--is explored. Silver sulfide (Ag2S)--a superionic conductor with excellent microforming properties--is investigated as a candidate material. Important parameters of the superionic stamp, including mechanical behavior, material flow during forming and feature recovery after embossing, are studied. Excellent feature transferability during embossing as well as etching is observed. To illustrate the capability of this approach silver nano-antennas with gaps < 10 nm were successfully fabricated. The possibility for large area patterning with stamp diameters > 6 mm is also demonstrated. Embossing-based metal patterning allows fabrication beyond two-dimensional nanofabrication and several patterning schemes are reported.

Solid-state superionic stamping with silver iodide-silver metaphosphate glass.

This paper demonstrates and analyzes the new use of the glassy solid electrolyte AgI-AgPO(3) for direct nanopatterning of thin silver films with feature resolutions of 30 nm. AgI-AgPO(3) has a high room temperature ionic conductivity with Ag( + ) as the mobile ion, leading to silver etch/patterning rates of up to 20 nm s( - 1) at an applied bias of 300 mV. The glass can be melt-processed at temperatures below 200 °C, providing a facile and economical pathway for creating large area stamps, including the 25 mm(2) stamps shown in this study. Further, the glass is sufficiently transparent to permit integration with existing tools such as aligners and imprint tools, enabling high overlay registration accuracy and facilitating insertion into multi-step fabrication recipes.

MiR-199a-5p suppresses proliferation and invasion of human laryngeal cancer cells.

OBJECTIVE: To explore the roles of micro ribonucleic acid (miR)-199a-5p in the proliferation, apoptosis, invasion and metastasis of laryngeal cancer cells, and its molecular mechanisms. PATIENTS AND METHODS: The expression of miR-199a-5p in 25 cases of laryngeal cancer tissues and paracancerous tissues was detected via quantitative real-time polymerase chain reaction (qRT-PCR). Its expression in TU212, TU686 and human epithelial type 2 (HEp-2) laryngeal cancer cell lines and normal nasopharyngeal epithelial cell line NP69 was also detected via qRT-PCR. HEp-2 cells were transiently transfected with miR-199a-5p mimic or miR-199a-5p inhibitor, and the expression of miR-199a-5p was verified using RT-PCR after transfection. The regulatory effects of miR-199a-5p on the proliferation, apoptosis, invasion and migration abilities of HEp-2 cells were observed through methyl thiazolyl tetrazolium (MTT) assay, flow cytometry, wound healing assay and transwell assay, respectively. Then, the mechanisms of miR-199a-5p in regulating Caspase-3 activity and epithelial-mesenchymal transition (EMT)-related proteins were further explored. RESULTS: The qRT-PCR results revealed that miR-199a-5p was significantly lowly expressed in the laryngeal cancer tissues and tumor cell lines, and overexpression of miR-199a-5p substantially inhibited the proliferation of HEp-2 cells. According to the results of flow cytometry, overexpression of miR-199a-5p promoted the apoptosis of HEp-2 cells, whereas down-regulating miR-199a-5p suppressed their apoptosis. It was found that the activity of Caspase-3 was notably enhanced after overexpression of miR-199a-5p, which was evidently weakened after down-regulating miR-199a-5p. Wound healing assay and transwell assay results manifested that overexpressing miR-199a-5p weakened the invasion and migration abilities of HEp-2 cells, which were facilitated by down-regulating miR-199a-5p. Based on Western blotting results, miR-199a-5p regulated the expressions of E-cadherin, N-cadherin and vimentin. Overexpression of miR-199a-5p could inhibit EMT process, whereas suppressing miR-199a-5p could accelerate the process. CONCLUSIONS: The expression of miR-199a-5p in laryngeal cancer tissues is substantially lower than that in the paracancerous tissues. MiR-199a-5p suppresses proliferation, invasion and migration in laryngeal cancer cell proliferation, while triggers cell apoptosis.

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

A high-resolution radiation hybrid map of the human genome draft sequence.

We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.

The association between intensive glycemic control and vascular complications in type 2 diabetes mellitus: a meta-analysis.

BACKGROUND AND AIM: In patients with type 2 diabetes mellitus, the relationship between lowering glycated hemoglobin (HbA(1c)) and macrovascular complications is not clear and therefore lowering the level of HbA(1c) is controversial. METHODS AND RESULTS: We searched for all randomized controlled trials comparing the effects of intensive and standard glycemic control on vascular events in patients with type 2 diabetes mellitus. The primary endpoint was combined macrovascular complications, including cardiac events, stroke and peripheral vascular disease. Fixed and random effect models were used to analyze the results. Eight studies were included according to selection criteria. The results showed no benefits of intensive glycemic control on macrovascular and microvascular complications (P>0.1), but a higher rate of severe hypoglycemia (P<0.00001) in the intensive control group when the target HbA(1c) level was <7.0%. When the target HbA(1c) level was lowered to 7.0-7.9%, intensive glycemic control showed benefits on the reduction of microvascular events (P<0.05) without increasing the risk of severe hypoglycemia (P=0.74), but no influence on macrovascular complications (P>0.1). CONCLUSION: The results of this analysis suggest that a target HbA(1c) level of 7.0-7.9% may be a better glycemic control target than that of <7.0% in patients with established type 2 diabetes mellitus.

Mid-infrared spectroscopy tracing of channel erosion in highly erosive catchments on the Chinese Loess Plateau.

Whether channel erosion or topsoil erosion constitutes the dominant erosion process throughout in the hilly region of the Chinese Loess Plateau (CLP), which suffers perhaps the most severe soil erosion in the world, had been controversial for a long time. The present article attempts to use the mid-infrared (MIR) spectroscopy fingerprinting method to trace sediment sources within nine small catchments in the hilly region of the CLP. Two major categories of sediment sources are identified: channel sediment and topsoil. Sediments trapped by check dams are used as the final sediment transferred by soil erosion. Discriminant analysis shows that MIR spectroscopy can differentiate between the two kinds of source sediments very well. The contributions of channel sediment and topsoil to the total final sediment are quantified using partial least squares regression (PLSR) analyses of MIR spectra to compare the trapped sediment samples with experimental models. The results of the root mean square error of calibration, root mean square error of validation and coefficient of determination for 18 models all show that the MIR-PLSR models boast very high prediction abilities in the nine catchments. A comparison between the geochemical fingerprinting method and the MIR spectroscopy method in one catchment reveals that although the two methods agree well on the channel sediment contributions, the two methods produce a significant difference (R2 = 0.4). Overall, the MIR-PLSR results show that channel sediments contribute 19% to 66% of the total sediment with an average of 33 ±â€¯16% in the nine small catchments. Our results indicate that although channel bank sediment is important, topsoil erosion is the predominant process in small dam-controlled catchments on the CLP. Furthermore, the MIR spectroscopy fingerprinting method can provide a useful, non-destructive, rapid and inexpensive tool for tracing sediment sources from different kinds of loess.

Bioinspired Ultra-Low Adhesive Energy Interface for Continuous 3D Printing: Reducing Curing Induced Adhesion.

Additive manufacturing based on liquid resin curing is one of the most promising methods to construct delicate structures. However, precision and speed are limited by the vertical adhesion of in situ cured resin at the curing interface. To overcome the unavoidable adhesion and to develop a general curing interface, we propose a slippery surface taking inspiration of the peristome surface of the pitcher plant. Such surface shows ultra-low adhesive energy at the curing interface due to the inhibition of the direct contact between the cured resin and the solid surface, which also increases the refilling speed of liquid resin. This ultra-low adhesive energy interface is effective for continuous 3D printing and provides insights into the physical mechanisms in reducing vertical solid-solid interfacial adhesion.