By fluorescence enhancement of a proximity-dependent DNA-scaffolded silver nanocluster probe pair and exonuclease III-mediated signal amplification, we present a new fluorescence turn-on mode and its application for specific DNA detection.
Accumulating evidence has suggested that microRNAs (miRNAs) may play potential role as ideal diagnostic indicators of esophageal squamous cell carcinoma (ESCC). However, previous studies have met discrepant results. Thus, we conducted this meta-analysis to assess the potential diagnostic value of miRNAs for ESCC. A systematic literature search was conducted in PubMed and other databases. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to evaluate the overall test performance. The Q statistic and the I (2) test were used to assess between-study heterogeneity. The potential sources of heterogeneity were further analyzed by subgroup analyses and meta-regression. Seventeen studies from eight articles, including 995 ESCC patients and 733 healthy controls, were included in this meta-analysis. The pooled SEN and SPE were 0.81 (95 % confidence interval (CI) 0.76-0.85) and 0.83 (95 % CI 0.76-0.88), respectively. The pooled PLR was 4.6 (95 % CI 3.3-6.5), NLR was 0.23 (95 % CI 0.19-0.29), and DOR was 20 (95 % CI 13-31). The pooled AUC was 0.91 (95 % CI 0.88-0.93). Subgroup analyses indicated that blood-based miRNA assay displays better diagnostic accuracy than saliva-based miRNA assay. In summary, miRNA analysis may serve as novel noninvasive biomarkers for ESCC with excellent diagnostic characteristic. In addition, subgroup analysis suggested that blood-based assay yields better diagnostic characteristics than saliva-based assay. However, many issues should be managed before these findings can be translated into a clinically useful detection method for ESCC.
A terahertz parametric oscillator based on KTiOAsO(4) crystal is demonstrated for the first time. With the near-forward scattering configuration X(ZZ)X + ??, the polarizations of the pump, the Stokes and the generated THz waves are parallel to the z-axis of the crystal KTA. When the incident angle ?ext of the pump wave is changed from 1.875° to 6.500°, the THz wave is intermittently tuned from 3.59 to 3.96 THz, from 4.21 to 4.50 THz, from 4.90 to 5.16 THz, from 5.62 to 5.66 THz and from 5.92 to 6.43 THz. The obtained maximum THz wave energy is 627 nJ at 4.30 THz with a pump energy of 100 mJ. It is believed that the terahertz wave generation is caused by the stimulated scattering of the polaritons associated with the most intensive transverse A(1) mode of 233.8 cm(-1). Four much weaker transverse A(1) modes of 132.9 cm(-1), 156.3 cm(-1),175.1 cm(-1), and 188.4 cm(-1) cause four frequency gaps, from 3.97 THz to 4.20 THz, from 4.51 to 4.89 THz, from 5.17 to 5.61 THz and from 5.67 to 5.91 THz, respectively.
The use of phosphenes evoked by transcorneal electrical stimulation (TcES) has been proposed as a means of residual visual function evaluation and candidate selection before implantation of retinal prostheses. Compared to the subjective measures, measurement of neuronal activity in visual cortex can objectively and quantitatively explore their response properties to electrical stimulation. The purpose of this study was to investigate systematically the properties of cortical responses evoked by TcES.
The ligation-mediated polymerase chain reaction (PCR) method is widely applied for detecting short-length DNA target. The primary principle of this method is based on the linkage of two separated DNA probes as PCR templates via simultaneous hybridization with DNA target by DNA ligase. Even before taking into account low ligation efficiency, a 1:1 stoichiometric ratio between DNA target and the produced PCR template would put an intrinsic limitation on the detection sensitivity. In order to solve this problem, we have developed an improved ligation-mediated PCR method. It is designed such that a transcription reaction by T7 RNA polymerase is integrated into the ligation reaction. In this way, the produced joint DNA strand composed by two DNA probes can be used as a template both in the transcription reaction and the following PCR process. Then a great number of RNA strands containing the same sequence as DNA target are transcribed to act as a target to initiate new cyclic reactions of ligation and transcription. The results indicate that our proposed method can improve the detection sensitivity by ~2 orders of magnitude compared with the conventional ligation-mediated PCR method.
KTiOPO? (KTP) crystal is used as the nonlinear medium in a surface-emitted terahertz-wave parametric oscillator for the first time. The oscillating Stokes beam propagates along the x axis of the KTP crystal, the pumping beam propagates with a small incident angle ?(ext) to the x axis, and the polarizations of the pumping beam, the Stokes beam, and the THz wave are along the z axis. When ?(ext) is changed from 1.250° to 6.000°, the THz wave is intermittently tuned from 3.17 to 3.44 THz, from 4.19 to 5.19 THz, and from 5.55 to 6.13 THz. The maximum output of the THz wave is 336 nJ, obtained at 5.72 THz with a pumping energy of 80 mJ. The two frequency gaps, from 3.44 to 4.19 THz and from 5.19 to 5.55 THz, are located in the vicinities of the A? modes of 134 and 178.7??cm?¹, which are strongly infrared absorbing.
In plants, the R2R3-MYB gene family contains many pairs of paralogous genes, which play the diverse roles in developmental processes and environmental responses. The paper reports the characterization of 81 pairs of Populus R2R3-MYB genes. Chromosome placement, phylogenetic, and motif structure analyses showed that these gene pairs resulted from multiple types of gene duplications and had five different gene fates. Tissue expression patterns revealed that most duplicated genes were specifically expressed in the tissues examined. qRT-PCR confirmed that nine pairs were highly expressed in xylem, of which three pairs (PdMYB10/128, PdMYB90/167, and PdMYB92/125) were further functionally characterized. The six PdMYBs were localized to the nucleus and had transcriptional activities in yeast. The heterologous expression of PdMYB10 and 128 in Arabidopsis increased stem fibre cell-wall thickness and delayed flowering. In contrast, overexpression of PdMYB90, 167, 92, and 125 in Arabidopsis decreased stem fibre and vessel cell-wall thickness and promoted flowering. Cellulose, xylose, and lignin contents were changed in overexpression plants. The expression levels of several genes involved in secondary wall formation and flowering were affected by the overexpression of the six PdMYBs in Arabidopsis. This study addresses the diversity of gene duplications in Populus R2R3-MYBs and the roles of these six genes in secondary wall formation and flowering control.
Heat has always been a killing matter for traditional semiconductor machines. The underlining physical reason is that the intrinsic carrier density of a device made from a traditional semiconductor material increases very fast with a rising temperature. Once reaching a temperature, the density surpasses the chemical doping or gating effect, any p-n junction or transistor made from the semiconductor will fail to function. Here, we measure the intrinsic Fermi level (|EF| = 2.93 kBT) or intrinsic carrier density (nin = 3.87 × 10(6) cm(-2)K(-2)· T(2)), carrier drift velocity, and G mode phonon energy of graphene devices and their temperature dependencies up to 2400 K. Our results show intrinsic carrier density of graphene is an order of magnitude less sensitive to temperature than those of Si or Ge, and reveal the great potentials of graphene as a material for high temperature devices. We also observe a linear decline of saturation drift velocity with increasing temperature, and identify the temperature coefficients of the intrinsic G mode phonon energy. Above knowledge is vital in understanding the physical phenomena of graphene under high power or high temperature.
Nanostructured silicon solar cells show great potential for new-generation photovoltaics due to their ability to approach ideal light-trapping. However, the nanofeatured morphology that brings about the optical benefits also introduces new recombination channels, and severe deterioration in the electrical performance even outweighs the gain in optics in most attempts. This Research News article aims to review the recent progress in the suppression of carrier recombination in silicon nanostructures, with the emphasis on the optimization of surface morphology and controllable nanostructure height and emitter doping concentration, as well as application of dielectric passivation coatings, providing design rules to realize high-efficiency nanostructured silicon solar cells on a large scale.
Wood biomass is mainly made of secondary cell walls, whose formation is controlled by a multilevel network. The tandem CCCH zinc finger (TZF) proteins involved in plant secondary wall formation are poorly understood. Two TZF genes, PdC3H17 and PdC3H18, were isolated from Populus deltoides and functionally characterized in Escherichia coli, tobacco, Arabidopsis and poplar. PdC3H17 and PdC3H18 are predominantly expressed in cells of developing wood, and the proteins they encode are targeted to cytoplasmic foci. Transcriptional activation assays showed that PdMYB2/3/20/21 individually activated the PdC3H17 and PdC3H18 promoters, but PdMYB3/21 were most significant. Electrophoretic mobility shift assays revealed that PdMYB3/21 bound directly to the PdC3H17/18 promoters. Overexpression of PdC3H17/18 in poplar increased secondary xylem width and secondary wall thickening in stems, whereas dominant repressors of them had the opposite effects on these traits. Similar alteration in secondary wall thickening was observed in their transgenic Arabidopsis plants. qRT-PCR results showed that PdC3H17/18 regulated the expression of cellulose, xylan and lignin biosynthetic genes, and several wood-associated MYB genes. These results demonstrate that PdC3H17 and PdC3H18 are the targets of PdMYB3 and PdMYB21 and are an additional two components in the regulatory network of secondary xylem formation in poplar.
The serine threonine kinase Akt1 has been implicated in the control of cellular metabolism, survival and growth. Herein, disruption of the ubiquitously expressed member of the Akt family of genes, Akt1, in the mouse, demonstrates a requirement for Akt1 in miRNA-mediated cellular apoptosis. The miR-17/20 cluster is known to inhibit breast cancer cellular proliferation through G1/S cell cycle arrest via binding to the cyclin D1 3'UTR. Here we show that miR-17/20 overexpression sensitizes cells to apoptosis induced by either Doxorubicin or UV irradiation in MCF-7 cells via Akt1. miR-17/20 mediates apoptosis via increased p53 expression which promotes Akt degradation. Akt1?/? mammary epithelial cells which express Akt2 and Akt3 demonstrated increased apoptosis to DNA damaging agents. Akt1 deficiency abolished the miR-17/20-mediated apoptosis. These results demonstrated a novel pathway through which miR17/20 regulate p53 and Akt controlling breast cancer cell apoptosis.
Endogenous reactive oxygen species (ROS) control is important for the maintenance of self-renewal of embryonic stem (ES) cells. Although miRNAs have been found to be critically involved in the regulation of the self-renewal, whether miRNAs can regulate the signaling axis to control ROS in ES cells is unclear. Here we show that miR-29b specifically regulates the self-renewal of mouse ES cells in response to ROS generated by antioxidant-free culture. Sirt1 is the direct target of miR-29b and can also make mES cells sensitive to ROS and regulate the self-renewal of mES cells during the response of ROS. We further found that Sirt1 could attenuate the miR-29b function in regulating mES cells' self-renewal in response to ROS. Our results determined that miR-29b-Sirt1 axis regulates self-renewal of mES cells in response to ROS.
A MgO:LiNbO? slab configuration for the surface-emitted terahertz-wave parametric oscillator (TPO) is presented. The pump and the oscillating Stokes beams were totally reflected at the slab surface and propagated zigzaggedly in the slab MgO:LiNbO? crystal. Up to five terahertz beams were emitted perpendicularly to the surface of the crystal. The total output energy of the five THz-wave beams was 3.56 times as large as that obtained from the conventional surface-emitted TPO at the same experimental conditions. The intensity distributions of the THz wave beams were measured, and they were unsymmetrical in the horizontal direction while symmetrical in the vertical direction.
Brain metastases generally present in the parenchyma of the brain. In the current report, a very rare case of brain metastasis, which simultaneously invaded the subgaleal region, the skull, and the dural and cavernous sinuses is presented. The patient, a 54-year-old female, complained of a progressive headache and exhibited the symptoms of intracranial hypertension. Coronal contrast-enhanced T1-weighted magnetic resonance imaging (MRI) showed high intensity signals in the subgaleal tissue of the left frontoparietal area, as well as in the dural and the cavernous sinuses. The patient was initially diagnosed with an intracranial infection, however, the administered treatment was ineffective. The patient subsequently underwent a biopsy and the pathological diagnosis was determined as a metastatic adenocarcinoma; a primary tumor was not identified during the examinations. Surgical removal of certain metastases and a decompressive craniectomy were performed to relieve the intracranial hypertension. However, the prognosis was unsatisfactory. The patient's neurological condition progressively worsened and an axial computed tomography scan with a bone window demonstrated a bulging growth in the brain tissue. The patient succumbed after one month due to the widespread metastasis. Thus, this case presents the unusual clinical development of this type of metastatic adenocarcinoma. In addition, due to the intracranial hypertension, the unusual sites of the high intensity signals in the MRI and the lack of a primary tumor, the patient was misdiagnosed with an intracranial infection. Furthermore, this case highlights the necessity for conducting a biopsy as soon as possible and demonstrates the poor prognosis associated with this type of patient.
The miniaturization of bioelectronic intracellular probes with a wide dynamic frequency range can open up opportunities to study biological structures inaccessible by existing methods in a minimally invasive manner. Here, we report the design, fabrication, and demonstration of intracellular bioelectronic devices with probe sizes less than 10 nm. The devices are based on a nanowire-nanotube heterostructure in which a nanowire field-effect transistor detector is synthetically integrated with a nanotube cellular probe. Sub-10-nm nanotube probes were realized by a two-step selective etching approach that reduces the diameter of the nanotube free-end while maintaining a larger diameter at the nanowire detector necessary for mechanical strength and electrical sensitivity. Quasi-static water-gate measurements demonstrated selective device response to solution inside the nanotube, and pulsed measurements together with numerical simulations confirmed the capability to record fast electrophysiological signals. Systematic studies of the probe bandwidth in different ionic concentration solutions revealed the underlying mechanism governing the time response. In addition, the bandwidth effect of phospholipid coatings, which are important for intracellular recording, was investigated and modeled. The robustness of these sub-10-nm bioelectronics probes for intracellular interrogation was verified by optical imaging and recording the transmembrane resting potential of HL-1 cells. These ultrasmall bioelectronic probes enable direct detection of cellular electrical activity with highest spatial resolution achieved to date, and with further integration into larger chip arrays could provide a unique platform for ultra-high-resolution mapping of activity in neural networks and other systems.
To investigate CTX-M genotypes among extended-spectrum ?-lactamase-producing Escherichia coli (ESBL-EC) isolated from patients with community-onset and hospital-onset infections in China, their clonality and the distribution of CTX-M variants in different specimens of community-onset and hospital-onset infections.
Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), which arises preferentially in the setting of infection with human immunodeficiency virus (HIV). Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+) PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells propagated in vivo exhibit unique biology, differing from one another or from their parental cell lines propagated through in vitro culture. Therefore, we used a KSHV(+) PEL/BCBL-1 xenograft model involving non-obese diabetic/severe-combined immunodeficient (NOD/SCID) mice, and compared characteristics of effusion and solid tumors with their parent cell culture-derived counterparts. Our results indicate that although this xenograft model can be used for study of effusion and solid lymphoma observed in patients, tumor cells in vivo display unique features to those passed in vitro, including viral lytic gene expression profile, rate of solid tumor development, the host proteins and the complex of tumor microenvironment. These items should be carefully considered when the xenograft model is used for testing novel therapeutic strategies against KSHV-related lymphoma.
A coherent random fiber laser based on stimulated Brillouin scattering as gain and Rayleigh scattering as distributed feedback mirror was constructed. Its frequency is stabilized by a high finesse narrow-band Fabry-Perot interferometer (FPI) to select lasing frequency within the gain bandwidth. The light confinement within single-mode fiber enhances largely the random lasing directionality, which enables a high-quality coherent random lasing in the weak scattering region by using a milliwatt continuous-wave pump source. The FPI in the laser configuration acts as a frequency selection on the Rayleigh feedback light, and thus the random lasing frequency was locked at one of its transmission peaks giving a relative frequency fluctuation of ~2.5 × 10(-11) at 100 s. The measured frequency jitter is within ~~ ± 20 kHz over 3 hours, 3 dB linewidth is ~50 Hz and frequency noise is ~20 mHz/Hz(1/2) at 10 kHz.
Hand motion classification using surface electromyography (sEMG) has been widely studied for its applications in upper-limb prosthesis and human-machine interface etc. Pattern-recognition based control methods have many advantages, and the reported classification accuracy can meet the requirements of practical applications. However, the pattern instability of sEMG in actual use limited their real implementations, and limb position variations may be one of the potential factors.
Semiconducting nanomaterials are being intensively studied as active elements in bioelectronic devices, with the aim of improving spatial resolution. Yet, the consequences of size-reduction on fundamental noise limits, or minimum resolvable signals, and their impact on device design considerations have not been defined. Here, we address these key issues by quantifying the size-dependent performance and limiting factors of graphene (Gra) transducers under physiological conditions. We show that suspended Gra devices represent the optimal configuration for cardiac extracellular electrophysiology in terms of both transducer sensitivity, systematically ~5× higher than substrate-supported devices, and forming tight bioelectronic interfaces. Significantly, noise measurements on free-standing Gra together with theoretical calculations yield a direct relationship between low-frequency 1/f noise and water dipole-induced disorders, which sets fundamental sensitivity limits for Gra devices in physiological media. As a consequence, a square-root-of-area scaling of Gra transducer sensitivity was experimentally revealed to provide a critical design rule for their implementation in bioelectronics.
Elevated intracranial pressure (ICP) is generally observed in brain injury and intracerebral hemorrhage (ICH) patients and is consistently associated with poor neurological outcome. Intracranial pressure variability (IPV) is a better predictor of long-term neurological outcome than mean ICP in traumatic brain injury patients. However, whether IPV regulates functional outcome in ICH patients has not been investigated. In the present study, we investigated the relationship between IPV and functional outcome in ICH patients and determined whether IPV is a valid predictor of neurological outcome in ICH patients.
In this study, a novel fiber-optic sensor consisting of a tapered bend-insensitive fiber based Mach-Zehnder interferometer is presented to realize damped and continuous vibration measurement. The double cladding structure and the central coating region of the in-fiber interferometer ensure an enhanced mechanical strength, reduced external disturbance, and a more uniform spectrum. A damped vibration frequency range of 29-60 Hz as well as continuous vibration disturbances ranging from 1 Hz up to 500 kHz are successfully demonstrated.
Emmprin (CD147; basigin) is a multifunctional glycoprotein expressed at higher levels by cancer cells and stromal cells in the tumor microenvironment. Through direct effects within tumor cells and promotion of tumor-stroma interactions, emmprin participates in induction of tumor cell invasiveness, angiogenesis, metastasis and chemoresistance. Although its contribution to cancer progression has been widely studied, the role of emmprin in viral oncogenesis still remains largely unclear, and only a small body of available literature implicates emmprin-associated mechanisms in viral pathogenesis and tumorigenesis. We summarize these data in this review, focusing on the role of emmprin in pathogenesis associated with the Kaposi sarcoma-associated herpesvirus (KSHV), a common etiology for cancers arising in the setting of immune suppression. We also discuss future directions for mechanistic studies exploring roles for emmprin in viral cancer pathogenesis.
Src is an attractive target since it is overexpressed in a number of malignancies, including glioma. However, the mechanism of Src signaling as well as its silencing effect on temozolomide in glioma is not well known. We hypothesized that downregulation of Src may enhance the cytotoxic effect of temozolomide on glioma. As expected, Src was overexpressed in glioblastoma multiforme (GBM) compared with normal brain tissues. Src silencing suppressed tumor proliferation and induced apoptosis in glioma. In addition, Src silencing combined with temozolomide treatment resulted in significant inhibition of tumor growth. These effects may be mediated by AKT which is a downstream effector of Src, since downregulation of AKT exhibited a similar effect as Src siRNA when combined with temozolomide. Finally, we demonstrated that overexpression of AKT suppressed the enhanced cytotoxic effect of temozolomide mediated by Src silencing. Thus, the present study demonstrated that Src plays a biologically significant role in tumor proliferation and apoptosis and enhances the cytotoxic effect of temozolomide through AKT supression in glioma.
We previously showed that L-arginine (Arg) accumulates in colorectal cancer tissues. The aim of this study was to investigate the mechanism by which Arg accumulates and determine its biological significance. The concentration of Arg and Citrulline (Cit) in sera and tumor tissues from colorectal cancer (CRC) patients was analyzed by high-performance liquid chromatography (HPLC). The expression of Arg transporters was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analysis of tissue microarray. We also transfected the colon cancer cell line HCT-116 with siRNA specific for the Arg transporter CAT-1 and measured the induction of apoptosis by flow cytometry and cell proliferation by MTT assay. Consistent with our previous results, serum Arg and Cit concentrations in colorectal cancer patients were significantly lower than those in normal volunteers, while Arg and Cit concentrations in colorectal cancer tissues were significantly higher than in matched adjacent normal colon tissues. Quantitative RT-PCR showed that the CAT-1 gene was highly overexpressed in 70.5% of colorectal cancer tissue samples relative to adjacent normal colon tissues in all 122 patients with colorectal cancer. Immunohistochemical analysis of tissue microarray confirmed that the expression of CAT-1 was higher in all 25 colorectal cancer tissues tested. CAT-1 siRNA significantly induced apoptosis of HCT-116 cells and subsequently inhibited cell growth by 20-50%. Our findings indicate that accumulation of L-Arg and Cit and cell growth in colorectal cancer tissues is associated with over-expression of the Arg transporter gene CAT-1. Our results may be useful for the development of molecular diagnostic tools and targeted therapy for colorectal cancer.
The LIM homeodomain transcription factor Islet1 (Isl1) is expressed in multiple organs and plays essential roles during embryogenesis. Isl1 is required for the survival and specification of spinal cord motor neurons. Due to early embryonic lethality and loss of motor neurons, the role of Isl1 in other aspects of motor neuron development remains unclear. In this study, we generated Isl1 mutant mouse lines expressing graded doses of Isl1. Our study has revealed essential roles of Isl1 in multiple aspects of motor neuron development, including motor neuron cell body localization, motor column formation and axon growth. In addition, Isl1 is required for survival of cranial ganglia neurons.
Epidemiological studies have demonstrated a close correlation between nickel exposure and the incidence of lung cancer. Several studies have suggested that nickel contributes to tumor progression of human lung cancer. In this in vitro study, we found that nickel, as nickel chloride, could significantly enhance the invasive potential of human lung cancer cells, accompanied by elevated expression of IL-8, TGF-?, MMP2 and MMP9 in human lung cancer cells. Importantly, we demonstrated that nickel could activate TLR4 signaling in human lung cancer cells. Further studies showed that the TLR4/MyD88 signaling conferred the enhanced invasive potential of human lung cancer cells induced by nickel. Finally, we revealed that the p38MAPK pathway and NF-kB pathway were necessary for the enhanced invasive potential of human lung cancer cells induced by nickel. Our data provide a mechanistic explanation for nickel induced invasion of human lung cancer, and they suggest new strategies for nickel-related lung cancer clinical biotherapies.
Bioavailability and toxicity of metals to soil organisms varies among different soils, and knowledge of this variance is useful for the development of soil environmental quality guidelines. In the present study, laboratory experiments were performed to investigate the effects of variations in nickel (Ni) uptake and toxicity on growth, cocoon output, and juvenile production in the earthworm Eisenia fetida in 13 Chinese soils spiked with nickel chloride. Body weight development of E. fetida was rather insensitive to Ni, and significant inhibition of growth was observed only at high Ni concentrations, such as 560 and 1000 mg/kg. The 50% inhibition effect concentrations (EC50s) for cocoon and juvenile production, based on measured Ni concentrations in soils, varied from 169 to 684 mg/kg and from 159 to 350 mg/kg, respectively. The EC50s represented approximately fourfold variation for cocoon output and twofold variation for juvenile production among 13 Chinese soils. Juvenile production, compared to cocoon output, was a more sensitive endpoint parameter to Ni. Nickel uptake in E. fetida increased as simple linear functions of increasing soil Ni concentrations. Tissue Ni-based EC50s (based on Ni concentrations in earthworm tissues) for cocoon production varied from 37 to 121 mg/kg (threefold variation) in 12 of 13 soils, suggesting a similar variation to that of soil Ni-based EC50s. Relationship analysis between soil properties and Ni toxicity showed that neither the EC50s for cocoon output nor those for juvenile production presented significant correlation with soil properties (pH, organic matter content, cation exchange capacity, clay content, Ca²? and Mg²?). This may be ascribed to the narrow range of properties of selected soils. The soil factors that determined Ni toxicity to earthworm reproduction remain undetermined in the present study, and these data should be used cautiously when developing toxicity prediction models because of the narrow selection of soil properties.
By combining atomic force microscopy and trans-port measurements, we systematically investigated effects of thermal annealing on surface morphologies and electrical properties of single-layer graphene devices fabricated by electron beam lithography on silicon oxide (SiO(2)) substrates. Thermal treatment above 300 °C in vacuum was required to effectively remove resist residues on graphene surfaces. However, annealing at high temperature was found to concomitantly bring graphene in close contact with SiO(2) substrates and induce increased coupling between them, which leads to heavy hole doping and severe degradation of mobilities in graphene devices. To address this problem, a wet-chemical approach employing chloroform was developed in our study, which was shown to enable both intrinsic surfaces and enhanced electrical properties of graphene devices. Upon the recovery of intrinsic surfaces of graphene, the adsorption and assisted fibrillation of amyloid ?-peptide (A?1-42) on graphene were electrically measured in real time.
We report studies on surface modification of graphene with 1-octadecanethiol and its application as heavy metal sensors. The alkanethiol molecules can self-assemble into large-scale highly ordered monolayers on single-layer graphene regardless of the roughness of graphene surfaces inherited from the underlying amorphorous silicon oxide (SiO2) dielectric substrates. Atomically resolved scanning tunneling microscopy imaging of modified graphene sheets on SiO2 was conducted to reveal configuration details of the self-assembled structure. Functionalization of graphene field effect transistors (Gra-FETs) with 1-octadecanethiol was realized and successfully explored for mercury(II) (Hg2+) detection at 10 ppm.
Adoptive cell transfer immunotherapy using tumor infiltrating lymphocytes (TILs) was an important therapeutic strategy against tumors. But the efficacy remains limited and development of new strategies is urgent. Recent evidence suggested that CpG-ODNs might be a potent candidate for tumor immunotherapy. Here we firstly reported that CpG-ODNs could significantly enhance the antitumor efficacy of adoptively transferred TILs in vivo accompanied by enhanced activity capacity and proliferation of CD8(+) T cells and CD8(+) T cells, as well as a Th1 polarization immune response. Most importantly, we found that CpG-ODNs could significantly elevate the infiltration of Th17 cells in tumor mass, which contributed to anti-tumor efficacy of TILs in vivo. Our findings suggested that CpG ODNs could enhance the anti-tumor efficacy of adoptively transferred TILs through modifying Th1 polarization and local infiltration of Th17 cells, which might provide a clue for developing a new strategy for ACT based on TILs.
We report enhanced performance of suspended graphene field effect transistors (Gra-FETs) as sensors in aqueous solutions. Etching of the silicon oxide (SiO(2)) substrate underneath graphene was carried out in situ during electrical measurements of devices, which enabled systematic comparison of transport properties for same devices before and after suspension. Significantly, the transconductance of Gra-FETs in the linear operating modes increases 1.5 and 2 times when the power of low-frequency noise concomitantly decreases 12 and 6 times for hole and electron carriers, respectively, after suspension of graphene in solution from the SiO(2) substrate. Suspended graphene devices were further demonstrated as direct and real-time pH sensors, and complementary pH sensing with the same nanodevice working as either a p-type or n-type transistor was experimentally realized by offsetting the electrolyte gate potential in solution. Our results highlight the importance to quantify fundamental parameters that define resolution of graphene-based bioelectronics and demonstrate that suspended nanodevices represent attractive platforms for chemical and biological sensors.
Although immune reactions against heat shock proteins have been implicated in the pathogenesis of atherosclerosis, conflicting associations between Hsp70, anti-Hsp70 antibody and coronary heart disease (CHD) have been reported. This study assessed whether there is a significant association between extracellular human Hsp70, anti-Hsp70 antibody and acute coronary syndrome (ACS) and stable angina (SA), and examined dynamic changes in Hsp70 and anti-Hsp70 antibody levels induced by acute myocardial infarction (AMI). Plasma Hsp70 and anti-Hsp70 antibody levels in 291 patients with ACS (179 AMI, 112 unstable angina), 126 patients with SA and 417 age and sex-matched healthy subjects, and in 40 patients after admission for AMI, and on day 2, 3, and 7 after the onset of AMI were determined using enzyme-linked immunosorbent assays. Hsp70 levels were significantly higher in ACS and SA and anti-Hsp70 antibody levels were only markedly lower in ACS than controls. After adjustment for traditional CHD risk factors, increasing levels of Hsp70 were significantly associated with an increased risk and severity of ACS (P for trend < 0.001), whereas increasing levels of anti-Hsp70 antibody were associated with a decreased risk of ACS (P for trend = 0.0003). High levels of Hsp70 combined with low levels of anti-Hsp70 antibody had a joint effect on the risk of ACS (OR, 5.14, 95% CI, 3.00-8.79; P < 0.0001). In patients with AMI, Hsp70 levels decreased rapidly from days 1-7 after onset, whereas anti-Hsp70 antibody levels increased in patients with AMI. These findings suggest that higher Hsp70 levels or lower anti-Hsp70 antibody levels are independently associated with a higher risk of ACS. Higher Hsp70 levels and lower anti-Hsp70 antibody levels combine to further increase this risk.
Accumulating data suggested that functional TLR9 was expressed in various tumor cells and TLR9 signaling could enhance the progression of tumor cells. However, the underlying mechanism of TLR9 signaling on the progression of tumors cells remains largely undefined. Our previous study demonstrated that the TLR9 agonist CpG ODNs could significantly enhance the progression of human lung cancer cells in vivo. Here we further evaluated the direct effect of CpG ODNs on the proliferation and cell cycle of human lung cancer cells. Our data showed that TLR9 agonist CpG ODNs could robustly elevate the proliferation and stimulate cell cycle entry of 95D cells in vitro, accompanied by the selectively up-regulated expression of CDK2. Furthermore, we found that down-regulation of CDK2 expression using siRNA against CDK2 could significantly inhibit the enhanced proliferation of 95D cells induced by CpG ODNs. Finally, we investigated that the CpG ODNs could selectively enhance the promoter activity of CDK2. Our findings indicated that TLR9 signaling could selectively up-regulate the expression of CDK2, which was critical for the enhanced proliferation of human lung cancer cells. Our results might provide novel insight into the understanding of functional expression of TLR9 on the progression of tumor cells.
We report in-depth studies of nanostructures formed in graphene on soft substrates. Periodic buckles with amplitude of nanometer scale spontaneously appear at edges of single-layer membranes after cooling of samples from above the substrates glass-transition temperature. Stress modulation at step-edges between single- and few-layer further induces penetrating nanobuckles into the few-layer. The evolvement of single-layer folding into double and triple-layer stacks at elevated temperature was also probed in detail, and we show that the developed interfaces are clear of polymer contamination. Our results underscore the possibility to construct diverse nanostructures and to design novel devices based on graphene.
An analytical scheme to determine groups of petroleum hydrocarbon compounds in crude oil was developed and used for the qualitative and quantitative characterization of crude oil samples from the Shengli oilfield, the second largest oilfield in China. Crude oil samples were fractionated and analyzed by thin-layer chromatography with flame ionization detection (TLC-FID). Relative standard deviation (RSD) values for retention time, peak height and half peak width were less than 5.2% for all classes of compounds, based on nine independent replicates. The crude oil light fraction was further analyzed by GC-MS and the majority of identified compounds were methyl- or hydro-derivatives of long-chain hydrocarbons and aromatic compounds. The external standard method used in the present study can lower detection limits of petroleum hydrocarbon compound classes to 20.0 mg L(-1), and the crude oil concentration in the range of 30 and 35,000 mg L(-1) has a high linear correlation (r(2)>0.97, P<0.05) with peak area. A comparison between elution chromatography (EC) and TLC-FID regarding the recovery of petroleum hydrocarbon compounds was carried out with aged crude oil contaminated soils of 50, 80, 200 and 300 mg g(-1). The tested TLC-FID method showed a 10% higher recovery for total extractable materials than the reference EC method. The calibration factor was fraction-dependent and varied with the recovery rate of TLC/EC. Regarding the tested extraction procedures, accelerated solvent extraction (ASE) had a higher extraction efficiency for crude oil contaminated soils than Soxhlet and ultrasonic extractions.
Although excitation-emission matrix spectroscopy (EEMS) has been widely used to characterize dissolved organic matter (DOM), there has no report that EEMS has been used to study the effects of acid rain on DOM and its composition in soil. In this work, we employed three-dimensional EEMS to characterize the compositions of DOM leached by simulated acid rain from red soil. The red soil was subjected to leaching of simulated acid rain of different acidity, and the leached DOM presented five main peaks in its EEMS: peak-A, related to humic acid-like (HA-like) material, at Ex/Em of 310-330/395-420nm; peak-B, related to UV fulvic acid-like (FA-like) material, at Ex/Em of 230-280/400-435nm; peak-C and peak-D, both related to microbial byproduct-like material, at Ex/Em of 250-280/335-355nm and 260-280/290-320nm, respectively; and peak-E, related to simple aromatic proteins, at Ex/Em of 210-240/290-340nm. EEMS analysis results indicated that most DOM could be lost from red soil in the early phase of acid rain leaching. In addition to the effects of the pH of acid rain, the loss of DOM also depended on the properties of its compositions and the solubility of their complexes with aluminum. HA-like and microbial byproduct-like materials could be more easily released from red soil by acid rain at both higher pH (4.5 and 5.6) and lower pH (2.5 and 3) than that at middle pH (3.5). On the contrary, FA-like material lost in a similar manner under the action of different acid rains with pH ranging from 2.5 to 5.6.
This paper proposes three training strategies based on impedance control, including passive training, damping-active training and spring-active training, for a 3-DOF lower limb rehabilitation robot designed for patients with paraplegia or hemiplegia. Controllers with similar structure are developed for these training strategies, consisting of dual closed loops, the outer impedance control loop and the inner position/velocity control loop, known as position-based impedance control method. Simulation results verify that position-based impedance control approach is feasible to accomplish the training strategies.
We propose the continuous wavelet transform for non-stationary vibration measurement by distributed vibration sensor based on phase optical time-domain reflectometry (OTDR). The continuous wavelet transform approach can give simultaneously the frequency and time information of the vibration event. Frequency evolution is obtained by the wavelet ridge detection method from the scalogram of the continuous wavelet transform. In addition, a novel signal processing algorithm based on the global wavelet spectrum is used to determine the location of vibration. Distributed vibration measurements of 500 Hz and 500 Hz to 1 kHz sweep events over 20 cm fiber length are demonstrated using a single mode fiber.
The acute respiratory distress syndrome (ARDS), a clinical complication of severe acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. Despite decades of research, few therapeutic strategies for clinical ARDS have emerged. Here we carefully evaluated the effect of progranulin (PGRN) in treatment of ARDS using the murine model of lipopolysaccharide (LPS)-induced ALI. We reported that administration of PGRN maintained the body weight and survival of ALI mice. We revealed that administration of PGRN significantly reduced LPS-induced pulmonary inflammation, as reflected by reductions in total cell and neutrophil counts, proinflammatory cytokines, as well as chemokines in bronchoalveolar lavage (BAL) fluid. Furthermore, administration of PGRN resulted in remarkable reversal of LPS-induced increases in lung permeability as assessed by reductions in total protein, albumin, and IgM in BAL fluid. Consistently, we revealed a significant reduction of histopathology changes of lung in mice received PGRN treatment. Finally, we showed that PGRN/TNFR2 interaction was crucial for the protective effect of PGRN on the LPS-induced ALI. Our findings strongly demonstrated that PGRN could effectively ameliorate the LPS-induced ALI in mice, suggesting a potential application for PGRN-based therapy to treat clinical ARDS.
Autoimmune hemolytic anemia (AIHA) is defined as the increased destruction of red blood cells (RBCs) in the presence of anti-RBC autoantibodies with or without complement activation. However, the underlying mechanism for the development of AIHA remains largely unclear. In this study, we carefully evaluated the potential role of Th17 cells in the development of AIHA. We found an elevated frequency of Th17 cells in patients with AIHA, which were closely correlated with their disease activity, including the level of anti-RBC IgG antibodies, hemoglobin, serum C3, and lactate dehydrogenase activity. Furthermore, we observed that interleukin (IL)-17 was also closely correlated with the disease activity in AIHA patients. To further elucidate the potential role of Th17 cells in induction of AIHA, we used the Marshall-Clarke and Playfair model of murine AIHA. Notably, we found that Th17 cells affected development of AIHA by enhancing the adaptive humoral responses. Specifically, we found that adoptive transfer of Th17 cells heightened the initial anti-rat RBC antibody responses and concomitantly increased the onset of AIHA. In addition, in vivo neutralization of IL-17 abrogated the development of AIHA, while initiation of anti-rat RBC IgG responses and induction of AIHA in IL-17(-/-) mice were impaired. Our findings suggest that Th17 cells contribute to the development of AIHA, which could facilitate our better understanding of AIHA pathogenesis and provide clues to developing novel forms of immunotherapy against AIHA.
A laboratory repacked soil-leaching column experiment was conducted to study the effects of simulated acid rain or EDTA by themselves or in combination, on migration and chemical speciation distribution of Pb and its alternative rare metals including Ag, Bi, In, Sb, and Sn. Experimental results demonstrate that leaching with simulated acid rain promoted the migration of Bi, In and Pb, and their migration reached down to 8 cm in the soil profile, no enhancement of Sb, Ag or Sn migration was observed. Addition of EDTA significantly enhanced the migration of all six metals, especially Bi, In and Pb. The migration of metals was in the order Pb>Bi>In>Sb>Sn>Ag. The individual and combined effects of acid rain and EDTA increased the environmental risk of metals, by increasing the soluble content of metals in soil solutions and the relative distribution of the exchangeable fraction. Leaching risks of Bi, In and Pb were higher than other three metals.
The distributed vibration or dynamic strain information can be obtained using time-resolved optical frequency-domain reflectometry. Time-domain information is resolved by measuring Rayleigh backscatter spectrum in different wavelength ranges which fall in successive time sequence due to the linear wavelength sweep of the tunable laser source with a constant sweeping rate. The local Rayleigh backscatter spectrum shift of the vibrated state with respect to that of the non-vibrated state in time sequence can be used to determine dynamic strain information at a specific position along the fiber length. Standard single-mode fibers can be used as sensing head, while the measurable frequency range of 0-32 Hz with the spatial resolution of 10 cm can be achieved up to the total length of 17 m.
High-mobility group box 1 (HMGB1) has been implicated in a variety of biologically important processes, including transcription, DNA repair, differentiation, development, and extracellular signaling. However, the potential role of HMGB1 in tumor biology still remains intractable. Our previous study showed that TLR9 response to CpG oligonucleotide (ODN) in 95D human lung cancer cells could enhance their growth and invasive potential in vitro and in vivo. Here we found that CpG ODN stimulation to 95D cells induced the secretion of HMGB1 in a dose dependent manner. We further showed that blockade of extracellular HMGB1 using A box peptide and ethyl pyruvate significantly abrogated the CpG ODN enhanced progression of 95D cells. Interestingly, we found that HMGB1 alone or acted synergistic with CpG ODN could enhance the progression of 95D cells. Notably, we revealed that RAGE and TLR4 were critical for HMGB1 to exert the synergistic function. We observed a MyD88-dependent upregulation of matrix metalloproteinase (MMP) 2, MMP9 and cyclin-dependent kinase (CDK) 2 in 95D cells in response to HMGB1. These findings might further our understanding of TLR9 signaling in tumor biology and be helpful for developing HMGB1-based strategy against lung cancer.
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