Multiphoton excitation laser scanning microscopy, relying on the simultaneous absorption of two or more photons by a molecule, is one of the most exciting recent developments in biomedical imaging. ...Thanks to its superior imaging capability of deeper tissue penetration and efficient light detection, this system becomes more and more an inspiring tool for intravital bulk tissue imaging. Two-photon excitation microscopy including 2-photon fluorescence and second harmonic generated signal microscopy is the most common multiphoton microscopic application. In the present review we take diverse ocular tissues as intravital samples to demonstrate the advantages of this approach. Experiments with registration of intracellular 2-photon fluorescence and extracellular collagen second harmonic generated signal microscopy in native ocular tissues are focused. Data show that the in-tandem combination of 2-photon fluorescence and second harmonic generated signal microscopy as two-modality microscopy allows for in situ co-localization imaging of various microstructural components in the whole-mount deep intravital tissues. New applications and recent developments of this high technology in clinical studies such as 2-photon-controlled drug release, in vivo drug screening and administration in skin and kidney, as well as its uses in tumourous tissues such as melanoma and glioma, in diseased lung, brain and heart are additionally reviewed. Intrinsic emission two-modal 2-photon microscopy/tomography, acting as an efficient and sensitive non-injurious imaging approach featured by high contrast and subcellular spatial resolution, has been proved to be a promising tool for intravital deep tissue imaging and clinical studies. Given the level of its performance, we believe that the non-linear optical imaging technique has tremendous potentials to find more applications in biomedical fundamental and clinical research in the near future.
In this study, a novel inter-pass cooling technology was applied during rough rolling (R-IPC) to process a 60 mm ultra-heavy EH47 steel plate with excellent toughness and ductility. The plate was ...compared to a plate processed through conventional thermo-mechanical controlled processing (TMCP). The microstructure evolution at 1/4-thickness and 1/2-thickness of the plates was studied, while the relationship between microstructure and mechanical properties, through tensile and Charpy V-notch impact toughness, was established. In this study, it was reported that the R-IPC steel deformation penetration was higher compared to the TMCP steel. The ferrite fractions of the R-IPC and TMCP steels were 47% and 10% at 1/4-thickness, as well as 35% and 0.5% at 1/2-thickness, while the acicular ferrite fractions at 1/2-thickness of the R-IPC and TMCP steels were 50% and 9.5%, respectively. The granular bainite width at 1/2-thickness of the R-IPC steel (14 ± 4 µm) was significantly lower than the TMCP steel (27 ± 10 µm). The M/A island volume fraction in R-IPC steel was higher than the TMCP steel at 1/4-thickness, whereas it was reduced dramatically at 1/2-thickness. The high intensity of the desired texture {112} was obtained at 1/2-thickness of the R-IPC steel, while the undesired {411} was obtained at 1/2-thickness of the TMCP steel, which was responsible for the R-IPC steel superior toughness compared to the TMCP steel. The tensile and yield strengths of the two rolled plates were similar, while the elongation at 1/4-thickness of the R-IPC steel was higher compared to the TMCP steel. The low temperature impact energy of the R-IPC steel was significantly higher compared to the TMCP steel, resulting from finer grain size, higher ferrite fraction and higher area of the {110} texture parallel to the impact direction.
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•Core/shell NiCo2O4@α-Co(OH)2 nanowires were synthesized by a two-step route first.•The optimized electrode exhibits a high specific capacitance of 1298 F g−1 at 1 A g−1.•An ...asymmetric capacitor of NiCo2O4@Co(OH)2//AC has an energy density of 39.7 Wh kg−1.
The composites of NiCo2O4 with unique structures are extensively explored as promising electrodes. In this work, core-shell structured nanowires anchored on nickel foam are synthesized by the hydrothermal synthesis of NiCo2O4 as core and subsequent electrodeposition of α-Co(OH)2 as shell. The core-shell composites exhibit enhanced electrochemical performances ascribing to the synergistic reactions from both materials, showing higher specific capacitance than any single component. By changing the deposition time, the mass loading of α-Co(OH)2 can be easily controlled. The electrochemical performances of the hybrid electrodes are diverse with the mass loading of Co(OH)2. The optimized hybrid electrode with 3 mins electrodeposition exhibits the highest specific capacitance (1298 F g−1 at 1 A g−1) among all electrodes. The redox reaction is a main contributor to the total specific capacitance through electrochemical kinetics analysis. An asymmetric supercapacitor assembled by the optimized material as positive electrode and activated carbon as negative electrode can achieve a relatively high energy density of 39.7 Wh kg−1 at a power density of 387.5 W kg−1 (at 0.5 A g−1) in a voltage of 1.55 V.
Cellular senescence is an irreversible arrest of cell growth. Biochemical and morphological changes occur during cellular senescence, including the formation of a unique cellular morphology such as ...flattened cytoplasm. Function of mitochondria, endoplasmic reticulum and lysosomes are affected resulting in the inhibition of lysosomal and proteosomal pathways. Cellular senescence can be triggered by a number of factors including, aging, DNA damage, oncogene activation and oxidative stress. While the molecular mechanism of senescence involves p16 and p53 tumor suppressor genes and telomere shortening, this review is focused on the mechanism of p16 control. The p16‐mediated senescence acts through the retinoblastoma (Rb) pathway inhibiting the action of the cyclin dependant kinases leading to G1 cell cycle arrest. Rb is maintained in a hypophosphorylated state resulting in the inhibition of transcription factor E2F1. Regulation of p16 expression is complex and involves epigenetic control and multiple transcription factors. PRC1 (Pombe repressor complex (1) and PRC2 (Pombe repressor complex (2) proteins and histone deacetylases play an important role in the promoter hypermethylation for suppressing p16 expression. While transcription factors YY1 and Id1 suppress p16 expression, transcription factors CTCF, Sp1 and Ets family members activate p16 transcription. Senescence occurs with the inactivation of suppressor elements leading to the enhanced expression of p16.
ABSTRACT
We report the phase-connected timing ephemeris, polarization pulse profiles, Faraday rotation measurements, and Rotating-Vector-Model (RVM) fitting results of 12 millisecond pulsars (MSPs) ...discovered with the Five-hundred-meter Aperture Spherical radio Telescope (FAST) in the Commensal Radio Astronomy FAST survey (CRAFTS). The timing campaigns were carried out with FAST and Arecibo over 3 yr. 11 of the 12 pulsars are in neutron star–white dwarf binary systems, with orbital periods between 2.4 and 100 d. 10 of them have spin periods, companion masses, and orbital eccentricities that are consistent with the theoretical expectations for MSP–Helium white dwarf (He WD) systems. The last binary pulsar (PSR J1912−0952) has a significantly smaller spin frequency and a smaller companion mass, the latter could be caused by a low orbital inclination for the system. Its orbital period of 29 d is well within the range of orbital periods where some MSP–He WD systems have shown anomalous eccentricities, however, the eccentricity of PSR J1912−0952 is typical of what one finds for the remaining MSP–He WD systems.
The development of genetic tools allowed for the validation of the pro-aging and pro-disease functions of senescent cells in vivo. These discoveries prompted the development of ...senotherapies-pharmaceutical interventions aimed at interfering with the detrimental effect of senescent cells-that are now entering the clinical stage. However, unequivocal identification and examination of cellular senescence remains highly difficult because of the lack of universal and specific markers. Here, to overcome the limitation of measuring individual markers, we describe a detailed two-phase algorithmic assessment to quantify various senescence-associated parameters in the same specimen. In the first phase, we combine the measurement of lysosomal and proliferative features with the expression of general senescence-associated genes to validate the presence of senescent cells. In the second phase we measure the levels of pro-inflammatory markers for specification of the type of senescence. The protocol can help graduate-level basic scientists to improve the characterization of senescence-associated phenotypes and the identification of specific senescent subtypes. Moreover, it can serve as an important tool for the clinical validation of the role of senescent cells and the effectiveness of anti-senescence therapies.
Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the ...purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM.
Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled.
A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P<0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P=0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression.
CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.
Chlorophyll in leaves plays a vital role in plant growth and can be used as an indicator of a plant’s nutritional status. In this paper, an experimental setup for measuring total chlorophyll content ...using three-wavelength diffuse reflectance is proposed, for which light-emitting diodes with peak wavelengths of 640, 660, and 940 nm are used. Two different maize strains, Zhengdan-958 and Xundan-20, fertilized at different levels before the jointing stage, were used to validate this setup. Regression analyses between remission function values of diffuse reflectance and SPAD values, as well as remission function values of diffuse reflectance and the actual total chlorophyll content, were performed. The determination coefficients between remission function values and the actual total chlorophyll content were 0.9766 for Zhengdan-958 leaves and 0.9612 for Xundan-20 leaves. The experimental results validated the feasibility of using the diffuse reflectance spectrum to determine the total chlorophyll content. This paper also provides guidance for the development of a portable instrument to determine the actual chlorophyll content.
Analysis of the mechanical behavior of nanos- tructures has been very challenging. Surface energy and non- local elasticity of materials have been incorporated into the traditional continuum analysis ...to create modified continuum mechanics models. This paper reviews recent advancements in the applications of such modified continuum models in nanostructures such as nanotubes, nanowires, nanobeams, graphenes, and nanoplates. A variety of models for these nanostructures under static and dynamic loadings are men- tioned and reviewed. Applications of surface energy and nonlocal elasticity in analysis of piezoelectric nanomateri- als are also mentioned. This paper provides a comprehensive introduction of the development of this area and inspires fur- ther applications of modified continuum models in modeling nanomaterials and nanostructures.
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