GJA4 expressed on cancer associated fibroblasts (CAFs)-A 'promoter' of the mesenchymal phenotype.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Connexin is a transmembrane protein involved in gap junctions (GJs) formation. Our previous study found that connexin 37 (Cx37), encoded by gap junction protein alpha 4 (GJA4), expressed on fibroblasts acts as a promoter of CRC and is closely related to epithelial-mesenchymal transition (EMT) and tumor immune microenvironment. However, to date, the mechanism concerning the malignancy of GJA4 in tumor stroma has not been studied. METHODS: Hematoxylin-eosin (HE) and immunohistochemical (IHC) staining were used to validate the expression and localization of GJA4. Using single-cell analysis, enrichment analysis, spatial transcriptomics, immunofluorescence staining (IF), Sirius red staining, wound healing and transwell assays, western blotting (WB), Cell Counting Kit-8 (CCK8) assay and in vivo experiments, we investigated the possible mechanisms of GJA4 in promoting CRC. RESULTS: We discovered that in CRC, GJA4 on fibroblasts is involved in promoting fibroblast activation and promoting EMT through a fibroblast-dependent pathway. Furthermore, GJA4 may act synergistically with M2 macrophages to limit T cell infiltration by stimulating the formation of an immune-excluded desmoplasic barrier. Finally, we found a significantly correlation between GJA4 and pathological staging (P < 0.0001) or D2 dimer (R = 0.03, P < 0.05). CONCLUSION: We have identified GJA4 expressed on fibroblasts is actually a promoter of the tumor mesenchymal phenotype. Our findings suggest that the interaction between GJA4+ fibroblasts and M2 macrophages may be an effective target for enhancing tumor immunotherapy.

Danielozyma pruni sp. nov., an asexual yeast species isolated from insect frass.

Two strains (NYNU 218101 and NYNU 218104) of an asexual yeast species were isolated from insect frass collected in insect tunnels of red leaf plum trees in the Henan Province, central China. Molecular phylogenetic analysis of the D1/D2 domain of the large subunit rRNA gene and the internal transcribed spacer (ITS) region showed that these two strains belonged to the genus Danielozyma, with Danielozyma litseae as the closest known species. They differed from the type strain of D. litseae by 0.6 % substitutions (three substitutions and one gap) in the D1/D2 domain and by 5.1 % substitutions (19 substitutions and six gaps) in the ITS region, respectively. When compared with the partial ACT1, TEF1 and RPB1 gene sequences, they differed by 3 % (26 substitutions), 2.7 % (25 substitutions) and 9 %(54 substitutions) from D. litseae NRRL YB-3246T in these regions. Physiologically, they also differed from its closest known species D. litseae based on the ability to assimilate inulin and galactitol, as well as to grow in 0.1 % cycloheximide and its inability to ferment maltose and raffinose. In order to classify the two new isolates based on morphological and molecular evidence, we proposed the description of a novel species Danielozyma pruni sp. nov. with strain JCM 35735T as holotype (Mycobank MB 849101).

Genome-wide analysis of AP2/ERF superfamily in Isatis indigotica / 中西医结合学报

OBJECTIVE@#AP2/ERF (APETALA2/ethylene-responsive factor) superfamily is one of the largest gene families in plants and has been reported to participate in various biological processes, such as the regulation of biosynthesis of active lignan. However, few studies have investigated the genome-wide role of the AP2/ERF superfamily in Isatis indigotica. This study establishes a complete picture of the AP2/ERF superfamily in I. indigotica and contributes valuable information for further functional characterization of IiAP2/ERF genes and supports further metabolic engineering.@*METHODS@#To identify the IiAP2/ERF superfamily genes, the AP2/ERF sequences from Arabidopsis thaliana and Brassica rapa were used as query sequences in the basic local alignment search tool. Bioinformatic analyses were conducted to investigate the protein structure, motif composition, chromosome location, phylogenetic relationship, and interaction network of the IiAP2/ERF superfamily genes. The accuracy of omics data was verified by quantitative polymerase chain reaction and heatmap analyses.@*RESULTS@#One hundred and twenty-six putative IiAP2/ERF genes in total were identified from the I. indigotica genome database in this study. By sequence alignment and phylogenetic analysis, the IiAP2/ERF genes were classified into 5 groups including AP2, ERF, DREB (dehydration-responsive element-binding factor), Soloist and RAV (related to abscisic acid insensitive 3/viviparous 1) subfamilies. Among which, 122 members were unevenly distributed across seven chromosomes. Sequence alignment showed that I. indigotica and A. thaliana had 30 pairs of orthologous genes, and we constructed their interaction network. The comprehensive analysis of gene expression pattern in different tissues suggested that these genes may play a significant role in organ growth and development of I. indigotica. Members that may regulate lignan biosynthesis in roots were also preliminarily identified. Ribonucleic acid sequencing analysis revealed that the expression of 76 IiAP2/ERF genes were up- or down-regulated under salt or drought treatment, among which, 33 IiAP2/ERF genes were regulated by both stresses.@*CONCLUSION@#This study undertook a genome-wide characterization of the AP2/ERF superfamily in I. indigotica, providing valuable information for further functional characterization of IiAP2/ERF genes and discovery of genetic targets for metabolic engineering.

Palladium-catalyzed hydroamination of vinylidenecyclopropane-diester with pyrroles and indoles: an approach to azaaromatic vinylcyclopropanes.

A new method for the synthesis of azaaromatic vinylcyclopropanes (VCPs) has been disclosed in this paper by using pyrrole or indole derivatives as nucleophilic reagents to react with vinylidenecyclopropane-diesters (VDCP-diesters) in the presence of a Pd catalyst, a phosphine ligand and a base under mild conditions in up to 98% yield with a reasonable substrate scope. This reaction is one of the few examples of hydroamination at electron-rich allene's ß-position. A plausible reaction mechanism has also been proposed through a zwitterionic π-propargyl N-palladium species according to the previous work and the obtained deuterium labeling experimental result.

Effect of light-emitting diodes with different color rendering indexes on the ocular tissues of rat.

AIM: To compare the damage of light-emitting diodes (LEDs) with different color rendering indexes (CRIs) to the ocular surface and retina of rats. METHODS: Totally 20 Sprague-Dawley (SD) rats were randomly divided into four groups: the first group was normal control group without any intervention, other three groups were exposed by LEDs with low (LED-L), medium (LED-M), and high (LED-H) CRI respectively for 12h a day, continuously for 4wk. The changes in tear secretion (Schirmer I test, SIt), tear film break-up time (BUT), and corneal fluorescein sodium staining (CFS) scores were compared at different times (1d before experiment, 2 and 4wk after the experiment). The histopathological changes of rat lacrimal gland and retina were observed at 4wk, and the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lacrimal gland were detected by immunofluorescence method. RESULTS: With the increase of light exposed time, the CFS value of each light exposed group continued to increase, and the BUT and SIt scores continued to decrease, which were different from the control group, and the differences between the light exposed groups were statistically significant. Hematoxylin-eosin (HE) results showed that the lacrimal glands of each exposed group were seen varying degrees of acinar atrophy, vacuole distribution, increasing of eosinophil granules, etc.; the retina showed obvious reduction of photoreceptor cell layer and changes in retinal thickness; LED-L group has the most significant change in all tests. Immunofluorescence suggested that the positive expressions of TNF-α and IL-6 in the lacrimal glands of each exposed group were higher than those of the control group. CONCLUSION: LED exposure for 4wk can cause the pathological changes of lacrimal gland and retina of rats, and increase the expression of TNF-α and IL-6 in lacrimal gland, the degree of damage is negatively correlated with the CRI.

[Analysis of Ozone Pollution Spatio-temporal Evolution Characteristics and Identification of Its Long-term Variation Driving Factor over Hunan Province].

Despite the alleviation of particulate matter (PM), the ambient ozone (O3) concentration is continuously increasing in Hunan province where the investigation of O3 pollution has been rarely reported. Accordingly, the spatio-temporal evolution of O3 pollution was first analyzed based on hourly air quality data observed by national monitoring stations from 2015 to 2020 over 14 cities in Hunan province. Afterwards, the combination of meteorological data from the European Center for Medium-range Weather Forecast (ECMWF) and the generalized additive model (GAM) was applied to investigate the driving factors of the O3 long-term trend during this period. The results presented obvious diurnal, monthly, and seasonal characteristics of O3 variations. High O3 concentrations occurred in May and September monthly, and the peak O3 season was autumn. Furthermore, the 90th percentile O3 increased at a rate of 4.7 µg·(m3·a)-1 temporally, and high O3 values mainly occurred in the north-eastern region spatially, in contrast to the low O3 values in the western region. The modeling results indicated that the increase in O3 was mainly ascribed to precursor emissions. Furthermore, meteorology promoted a rise in O3 with the impact magnitude of 1 µg·(m3·a)-1. Remarkably, meteorology accelerated the O3 increases in spring, summer, and the eastern region, whereas it restrained increases in autumn, winter, and the northwest. The effect of meteorology on PM10 was different from O3 during this period. Overall, this study highlighted the importance of meteorological impacts when regulating emission reduction measures for O3 abatement. It required greater effort regarding O3 mitigation to offset the side-effect from meteorology in meteorology-sensitive seasons and regions. Additionally, the regional corporation is indispensable to reduce O3 transportation from upwind.

Evaluation of eye injury degree of laser irradiation frequency and single duration / 中华实验眼科杂志

Objective:To explore the effects of laser irradiation parameters (irradiation frequency and single duration) on tear secretion, lens and retina.Methods:Thirty-six healthy guinea pigs were randomly divided into 6 groups with random number table method according to different frequency and single exposure duration of laser to the eye, namely, high frequency short time (HFST) group, high frequency long time (HFLT) group, medium frequency short time (MFST) group, medium frequency long time (MFLT) group, low frequency short time (LFST) group and low frequency long time (LFLT) group, 6 for each group.The right eyes were irradiated with 500 lx laser as experimental eyes, and the left eyes of the guinea pigs served as the control eyes.The high, medium and low irradiation frequencies were defined as 15 times, 10 times and 5 times, respectively, and the short and long period was defined as 30 seconds and 60 seconds each time, respectively.The right eyes were irradiated based on the grouping at a 10-minute interval.The tear secretion was detected by SchirmerⅠtest; lens opacity was assessed under the slit-lamp microscope; fundus photography was performed to evaluate the general morphology of retina; retinal function was evaluated by electroretinogram (ERG) record and the thickness of retinal outer nuclear layer was measured by histopathology examination.This study protocol was approved by the Medical Ethics Committee of Air Force Military Medical University (No.20181203), and the use and care of the experimental animals complied with the ARVO statement.Results:The tear secretion was 8.00(7.37, 9.00), 8.75(8.25, 9.00), 8.50(7.75, 9.50), 9.00(8.50, 9.50), 8.00(7.37, 8.75) and 8.25(7.75, 8.75) mm/5 min in the HFST group, HFLT group, MFST group, MFLT group, LFST group and LFLT group, respectively, without significant difference among the groups(χ 2=5.502, P=0.240); after laser irradiation, there were no statistically significant differences in tear secretion between the control eyes and laser-irradiated eyes in all the groups (all at P>0.05). The lenses were clear and the fundus was normal through the experimental duration in all the groups.The amplitude of ERG a-wave was significantly reduced in the HFST group in comparison with the LFST group (P<0.05), and there was no significant difference in the b-wave amplitude among the six groups (F=1.358, P=0.268). The ERG a-, b-wave amplitudes were not significantly different between the control eyes and laser-irradiated eyes in various groups (both at P>0.05). There was no significant difference in the thickness of the outer nuclear layer of retina among the HFST group, HFLT group, MFST group, MFLT group, LFST group and LFLT group (F=0.952, P=0.463). Conclusions:The 500 lx laser irradiation is safe to ocular surface and lens, but there are some injuries to retinal function, and the injury degree is related to laser irradiation frequency.

Kα X-ray Emission from Nanowire Cu Targets Driven by Femtosecond Laser Pulses for X-ray Conversion and Backlight Imaging.

A high-quality X-ray source was proposed by modifying the target material structure characteristics driven by ultrahigh laser energy. The experiments were performed on the Ti:sapphire femtosecond laser beam device (4.3-6 J, 30 fs), one of the three XG-III lasers in Laser Fusion Research Center of China Academy of Engineering Physics. The femtosecond laser beam drove the nanowire copper material with an average length of 18-50 µm and a diameter of about 260 nm. A single-photon counting charge-coupled device was employed to measure the copper Kα X-ray emission of the nanowire and foil targets. A clear maximum photon yield of the nanowire target was calculated to be 3.6 × 108 photons sr-1 s-1, the conversion efficiency was up to 0.0087%, and the average yield was 2.5 times that of the copper foil targets. In addition, by using a pinhole imaging method of φ10 µm, the minimum full width at half maximum spot size of the X-ray source was calculated in the range of 85-240 µm, which was similar to that of the copper foil material with a long radius of 170 µm and a short radius of 63 µm. The experimental data illustrate that the nanowire has the potential to enhance the energy absorption of femtosecond laser for X-ray conversion and backlight imaging.

Ghost spintronic THz-emitter-array microscope.

Terahertz (THz) waves show great potential in nondestructive testing, biodetection and cancer imaging. Despite recent progress in THz wave near-field probes/apertures enabling raster scanning of an object's surface, an efficient, nonscanning, noninvasive, deep subdiffraction imaging technique remains challenging. Here, we demonstrate THz near-field microscopy using a reconfigurable spintronic THz emitter array (STEA) based on the computational ghost imaging principle. By illuminating an object with the reconfigurable STEA followed by computing the correlation, we can reconstruct an image of the object with deep subdiffraction resolution. By applying an external magnetic field, in-line polarization rotation of the THz wave is realized, making the fused image contrast polarization-free. Time-of-flight (TOF) measurements of coherent THz pulses further enable objects at different distances or depths to be resolved. The demonstrated ghost spintronic THz-emitter-array microscope (GHOSTEAM) is a radically novel imaging tool for THz near-field imaging, opening paradigm-shifting opportunities for nonintrusive label-free bioimaging in a broadband frequency range from 0.1 to 30 THz (namely, 3.3-1000 cm-1).

Giant dual-mode graphene-based terahertz modulator enabled by Fabry-Perot assisted multiple reflection.

We report a high-performance terahertz (THz) modulator with dual operation mode. For the pulse operation mode, the proposed THz modulator has the advantage of high modulation depth (MD) and can operate in a broadband frequency range. We have experimentally achieved a MD larger than 90% for the fifth-order pulse THz echo at 0.8 THz, and the MD stays larger than 75% in a broadband frequency range larger than 1 THz, whereas, for the coherent operation mode, the Fabry-Perot (F-P) interference effect has been taken into consideration and a MD larger than 75% at 0.76 THz has also been realized.

Terahertz wave near-field compressive imaging with a spatial resolution of over λ/100.

We demonstrate terahertz (THz) wave near-field imaging with a spatial resolution of ∼4.5 µm using single-pixel compressive sensing enabled by femtosecond-laser (fs-laser) driven vanadium dioxide (VO2)-based spatial light modulator. By fs-laser patterning a 180 nm thick VO2 nanofilm with a digital micromirror device, we spatially encode the near-field THz evanescent waves. With single-pixel Hadamard detection of the evanescent waves, we reconstructed the THz wave near-field image of an object from a serial of encoded sequential measurements, yielding improved signal-to-noise ratio by one order of magnitude over a raster-scanning technique. Further, we demonstrate that the acquisition time was compressed by a factor of over four with 90% fidelity using a total variation minimization algorithm. The proposed THz wave near-field imaging technique inspires new and challenging applications such as cellular imaging.

Comparative transcriptomic analysis reveals adriamycin-induced apoptosis via p53 signaling pathway in retinal pigment epithelial cells.

OBJECTIVE: This paper applied a transcriptomic approach to investigate the mechanisms of adriamycin (ADR) in treating proliferative vitreoretinopathy (PVR) using ARPE-19 cells. METHODS: The growth inhibitory effects of ADR on ARPE-19 cells were assessed by sulforhodamine B (SRB) assay and propidium iodide (PI) staining using flow cytometry. The differentially expressed genes between ADR-treated ARPE-19 cells and normal ARPE-19 cells and the signaling pathways involved were investigated by microarray analysis. Mitochondrial function was detected by JC-1 staining using flow cytometry and the Bcl-2/Bax protein family. The phosphorylated histone H2AX (γ-H2AX), phosphorylated checkpoint kinase 1 (p-CHK1), and phosphorylated checkpoint kinase 2 (p-CHK2) were assessed to detect DNA damage and repair. RESULTS: ADR could significantly inhibit ARPE-19 cell proliferation and induce caspase-dependent apoptosis in vitro. In total, 4479 differentially expressed genes were found, and gene ontology items and the p53 signaling pathway were enriched. A protein-protein interaction analysis indicated that the TP53 protein molecules regulated by ADR were related to DNA damage and oxidative stress. ADR reduced mitochondrial membrane potential and the Bcl-2/Bax ratio. p53-knockdown restored the activation of c-caspase-3 activity induced by ADR by regulating Bax expression, and it inhibited ADR-induced ARPE-19 cell apoptosis. Finally, the levels of the γ-H2AX, p-CHK1, and p-CHK2 proteins were up-regulated after ADR exposure. CONCLUSIONS: The mechanism of ARPE-19 cell death induced by ADR may be caspase-dependent apoptosis, and it may be regulated by the p53-dependent mitochondrial dysfunction, activating the p53 signaling pathway through DNA damage.

Giant impact of self-photothermal on light-induced ultrafast insulator-to-metal transition in VO2 nanofilms at terahertz frequency.

Ultrafast detection and switching of light are key processes in high-speed optoelectronic devices. However, the performances of VO2-based optoelectronics are strongly degraded by photothermal. The mechanism of the latter is still unclear. Here, by using femtosecond-laser (fs-laser) driven kinetic terahertz wave absorption, we quantitatively separate slow photothermal response and ultrafast photodoping response (e.g. light-induced insulator-to-metal transition) from second- to picosecond-timescales, and discover the competing interplay between them. With self-photothermal (mainly determined by fs-laser pulse repetition rate and pump fluence), the ultrafast transition time was degraded by 190% from 50 ps to 95 ps, the ultrafast transition threshold was decreased to 82% from 11mJ/cm2 to 9mJ/cm2, while the amplitudes of the two photoresponse are competing. Percolation theory, along with the macroscopic conductivity response, is used to explain the competing interplay. Our findings are relevant for designing and optimizing VO2-based ultrafast optoelectronic devices.

Ultrasensitive specific terahertz sensor based on tunable plasmon induced transparency of a graphene micro-ribbon array structure.

We proposed an ultrasensitive specific terahertz sensor consisting of two sets of graphene micro-ribbon with different widths. The interference between the plasmon resonances of the wide and narrow graphene micro-ribbons gives rise to the plasmon induced transparency (PIT) effect and enables ultrasensitive sensing in terahertz region. The performances of the PIT sensor have been analyzed in detail considering the thickness and refractive index sensing applications using full wave electromagnetic simulations. Taking advantage of the electrical tunability of graphene's Fermi level, we demonstrated the specific sensing of benzoic acid with detection limit smaller than 6.35 µg/cm2. The combination of specific identification and enhanced sensitivity of the PIT sensor opens exciting prospects for bio/chemical molecules sensing in the terahertz region.

Exotic Spectra and Lattice Vibrations of Ice X Using the DFT Method.

A typical vibrational spectrum in the ice phase has four separate bands: Translation, libration, bending, and stretching. Ice X, the final ice phase under high pressure, shows an exotic vibrational spectrum. Based on harmonic approximation, an ideal crystal of ice X has one peak, at 998 cm-1, for Raman scattering and two peaks, at 450 cm-1 and 1507 cm-1, for infrared absorption in this work. These three characteristic peaks are indicators of the phase transition between ice VII and VIII and ice X. Despite many experimental and theoretical works on ice X, only this study has clearly indicated these characteristic peaks in the region of the IR band. The phonon density of states shows quite different features than ice VIII, which could be verified by inelastic neutron scattering in the future. The dynamic processes of 15 vibrational normal modes are discussed and the typical hydrogen bonds are missing.

DFT Simulations of the Vibrational Spectrum and Hydrogen Bonds of Ice XIV.

It is always a difficult task to assign the peaks recorded from a vibrational spectrum. Herein, we explored a new pathway of density functional theory (DFT) simulation to present three kinds of spectra of ice XIV that can be referenced as inelastic neutron scattering (INS), infrared (IR), and Raman experimental spectrum. The INS spectrum is proportional to the phonon density of states (PDOS) while the photon scattering signals reflect the normal vibration frequencies near the Brillouin zone (BZ) center. Based on good agreements with the experimental data, we identified the relative frequency and made scientific assignments through normal vibration modes analysis. The two hydrogen bond (H-bond) peaks among the ice phases from INS were discussed and the dynamic process of the H-bond vibrations was found to be classified into two basic modes. We deduced that two H-bond modes are a general rule among the ice family and more studies are ongoing to investigate this subject.

Label-free monitoring of cell death induced by oxidative stress in living human cells using terahertz ATR spectroscopy.

We demonstrated that attenuated total reflectance terahertz time-domain spectroscopy (ATR THz-TDS) is able to monitor oxidative stress response of living human cells, which is proven in this work that it is an efficient non-invasive, label-free, real-time and in situ monitoring of cell death. Furthermore, the dielectric constant and dielectric loss of cultured living human breast epithelial cells, and along with their evolution under oxidative stress response induced by high concentration of H2O2, were quantitatively determined in the work. Our observation and results were finally confirmed using standard fluorescence-labeled flow cytometry measurements and visible fluorescence imaging.

Induction of chorioretinopathy by adrenaline injection in different strains of rabbits / 中华实验眼科杂志

Objective To establish a central serous chorioretinopathy (CSC) model on different strains of rabbits by intravenous injection of adrenaline,which may contribute to related researches of CSC.Methods This study was approved by Bioethics Committee of Fourth Military University and complied with Statement for the Use of Animals in Ophthalmic and Visual Research.Fundus fluorescein angiography (FFA) was initially performed on male New Zealand white rabbits (10),Belgium rabbits (5) and Chinchilla rabbits (10) to make sure that the retinas of subjects were normal.For the New Zealand white rabbits,adrenaline was injected via ear vein at a dose of 0.04 mg/kg once per day for the first 8 weeks and followed by a dose of 0.08 mg/kg for the next 4 weeks,while 0.04 mg/kg adrenaline was injected in the same way for 8 weeks in the Belgium rabbits and Chinchilla rabbits.FFA was performed every week after injection of adrenaline to evaluate the fluorescence leakage in ocular fundus.New Zealand white rabbits were sacrificed in 4 (3 rabbits),8 (3 rabbits) and 12 weeks (4 rabbits) after injection respectively,and Belgium rabbits and Chinchilla rabbits were sacrificed in the 8 weeks after injection.The eyeballs of the rabbits were enucleated to prepare the retinal sections for histopathological examination after hematoxylin-eosin staining.The results of FFA and retinal structure were compared among different strains of rabbits.Results No fluorescence leakage was found by FFA in ocular fundus,and the retinal structure was normal in all the 10 New Zealand white rabbits during the experiment.Fluorescence leakage was found by FFA in 2 Belgium rabbits at 1 week and 2 weeks after injection respectively,and retinal detachment and depigmentation of retinal pigment epithelium (RPE) with an enlarged intercellular space were shown by hematoxylin-eosin staining.For the Chinchilla rabbits,fluorescence leakages were found in 7 rabbits throughout the whole period of adrenaline administration.Circumscribed retinal detachment,depigmentation of RPE with enlarged intercellular space were also found in leakage lesions.Conclusions Repeated intravenous injection of adrenaline can induce CSC-like lesions in colored rabbits but not in albino rabbits.

Comparative transcriptomic analysis reveals adriamycin-induced apoptosis via p53 signaling pathway in retinal pigment epithelial cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#This paper applied a transcriptomic approach to investigate the mechanisms of adriamycin (ADR) in treating proliferative vitreoretinopathy (PVR) using ARPE-19 cells.@*METHODS@#The growth inhibitory effects of ADR on ARPE-19 cells were assessed by sulforhodamine B (SRB) assay and propidium iodide (PI) staining using flow cytometry. The differentially expressed genes between ADR-treated ARPE-19 cells and normal ARPE-19 cells and the signaling pathways involved were investigated by microarray analysis. Mitochondrial function was detected by JC-1 staining using flow cytometry and the Bcl-2/Bax protein family. The phosphorylated histone H2AX (γ-H2AX), phosphorylated checkpoint kinase 1 (p-CHK1), and phosphorylated checkpoint kinase 2 (p-CHK2) were assessed to detect DNA damage and repair.@*RESULTS@#ADR could significantly inhibit ARPE-19 cell proliferation and induce caspase-dependent apoptosis in vitro. In total, 4479 differentially expressed genes were found, and gene ontology items and the p53 signaling pathway were enriched. A protein-protein interaction analysis indicated that the TP53 protein molecules regulated by ADR were related to DNA damage and oxidative stress. ADR reduced mitochondrial membrane potential and the Bcl-2/Bax ratio. p53-knockdown restored the activation of c-caspase-3 activity induced by ADR by regulating Bax expression, and it inhibited ADR-induced ARPE-19 cell apoptosis. Finally, the levels of the γ-H2AX, p-CHK1, and p-CHK2 proteins were up-regulated after ADR exposure.@*CONCLUSIONS@#The mechanism of ARPE-19 cell death induced by ADR may be caspase-dependent apoptosis, and it may be regulated by the p53-dependent mitochondrial dysfunction, activating the p53 signaling pathway through DNA damage.

Dual-mode tunable terahertz generation in lithium niobate driven by spatially shaped femtosecond laser.

A new approach for dual-mode (namely broadband mode and narrowband mode) terahertz (THz) pulses generation in a single lithium niobate (LN) crystal excited by spatially shaped tilted-pulse-front femtosecond (fs) laser pulse was proposed and experimentally demonstrated. The two THz emission modes are generated simultaneously while spatially separated. Both central frequency and bandwidth of narrowband THz emission is controllable by in situ tuning the spatial modulation period and beam size of the fs-laser, and the broadband (0.1-1.5 THz) THz emission keeps almost unchanged while tuning the narrowband emission. Further optimization achieves the narrowband THz emission with energy spectral density up to 0.27 µJ/THz and with bandwidth narrowly down to 23 GHz. Such dual-mode THz source is useful for nonlinear THz optics, such as selected resonant THz excitation with broadband THz probe spectroscopy of crystalline matters.