Somatic PDGFRB activating variants promote smooth muscle cell phenotype modulation in intracranial fusiform aneurysm.

BACKGROUND: The fusiform aneurysm is a nonsaccular dilatation affecting the entire vessel wall over a short distance. Although PDGFRB somatic variants have been identified in fusiform intracranial aneurysms, the molecular and cellular mechanisms driving fusiform intracranial aneurysms due to PDGFRB somatic variants remain poorly understood. METHODS: In this study, single-cell sequencing and immunofluorescence were employed to investigate the phenotypic changes in smooth muscle cells within fusiform intracranial aneurysms. Whole-exome sequencing revealed the presence of PDGFRB gene mutations in fusiform intracranial aneurysms. Subsequent immunoprecipitation experiments further explored the functional alterations of these mutated PDGFRB proteins. For the common c.1684 mutation site of PDGFRß, we established mutant smooth muscle cell lines and zebrafish models. These models allowed us to simulate the effects of PDGFRB mutations. We explored the major downstream cellular pathways affected by PDGFRBY562D mutations and evaluated the potential therapeutic effects of Ruxolitinib. RESULTS: Single-cell sequencing of two fusiform intracranial aneurysms sample revealed downregulated smooth muscle cell markers and overexpression of inflammation-related markers in vascular smooth muscle cells, which was validated by immunofluorescence staining, indicating smooth muscle cell phenotype modulation is involved in fusiform aneurysm. Whole-exome sequencing was performed on seven intracranial aneurysms (six fusiform and one saccular) and PDGFRB somatic mutations were detected in four fusiform aneurysms. Laser microdissection and Sanger sequencing results indicated that the PDGFRB mutations were present in smooth muscle layer. For the c.1684 (chr5: 149505131) site mutation reported many times, further cell experiments showed that PDGFRBY562D mutations promoted inflammatory-related vascular smooth muscle cell phenotype and JAK-STAT pathway played a crucial role in the process. Notably, transfection of PDGFRBY562D in zebrafish embryos resulted in cerebral vascular anomalies. Ruxolitinib, the JAK inhibitor, could reversed the smooth muscle cells phenotype modulation in vitro and inhibit the vascular anomalies in zebrafish induced by PDGFRB mutation. CONCLUSION: Our findings suggested that PDGFRB somatic variants played a role in regulating smooth muscle cells phenotype modulation in fusiform aneurysms and offered a potential therapeutic option for fusiform aneurysms.

Establishment of a Diamond-Blackfan anemia like model in zebrafish.

BACKGROUND: Anemia is defined as a lack of erythrocytes, low hemoglobin levels, or abnormal erythrocyte morphology. Diamond-Blackfan anemia (DBA) is a rare and severe congenital hypoplastic anemia that occurs due to the dominant inheritance of a ribosomal protein gene mutation. Even rarer is a case described as Diamond-Blackfan anemia like (DBAL), which occurs due to a loss-of-function EPO mutation recessive inheritance. The effective cures for DBAL are bone marrow transfusion and treatment with erythropoiesis-stimulating agents (ESAs). To effectively manage the condition, construction of DBAL models to identify new medical methods or screen drugs are necessary. RESULTS: Here, an epoa-deficient mutant zebrafish called epoaszy8 was generated to model DBAL. The epoa-deficiency in zebrafish caused developmental defects in erythroid cells, leading to severe congenital anemia. Using the DBAL model, we validated a loss-of-function EPO mutation using an in vivo functional analysis and explored the ability of ESAs to alleviate congenital anemia. CONCLUSIONS: Together, our study demonstrated that epoa deficiency in zebrafish leads to a phenotype resembling DBAL. The DBAL zebrafish model was found to be beneficial for the in vivo assessment of patient-derived EPO variants with unclear implications and for devising potential therapeutic approaches for DBAL.

Thermo-optic epsilon-near-zero effects.

Nonlinear epsilon-near-zero (ENZ) nanodevices featuring vanishing permittivity and CMOS-compatibility are attractive solutions for large-scale-integrated systems-on-chips. Such confined systems with unavoidable heat generation impose critical challenges for semiconductor-based ENZ performances. While their optical properties are temperature-sensitive, there is no systematic analysis on such crucial dependence. Here, we experimentally report the linear and nonlinear thermo-optic ENZ effects in indium tin oxide. We characterize its temperature-dependent optical properties with ENZ frequencies covering the telecommunication O-band, C-band, and 2-µm-band. Depending on the ENZ frequency, it exhibits an unprecedented 70-93-THz-broadband 660-955% enhancement over the conventional thermo-optic effect. The ENZ-induced fast-varying large group velocity dispersion up to 0.03-0.18 fs2nm-1 and its temperature dependence are also observed for the first time. Remarkably, the thermo-optic nonlinearity demonstrates a 1113-2866% enhancement, on par with its reported ENZ-enhanced Kerr nonlinearity. Our work provides references for packaged ENZ-enabled photonic integrated circuit designs, as well as a new platform for nonlinear photonic applications and emulations.

Active Micelle Pumping Channel Triggers Nonequilibrium Surface Excess Aggregation.

Adsorbate transport during the electrochemical process mostly follows the electric-field direction or the high-to-low direction along the concentration gradient and thus often limits the reactant concentration at the adsorption site and requires specific mechanical or chemical bonds of adsorbates to trigger local excess aggregation for advanced framework structure assembly. Herein, we have discovered an active pumping channel during electrochemical adsorption of a manganese colloid, which follows a low-to-high direction inverse concentration gradient. It triggers surface excess micelle aggregation with even over 16-folds higher concentration than that in bulk owing to hydrogen-bonding difference of the micelle surface between in bulk and at the water surface. Micelles in the channel exhibit unique polymerization behaviors by directly polymerizing monomer micelles to form highly catalytic MnO2 of dendritic frameworks, which can serve as a scalable thin-layer aqueous-phase reactor. It increases the understanding of the interface-dependent dynamic nature of micelle or more adsorbates and inspires transformative synthesizing approaches for advanced oxide materials.

Manufacturing-Enabled Tunability of Linear and Nonlinear Epsilon-Near-Zero Properties in Indium Tin Oxide Nanofilms.

Epsilon-near-zero (ENZ) materials have attracted great interest due to their exotic linear and nonlinear responses, which makes it significant to tune ENZ wavelengths for wavelength-dependent applications. However, studies to achieve tunability in a wide spectral range and link the fabrication parameters with linear and nonlinear ENZ properties have been uncovered. ENZ indium tin oxide (ITO) nanofilms are fabricated by magnetron sputtering, through which the control of ENZ properties is demonstrated. Factors in the sputtering process, such as the gas ratio and annealing, have a great impact on the ITO samples. Tunable ENZ parameters are listed to provide a beneficial database for ENZ ITO, mainly attributed to the change of carrier concentration. The influence of ENZ parameters on optical characteristics via annealing treatment is further explored. The ENZ wavelength is blue-shifted by 609 nm, and the intrinsic loss is reduced by 63.2%, while the ITO samples exhibit better linear scattering properties and stronger field intensity enhancement. Additionally, the laser testing system illustrates the change from reverse saturable absorption to saturable absorption with an absolute modulation depth of 21.9%, improved by 222.1%, and the nonlinear refractive index n2 and nonlinear absorption coefficient ß are 2.07 × 10-16 m2 W-1 and -3.16 × 10-10 m W-1 for post-annealed ITO samples, respectively. The proposed sputtering protocol offers a feasible technique to control the linear and nonlinear ENZ performance, which has great potential in laser technology and nanophotonics.

Semantic matching based legal information retrieval system for COVID-19 pandemic.

Recently, the pandemic caused by COVID-19 is severe in the entire world. The prevention and control of crimes associated with COVID-19 are critical for controlling the pandemic. Therefore, to provide efficient and convenient intelligent legal knowledge services during the pandemic, we develop an intelligent system for legal information retrieval on the WeChat platform in this paper. The data source we used for training our system is "The typical cases of national procuratorial authorities handling crimes against the prevention and control of the new coronary pneumonia pandemic following the law", which is published online by the Supreme People's Procuratorate of the People's Republic of China. We base our system on convolutional neural network and use the semantic matching mechanism to capture inter-sentence relationship information and make a prediction. Moreover, we introduce an auxiliary learning process to help the network better distinguish the relation between two sentences. Finally, the system uses the trained model to identify the information entered by a user and responds to the user with a reference case similar to the query case and gives the reference legal gist applicable to the query case.

Bright and dark Talbot pulse trains on a chip.

Temporal Talbot effect, the intriguing phenomenon of the self-imaging of optical pulse trains, is extensively investigated using macroscopic components. However, the ability to manipulate pulse trains, either bright or dark, through the Talbot effect on integrated photonic chips to replace bulky instruments has rarely been reported. Here, we design and experimentally demonstrate a proof-of-principle integrated silicon nitride device capable of imprinting the Talbot phase relation onto in-phase optical combs and generating the two-fold self-images at the output. We show that the GHz-repetition-rate bright and dark pulse trains can be doubled without affecting their spectra as a key feature of the temporal Talbot effect. The designed chip can be electrically tuned to switch between pass-through and repetition-rate-multiplication outputs and is compatible with other related frequencies. The results of this work lay the foundations for the large-scale system-on-chip photonic integration of Talbot-based pulse multipliers, enabling the on-chip flexible up-scaling of pulse trains' repetition rate without altering their amplitude spectra.

Ultrafast dynamic switching of optical response based on nonlinear hyperbolic metamaterial platform.

The pursuit of high-speed and on-chip optical communication systems has promoted extensive exploration of all-optical control of light-matter interactions via nonlinear optical processes. Here, we have numerically investigated the ultrafast dynamic switching of optical response using tunable hyperbolic metamaterial (HMM) which consists of five pairs of alternating layers of indium tin oxide (ITO) and SiO2. The nonlinearity of the HMM is analyzed by the ultrafast dynamics of the hot electrons in the epsilon-near-zero (ENZ) ITO. Our approach allows large and broad all-optical modulation of the effective permittivity and topology of the HMM on the femtosecond time-scale. Based on the proposed HMM platform, we have shown considerable tunability in the extinction ratio and Purcell enhancement under various pump fluence. In addition, we have achieved all-optical control of the coupling strength through depositing plasmonic resonators on the HMM platform. A significant tuning of the coupled resonance is observed by changing pump fluence, which leads to a switching time within 213 fs at a specific wavelength with a relative modulation depth more than 15 dB.

Ultrafast dynamic switching of optical response based on nonlinear hyperbolic metamaterial platform: erratum.

We present an erratum to our previously published work ["Ultrafast dynamic switching of optical response based on nonlinear hyperbolic metamaterial platform," Opt. Express30(12), 21634 (2022).10.1364/OE.457875]. The corrections do not affect the results and conclusion of the original paper.

All-optical switching in epsilon-near-zero asymmetric directional coupler.

We propose an all-optical switch based on an asymmetric directional coupler structure with epsilon-near-zero (ENZ) layer. The nonlinear optical properties the of ENZ layer are analyzed by hot-electron dynamics process, and the all-optical operating performance of the switch on the silicon nitride platform is investigated. It is found that the pump-induced refractive index change in ENZ layer gives rise to a transfer of signal light in the optical system. We demonstrate that the proposed switch design features an insertion loss of < 2.7 dB, low crosstalk of < - 18.93 dB, and sub-pico-second response time at the communication wavelength of 1.55 µm. With ultrafast response, high performance, and simple structure, the device provides new possibilities for all-optical communication and signal processing.

Research on Hyperparameter Optimization of Concrete Slump Prediction Model Based on Response Surface Method.

In this paper, eight variables of cement, blast furnace slag, fly ash, water, superplasticizer, coarse aggregate, fine aggregate and flow are used as network input and slump is used as network output to construct a back-propagation (BP) neural network. On this basis, the learning rate, momentum factor, number of hidden nodes and number of iterations are used as hyperparameters to construct 2-layer and 3-layer neural networks respectively. Finally, the response surface method (RSM) is used to optimize the parameters of the network model obtained previously. The results show that the network model with parameters obtained by the response surface method (RSM) has a better coefficient of determination for the test set than the model before optimization, and the optimized model has higher prediction accuracy. At the same time, the model is used to evaluate the influencing factors of each variable on slump. The results show that flow, water, coarse aggregate and fine aggregate are the four main influencing factors, and the maximum influencing factor of flow is 0.875. This also provides a new idea for quickly and effectively adjusting the parameters of the neural network model to improve the prediction accuracy of concrete slump.

Temporal Talbot effect of optical dark pulse trains.

The temporal Talbot effect describes the periodic self-imaging of an optical pulse train along dispersive propagation. This is well studied in the context of bright pulse trains, where identical or multiplied pulse trains with uniform bright waveforms can be created. However, the temporal self-imaging has remained unexplored in the dark pulse regime. Here, we disclose such a phenomenon for optical dark pulse trains, and discuss the comparison with their bright pulse counterparts. It is found that the dark pulse train also revives itself at the Talbot length. For higher-order fractional self-imaging, a mixed pattern of bright and dark pulses is observed, as a result of the interference between the Talbot pulses and the background. Such unconventional behaviors are theoretically predicted and experimentally demonstrated by using programmable spectral shaping as well as by optical fiber propagation.

Establishment of a Bernard-Soulier syndrome model in zebrafish.

Platelets play an essential role in thrombosis and hemostasis. Abnormal hemostasis can cause spontaneous or severe post-traumatic bleeding. Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder caused by a complete quantitative deficiency in the GPIb-IX-V complex. Multiple mutations in GP9 lead to the clinical manifestations of BSS. Understanding the roles and underlying mechanisms of GP9 in thrombopoiesis and establishing a proper animal model of BSS would be valuable to understand the disease pathogenesis and to improve its medical management. Here, by using CRISPR-Cas9 technology, we created a zebrafish gp9SMU15 mutant to model human BSS. Disruption of zebrafish gp9 led to thrombocytopenia and a pronounced bleeding tendency, as well as an abnormal expansion of progenitor cells. The gp9SMU15 zebrafish can be used as a BSS animal model as the roles of GP9 in thrombocytopoiesis are highly conserved from zebrafish to mammals. Utilizing the BSS model, we verified the clinical GP9 mutations by in vivo functional assay and tested clinical drugs for their ability to increase platelets. Thus, the inherited BSS zebrafish model could be of benefit for in vivo verification of patient-derived GP9 variants of uncertain significance and for the development of potential therapeutic strategies for BSS.

Manipulation of epsilon-near-zero wavelength for the optimization of linear and nonlinear absorption by supercritical fluid.

We introduce supercritical fluid (SCF) technology to epsilon-near-zero (ENZ) photonics for the first time and experimentally demonstrate the manipulation of the ENZ wavelength for the enhancement of linear and nonlinear optical absorption in ENZ indium tin oxide (ITO) nanolayer. Inspired by the SCF's applications in repairing defects, reconnecting bonds, introducing dopants, and boosting the performance of microelectronic devices, here, this technique is used to exploit the influence of the electronic properties on optical characteristics. By reducing oxygen vacancies and electron scattering in the SCF oxidation process, the ENZ wavelength is shifted by 23.25 nm, the intrinsic loss is reduced by 20%, and the saturable absorption modulation depth is enhanced by > 30%. The proposed technique offers a time-saving low-temperature technique to optimize the linear and nonlinear absorption performance of plasmonics-based ENZ nanophotonic devices.

Self-interaction of ultrashort pulses in an epsilon-near-zero nonlinear material at the telecom wavelength.

Dynamics of femtosecond pulses with the telecom carrier wavelength is investigated numerically in a subwavelength layer of an indium tin oxide (ITO) epsilon-near-zero (ENZ) material with high dispersion and high nonlinearity. Due to the subwavelength thickness of the ITO ENZ material, and the fact that the pulse's propagation time is shorter than its temporal width, multiple reflections give rise to self-interaction in both spectral and temporal domains, especially at wavelengths longer than at the ENZ point, at which the reflections are significantly stronger. A larger absolute value of the pulse's chirp strongly affects the self-interaction by redistributing energy between wavelengths, while the sign of the chirp affects the interaction in the temporal domain. It is also found that, when two identical pulses are launched simultaneously from both ends, a subwavelength counterpart of a standing-wave state can be established. It shows robust energy localization in the middle of the sample, in terms of both the spectral and temporal intensity distributions.

Nitric Oxide Enhances Cytotoxicity of Lead by Modulating the Generation of Reactive Oxygen Species and Is Involved in the Regulation of Pb2+ and Ca2+ Fluxes in Tobacco BY-2 Cells.

Lead is a heavy metal known to be toxic to both animals and plants. Nitric oxide (NO) was reported to participate in plant responses to different heavy metal stresses. In this study, we analyzed the function of exogenous and endogenous NO in Pb-induced toxicity in tobacco BY-2 cells, focusing on the role of NO in the generation of reactive oxygen species (ROS) as well as Pb2+ and Ca2+ fluxes using non-invasive micro-test technology (NMT). Pb treatment induced BY-2 cell death and rapid NO and ROS generation, while NO burst occurred earlier than ROS accumulation. The elimination of NO by 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) resulted in a decrease of ROS, and the supplementation of NO by sodium nitroprusside (SNP) caused an increased accumulation of ROS. Furthermore, the addition of exogenous NO stimulated Pb2+ influx, thus promoting Pb uptake in cells and aggravating Pb-induced toxicity in cells, whereas the removal of endogenous NO produced the opposite effect. Moreover, we also found that both exogenous and endogenous NO enhanced Pb-induced Ca2+ effluxes and calcium homeostasis disorder. These results suggest that exogenous and endogenous NO played a critical regulatory role in BY-2 cell death induced by Pb stress by promoting Pb2+ influx and accumulation and disturbing calcium homeostasis.

Shear-Assisted Production of Few-Layer Boron Nitride Nanosheets by Supercritical CO2 Exfoliation and Its Use for Thermally Conductive Epoxy Composites.

Boron nitride nanosheets (BNNS) hold the similar two-dimensional structure as graphene and unique properties complementary to graphene, which makes it attractive in application ranging from electronics to energy storage. The exfoliation of boron nitride (BN) still remains challenge and hinders the applications of BNNS. In this work, the preparation of BNNS has been realized by a shear-assisted supercritical CO2 exfoliation process, during which supercritical CO2 intercalates and diffuses between boron nitride layers, and then the exfoliation of BN layers is obtained in the rapid depressurization process by overcoming the van der Waals forces. Our results indicate that the bulk boron nitride has been successfully exfoliated into thin nanosheets with an average 6 layers. It is found that the produced BNNS is well-dispersed in isopropyl alcohol (IPA) with a higher extinction coefficient compared with the bulk BN. Moreover, the BNNS/epoxy composite used as thermal interface materials has been prepared. The introduction of BNNS results in a 313% enhancement in thermal conductivity. Our results demonstrate that BNNS produced by supercritical CO2 exfoliation show great potential applications for heat dissipation of high efficiency electronics.

Ultrastrong extraordinary transmission and reflection in PT-symmetric Thue-Morse optical waveguide networks.

In this paper, we construct a 1D PT-symmetric Thue-Morse aperiodic optical waveguide network (PTSTMAOWN) and mainly investigate the ultrastrong extraordinary transmission and reflection. We propose an approach to study the photonic modes and solve the problem of calculating photonic modes distributions in aperiodic networks due to the lack of dispersion functions and find that in a PTSTMAOWN there exist more photonic modes and more spontaneous PT-symmetric breaking points, which are quite different from other reported PT-symmetric optical systems. Additionally, we develop a method to sort spontaneous PT-symmetric breaking point zones to seek the strongest extraordinary point and obtain that at this point the strongest extraordinary transmission and reflection arrive at 2.96316 × 105 and 1.32761 × 105, respectively, due to the PT-symmetric coupling resonance and the special symmetry pattern of TM networks. These enormous gains are several orders of magnitude larger than the previous results. This optical system may possess potential in designing optical amplifier, optical logic elements in photon computers and ultrasensitive optical switches with ultrahigh monochromatity.