Study on the interaction protein of transcription factor Smad3 based on TurboID proximity labeling technology.

TurboID is a highly efficient biotin-labelling enzyme, which can be used to explore a number of new intercalating proteins due to the very transient binding and catalytic functions of many proteins. TGF-ß/Smad3 signaling pathway is involved in many diseases, especially in diabetic nephropathy and inflammation. In this paper, a stably cell line transfected with Smad3 were constructed by using lentiviral infection. To further investigate the function of TGF-ß/Smad3, the protein labeling experiment was conducted to find the interacting protein with Smad3 gene. Label-free mass spectrometry analysis was performed to obtain 491 interacting proteins, and the interacting protein hnRNPM was selected for IP and immunofluorescence verification, and it was verified that the Smad3 gene had a certain promoting effect on the expression of hnRNPM gene, and then had an inhibitory effect on IL-6. It lays a foundation for further study of the function of Smad3 gene and its involved regulatory network.

Deep learning-based inverse design of multi-functional metasurface absorbers.

A novel approach-integrating a simulated annealing (SA) algorithm with deep learning (DL) acceleration-is presented for the rapid and accurate development of terahertz perfect absorbers through forward prediction and backward design. The forward neural network (FNN) effectively deduces the absorption spectrum based on metasurface geometry, resulting in an 80,000-fold increase in computational speed compared to a full-wave solver. Furthermore, the absorber's structure can be precisely and promptly derived from the desired response. The incorporation of the SA algorithm significantly enhances design efficiency. We successfully designed low-frequency, high-frequency, and broadband absorbers spanning the 4 to 16 THz range with an error margin below 0.02 and a remarkably short design time of only 10 min. Additionally, the proposed model in this Letter introduces a novel, to our knowledge, method for metasurface design at terahertz frequencies such as the design of metamaterials across optical, thermal, and mechanical domains.

Tunability-selective lithium niobate light modulators via high-Q resonant metasurface.

Herein, we propose and demonstrate an efficient light modulator by intercalating the nonlinear thin film into the optical resonator cavities, which introduce the ultra-sharp resonances and simultaneously lead to the spatially overlapped optical field between the nonlinear material and the resonators. Differential field intensity distributions in the geometrical perturbation-assisted optical resonator make the high quality-factor resonant modes and strong field confinement. Multiple channel light modulation is achieved in such layered system, which enables the capability for tunability-selective modulation. The maximal modulation tunability is up to 1.968 nm/V, and the figure of merit (FOM) reaches 65.6 V-1, showing orders of magnitude larger than that of the previous state-of-the-art modulators. The electrical switch voltage is down to 0.015 V, the maximal switching ratio is 833%, and the extinction ratio is also up to 9.70 dB. These features confirm the realization of high-performance modulation and hold potential for applications in switches, communication and information, augmented and virtual reality, etc.

High-performance etchless lithium niobate layer electro-optic modulator enabled by quasi-BICs.

A facile strategy is proposed for a high-performance electro-optic modulator with an etchless lithium niobate (LN) layer assisted by the silicon resonator metasurface, which pioneers the way to engineer an ultra-sharp spectral line shape via the excitation of quasi-bound states in the continuum (BICs). Meanwhile, strong out-of-plane electric/magnetic fields within the proximity area to the electro-optic layer lead to ultra-sensitive modulations. As a result, only a slight voltage change of 0.2 V is needed to fully shift the resonances and then realize switching modulation between the "off" and "on" states. The findings pave new, to the best of our knowledge, insights in reconfiguration of spatial optical fields and offer prospects for functional optoelectronic devices.

Ultra-slow-light and dynamically quantitative optical storage modulation via quasi-BICs.

We achieve dynamically tunable dual quasi-bound states in the continuum (quasi-BICs) by implementing them in a silicon-graphene multilayer composite structure and utilize the quasi-BIC modes to achieve ultra-large group delays (velocity of light slows down 105 times), showing 2-3 orders of magnitude higher than the group delays of previous electromagnetically induced transparency modes. The double-layer graphene holds great tuning capability and leads to the dramatically reduced group delay from 1929.82 to 1.58 ps with only 100 meV. In addition, the log-linear variation rule of group delay with Fermi level (Ef) in the range of 0-10 meV is analyzed in detail, and the double-logarithmic function relationship between the group delay and quality factor (Q-factor) is theoretically verified. Finally, the quantitative modulation of the optical storage is further realized in this basis. Our research provides ideas for the reform and upgrading of slow optical devices.

MicroRNA-26a in respiratory diseases: mechanisms and therapeutic potential.

MicroRNAs (miRNAs) are short, non-coding single-stranded RNA molecules approximately 22 nucleotides in length, intricately involved in post-transcriptional gene expression regulation. Over recent years, researchers have focused keenly on miRNAs, delving into their mechanisms in various diseases such as cancers. Among these, miR-26a emerges as a pivotal player in respiratory ailments such as pneumonia, idiopathic pulmonary fibrosis, lung cancer, asthma, and chronic obstructive pulmonary disease. Studies have underscored the significance of miR-26a in the pathogenesis and progression of respiratory diseases, positioning it as a promising therapeutic target. Nevertheless, several challenges persist in devising medical strategies for clinical trials involving miR-26a. In this review, we summarize the regulatory role and significance of miR-26a in respiratory diseases, and we analyze and elucidate the challenges related to miR-26a druggability, encompassing issues such as the efficiency of miR-26a, delivery, RNA modification, off-target effects, and the envisioned therapeutic potential of miR-26a in clinical settings.

Prenatal triphenyl phosphate exposure impairs placentation and induces preeclampsia-like symptoms in mice.

Triphenyl phosphate (TPhP) is an organophosphate flame retardant that is widely used in many commercial products. The United States Environmental Protection Agency has listed TPhP as a priority compound that requires health risk assessment. We previously found that TPhP could accumulate in the placentae of mice and impair birth outcomes by activating peroxisome proliferator-activated receptor gamma (PPARγ) in the placental trophoblast. However, the underlying mechanism remains unknown. In this study, we used a mouse intrauterine exposure model and found that TPhP induced preeclampsia (PE)-like symptoms, including new on-set gestational hypertension and proteinuria. Immunofluorescence analysis showed that during placentation, PPARγ was mainly expressed in the labyrinth layer and decidua of the placenta. TPhP significantly decreased placental implantation depth and impeded uterine spiral artery remodeling by activating PPARγ. The results of the in vitro experiments confirmed that TPhP inhibited extravillous trophoblast (EVT) cell migration and invasion by activating PPARγ and inhibiting the PI3K-AKT signaling pathway. Overall, our data demonstrated that TPhP could activate PPARγ in EVT cells, inhibit cell migration and invasion, impede placental implantation and uterine spiral artery remodeling, then induce PE-like symptom and impair birth outcomes. Although the exposure doses used in this study was several orders of magnitude higher than human daily intake, our study highlights the placenta as a potential target organ of TPhP worthy of further research.

Triphenyl phosphate interferes with the synthesis of steroid hormones through the PPARγ/CD36 pathway in human trophoblast JEG-3 cells.

Triphenyl phosphate (TPhP), a chemical commonly found in human placenta and breast milk, has been shown to disturb the endocrine system. Our previous study confirmed that TPhP could accumulate in the placenta and interference with placental lipid metabolism and steroid hormone synthesis, as well as induce endoplasmic reticulum (ER) stress through PPARγ in human placental trophoblast JEG-3 cells. However, the molecular mechanism underlying this disruption remains unknown. Our study aimed to identify the role of the PPARγ/CD36 pathway in TPhP-induced steroid hormone disruption. We found that TPhP increased lipid accumulation, total cholesterol, low- and high-density protein cholesterol, progesterone, estradiol, glucocorticoid, and aldosterone levels, and genes related to steroid hormones synthesis, including 3ßHSD1, 17ßHSD1, CYP11A, CYP19, and CYP21. These effects were largely blocked by co-exposure with either a PPARγ antagonist GW9662 or knockdown of CD36 using siRNA (siCD36). Furthermore, an ER stress inhibitor 4-PBA attenuated the effect of TPhP on progesterone and glucocorticoid levels, and siCD36 reduced ER stress-related protein levels induced by TPhP, including BiP, PERK, and CHOP. These findings suggest that ER stress may also play a role in the disruption of steroid hormone synthesis by TPhP. As our study has shed light on the PPARγ/CD36 pathway's involvement in the disturbance of steroid hormone biosynthesis by TPhP in the JEG-3 cells, further investigations of the potential impacts on the placental function and following birth outcome are warranted.

B7H3 increases ferroptosis resistance by inhibiting cholesterol metabolism in colorectal cancer.

Ferroptosis, a newly discovered form of regulated cell death, has been reported to be associated with multiple cancers, including colorectal cancer (CRC). However, the underlying molecular mechanism is still unclear. In this study, we identified B7H3 as a potential regulator of ferroptosis resistance in CRC. B7H3 knockdown decreased but B7H3 overexpression increased the ferroptosis resistance of CRC cells, as evidenced by the expression of ferroptosis-associated genes (PTGS2, FTL, FTH, and GPX4) and the levels of important indicators of ferroptosis (malondialdehyde, iron load). Moreover, B7H3 promoted ferroptosis resistance by regulating sterol regulatory element binding protein 2 (SREBP2)-mediated cholesterol metabolism. Both exogenous cholesterol supplementation and treatment with the SREBP2 inhibitor betulin reversed the effect of B7H3 on ferroptosis in CRC cells. Furthermore, we verified that B7H3 downregulated SREBP2 expression by activating the AKT pathway. Additionally, multiplex immunohistochemistry was carried out to show the expression of B7H3, prostaglandin-endoperoxide synthase 2, and SREBP2 in CRC tumor tissues, which was associated with the prognosis of patients with CRC. In summary, our findings reveal a role for B7H3 in regulating ferroptosis by controlling cholesterol metabolism in CRC.

Silicon-based asymmetric dimer-resonator grating for narrowband perfect absorption and sensing.

In this work, a method for designing an ultra-narrowband absorber platform is presented with asymmetric silicon-based dimer-resonators grating. Within the infrared range of 3000 ∼ 4000 nm, two narrowband absorption peaks with absorptivity greater than 99% are produced by the absorber. Moreover, during the optical sensing, such an absorber platform shows high-performance sensitivity factors for the absorption wavelengths at λ1 = 3468 nm (S = 3193 nm/RIU, FOM = 532) and at λ2 = 3562 nm (S = 3120 nm/RIU, FOM = 390). Strong scattering coupling and the magnetic resonances supported in this silicon based grating produce the high absorption. Otherwise, additional methods such as the polarization and incident angles are used to further tune the absorption responses in the intensity and wavelengths, indicating the feasibility for artificial manipulations. The achieved ultra-sharp perfect absorption and the related sensitive response hold the silicon based resonant scheme with wide applications in bio-sensing, spectral filtering and other fields.

Gradient-assisted metasurface absorber with dual-band chiral switching and quasi-linearly tunable circular dichroism.

Chiral metasurfaces with tunable or switchable circular dichroism (CD) responses hold great potential for advanced optical devices. In this work, we theoretically propose and numerically demonstrate a chiral metasurface absorber composed of periodically serrated Ge2Sb2Te5 (GST) resonators. By harnessing strong plasmonic resonance using the gradient geometry, we achieve a strongly enhanced chiral response with a CD value of 0.98 at λ2 = 2359 nm and a CD value of 0.7 at λ1 = 2274 nm. Additionally, by controlling the gradient difference in the serrated GST resonator, we can modify the CD intensity in multiple dimensions and near-perfectly optimize the chiral properties. Furthermore, it is worth noting that the CD value can be strongly varied by adjusting the phase transition characteristics of GST in the range of 0.007 to 0.7 at λ1 and 0.002 to 0.98 at λ2, corresponding to a switch between "on" and "off" states. The findings give new insight into multi-functional chiroptics and hold wide applications.

Spatial and frequency-selective optical field coupling absorption in an ultra-thin random metasurface.

Simplified thin-film structures with the capability of spatial and frequency-selective optical field coupling and absorption are desirable for nanophotonics. Herein, we demonstrate the configuration of a 200-nm-thick random metasurface formed by refractory metal nanoresonators, showing near-unity absorption (absorptivity > 90%) covering the visible and near-infrared range (0.380-1.167 µm). Importantly, the resonant optical field is observed to be concentrated in different spatial areas according to different frequencies, paving a feasible way to artificially manipulate spatial coupling and optical absorption via the spectral frequency. The methods and conclusions derived in this work are applicable throughout a wide energy range and hold applications for frequency-selective nanoscale optical field manipulation.

Near-perfect quantitatively tunable Q factors of quasi-bound states in the continuum via material-based thermal-optic perturbations.

We successfully achieved high-Q dual-band quasi-bound states in the continuum (BICs) by introducing geometrical perturbations and thermally induced material perturbations into silicon half-disk nanodimers. Importantly, it is found that the Q factor obtained from the thermally induced material perturbations fits better with the inverse quadratic function of the asymmetry relation than that of the geometrical-perturbations-based system. Notably, we demonstrated that changes occurring at the sub-K scale can enable the simultaneous realization of the full width at half maximum offset distance for quasi-BICs and a maximum contrast ratio exceeding 44 dB. Our research provides novel, to the best of our knowledge, insights for potential applications in nano-lasers, temperature sensors, and infrared imaging.

Multipolar silicon-based resonant meta-surface for electro-optical modulation and sensing.

A multipolar silicon-based resonant meta-surface scheme is proposed and numerically presented via intercalating oblique slits into the silicon patches, leading to an ultra-sharp resonant spectrum via the excitation of electric and magnetic quadrupoles and their hybridization coupling. High-performance electro-optical modulator is demonstrated, showing a spectrally shifted modulation sensitivity up to 1.546 nm/V. Moreover, novel, to the best of our knowledge, optical sensing for ion solution concentration with the detection limitation down to 5.15 × 10-3 is demonstrated as another application. These findings provide an impressive strategy for resonant silicon-based nano-photonics and opto-electronic devices.

Electromagnetic heating-assisted metasurface for stably tunable, fast-responding chiroptics.

Herein, a graphene-dielectric metasurface with the function of stably tunable and fast responding on the chiroptics is theoretically investigated and numerically demonstrated. Via utilizing the intrinsic thermo-optical effect of the silicon, the circular dichroism (CD) peak position can be linearly scaled with a spectral sensitivity of up to 0.06 nm/K by artificially adjusting the temperature. Moreover, a perfectly adjusting manipulation with a wavelength shift of full width at half maximum for the resonant spectrum and the simultaneously maintained CD values can be realized by a slight temperature variation of ∼0.8 K. Additionally, we take a graphene layer as the heating source to actually demonstrate the ultra-fast thermal generation. Applying an input voltage of 2 V to the graphene with only 10 µs can rapidly increase the metasurface temperature of up to 550 K. Such performances hold the platform with wide applications in functional chiroptics and optoelectronics.

Kerr nonlinear medium assisted double-face absorbers for differential manipulation via an all-optical operation.

Recently, light absorbers have attracted great attentions due to their promising in applications in functional optoelectronic devices. Herein, we theoretically propose and numerically demonstrate a new absorber platform, which consists of a 280-nm-thick photonic nonlinear waveguide film covering on the metal grating structure. Strong reflection inhibition and absorption enhancement is achieved in both the forward and backward directions, which indicates potential novel performances since the previous reports only achieved absorption in one side due to the using of opaque metal film substrate or the reflective mirror. The anti-reflection bands or the absorption peaks at the shorter and longer wavelength ranges are related to the excitation of the propagating surface plasmon resonance by the slit-assisted grating and the cavity mode by the slit in the metal film. Strong differential manipulation is realized for the double-face absorbers via the all-optical operation. Moreover, the operation wavelengths for the double-face light absorber can be modified strongly via using an asymmetric dielectric medium for the coating films. These new findings pave approaches for subtractive lightwave modulation technology, selective filtering, multiplex sensing and detection, etc.

Dynamically electrical/thermal-tunable perfect absorber for a high-performance terahertz modulation.

We present a high-performance functional perfect absorber in a wide range of terahertz (THz) wave based on a hybrid structure of graphene and vanadium dioxide (VO2) resonators. Dynamically electrical and thermal tunable absorption is achieved due to the management on the resonant properties via the external surroundings. Multifunctional manipulations can be further realized within such absorber platform. For instance, a wide-frequency terahertz perfect absorber with the operation frequency range covering from 1.594 THz to 3.272 THz can be realized when the conductivity of VO2 is set to 100000 S/m (metal phase) and the Fermi level of graphene is 0.01 eV. The absorption can be dynamically changed from 0 to 99.98% and in verse by adjusting the conductivity of VO2. The impedance matching theory is introduced to analyze and elucidate the wideband absorption rate. In addition, the absorber can be changed from wideband absorption to dual-band absorption by adjusting the Fermi level of graphene from 0.01 eV to 0.7 eV when the conductivity of VO2 is fixed at 100000 S/m. Besides, the analysis of the chiral characteristics of the helical structure shows that the extinction cross-section has a circular dichroic response under the excitation of two different circularly polarized lights (CPL). Our study proposes approaches to manipulate the wide-band terahertz wave with multiple ways, paving the way for the development of technologies in the fields of switches, modulators, and imaging devices.

Multiple dipolar resonant silicon-based metamaterials for high-performance optical switching and sensing.

Dielectric nanostructures reinforcing light-matter interactions by manipulating geometric parameters have a sound momentum in optoelectronic applications. Here, we construct and numerically demonstrate a new platform with multiple dipolar resonant behaviors or impressive switching operation and optical sensing with a high sensitivity and figure of merit (FOM) via the graphene-silicon combined metamaterials. Ultra-sharp resonances are excited by introducing broken symmetry in such all-dielectric metamaterials (ADMs) consisting of two silicon trapezoidal bodies on a silica substrate. By analyzing the distributions of the electromagnetic fields and current densities, we find that two types of multipole modes have been excited to support multiple ultra-narrowband resonances in the near-infrared range. The influence of geometers, such as period, thickness, asymmetry parameters, and polarization angle of the incident light, has also been studied. In addition, by adjusting the Fermi levels of graphene, we realize a 95% amplitude modulation efficiency, which manifests perfect capacity for an optical switch. According to the calculated results, the highest sensitivity can reach 447.5 nm/RIU and a large FOM is also up to 1173 RIU-1. This platform not only introduces new insight onto the achievement of high-quality ultra-sharp resonant responses but also offers a distinct possibility for the further development of high-quality related applications in optical sensors, notch filtering, strong light-matter interactions including the nonlinear optics, and multispectral optoelectronics.

Polluting characteristics, sources, cancer risk, and cellular toxicity of PAHs bound in atmospheric particulates sampled from an economic transformation demonstration area of Dongguan in the Pearl River Delta, China.

The Songshan Lake Science and Technology Industrial Park is a national economic transition demonstration area, which centers at a traditional industrial region, in Dongguan, China. We were interested in the involved atmospheric particulates-bound PAHs regarding their sources, cancer risk, and related cellular toxicity for those in other areas under comparable conditions. In this study, the daily concentrations of TSP, PM10, and PM2.5 were averaged 127.95, 95.91, and 67.62 µg/m3, and the bound PAHs were averaged 1.31, 1.22, and 0.77 ng/m3 in summer and 12.72, 20.51 and 40.27 ng/m3 in winter, respectively. The dominant PAHs were those with 5-6 rings, and 4-6 rings in summer and winter, respectively. The incremental lifetime cancer risk (ILCR) (90th percentile probability) of total PAHs was above 1.00E-06 in each age group, particularly high in adolescents. Sensitivity analysis indicated that slope factor and body weight had greater impact than exposure duration and inhalation rate on the ILCR. Moreover, treatment of human bronchial epithelial BEAS-2B cells with mixed five indicative PAHs increased the formation of ROS, DNA damage (elevation in γ-H2AX), and protein levels of CAR, PXR, CYP1A1, 1A2, 1B1, while reduced the AhR protein, with the winter mixture more potent than summer. For the sources of PAHs, the stable carbon isotope ratio analysis and diagnostic ratios consistently pointed to petroleum and fossil fuel combustion as major sources. In conclusion, our findings suggest that particulates-bound PAHs deserve serious concerns for a cancer risk in such environment, and the development of new power sources for reducing fossil fuel combustion is highly encouraged.

Triphenyl phosphate disturbs placental tryptophan metabolism and induces neurobehavior abnormal in male offspring.

Epidemiological studies have shown that prenatal triphenyl phosphate (TPhP) exposure is related to abnormal neurobehavior in children. However, the neurodevelopmental toxicity of TPhP in mammals is limited. To study the neurodevelopmental toxicity of TPhP in mammals and investigate the underlying mechanism, we used a mouse intrauterine TPhP exposure model. We measured the inflammatory factors (IL-6, TNFα) and NFκB levels, and tryptophan metabolism in placentae, detected the fetal brain transcriptome, hippocampal neuron development and neurobehavioral in the male offspring. The results showed that the protein level of IL-6, TNFα and NFκB in the placenta of the TPhP treatment group (1, 5 mg/kg) were significantly increased. Change of the protein level of these pro-inflammatory factors in maternal serum or fetal brain was not observed. Expression of genes along tryptophan-serotonin metabolism pathway were significantly decreased. While, the concentration of 5-HT levels in the placenta or fetal brain were significantly increased. Consistent with the increased 5-HT, the Nissl body was reduced in the hippocampus of treatment group. The expression of serotonergic neuron gene markers including Tph2, Htr1A, Htr2A, Pet1 and Lmx1b in the hippocampus of treatment group was significantly decreased. The neurobehavioral test showed that TPhP decreased center time that represent anxiety-like behavior, and reduced learning and memory in male offspring. Meanwhile, expression of genes along tryptophan-kynurenine metabolism pathway were significantly increased. The result of the transcriptome analysis of fetal brain showed that the differentially expressed genes are mainly involved in the transcription regulation of DNA as a template in the nucleus, and the enriched pathways are mainly signal pathways regulated by axon guidance and neurotrophic factors, dopaminergic and cholinergic synapses, suggest that not only serotonergic neuronal was affected. Overall, this study demonstrates that TPhP has the potential to induce placental inflammatory response in the placenta, disturb placental tryptophan metabolism, compromise the neuronal development and synaptic transmission, and cause abnormal neurobehavior in male offspring.