Ultra-broadband TM-pass polarizer based on anisotropic metamaterials in lithium niobate on an insulator.

An ultra-broadband TM-pass polarizer is designed, fabricated, and experimentally demonstrated based on subwavelength grating (SWG) metamaterials in a lithium niobate on an insulator (LNOI) platform. According to our simulation, the designed device is predicted to work at a 220 nm wavelength range from 1460 to 1680 nm, covering the S-, C-, L-, U-bands of optical fiber communication. By depositing and subsequently etching a silicon nitride thin film atop the LNOI chip, the SWG structures are formed successfully by using complementary metal-oxide semiconductor (CMOS)-compatible fabrication processes. The measured results show a high polarization extinction ratio larger than 20 dB and a relatively low insertion loss below 2.5 dB over a 130 nm wavelength range from 1500 to 1630 nm, mainly limited by the operation bandwidth of our laser source.

Correlation analysis of hepatic steatosis and hepatitis B virus: a cross-sectional study.

BACKGROUND: The co-occurrence of chronic hepatitis B (CHB) and metabolic dysfunction-associated fatty liver disease (MAFLD) has drawn considerable attention due to its impact on disease outcomes. This study aimed to investigate the association between hepatic steatosis and hepatitis B virus (HBV) and analyzed the influence of hepatic steatosis on hepatitis B virology in patients with CHB. METHODS: In this cross-sectional study, 272 patients infected with HBV who were treatment-naïve or had ceased antiviral treatment for > 6 months were categorized into the CHB group (n = 128) and CHB + MAFLD group (n = 144). Furthermore, based on whether HBV DNA was higher than 2000 IU/mL, patients were categorized into the high-level HBV DNA group (n = 129) and the low-level HBV DNA group (n = 143). The impact of hepatic steatosis on hepatitis B virology was analyzed within the CHB cohort. Multivariate logistic regression analysis was employed to identify independent factors influencing pre-genomic RNA (pgRNA) levels below the lower limit of detection (LLD) in patients with CHB. RESULTS: Among the 272 patients, compared with CHB group, HBV DNA levels (4.11 vs. 3.62 log10 IU/mL, P = 0.045), hepatitis B surface antigen (HBsAg) levels (3.52 vs. 3.20 log10 IU/mL, P = 0.008) and the hepatitis B e antigen (HBeAg) positive rate (33.6% vs. 22.2%, P = 0.036) were significantly decreased in the CHB + MAFLD group; In 143 low-level HBV DNA patients, the CHB + MAFLD group exhibited decreased levels of pgRNA and HBsAg compared to the CHB group. However, in 129 high-level HBV DNA patients, a more significant decrease was observed in pgRNA (3.85 vs 3.35 log10 copies/mL, P = 0.044) and HBsAg (3.85 vs 3.59 log10 IU/mL, P = 0.033); Spearman correlation analysis revealed a negative correlation between hepatic steatosis and pgRNA (r = - 0.529, P < 0.001), HBV DNA (r = - 0.456, P < 0.001), HBsAg (r = - 0.465, P < 0.001) and HBeAg (r = - 0.339, P < 0.001) levels; Multivariate logistic regression analysis identified HBV DNA (odds ratio [OR] = 0.283, P < 0.001), HBsAg (OR = 0.300, P < 0.001), and controlled attenuation parameter (CAP) values (OR = 1.013, P = 0.038) as independent factors influencing pgRNA levels below the LLD in patients with CHB. CONCLUSIONS: This study establishes a negative correlation between hepatic steatosis and hepatitis B virology, demonstrating decreased HBV expression in patients with CHB + MAFLD.

miRNA-363-3p Hinders Proliferation, Migration, Invasion and Autophagy of Thyroid Cancer Cells by Controlling SYT1 Transcription to affect NF-κB.

BACKGROUND: Thyroid cancer (TC) is a frequent endocrine malignant tumor with various pathologic types. miRNA-363-3p plays a pivotal part in the occurrence, development, prognosis, and treatment of cancer. OBJECTIVE: To explore the mechanism of miRNA-363-3p in TC and provide a new idea for targeted therapy of TC. METHODS: Differential miRNAs and downstream target mRNAs in TC tissues were predicted with bioinformatics analysis. Expression levels of miRNA-363-3p and Synaptotagmin I (SYT1) in TC cells were ascertained by qRT-PCR. Cell migration, invasion, and proliferation were detected by wound healing assay, transwell assay, colony formation assay, CCK-8, and BrdU fluorescence experiment, respectively. Flow cytometry was utilized to detect the levels of apoptosis and necrosis. Immunofluorescence assay was used for detecting autophagosome formation in cells, and the expression levels of autophagy-related proteins, as well as NF-κB related proteins, were measured by western blot. Dual-luciferase reporter gene assay was applied for detecting the interaction between miRNA-363-3p and SYT1. RESULTS: miRNA-363-3p was prominently down-regulated in TC cells. miRNA-363-3p overexpression suppressed migration, invasion, and proliferation, promoting apoptosis and necrosis of TC cells. As the downstream target of miRNA-363-3p, SYT1 was up-regulated in TC cells. SYT1 overexpression reversed the inhibition of TC cell proliferation, invasion, migration, and autophagy mediated by miRNA-363-3p overexpression. In addition, miRNA-363-3p overexpression inhibited the activation of the NF-κB pathway in cells, while further overexpression of SYT1 weakened the inhibition of miRNA-363-3p overexpression on the NF-κB pathway. CONCLUSION: miRNA-363-3p affected the NF-κB signaling pathway by down-regulating SYT1 expression to inhibit the malignant progression of TC cells, providing theoretical support for the treatment of TC.

Mechanisms and Therapeutic Strategies for MAFLD Targeting TLR4 Signaling Pathways.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases. The underlying pathophysiological mechanisms are intricate and involve various factors. Unfortunately, there is currently a lack of available effective treatment options. Toll-like receptors (TLRs) are a group of pattern-recognition receptors that are responsible for activating the innate immune system. Research has demonstrated that TLR4 plays a pivotal role in the progression of MAFLD by facilitating the pathophysiological mechanisms. SUMMARY: Lipid peroxidation, pro-inflammatory factors, insulin resistance (IR), and dysbiosis of intestinal microbiota are considered as the pathogenic mechanisms of MAFLD. This review summarizes the impact of TLR4 signaling pathways on the progression of MAFLD, specifically in relation to lipid metabolic disorders, IR, oxidative stress, and gut microbiota disorders. Additionally, we emphasize the potential therapeutic approaches for MAFLD that target TLR4 signaling pathways, including the use of plant extracts, traditional Chinese medicines, probiotics, pharmaceuticals such as peroxisome proliferator-activated receptor antagonists and farnesol X agonists, and lifestyle modifications such as dietary changes and exercise also considered. Furthermore, TLR4 signaling pathways have also been linked to the lean MAFLD. KEY MESSAGES: TLR4 plays a crucial role in MAFLD by triggering IR, buildup of lipids, imbalance in gut microbiota, oxidative stress, and initiation of immune responses. The mitigation of MAFLD can be accomplished by suppressing the TLR4 signaling pathway. In the future, it could potentially emerge as a therapeutic target for the condition.

Low dark current density extended short-wavelength infrared superlattice photodetector with atomic layer deposited Al2O3 passivation.

We report on a low dark current density P-B-i-N extended short-wavelength infrared photodetector with atomic layer deposited (ALD) A l 2 O 3 passivation based on a InAs/GaSb/AlSb superlattice. The dark current density of the A l 2 O 3 passivated device was reduced by 38% compared to the unpassivated device. The cutoff wavelength of the photodetector is 1.8 µm at 300 K. The photodetector exhibited a room-temperature (300 K) peak responsivity of 0.44 A/W at 1.52 µm, corresponding to a quantum efficiency of 35.8%. The photodetector exhibited a specific detectivity (D ∗) of 1.08×1011 c m⋅H z 1/2/W with a low dark current density of 3.4×10-5 A/c m 2 under -50m v bias at 300 K. The low dark current density A l 2 O 3 passivated device is expected to be used in the fabrication of extended short-wavelength infrared focal plane arrays for imaging.

Adaptive dispersion compensation using a photonic integrated circuit finite impulse response filter.

Optical equalization can be used for chromatic dispersion compensation in optical communication systems to improve the system performance; however, optical signal processing (OSP) is generally specifically designed for transmission channels, that is non-adaptive to dynamic transmission distortions compared with digital signal processing (DSP). In this contribution, we demonstrate optical equalization using a photonic integrated circuit (PIC) filter for chromatic dispersion compensation, with static and adaptive techniques: (a) the static optical equalizer is calibrated based on the known fiber dispersion and length, by using the fractional delay reference method; (b) the adaptive optical equalizer is updated iteratively to compensate transmission impairments based on a least-mean squares (LMS) algorithm. Experimental results show that both the static optical equalizer and the adaptive optical LMS equalizer can give an 18-dB Q-factor for a 14-Gbd QPSK signal transmitting over 30 km. To highlight the capability of the optical equalizers, we use simulations to show the improvement in dispersion compensating characteristics by implementing additional taps.

Ridge resonators with compact guided mode coupling.

Ridge resonators are a recently introduced integrated photonic circuit element based on bound states in the continuum (BICs) which can produce a single, sharp resonance over a broad wavelength range with high extinction ratio. However, to excite these resonators, a broad beam of laterally unbound slab mode is required, resulting in a large device footprint, which is not attractive for integrated photonic circuits. In this contribution, we propose and numerically validate a guided-mode waveguide structure that can be analogue to the BIC-based ridge resonators. Our simulations show that the proposed guided-mode waveguide structure can produce resonances with similar characteristics, yet with a significantly reduced footprint. Furthermore, we investigate the influence of the resonator's dimensions on the bandwidth of the resonance, demonstrating that resonances with Q-factors from low to very high (> 10000) are feasible. We believe that the reduced footprint and ability to design filters systematically make the guided-mode waveguide resonators an attractive photonic circuit component with particular value for foundry fabricated silicon photonic circuits.

Si-Based Polarizer and 1-Bit Phase-Controlled Non-Polarizing Beam Splitter-Based Integrated Metasurface for Extended Shortwave Infrared.

Metasurfaces, composed of micro-nano-structured planar materials, offer highly tunable control over incident light and find significant applications in imaging, navigation, and sensing. However, highly efficient polarization devices are scarce for the extended shortwave infrared (ESWIR) range (1.7~2.5 µm). This paper proposes and demonstrates a highly efficient all-dielectric diatomic metasurface composed of single-crystalline Si nanocylinders and nanocubes on SiO2. This metasurface can serve as a nanoscale linear polarizer for generating polarization-angle-controllable linearly polarized light. At the wavelength of 2172 nm, the maximum transmission efficiency, extinction ratio, and linear polarization degree can reach 93.43%, 45.06 dB, and 0.9973, respectively. Moreover, a nonpolarizing beam splitter (NPBS) was designed and deduced theoretically based on this polarizer, which can achieve a splitting angle of ±13.18° and a phase difference of π. This beam splitter can be equivalently represented as an integration of a linear polarizer with controllable polarization angles and an NPBS with one-bit phase modulation. It is envisaged that through further design optimization, the phase tuning range of the metasurface can be expanded, allowing for the extension of the operational wavelength into the mid-wave infrared range, and the splitting angle is adjustable. Moreover, it can be utilized for integrated polarization detectors and be a potential application for optical digital encoding metasurfaces.

Integrated lithium niobate optical mode (de)interleaver based on an asymmetric Y-junction.

Lithium niobate on insulator (LNOI) platforms promise unique advantages in realizing high-speed, large-capacity, and large-scale photonic integrated circuits (PICs) by leveraging lithium niobate's attractive material properties, which include electro-optic and nonlinear optic properties, low material loss, and a wide transparency window. Optical mode interleavers can increase the functionality of future PICs in LNOI by enabling optical mode division multiplexing (MDM) systems, allowing variable mode assignment while maintaining high channel utilization and capacity. In this Letter, we experimentally demonstrate an optical mode interleaver based on an asymmetric Y-junction on the LNOI platform, which exhibits an insertion loss of below 0.46 dB and modal cross talk of below -13.0 dB over a wavelength range of 1500-1600 nm. The demonstrated mode interleaver will be an attractive circuit component in future high-speed and large-capacity PICs due to its simple structure, scalability, and capacity for efficient and flexible mode manipulation on the LNOI platform.

Comparative evaluation of the volume of occlusal adjustment of repositioning occlusal devices designed by using an average value digital articulator and the jaw movement analyzer.

STATEMENT OF PROBLEM: The volume of occlusal adjustment of digital occlusal devices designed with different digital occlusal articulators is unknown. PURPOSE: The purpose of this clinical study was to evaluate and compare the clinical efficacy and volume of occlusal adjustment of digital occlusal devices designed by using an average value digital articulator and the jaw movement analyzer (JMA). MATERIAL AND METHODS: Thirty participants were randomly divided into 2 groups, an Average value group and a JMA group, with 15 participants in each group. The centric relation position of the participants was determined by an experienced investigator with the aid of a leaf gauge. An intraoral scanner (TRIOS 3) was used to obtain digital scans of the maxillary and mandibular dentition and the maxillomandibular relationship record in the centric relation position. Personalized articulator parameters of participants in the JMA group were obtained by using a JMA (JMAnalyser). Different articulator parameters were used to fabricate an occlusal device in a denture design software program (exocad DentalCAD). The surface of the occlusal device was coated with a dental optical spray and then scanned by using a laboratory scanner (Kavo LS3). The process was repeated after the occlusal device was adjusted. The files of the 2 scans were imported into a reverse engineering software program, and the root mean square (RMS) values were obtained by best-fit alignment and 3-dimensional comparison. The Shapiro-Wilk normality test and homogeneity of variance test were performed, and t tests were used to evaluate differences in the RMS values between the groups (α=.05). RESULTS: The experimental data were generally normally distributed (P>.05). No statistically significant difference was found between the RMS values of the Average and the JMA groups (P>.05). CONCLUSIONS: No significant difference in the volume of occlusal adjustment was found when using occlusal devices made by using the digital average articulator or the JMA, suggesting that either method can be used to program articulators for the fabrication of occlusal devices.

Effect of internal structures on the accuracy of 3D printed full-arch dentition preparation models in different printing systems.

PURPOSE: The objective of this study was to investigate how internal structures influence the overall and marginal accuracy of full arch preparations fabricated through additive manufacturing in different printing systems. MATERIALS AND METHODS: A full-arch preparation digital model was set up with three internal designs, including solid, hollow, and grid. These were printed using three different resin printers with nine models in each group. After scanning, each data was imported into the 3D data processing software together with the master cast, aligned and trimmed, and then put into the 3D data analysis software again to compare the overall and marginal deviation whose results are expressed using root mean square values and color maps. To evaluate the trueness of the resin model, the test data and reference data were compared, and the precision was evaluated by comparing the test data sets. Color maps were observed for qualitative analysis. Data were statistically analyzed by one-way analysis of variance and Bonferroni method was used for post hoc comparison (α = .05). RESULTS: The influence of different internal structures on the accuracy of 3D printed resin models varied significantly (P < .05). Solid and grid models showed better accuracy, while the hollow model exhibited poor accuracy. The color maps show that the resin models have a tendency to shrink inwards. CONCLUSION: The internal structure design influences the accuracy of the 3D printing model, and the effect varies in different printing systems. Irrespective of the kind of printing system, the printing accuracy of hollow model was observed to be worse than those of solid and grid models.

ß-catenin promotes resistance to trastuzumab in breast cancer cells through enhancing interaction between HER2 and SRC.

More than 1 million women worldwide are diagnosed with breast cancer (BC) each year. This study aims to explore the molecular mechanisms of ß-catenin affecting the trastuzumab tolerance in HER2-positive BC. ß-catenin in BC and non-BC tissue samples were assessed by immunohistochemistry. ß-catenin and HER2 were over-expressed and knockdown to evaluate their role in tumorigenicity and trastuzumab resistance in cell and animal models using soft-agar and xenograft assays. Confocal laser immunofluorescence assay and co-immunoprecipitation were used to assess protein-protein binding. Expression of genes was detected using Western blot analysis. ß-catenin was highly expressed in primary and metastatic BC, overexpression of ß-catenin increased the colony formation of MCF7 cells when it was co-expressed with HER2 and synergically increased the tumor size in immunodeficient mice. Overexpression of ß-catenin also increased the phosphorylation of HER2 and HER3 and increased the size of tumor derived from HER2-elevated cells. Confocal laser immunofluorescence assay showed that ß-catenin and HER2 were co-localized on the membrane of MDA-MB-231 cells, suggesting that ß-catenin binds HER2 to activate the HER2 signaling pathway. Immunoprecipitation of ß-catenin and HER2 also confirmed this binding. On the other hand, knockdown of ß-catenin in MDA-MB-231 cell lines decreased the activity of SRC and decreased phosphorylation of HER2 at Y877 and Y1248. The interaction between HER2 and SRC was enhanced when ß-catenin was overexpressed, and ß-catenin increased the resistance of tumor derived from HER2 elevated BT474 cells to trastuzumab. Further analysis showed that trastuzumab inhibited the activation of HER3, but SRC was still highly expressed in cells overexpressing ß-catenin. Our work demonstrates that ß-catenin is highly expressed in BC and it synergically promotes formation and progress of BC with HER2. ß-catenin binds with HER2 leading to enhanced interaction with SRC and resistance to trastuzumab.

Minimum complexity integrated photonic architecture for delay-based reservoir computing.

Reservoir computing is an analog bio-inspired computation scheme for efficiently processing time-dependent signals, the photonic implementations of which promise a combination of massive parallel information processing, low power consumption, and high-speed operation. However, most of these implementations, especially for the case of time-delay reservoir computing, require extensive multi-dimensional parameter optimization to find the optimal combination of parameters for a given task. We propose a novel, largely passive integrated photonic TDRC scheme based on an asymmetric Mach-Zehnder interferometer in a self-feedback configuration, where the nonlinearity is provided by the photodetector, and with only one tunable parameter in the form of a phase shifting element that, as a result of our configuration, allows also to tune the feedback strength, consequently tuning the memory capacity in a lossless manner. Through numerical simulations, we show that the proposed scheme achieves good performance -when compared to other integrated photonic architectures- on the temporal bitwise XOR task and various time series prediction tasks, while greatly reducing hardware and operational complexity.

Integrated lithium niobate polarization beam splitter based on a photonic-crystal-assisted multimode interference coupler.

Lithium niobate on insulator (LNOI) is a promising platform for high-speed photonic integrated circuits (PICs) that are used for communication systems due to the excellent electro-optic properties of lithium niobate (LN). In such circuits, the high-speed electro-optical modulators and switches need to be integrated with passive circuit components that are used for routing the optical signals. Polarization beam splitters (PBSs) are one of the fundamental passive circuit components for high-speed PICs that can be used to (de)multiplex two orthogonal polarization optical modes, enabling on-chip polarization division multiplexing (PDM) systems, which are suitable for enhancing the data capacity of PICs. In this Letter, we design and experimentally demonstrate a high-performance PBS constructed by a photonic crystal (PC)-assisted multimode interference (MMI) coupler. The measured polarization extinction ratio (ER) of the fabricated device is 15 dB in the wavelength range from 1525 to 1565 nm, which makes them suitable for the high-speed and large data capacity PICs required for future communication systems.

Aspirin blocks AMPK/SIRT3-mediated glycolysis to inhibit NSCLC cell proliferation.

Non-small cell lung cancer (NSCLC) has the highest incidence and mortality in the world. Aspirin has been reported to promote apoptosis, inhibit proliferation, stemness, angiogenesis, cancer-associated inflammation and migration in NSCLC. But the effect of aspirin on aerobic glycolysis in NSCLC is less reported. In the present study, we investigated whether aspirin blocked aerobic glycolysis of NSCLC cells to inhibit proliferation. Our results showed that aspirin inhibited viability, PCNA expression, ability of colony formation, dimished extracellular acidification rate (ECAR), oxygen consumption rate (OCR) and production of pyruvic acid and lactic acid, accompanied with reduced mitochondrial membrane potential (MMP), PGC-1α expression and ROS production, indicating mitochondrial dysfunction in NSCLC cells. AMPK and mitochondrial-localized deacetylase sirtuin 3 (SIRT3) were identified as the relevant molecular targets in glycolysis, but mechanism and relationship between AMPK and SIRT3 for aspirin induced glycolysis inhibition remain unknown in cancer cells. The investigation of underlying mechanism indicated that aspirin activated AMPK pathway to inhibit aerobic glycolysis and proliferation by upregulating SIRT3 after application of compound C (CC), an inhibitor of AMPK activity or SIRT3 siRNA. Upon activation of SIRT3, aspirin promoted the release of hexokinase-II (HK-II) from mitochondrial outer membrane to cytosol by deacetylating cyclophilin D (CypD). Consistently, aspirin significantly inhibited the growth of NSCLC xenografts and exhibited antitumor activity probably through AMPK/SIRT3/HK-II pathway in vivo. Collectively, AMPK/SIRT3/HK-II pathway plays a critical role in anticancer effects of aspirin, and our findings might serve as potential target for clinical practice and chemoprevention of aspirin in NSCLC.

Arbitrary access to optical carriers in silicon photonic mode/wavelength hybrid division multiplexing circuits.

The manipulation of optical modes directly in a multimode waveguide without affecting the transmission of undesired signal carriers is of significance to realize a flexible and simple structured optical network-on-chip. In this Letter, an arbitrary optical mode and wavelength carrier access scheme is proposed based on a series of multimode microring resonators and one multimode bus waveguide with constant width. As a proof-of-concept, a three-mode (de)multiplexing device is designed, fabricated, and experimentally demonstrated. A new, to the best of our knowledge, phase-matching idea is employed to keep the bus waveguide width constant. The mode coupling regions and transmission regions of the microring resonators are designed carefully to selectively couple and transmit different optical modes. The extinction ratio of the microring resonators is larger than 21.0 dB. The mode and wavelength cross-talk for directly (de)multiplexing are less than -12.8 dB and -19.0 dB, respectively. It would be a good candidate for future large-scale multidimensional optical networks.

Wafer-Scale Synthesis of 2D Dirac Heterostructures for Self-Driven, Fast, Broadband Photodetectors.

Type-II Dirac semimetal platinum ditelluride (PtTe2) is a promising functional material for photodetectors because of its specially tilted Dirac cones, strong light absorption, and high carrier mobilities. The stack of two-dimensional (2D) Dirac heterostructures consisting of PtTe2 and graphene could overcome the limit of detection range and response time occurring in the heterostructures of graphene and other low-mobility and large-gap transition metal dichalcogenides (TMDs). Here, we report an approach for achieving highly controllable, wafer-scale production of 2D Dirac heterostructures of PtTe2/graphene with tunable thickness, variable size, and CMOS compatibility. More importantly, the optimized recipes achieve the exact stoichiometric ratio of 1:2 for Pt and Te elements without contaminating the underlayer graphene film. Because of the built-in electric field at the junction area, the photodetectors based on the PtTe2/graphene heterostructure are self-driven with a broadband photodetection from 405 to 1850 nm. In particular, the photodetectors have a high responsivity of up to ∼0.52 AW-1 (without bias) and a fast response time of ∼8.4 µs. Our work demonstrated an approach to synthesizing hybrid 2D Dirac heterostructures, which can be applied in the integration of on-chip, CMOS-compatible photodetectors with near-infrared detection, high sensitivity, and low energy consumption.

Plasmonic metal oxides and their biological applications.

Metal oxides modified with dopants and defects are an emerging class of novel materials supporting the localized surface plasmon resonance across a wide range of optical wavelengths, which have attracted tremendous research interest particularly in biological applications in the past decade. Compared to conventional noble metal-based plasmonic materials, plasmonic metal oxides are particularly favored for their cost efficiency, flexible plasmonic properties, and improved biocompatibility, which can be important to accelerate their practical implementation. In this review, we first explicate the origin of plasmonics in dopant/defect-enabled metal oxides and their associated tunable localized surface plasmon resonance through the conventional Mie-Gans model. The research progress of dopant incorporation and defect generation in metal oxide hosts, including both in situ and ex situ approaches, is critically discussed. The implementation of plasmonic metal oxides in biological applications in terms of therapy, imaging, and sensing is summarized, in which the uniqueness of dopant/defect-driven plasmonics for inducing novel functionalities is particularly emphasized. This review may provide insightful guidance for developing next-generation plasmonic devices for human health monitoring, diagnosis and therapy.

STAT6 Upregulates NRP1 Expression in Endothelial Cells and Promotes Angiogenesis.

The role of signal transducer and activator of transcription 6 (STAT6) in tumor growth has been widely recognized. However, its effects on the regulation of angiogenesis remain unclear. In this study, we found that STAT6 promoted angiogenesis, possibly by increasing the expression of neuropilin-1 (NRP1) in endothelial cells (ECs). Both STAT6 inhibitor (AS1517499) and STAT6 siRNA reduced EC proliferation, migration, and tube-formation, accompanied by downregulation of NRP1, an angiogenesis regulator. Furthermore, IL-13 induced activation of STAT6 and then increased NRP1 expression in ECs. IL-13-induced EC migration and tube formation were inhibited by NRP1 siRNA. Luciferase assay and chromatin immunoprecipitation assay demonstrated that STAT6 could directly bind to human NRP1 promoter and increase the promoter activity. In tumor xenograft models, inhibition of STAT6 reduced xenograft growth, tumor angiogenesis, and NRP1 expression in vivo. Overall, these results clarified the novel mechanism by which STAT6 regulates angiogenesis, and suggested that STAT6 may be a potential target for anti-angiogenesis therapy.

Abies spectabilis-Mediated Silver Nanoparticles Inhibits Cell Growth and Promotes Apoptosis in Breast Cancer MCF-7 Cells.

Breast cancer is the second most cause of mortality among women worldwide due to the uncontrolled proliferation of tumor cells in the mammary epithelial tissues. The silver nanoparticles were formulated from the Abies spectabilis leaf (AS-AgNPs) and characterized by various practices like UV-vis spectroscopy, FTIR, SEM, and XRD. The in vitro anticancer potential of fabricated AS-AgNPs against the MCF-7 cells were analyzed. The MTT test was executed to investigate the cytotoxic nature of fabricated AS-AgNPs against MCF-7 cells. The magnitudes of ROS accumulation and MMP level in the AS-AgNPs supplemented MCF-7 cells were studied using fluorescent staining techniques. Caspase activities were studied using assay kits. The contents of oxidative stress and antioxidant biomarker (TBARS, SOD, CAT, and GSH) levels were scrutinized by standard methods. The expressions of apoptotic markers like Bax and Bcl-2 in the AS-AgNPs administered MCF-7 cells were detected by RT-PCR assay. The MTT findings showed that both extract and fabricated AS-AgNPs remarkably decreased the MCF-7 cells. Nonetheless, both plant extract and AS-AgNPs did not affect the cell viability of MCF-10A cells. Furthermore, the fabricated AS-AgNPs improved the ROS accumulation, and depleted the MMP status in the MCF-7 cells. AS-AgNPs administered MCF-7 cells demonstrated the improved TBARS content and depleted antioxidants. The treatment with AS-AgNPs considerably elevated the caspase-9 and -3 activities and Bax expression, while decreasing the Bcl-2 expression in MCF-7 cells. Hence the current investigation reports that the formulated AS-AgNPs exhibited remarkable in vitro anticancer action against MCF-7 cells through increased ROS, oxidative stress, and apoptotic protein expression. The fabricated AS-AgNPs could be a possible anticancer remedy in the future.