Microcomb-driven silicon photonic systems.

Microcombs have sparked a surge of applications over the past decade, ranging from optical communications to metrology1-4. Despite their diverse deployment, most microcomb-based systems rely on a large amount of bulky elements and equipment to fulfil their desired functions, which is complicated, expensive and power consuming. By contrast, foundry-based silicon photonics (SiPh) has had remarkable success in providing versatile functionality in a scalable and low-cost manner5-7, but its available chip-based light sources lack the capacity for parallelization, which limits the scope of SiPh applications. Here we combine these two technologies by using a power-efficient and operationally simple aluminium-gallium-arsenide-on-insulator microcomb source to drive complementary metal-oxide-semiconductor SiPh engines. We present two important chip-scale photonic systems for optical data transmission and microwave photonics, respectively. A microcomb-based integrated photonic data link is demonstrated, based on a pulse-amplitude four-level modulation scheme with a two-terabit-per-second aggregate rate, and a highly reconfigurable microwave photonic filter with a high level of integration is constructed using a time-stretch approach. Such synergy of a microcomb and SiPh integrated components is an essential step towards the next generation of fully integrated photonic systems.

Study on hydraulic conductivity of dredged sediment-attapulgite vertical cutoff walls under confining pressure.

Landfills require effective containment systems to prevent the leakage of leachate into the underground environment. Cutoff walls are commonly employed for this purpose, with options including rigid and flexible designs. In areas where structural strength is not a primary concern, flexible cutoff walls offer lower permeability and environmental benefits due to their lack of cement content, thereby reducing CO2 emissions. This study investigates the use of dredged sediment and attapulgite as materials for flexible cutoff walls. Through analyses of bound water content, free water content, hydraulic conductivity, and scanning electron microscopy, we explore the impact of confining pressures on cutoff wall permeability. Our findings reveal that the consolidation induced by confining pressure does not significantly alter the bound water content within the cutoff wall. Instead, changes in water content are predominantly attributed to variations in free water content. Under identical confining pressures, we observe a positive correlation between permeability and hydraulic gradient, with permeability increasing as the hydraulic gradient rises, and anti-permeability decreasing accordingly. Additionally, when holding the hydraulic gradient constant, increasing confining pressure leads to a continuous decrease in permeability. Microscopic analyses highlight that high confining pressure not only compresses pore diameter but also alters pore morphology, thereby influencing permeability. This study contributes to the understanding of cutoff wall behavior under different conditions. Our results demonstrate that increasing confining pressure during soil consolidation effectively reduces cutoff wall permeability to meet design standards. However, the influence of high leachate head on permeability should also be considered. These findings provide a more environmentally friendly and lower permeability option for landfill sites, which is significant for the design and enhancement of containment systems in landfill sites.

Identification of a Novel Post-transcriptional Transactivator from the Equine Infectious Anemia Virus.

All lentiviruses encode a post-transcriptional transactivator, Rev, which mediates the export of viral mRNA from the nucleus to the cytoplasm and which is required for viral gene expression and viral replication. In the current study, we demonstrate that equine infectious anemia virus (EIAV), an equine lentivirus, encodes a second post-transcriptional transactivator that we designate Grev. Grev is encoded by a novel transcript with a single splicing event that was identified using reverse transcription-PCR (RT-PCR) and RNA-seq in EIAV-infected horse tissues and cells. Grev is about 18 kDa in size, comprises the first 18 amino acids (aa) of Gag protein together with the last 82 aa of Rev, and was detected in EIAV-infected cells. Similar to Rev, Grev is localized to the nucleus, and both are able to mediate the expression of Mat (a recently identified viral protein of unknown function from EIAV), but Rev can mediate the expression of EIAV Gag/Pol, while Grev cannot. We also demonstrate that Grev, similar to Rev, specifically binds to rev-responsive element 2 (RRE-2, located in the first exon of mat mRNAs) to promote nuclear export of mat mRNA via the chromosome region maintenance 1 (CRM1) pathway. However, unlike Rev, whose function depends on its multimerization, we could not detect multimerization of Grev using coimmunoprecipitation (co-IP) or bimolecular fluorescence complementation (BiFC) assays. Together, these data suggest that EIAV encodes two post-transcriptional transactivators, Rev and Grev, with similar, but not identical, functions. IMPORTANCE Nuclear export of viral transcripts is a crucial step for viral gene expression and viral replication in lentiviruses, and this export is regulated by a post-transcriptional transactivator, Rev, that is shared by all lentiviruses. Here, we report that the equine infectious anemia virus (EIAV) encodes a novel viral protein, Grev, and demonstrated that Grev, like Rev, mediates the expression of the viral protein Mat by binding to the first exon of mat mRNAs via the chromosome region maintenance 1 (CRM1) pathway. Grev is encoded by a single-spliced transcript containing two exons, whereas Rev is encoded by a multiple-spliced transcript containing four exons. Moreover, Rev is able to mediate EIAV Gag/Pol expression by binding to rev-responsive element (RRE) located within the Env-coding region, while Grev cannot. Therefore, the present study demonstrates that EIAV encodes two post-transcriptional regulators, Grev and Rev, suggesting that post-transcriptional regulation patterns in lentivirus are diverse and complex.

A Novel, Fully Spliced, Accessory Gene in Equine Lentivirus with Distinct Rev-Responsive Element.

All lentiviruses encode the accessory protein Rev, whose main biological function is to mediate the nuclear export of unspliced and incompletely spliced viral transcripts by binding to a viral cis-acting element (termed the Rev-responsive element, RRE) within the env-encoding region. Equine infectious anemia virus (EIAV) is a member of the lentivirus genus in the Retroviridae family and is considered an important model for the study of lentivirus pathogenesis. Here, we identified a novel transcript from the EIAV genome that encoded a viral protein, named Mat, with an unknown function. The transcript mat was fully spliced and comprised parts of the coding regions of MA and TM. Interestingly, the expression of Mat depended on Rev and the chromosome region maintenance 1 (CRM1) pathway. Rev could specifically bind to Mat mRNA to promote its nuclear export. We further identified that the first exon of Mat mRNA, which was located within the Gag-encoding region, acted as an unreported RRE. Altogether, we identified a novel fully spliced transcript mat with an unusual RRE, which interacted with Rev for nuclear export through the CRM1 pathway. These findings updated the EIAV genome structure, highlighted the diversification of posttranscriptional regulation patterns in EIAV, and may help to expand the understanding of gene transcription and expression of lentivirus. IMPORTANCE In lentiviruses, the nuclear export of viral transcripts is an important step in controlling viral gene expression. Generally, the unspliced and incompletely spliced transcripts are exported via the CRM1-dependent export pathway in a process mediated by the viral Rev protein by binding to the Rev-responsive element (RRE) located within the Env-coding region. However, the completely spliced transcripts are exported via an endogenous cellular pathway, which was Rev independent. Here, we identified a novel fully spliced transcript from EIAV and demonstrated that it encoded a viral protein, termed Mat. Interestingly, we determined that the expression of Mat depended on Rev and identified that the first exon of Mat mRNA could specifically bind to Rev and be exported to the cytoplasm, which suggested that the first exon of Mat mRNA was a second RRE of EIAV. These findings provided important insights into the Rev-dependent nuclear export of completely spliced transcripts in lentiviruses.

Truncation of the Cytoplasmic Tail of Equine Infectious Anemia Virus Increases Virion Production by Improving Env Cleavage and Plasma Membrane Localization.

Envelope glycoproteins (Envs) of lentiviruses harbor unusually long cytoplasmic tails (CTs). Natural CT truncations always occur in vitro and are accompanied by attenuated virulence, but their effects on viral replication have not been fully elucidated. The Env in equine infectious anemia virus (EIAV) harbors the longest CT in the lentiviral family, and a truncated CT was observed in a live attenuated vaccine. This study demonstrates that CT truncation significantly increased EIAV production, as determined by comparing the virion yields from EIAV infectious clones in the presence and absence of the CT. A significant increase in a cleaved product from the CT-truncated Env precursor, but not the full-length Env, was observed. We further confirmed that the presence of the CT inhibited the cleavage of the Env precursor and found that a functional domain located at the C terminus was responsible for this function. Moreover, CT-truncated Env was mainly localized at the plasma membrane (PM), while full-length Env was mainly localized in the cytoplasm. The CT truncation caused a dramatic reduction in the endocytosis of Env. These results suggest that the CT can modulate the processing and trafficking of EIAV Env and thus regulate EIAV replication. IMPORTANCE The mature lentivirus envelope glycoprotein (Env) is composed of a surface unit (SU) and a transmembrane unit (TM), which are cleaved products of the Env precursor. After mature Env is heterodimerically formed from the cleavage of the Env precursor, it is trafficked to the plasma membrane (PM) for incorporation and virion assembly. Env harbors a long cytoplasmic tail (CT), which has been increasingly found to play multiple roles in the Env biological cycle. Here, we revealed for the first time that the CT of equine infectious anemia virus (EIAV) Env inhibits cleavage of the Env precursor. Simultaneously, the CT promoted Env endocytosis, resulting in weakened Env localization at the PM. We also validated that the CT could significantly decrease EIAV production. These findings suggest that the CT regulates the processing and trafficking of EIAV Env to balance virion production.

Orexin A Suppresses the Expression of Exosomal PD-L1 in Colon Cancer and Promotes T Cell Activity by Inhibiting JAK2/STAT3 Signaling Pathway.

BACKGROUND: Colon cancer, ranked third in cancer related mortality, is the most common malignant cancer of digestive tract. Though immune checkpoint inhibitors show promising efficacy in colon cancer, a rather high unresponsive rate and recurrence rate requires further elucidation of the underlying regulatory mechanism of cancer-related immunity. AIMS: To study the regulatory function of Orexin A in the expression of exosomal PD-L1 and T cell activity. METHODS: Orthotopic colon cancer transplantation mice model were established to study the cancer growth and immune infiltration between Orexin A treated group and untreated group. In vitro studies using mouse CT-26 and human HCT-116 colon cancer cell model studied the effect of Orexin A on cellular and exosomal PD-L1 expression. Co-culturing Jurkat cells with exosomes delivered by cancer cells treated with Orexin A, PD-L1 knockdown and PBS studied different effects on T cell. Comparing Orexin A with WP1066, a JAK2/STAT3 inhibitor verified the mechanism of these changes. RESULTS: The growth rate of orthotopic transplanted colon cancer was slower in Orexin A treated group, with lower PD-L1 expression and higher immune infiltration. Orexin A could inhibit cellular and exosomal PD-L1 expression. The decreased expression of PD-L1 in exosomes could promote the activity of Jurkat cells secreting higher level of IFN-γ and IL-2. Orexin A showed a similar effect like WP1066 which proved JAK2/STAT3 signaling pathway was its downstream signaling pathway. CONCLUSIONS: Orexin A could suppress the expression of exosomal PD-L1 in colon cancer cells and promote T cells activity by inhibiting JAK2/STAT3 signaling pathway.

Ultra-compact hybrid plasmonic mode convertor based on unidirectional eigenmode expansion.

An ultra-compact hybrid plasmonic mode convertor is demonstrated based on a hybrid plasmonic slot waveguide structure. Benefiting from the unidirectional eigenmode expansion approach, a mode-interference-based ${{\rm TE}_{00}}$TE00-to-${{\rm TM}_{01}}$TM01 mode convertor is realized for the first time, to the best of our knowledge, with an ultra-compact footprint of only ${2}.{33} \times {7}\,\,\unicode{x00B5} {{\rm m}^2}$2.33×7µm2. At the wavelength of 1550 nm, the insertion loss is below 2.34 dB, and the extinction ratio is 25.6 dB with mode conversion purity as high as 94.6%. The extinction ratio is over 15.5 dB for the entire C-band with a bandwidth of extinction ratio above 10 dB larger than 110 nm. The transmissivity of the crosstalk ${{\rm TE}_{10}}$TE10 and ${{\rm TE}_{02}}$TE02 at 1550 nm is $ - {16.1}$-16.1 and $ - {22.7}\,\,{\rm dB}$-22.7dB, respectively.

Integration of Microstrip Slot Array Antenna with Dye-Sensitized Solar Cells.

This paper describes the integration of microstrip slot array antennas with dye-sensitized solar cells that can power array antennas at 5.8 GHz, ensuring normal communications. To appraise the antennas, a 2 × 2 circularly polarized microstrip slot array antenna integrated with dye-sensitized solar cells using a stacked design method was analyzed, fabricated and measured. The size of the entire array is 140 mm × 140 mm, where the size of each solar cell is 35 mm × 35 mm. The results show that the effect of the antenna has a slight influence on the output performance of the solar cells, and the interference of the output current of the solar cells to the antenna feeding system is negligible. The gain of the array antenna increases by 0.12 dB and the axial ratio is reduced to 1.50 dB after the integration of dye-sensitized solar cells. The integration saves a lot of space, and has the ability of self-sustaining power generation, thus providing reliable and long-term communication for various communication systems.

Demonstration of a robust insertion loss measuring approach for low-loss silicon photonic devices.

A robust optical insertion loss measuring approach based on a symmetrically coupled add-drop microring resonator is demonstrated on silicon-on-insulator platform. Utilizing resonant wavelengths and relative values of measured optical power, this approach frees the insertion loss measurement from the uncertainties caused by experimental set-up, including system alignment and wavelength dependence of the couplers. Strip-slot mode converters were fabricated and measured to present the exemplary insertion loss measurement process. A series of experimental results confirm that the insertion loss of the low-loss silicon photonic devices can be accurately and reliably obtained even the adopted couplers are wavelength-dependent, and the fibers are deviated 15 µm from the horizontal direction and 110 µm from the vertical direction, exhibiting excellent robustness to the experimental set-up.

Ultracompact, high extinction ratio polarization beam splitter-rotator based on hybrid plasmonic-dielectric directional coupling.

A polarization beam splitter-rotator based on asymmetric directional coupling is proposed. An ultrashort cross-polarization coupling length of 7.7 µm is achieved by manipulating the optical field distribution via the plasmonic effect, which is the shortest one reported so far, to the best of our knowledge. At the wavelength of 1.55 µm, the extinction ratios are as high as 50.9 dB and 28.2 dB for fundamental transverse magnetic (TM0) and transverse electric (TE0) polarizations, respectively, and the corresponding insertion losses are 1.545 dB and 0.037 dB. In addition, the TM0-to-TE0 polarization conversion efficiency is higher than 95% within a bandwidth of 70 nm.

Stability of Multivalent Ruthenium on CoWO4 Nanosheets for Improved Electrochemical Water Splitting with Alkaline Electrolyte.

Engineering low-cost electrocatalysts with desired features is vital to decrease the energy consumption but challenging for superior water splitting. Herein, we development a facile strategy by the addition of multivalence ruthenium (Ru) into the CoWO4/CC system. During the synthesis process, the most of Ru3+ ions were insinuated into the lattice of CoWO4, while the residual Ru3+ ions were reduced to metallic Ru and further attached to the interface between carbon cloth and CoWO4 sheets. The optimal Ru2(M)-CoWO4/CC exhibited superior performance for the HER with an overpotential of 85 mV@10 mA cm-2, which was much better than most of reported electrocatalysts, regarding OER, a low overpotential of 240 mV@10 mA cm-2 was sufficient. In comparison to Ru2(0)-CoWO4/CC with the same Ru mass loading, multivalence Ru2(M)-CoWO4/CC required a lower overpotential for OER and HER, respectively. The Ru2(M)-CoWO4/CC couple showed excellent overall water splitting performance at a cell voltage of 1.48 V@10 mA cm-2 for used as both anodic and cathodic electrocatalysts. Results of the study showed that the electrocatalytic activity of Ru2(M)-CoWO4/CC was attributed to the in-situ transformation of Ru/Co sites, the multivalent Ru ions and the synergistic effect of different metal species stimulated the intrinsic activity of CoWO4/CC.

Dimension-Dependent Nonlinear Optical Properties of Stanene Nanosheets.

Stanene (Sn)-based materials, with a graphene-like hexagonal structure, are now attracting considerable interest for potential applications in photoelectricity. However, the nonlinear optical properties of stanene remain largely unexplored. In this work, we prepared different sizes of stanene by liquid phase exfoliation and differential centrifugation methods, including two-dimensional (2D) Sn nanosheets (NSs) and zero-dimensional (0D) Sn nanodots (NDs). Z-scan measurements reveal that 2D Sn NSs exhibited high saturable absorption behavior, while the 0D Sn NDs led to reverse saturable absorption. Femtosecond ultrafast transient absorption spectra revealed that the reverse saturable absorption of Sn NDs is derived from a stronger excited state absorption and faster exciton relaxation dynamics. This research expands the potential applications of stanene in laser shielding and other ultrafast photonics technologies.

Slow-light silicon modulator with 110-GHz bandwidth.

Silicon modulators are key components to support the dense integration of electro-optic functional elements for various applications. Despite numerous advances in promoting the modulation speed, a bandwidth ceiling emerges in practices and becomes an obstacle toward Tbps-level throughput on a single chip. Here, we demonstrate a compact pure silicon modulator that shatters present bandwidth ceiling to 110 gigahertz. The proposed modulator is built on a cascade corrugated waveguide architecture, which gives rise to a slow-light effect. By comprehensively balancing a series of merits, the modulators can benefit from the slow light for better efficiency and compact size while remaining sufficiently high bandwidth. Consequently, we realize a 110-gigahertz modulator with 124-micrometer length, enabling 112 gigabits per second on-off keying operation. Our work proves that silicon modulators with 110 gigahertz are feasible, thus shedding light on its potentials in ultrahigh bandwidth applications such as optical interconnection and photonic machine learning.

Comparison of CrN Coatings Prepared Using High-Power Impulse Magnetron Sputtering and Direct Current Magnetron Sputtering.

Chromium Nitride (CrN) coatings have widespread utilization across numerous industrial applications, primarily attributed to their excellent properties. Among the different methods for CrN coating synthesis, direct current magnetron sputtering (DCMS) has been the dominant technique applied. Nonetheless, with the expanded applications of CrN coatings, the need for enhanced mechanical performance is concurrently escalating. High-power impulse magnetron sputtering (HiPIMS), an innovative coating deposition approach developed over the past three decades, is gaining recognition for its capability of yielding coatings with superior mechanical attributes, thereby drawing significant research interest. Considering that the mechanical performance of a coating is fundamentally governed by its microstructural properties, a comprehensive review of CrN coatings fabricated through both techniques is presented. This review of recent literature aims to embark on an insightful comparison between DCMS and HiPIMS, followed by an examination of the microstructure of CrN coatings fabricated via both techniques. Furthermore, the exploration of the underlying factors contributing to the disparities in mechanical properties observed in CrN coatings is revealed. An assessment of the advantages and potential shortcomings of HiPIMS is discussed, offering insight into CrN coating fabrication.

Microcomb-based integrated photonic processing unit.

The emergence of parallel convolution-operation technology has substantially powered the complexity and functionality of optical neural networks (ONN) by harnessing the dimension of optical wavelength. However, this advanced architecture faces remarkable challenges in high-level integration and on-chip operation. In this work, convolution based on time-wavelength plane stretching approach is implemented on a microcomb-driven chip-based photonic processing unit (PPU). To support the operation of this processing unit, we develop a dedicated control and operation protocol, leading to a record high weight precision of 9 bits. Moreover, the compact architecture and high data loading speed enable a preeminent photonic-core compute density of over 1 trillion of operations per second per square millimeter (TOPS mm-2). Two proof-of-concept experiments are demonstrated, including image edge detection and handwritten digit recognition, showing comparable processing capability compared to that of a digital computer. Due to the advanced performance and the great scalability, this parallel photonic processing unit can potentially revolutionize sophisticated artificial intelligence tasks including autonomous driving, video action recognition and image reconstruction.

An ultra-compact polarization-insensitive slot-strip mode converter.

Integrated waveguides with slot structures have attracted increasing attention due to their advantages of tight mode confinement and strong light-matter interaction. Although extensively studied, the issue of mode mismatch with other strip waveguide-based optical devices is a huge challenge that prevents integrated waveguides from being widely utilized in large-scale photonic-based circuits. In this paper, we demonstrate an ultra-compact low-loss slot-strip converter with polarization insensitivity based on the multimode interference (MMI) effect. Sleek sinusoidal profiles are adopted to allow for smooth connection between the slot and strip waveguide, resulting reflection reduction. By manipulating the MMI effect with structure optimization, the self-imaging positions of the TE0 and TM0 modes are aligned with minimized footprint, leading to low-loss transmission for both polarizations. The measurement results show that high coupling efficiencies of - 0.40 and - 0.64 dB are achieved for TE0 and TM0 polarizations, respectively. The device has dimensions as small as 1.1 µm × 1.2 µm and composed of factory-available structures. The above characteristics of our proposed compact slot-strip converter makes it a promising device for future deployment in multi-functional integrated photonics systems.

Emerging roles of the CBL-CIPK calcium signaling network as key regulatory hub in plant nutrition.

Plant physiology and development essentially depend on sufficient uptake of various essential nutritive ions via their roots and their appropriate transport and distribution within the organism. Many of these essential nutrients are heterogeneously distributed in the soil or are available in fluctuating concentrations. This natural situation requires constant regulatory adjustment and balancing of nutrient uptake and homeostasis. Here, we review recent findings on the role of Ca2+ signals and Ca2+-dependent regulation via the CBL-CIPK Ca2+ sensor-protein kinase network in these processes. We put special emphasis on Ca2+ controlled processes that contribute to establishing the homeostasis of macro-nutrients like potassium (K+), nitrogen (N), and magnesium (Mg2+) and on the micro-nutrient iron (Fe). Increasing experimental evidence indicates the occurrence of nutrient-specific, spatially and temporally defined cytoplasmic Ca2+ elevations as early responses to nutrient fluctuations. Specific CBL-CIPK complexes translate these signals into phosphorylation regulation of important channels and transporters like AKT1, NPF6.3/NRT1.1, AMT1, SLAC1, TPK1 and IRT1. We discuss a crucial and coordinating role for these Ca2+ signaling mechanisms in regulating the sensing, uptake, distribution and storage of various ions. Finally, we reflect on the emerging multifaceted and potentially integrating role of the "nutrient" kinase CIPK23 in regulating multiple nutrient responses. From this inventory, we finally deduce potential mechanisms that can convey the coordinated regulation of distinct steps in the transport of one individual ion and mechanisms that can bring about the integration of adaptive responses to fluctuations of different ions to establish a faithfully balanced plant nutrient homeostasis.

Optical coherent dot-product chip for sophisticated deep learning regression.

Optical implementations of neural networks (ONNs) herald the next-generation high-speed and energy-efficient deep learning computing by harnessing the technical advantages of large bandwidth and high parallelism of optics. However, due to the problems of the incomplete numerical domain, limited hardware scale, or inadequate numerical accuracy, the majority of existing ONNs were studied for basic classification tasks. Given that regression is a fundamental form of deep learning and accounts for a large part of current artificial intelligence applications, it is necessary to master deep learning regression for further development and deployment of ONNs. Here, we demonstrate a silicon-based optical coherent dot-product chip (OCDC) capable of completing deep learning regression tasks. The OCDC adopts optical fields to carry out operations in the complete real-value domain instead of in only the positive domain. Via reusing, a single chip conducts matrix multiplications and convolutions in neural networks of any complexity. Also, hardware deviations are compensated via in-situ backpropagation control provided the simplicity of chip architecture. Therefore, the OCDC meets the requirements for sophisticated regression tasks and we successfully demonstrate a representative neural network, the AUTOMAP (a cutting-edge neural network model for image reconstruction). The quality of reconstructed images by the OCDC and a 32-bit digital computer is comparable. To the best of our knowledge, there is no precedent of performing such state-of-the-art regression tasks on ONN chips. It is anticipated that the OCDC can promote the novel accomplishment of ONNs in modern AI applications including autonomous driving, natural language processing, and scientific study.

The N-glycosylation of Equine Tetherin Affects Antiviral Activity by Regulating Its Subcellular Localization.

Tetherin is an interferon-inducible type II transmembrane glycoprotein which inhibits the release of viruses, including retroviruses, through a "physical tethering" model. However, the role that the glycosylation of tetherin plays in its antiviral activity remains controversial. In this study, we found that mutation of N-glycosylation sites resulted in an attenuation of the antiviral activity of equine tetherin (eqTHN), as well as a reduction in the expression of eqTHN at the plasma membrane (PM). In addition, eqTHN N-glycosylation mutants colocalize obviously with ER, CD63, LAMP1 and endosomes, while WT eqTHN do not. Furthermore, we also found that N-glycosylation impacts the transport of eqTHN in the cell not by affecting the endocytosis, but rather by influencing the anterograde trafficking of the protein. These results suggest that the N-glycosylation of eqTHN is important for the antiviral activity of the protein through regulating its normal subcellular localization. This finding will enhance our understanding of the function of this important restriction factor.

17ß-Estradiol Regulates Glucose Metabolism and Insulin Secretion in Rat Islet ß Cells Through GPER and Akt/mTOR/GLUT2 Pathway.

Aims: To explore the molecular mechanism by which 17ß-estradiol (estrogen 2, E2) regulates glucose transporter 2 (GLUT2) and insulin secretion in islet ß cells through G protein-coupled estrogen receptor (GPER) via Akt/mTOR pathway. Methods: SPF-grade SD male rats were used to establish an in vivo type 2 diabetes model treated with E2. Rat insulinoma cells (INS-1) were cultured in normal or high glucose media with or without E2. Immunofluorescence double staining was used to detect GPER, GLUT2, insulin, and glucagon immunolocalization in rat islet tissues. Western blot was used to detect GPER, Akt, mTOR, and GLUT2 protein immunocontent. Real-time PCR detected Slc2a2 and glucose kinase (GK) content, and ELISA was used to detect insulin levels. Glucose uptake, GK activity and pyruvate dehydrogenase (PDH) activity were analyzed with glucose detection, GK activity and PDH activity assay kit. Results: Immunofluorescence double staining confocal indicated that E2 treatment up-regulated expression levels of GPER, GLUT2, and insulin, while down-regulated glucagon. Western blot results revealed E2 increased GPER, Akt/mTOR pathway, and GLUT2 protein immunocontent. Real-time PCR showed E2 elevated Slc2a2, GK content. Moreover, E2 improved insulin secretion, glucose uptake, GK activity, and PDH activity. Conclusion: Our findings indicated that exogenous E2 up-regulated GPER via the Akt/mTOR pathway to increase GLUT2 protein content and insulin secretion in islet ß cells.