Aberrant activation of Notch1 signaling in the mouse uterine epithelium promotes hyper-proliferation by increasing estrogen sensitivity.

In mammals, the endometrium undergoes dynamic changes in response to estrogen and progesterone to prepare for blastocyst implantation. Two distinct types of endometrial epithelial cells, the luminal (LE) and glandular (GE) epithelial cells play different functional roles during this physiological process. Previously, we have reported that Notch signaling plays multiple roles in embryo implantation, decidualization, and postpartum repair. Here, using the uterine epithelial-specific Ltf-iCre, we showed that Notch1 signaling over-activation in the endometrial epithelium caused dysfunction of the epithelium during the estrous cycle, resulting in hyper-proliferation. During pregnancy, it further led to dysregulation of estrogen and progesterone signaling, resulting in infertility in these animals. Using 3D organoids, we showed that over-activation of Notch1 signaling increased the proliferative potential of both LE and GE cells and reduced the difference in transcription profiles between them, suggesting disrupted differentiation of the uterine epithelium. In addition, we demonstrated that both canonical and non-canonical Notch signaling contributed to the hyper-proliferation of GE cells, but only the non-canonical pathway was involved with estrogen sensitivity in the GE cells. These findings provided insights into the effects of Notch1 signaling on the proliferation, differentiation, and function of the uterine epithelium. This study demonstrated the important roles of Notch1 signaling in regulating hormone response and differentiation of endometrial epithelial cells and provides an opportunity for future studies in estrogen-dependent diseases, such as endometriosis.

Porous Electropolymerized Films of Ruthenium Complex: Photoelectrochemical Properties and Photoelectrocatalytic Synthesis of Hydrogen Peroxide.

The photoelectrochemical cells (PECs) performing high-efficiency conversions of solar energy into both electricity and high value-added chemicals are highly desirable but rather challenging. Herein, we demonstrate that a PEC using the oxidatively electropolymerized film of a heteroleptic Ru(II) complex of [Ru(bpy)(L)2](PF6)2Ru1 {bpy and L stand for 2,2'-bipyridine and 1-phenyl-2-(4-vinylphenyl)-1H-imidazo[4,5-f][1,10]phenanthroline respectively}, polyRu1, as a working electrode performed both efficient in situ synthesis of hydrogen peroxide and photocurrent generation/switching. Specifically, when biased at -0.4 V vs. saturated calomel electrode and illuminated with 100 mW·cm-2 white light, the PEC showed a significant cathodic photocurrent density of 9.64 µA·cm-2. Furthermore, an increase in the concentrations of quinhydrone in the electrolyte solution enabled the photocurrent polarity to switch from cathodic to anodic, and the anodic photocurrent density reached as high as 11.4 µA·cm-2. Interestingly, in this single-compartment PEC, the hydrogen peroxide yield reached 2.63 µmol·cm-2 in the neutral electrolyte solution. This study will serve as a guide for the design of high-efficiency metal-complex-based molecular systems performing photoelectric conversion/switching and photoelectrochemical oxygen reduction to hydrogen peroxide.

Mst1/2 Is Necessary for Satellite Cell Differentiation to Promote Muscle Regeneration.

The diminished ability for muscle to regenerate is associated with aging, diabetes, and cancers. Muscle regeneration depends on the activation and differentiation of satellite cells (SCs). Inactivation of Mst1/2 promotes cell proliferation by activating Yap, and that has been reported as a potential therapeutic target for improving many organ regeneration. However, the function of Mst1/2 in SCs fate decision and that effect on muscle regeneration remain unknown. By using inducible conditional knockout Mst1/2 in the SCs of mice and an inhibitor of Mst1/2, we found that inhibition of Mst1/2 in SCs significantly decrease Yap phosphorylation, thus causing Yap to accumulate in the nucleus and impairing SC differentiation; Mst1/2 were slightly elevated by irisin stimulation during SC differentiation; but inhibiting Mst1/2 in SCs significantly impaired irisin-induced muscle regeneration. These results indicate that Mst1/2 is necessary for SC differentiation and inhibiting Mst1/2 as a therapeutic target has potential risks for muscle regeneration.

Photoelectrocatalytic Dioxygen Reduction Based on a Novel Thiophene-Functionalized Tricarbonylchloro(1,10-phenanthroline)rhenium(I).

A novel Re (I) complex of [Re(CO)3Cl(L)], {L = 2-([2,2'-bithiophen]-5-yl)-1-phenyl-1H-imidazo [4,5-f][1,10]phenanthroline}, was synthesized, and its optical (UV-Visible absorption and emission spectroscopy), cyclovoltammetric and photoelectrochemical oxygen reduction properties were studied. The geometric and electronic properties were also investigated by density functional theory calculations. It was found that the ITO electrode coated with drop-casted [Re(CO)3Cl(L)] film exhibited cathodic photocurrent generation characteristics. The illuminated film exhibited a maximum cathodic photocurrent up to 30.4 µA/cm2 with an illumination intensity of 100 mW/cm2 white light at a bias potential of -0.4 V vs. SCE in O2-saturated electrolyte solution, which was reduced by 5.1-fold when thoroughly deoxygenated electrolyte solution was used, signaling that the electrode performed well on the photoelectrochemical oxygen reduction. The photo-electrocatalytic hydrogen peroxide production was proved with a maximum H2O2 concentration of 6.39 µM during 5 h of the photoelectrocatalytic process. This work would guide the construction of more efficient rhenium-based photo(electro)catalytic molecular systems for O2 sensing, hydrogen peroxide production and other types of photoelectrochemical energy conversion and storage.

Rare Earth Complexes of Europium(II) and Substituted Bis(pyrazolyl)borates with High Photoluminescence Efficiency.

Rare earth europium(II) complexes based on d-f transition luminescence have characteristics of broad emission spectra, tunable emission colors and short excited state lifetimes, showing great potential in display, lighting and other fields. In this work, four complexes of Eu(II) and bis(pyrazolyl)borate ligands, where pyrazolyl stands for pyrazolyl, 3-methylpyrazolyl, 3,5-dimethylpyrazolyl or 3-trifluoromethylpyrazole, were designed and synthesized. Due to the varied steric hindrance of the ligands, different numbers of solvent molecules (tetrahydrofuran) are participated to saturate the coordination structure. These complexes showed blue-green to yellow emissions with maximum wavelength in the range of 490-560 nm, and short excited state lifetimes of 30-540 ns. Among them, the highest photoluminescence quantum yield can reach 100%. In addition, when the complexes were heated under vacuum or nitrogen atmosphere, they finally transformed into the complexes of Eu(II) and corresponding tri(pyrazolyl)borate ligands and sublimated away.

Notch1 is crucial for decidualization and maintaining the first pregnancy in the mouse†.

The endometrium undergoes a pregnancy-delivery-repair cycle multiple times during the reproductive lifespan in females. Decidualization is one of the critical events for the success of this essential process. We have previously reported that Notch1 is essential for artificial decidualization in mice. However, in a natural pregnancy, the deletion of Notch1 (PgrCre/+Notch1f/f, or Notch1d/d) only affects female fertility in the first 30 days of a 6-month fertility test, but not the later stages. In the present study, we undertook a closer evaluation at the first pregnancy of these mice to attempt to understand this puzzling phenomenon. We observed a large number of pregnancy losses in Notch1d/d mice in their first pregnancy, which led to the subfertility observed in the first 30 days of the fertility test. We then demonstrated that the initial pregnancy loss is a consequence of impaired decidualization. Furthermore, we identified a group of genes that contribute to Notch1 regulated decidualization in a natural pregnancy. Gene ontogeny analysis showed that these differentially expressed genes in the natural pregnancy are involved in cell-cell and cell-matrix interactions, different from genes that have been previously identified from the artificial decidualization model, which contribute to cell proliferation and apoptosis. In summary, we determined that Notch1 is essential for normal decidualization in the mouse uterus only in the first pregnancy but not in subsequent ones.

Unusual Photoelectrochemical Properties of Electropolymerized Films of a Triphenylamine-Containing Organic Small Molecule.

The electropolymerized films of poly(L)n on an indium-tin oxide (ITO) electrode was prepared by anodic electrooxidation of a dichloromethane solution of a triphenylamine-carrying organic molecule L and were characterized/studied by ultraviolet-visible absorption spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, electrochemical impedance spectroscopy, cyclic voltammetry, and photoelectrochemical measurements. Poly(L)n films were found to show surface-controlled TPA•+1/0 associated quasi-reversible redox and exceptionally high photocurrent generation properties. At a zero external bias potential and under 100 mW/cm2 white light irradiation, a photoelectrochemical device composed of a poly(L)1-modified ITO as the working electode, a platinum disk counter electrode, and saturated calomel electrode reference electrode in a 0.1 M Na2SO4 aqueous solution exhibited a significant cathode photocurrent density of 2.2 µA/cm2, which could be switched to be anodic and outperform most previously reported molecule-based modified ITO electrodes under similar experimental conditions. The results indicate that poly(L)n films offer a number of future perspectives ranging from organic photovoltaic to photoelectrochemical catalysis and sensing.

Near-IR/Visible-Emitting Thiophenyl-Based Ru(II) Complexes: Efficient Photodynamic Therapy, Cellular Uptake, and DNA Binding.

Near-IR-emitting and/or efficiently photodynamic water-soluble Ru(II) complexes that hold great application potentials as photodynamic therapy and/or photodetection agents for cancers have been poorly explored. In this paper, the solvatochromism, calf thymus DNA binding, and singlet oxygen generation properties of a known ruthenium(II) complex of visible-emitting [Ru(bpy)2(dtdpq)](ClO4)2 (Ru1) and a new homoleptic complex of near-IR-emitting [Ru(dtdpq)3](ClO4)2 (Ru2) (bpy = 2,2'-bipyridine, dtdpq = 2,3-bis(thiophen-2-yl)pyrazino[2,3-f][1,10]phenanothroline) in water are reported. Moreover, DNA photocleavage, singlet oxygen generation in HeLa cells, cellular uptake/localization, and in vitro photodynamic therapy for cancer cells of water-soluble Ru1 are described in detail. The results show that Ru1 acted as potent photodynamic cancer therapy and mitochondrial imaging agents. Ru2 exhibited very strong solvatochromism from a visible emission maximum at 588 nm in CH2Cl2 to the near-IR region at 700 nm in water and singlet oxygen generation yield in water (23%) and DNA binding properties (intercalative DNA binding constant on the order of 106 M-1) comparable to those of Ru1, which should make Ru2 attractive for the aforementioned applications of Ru1 if the water solubility of Ru2 can be improved enough for the studies above.

Constrained MLAMBDA Method for Multi-GNSS Structural Health Monitoring.

Deformation monitoring of engineering structures using the advanced Global Navigation Satellite System (GNSS) has attracted research interest due to its high-precision, constant availability and global coverage. However, GNSS application requires precise coordinates of points of interest through quick and reliable resolution of integer ambiguities in carrier phase measurements. Conventional integer ambiguity resolution algorithms have been extensively researched indeed in the past few decades, although the application of GNSS to structural health monitoring is still limited. In particular, known a priori information related to the structure of a body of interest is not normally considered. This study proposes a composite strategy that incorporates modified least-squares ambiguity decorrelation adjustment (MLAMBDA) method with priori information of the structural deformation. Data from the observation sites of Baishazhou Bridge are used to test method performance. Compared to MLAMBDA methods that do not consider priori information, the ambiguity success rate (ASR) improves by 20% for global navigation satellite system (GLONASS) and 10% for Multi-GNSS, while running time is reduced by 60 s for a single system and 180 s for Multi-GNSS system. Experimental results of Teaching Experiment Building indicate that our constrained MLAMBDA method improves positioning accuracy and meets the requirements of structural health monitoring, suggesting that the proposed strategy presents an improved integer ambiguity resolution algorithm.

Joint Cache Content Placement and Task Offloading in C-RAN Enabled by Multi-Layer MEC.

In this paper, we work on a Cache and Multi-layer MEC enabled C-RAN (CMM-CRAN) to handle various user tasks with minimized latency and energy cost. We intend to solve two particular problems of CMM-CRAN. First, because CMM-CRAN has to maximally cache the most frequently requested data from Service Provide Server (SPS) to Remote Radio Head (RRH) and later offered to proximity mobile users, the cache content placement from SPSs to RRHs becomes a many-to-many matching problem with peer effects. Second, because of multi-layer MEC, a user task has to be dynamically controlled to be offloaded to the best fit cloud, i.e., either local MEC or remote MEC, to get served. This dynamic task offloading is a Multi-Dimension Multiple-Choice Knapsack (MMCK) problem. To solve these two problems, we provide a Joint Cache content placement and task Offloading Solution (JCOS) to CMM-CRAN that utilizes Proportional Fairness (PF) as the user scheduling policy. JCOS applies a Gale-Shaply (GS) method to work out the cache content placement, and a Population Evolution (PE) game theory coupled with a use of Analytic Hierarchy Process(AHP) to work out the dynamic user task offloading. According to the simulation results, CMM-CRAN with JCOS is proved to be able to provide highly desired low-latency communication and computation services with decreased energy cost to mobile users.

pH-Switchable "Off-On-Off" Near-Infrared Luminescence Based on a Dinuclear Ruthenium(II) Complex.

The pH-switchable room-temperature near-infrared (NIR) phosphorescence emission based on ruthenium(II) polypyridyl complexes has been very rarely reported, even though it is very desirable for applications in sensing, switching, and logic molecular devices and bioimaging. Here we report a novel dinuclear ruthenium(II) complex in an aerated acetonitrile solution featuring a bright NIR emission centered at 760 nm with an absolute quantum yield of 1.03%, a large Stokes shift of 254 nm, and a long emission lifetime of 108.3 ± 0.4 ns. The complex in a Britton-Roberson buffer also exhibited pH-induced "off-on-off" NIR luminescent switches with a maximum intensity enhancement factor of 41 and one of the switching events occurring near the physiological pH range.

DNA Binding and Photocleavage Properties, Cellular Uptake and Localization, and in-Vitro Cytotoxicity of Dinuclear Ruthenium(II) Complexes with Varying Lengths in Bridging Alkyl Linkers.

Two new dinuclear Ru(II) polypyridyl complexes containing three and ten methylene chains in their bridging linkers are synthesized and characterized. Their calf thymus DNA-binding and plasmid DNA photocleavage behaviors are comparatively studied with a previously reported, six-methylene-containing analog by absorption and luminescence spectroscopy, steady-state emission quenching by [Fe(CN)6](4-), DNA competitive binding with ethidium bromide, DNA viscosity measurements, DNA thermal denaturation, and agarose gel electrophoresis analyses. Theoretical calculations applying the density functional theory (DFT) method for the three complexes are also performed to understand experimentally observed DNA binding properties. The results show that the two complexes partially intercalate between the base pairs of DNA. Cellular uptake and colocalization studies have demonstrated that the complexes could enter HeLa cells efficiently and localize within lysosomes. The in-vitro antitumor activity against HeLa and MCF-7 tumor cells of the complexes are studied by MTT cytotoxic analysis. A new method, high-content analysis (HCA), is also used to assess cytotoxicity, apoptosis and cell cycle arrest of the three complexes. The results show that the lengths of the alkyl linkers could effectively tune their biological properties and that HCA is suitable for rapidly identifying cytotoxicity and can be substituted for MTT assays to evaluate the cell cytotoxicity of chemotherapeutic agents.

An Electrostatically Self-Assembled Thin Film Made of Zn-Substituted Tungstoborate and Rhodamine B with Photoelectrochemical Properties.

An electrostatically self-assembled multilayer thin film consisting of alternating layers of Keggin polyoxometalate of Zn-substituted tungstoborate (BW11Zn) and Rhodamine B (RhB) has successfully been prepared on a quartz and indium-tin oxide (ITO) glass substrate. The ultraviolet-visible (UV-vis) absorption spectra demonstrated that the electrostatically self-assembled film of (BW11Zn/RhB)n was uniformly deposited layer by layer, and the RhB molecules in the film formed the J-aggregation. The photoelectrochemical investigations showed that the films generated stable cathodic photocurrents that originated from RhB, and the maximal cathodic photocurrent density generated by an eight-layer film was 4.9 µA/cm2 while the film was irradiated with 100 mW/cm2 polychromatic light of 730 nm > λ > 325 nm at an applied potential of 0 V versus a saturated calomel electrode.

Two-photon, three-photon, and four-photon near-infrared quantum cutting luminescence of an Er3+ activator in tellurium glass phosphor.

Multiphoton near-IR downconversion quantum cutting luminescence of Er3+-ion-doped tellurium glass is studied. We find that the excitation spectra of 1532.0 nm IR light and 550.0 nm visible light are very similar in wave shape and peak wavelength. When the concentration of Er3+ ions is increased from 0.5% to 3.2%, we observe that both the IR luminescence and excitation intensity of the samples are increased by a factor of 1.80-5.49, with a concomitant decrease in both visible luminescence and excitation intensity by a factor of 0.87-1.91. Therefore, we conclude that the present phenomenon is a multiphoton near-IR quantum cutting luminescence phenomenon. We also find that the near-IR quantum cutting efficiency up-limits of the I9/24, F9/24, S3/24, and H11/22 states are respectively 157%, 138%, 193%, and 192% for Er3+(3.2%):tellurium glass and 175%, 154%, 233%, and 233% for Er3+(5.0%):tellurium glass.

Preparation and photoelectrochemical properties of a self-assembled film based on wheel type polyoxomolybdate and hemicyanine derivative.

A new electrostatically self-assembled film has been successfully prepared on quartz and indium-tin-oxide (ITO) coated glass substrates by alternating adsorption of a wheel-shaped polyoxomolybdate {Mo154} and a hemicyanine of (E)-1,1'-methylenebis(4-(4-(dimethylamino)styryl)pyridinium) bromide (H1). The UV-visible spectra demonstrated that the film was uniform, reproducible, and the H1 in the film forms the J-aggregation. Photoelectrochemical investigations showed that the films can generate stable cathodic photocurrent, and the cathodic photocurrent density of three-layer film was 5.1 microA/cm2 while irradiated with 100 mW/cm2 polychromatic light of 730 nm > lambda > 325 nm at an applied potential of -0.3 V versus saturated calomel electrode.

Photoelectrochemical properties of graphene oxide-based electrostatically self-assembled film.

Graphene oxide (GO) and polyethylenimine were successfully assembled into ultrathin films by using the electrostatic layer-by-layer self-assembly technique. The film assembling process was monitored by ultraviolet-visible spectroscopy. A linear increase in the film absorption with the number of deposited layers indicated that the (GO/PEI)(n) film depositions were uniform and reproducible. The photoelectrochemical properties of these multilayer films were investigated in an aqueous Na2SO4 solution, and it was found that the GO(PEI/GO)2 film exhibited stable cathodic photocurrents.

The environmental effects of microplastics and microplastic derived dissolved organic matter in aquatic environments: A review.

Currently, microplastics (MPs) have ubiquitously distributed in different aquatic environments. Due to the unique physicochemical properties, MPs exhibit a variety of environmental effects with the coexisted contaminants. MPs can not only alter the migration of contaminants via vector effect, but also affect the transformation process and fate of contaminants via environmental persistent free radicals (EPFRs). The aging processes may enhance the interaction between MPs and co-existed contaminants. Thus, it is of great significance to review the aging mechanism of MPs and the influence of coexisted substances, the formation mechanism of EPFRs, environmental effects of MPs and relevant mechanism. Moreover, microplastic-derived dissolved organic matter (MP-DOM) may also influence the elemental biogeochemical cycles and the relevant environmental processes. However, the environmental implications of MP-DOM are rarely outlined. Finally, the knowledge gaps on environmental effects of MPs were proposed.

MST1/2 regulates fibro/adipogenic progenitor fate decisions in skeletal muscle regeneration.

Defective skeletal muscle regeneration is often accompanied by fibrosis. Fibroblast/adipose progenitors (FAPs) are important in these processes, however, the regulation of FAP fate decisions is unclear. Here, using inducible conditional knockout mice, we show that blocking mammalian Ste20-like kinases 1/2 (MST1/2) of FAPs prevented apoptosis and reduced interleukin-6 secretion in vivo and in vitro, which impaired myoblast proliferation and differentiation, as well as impaired muscle regeneration. Deletion of Mst1/2 increased co-localization of Yes-associated protein (YAP) with Smad2/3 in nuclei and promoted differentiation of FAPs toward myofibroblasts, resulting in excessive collagen deposition and skeletal muscle fibrosis. Meanwhile, inhibition of MST1/2 increased YAP/Transcriptional co-activator with PDZ-binding motif activation, which promoted activation of the WNT/ß-catenin pathway and impaired the differentiation of FAPs toward adipocytes. These results reveal a new mechanism for MST1/2 action in disrupted skeletal muscle regeneration and fibrosis via regulation of FAP apoptosis and differentiation. MST1/2 is a potential therapeutic target for the treatment of some myopathies.

Inactivation of MST1/2 Controls Macrophage Polarization to Affect Macrophage-Related Disease via YAP and Non-YAP Mechanisms.

Macrophage polarization is a critical process that regulates in inflammation, pathogen defense, and tissue repair. Here we demonstrate that MST1/2, a core kinase of Hippo pathway and a recently identified regulator of inflammation, plays a significant role in promoting M2 polarization. We provide evidence that inhibition of MST1/2, achieved through either gene-knockout or pharmacological treatment, leads to increased M1 polarization in a YAP-dependent manner, resulting in the development of M1-associated inflammatory disorders. Moreover, MST1/2 inhibition also leads to a substantial reduction in M2 polarization, but this occurs through the STAT6 and MEK/ERK signaling. The STAT6 is independent of YAP, but MEK/ERK is dependent of YAP. Consistent with these observations, both MST1/2-conditional knockout mice and wild-type mice treated with XMU-MP-1, a chemical inhibitor of MST1/2, exhibited reduced M2-related renal fibrosis, while simultaneously displaying enhanced LPS-mediated inflammation and improved clearance of MCR3-modified gram-negative bacteria. These findings uncover a novel role of MST1/2 in regulating macrophage polarization and establish it as a potential therapeutic target for the treatment of macrophage-related fibrotic diseases.

Layer-by-layer assembly of graphene oxide and a Ru(II) complex and significant photocurrent generation properties.

The multilayer films were fabricated by layer-by-layer electrostatically coassembling graphene oxide and a ruthenium complex of [Ru(bpy)2L](ClO4)2 {L = 2-(2,6-di(pyridin-2-yl)pyridine-4-yl)-1H-imidazo[4,5-f]-1,10-phenanthroline} and characterized using UV-vis absorption spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and cyclic voltammetry. The dependence of redox properties and cathodic photocurrents on the number of layers deposited and the photocurrent generation mechanism and polarity were studied in detail. The homogeneous growth and close packing of the two film-forming components, linear relationships of the dark cyclic voltometry peak currents and photocurrents vs number of layers deposited, and large cathodic photocurrent density of 4.1 µA/cm(2) for a four-layer film make this novel hybrid thin film promising applications ranging from molecular photovoltaic and photocatalytic molecular devices to photoelectrochemical sensing.