Recurrent implantation failure: A comprehensive summary from etiology to treatment

Implantation is the first step in human reproduction. Successful implantation depends on the crosstalk between embryo and endometrium. Recurrent implantation failure (RIF) is a clinical phenomenon characterized by a lack of implantation after the transfer of several embryos and disturbs approximately 10% couples undergoing in vitro fertilization and embryo transfer. Despite increasing literature on RIF, there is still no widely accepted definition or standard protocol for the diagnosis and treatment of RIF. Progress in predicting and preventing RIF has been hampered by a lack of widely accepted definitions. Most couples with RIF can become pregnant after clinical intervention. The prognosis for couples with RIF is related to maternal age. RIF can be caused by immunology, thrombophilias, endometrial receptivity, microbiome, anatomical abnormalities, male factors, and embryo aneuploidy. It is important to determine the most possible etiologies, and individualized treatment aimed at the primary cause seems to be an effective method for increasing the implantation rate. Couples with RIF require psychological support and appropriate clinical intervention. Further studies are required to evaluate diagnostic method and he effectiveness of each therapy, and guide clinical treatment

Energy Budget of High-speed Plasma Flows in the Terrestrial Magnetotail

Significant advances have been presented for the theoretical model and quantitative investigation of the energy input from the solar wind and its subsequent release into the ring current, the Joule heating, and particle precipitation energy flux that are closely related to high-speed flows in the plasma sheet of the terrestrial magnetotail during both isolated and storm-time substorms. Here we further determine the plasma flow vorticity/shear and heating observed in the terrestrial magnetotail by the Magnetospheric Multiscale (MMS) mission by deducing that other energy may be dissipated along with the above-mentioned three energy releases. The energy transported by the flow is also estimated here. Three-dimensional observations have shown new detailed information that can be compared with quasi-2D simulations. In this investigation, we calculate vorticity/shear directly from simultaneous observation of four MMS satellites. Our results generally indicate that plasma heating or temperature enhancements are related to both the flow vorticity/shear and current density, but more strongly with flow vorticity/shear. This research suggests that the ubiquitous energy input from the solar wind can be used to estimate plasma heating or temperature enhancements in the absence of any process or phenomenon relating to explosive energy release in planetary magnetospheres

Probing Interface of Perovskite Oxide Using Surface-specific Terahertz Spectroscopy

The surface/interface species in perovskite oxides play an essential role in many novel emergent physical phenomena and chemical processes. With low eigen-energy in the terahertz region, such species at buried interfaces remain poorly understood due to the lack of feasible experimental techniques. Here, we show that vibrational resonances and two-dimensional electron gas at the interface can be characterized using surface-specific nonlinear spectroscopy in the terahertz range. This technique uses intra-pulse difference frequency mixing (DFM) process, which is allowed only at surface/interface of a medium with inversion symmetry. Sub-monolayer sensitivity can be achieved using the state-of-the-art detection scheme for the terahertz emission from surface/interface. As a demonstration, Drude-like nonlinear response from the two-dimensional electron gas emerging at LaAlO3/SrTiO3 or Al2O3/ SrTiO3 interface was successfully observed. Meanwhile, the interfacial vibrational spectrum of the ferroelectric soft mode of SrTiO3 at 2.8 THz was also obtained that was polarized by the surface field in the interfacial region. The corresponding surface/interface potential, which is a key parameter for SrTiO3-based interface superconductivity and photocatalysis, can now be determined optically via quantitative analysis on the polarized phonon spectrum. The interfacial species with resonant frequencies in the THz region revealed by our method provide more insights into the understanding of physical properties of complex oxides.Comment: arXiv admin note: substantial text overlap with arXiv:2207.1461

Cyclodepsipeptide Toxin Promotes the Degradation of Hsp90 Client Proteins through Chaperone-Mediated Autophagy

Promoting the degradation of Hsp90 client proteins by inhibiting Hsp90, an important protein chaperone, has been shown to be a promising new anticancer strategy. In this study, we show that an oxazoline analogue of apratoxin A (oz-apraA), a cyclodepsipeptide isolated from a marine cyanobacterium, promotes the degradation of Hsp90 clients through chaperone-mediated autophagy (CMA). We identify a KFERQ-like motif as a conserved pentapeptide sequence in the kinase domain of epidermal growth factor receptor (EGFR) necessary for recognition as a CMA substrate. Mutation of this motif prevents EGFR degradation by CMA and promotes the degradation of EGFR through the proteasomal pathway in oz-apraA–treated cells. Oz-apraA binds to Hsc70/Hsp70. We propose that apratoxin A inhibits Hsp90 function by stabilizing the interaction of Hsp90 client proteins with Hsc70/Hsp70 and thus prevents their interactions with Hsp90. Our study provides the first examples for the ability of CMA to mediate degradation of membrane receptors and cross talks of CMA and proteasomal degradation mechanisms

Graphene/silicon heterojunction for reconfigurable phase-relevant activation function in coherent optical neural networks

Optical neural networks (ONNs) herald a new era in information and communication technologies and have implemented various intelligent applications. In an ONN, the activation function (AF) is a crucial component determining the network performances and on-chip AF devices are still in development. Here, we first demonstrate on-chip reconfigurable AF devices with phase activation fulfilled by dual-functional graphene/silicon (Gra/Si) heterojunctions. With optical modulation and detection in one device, time delays are shorter, energy consumption is lower, reconfigurability is higher and the device footprint is smaller than other on-chip AF strategies. The experimental modulation voltage (power) of our Gra/Si heterojunction achieves as low as 1 V (0.5 mW), superior to many pure silicon counterparts. In the photodetection aspect, a high responsivity of over 200 mA/W is realized. Special nonlinear functions generated are fed into a complex-valued ONN to challenge handwritten letters and image recognition tasks, showing improved accuracy and potential of high-efficient, all-component-integration on-chip ONN. Our results offer new insights for on-chip ONN devices and pave the way to high-performance integrated optoelectronic computing circuits

Study on rheological, adsorption and hydration properties of cement slurries incorporated with EPEG-based polycarboxylate superplasticizers

A series of polycarboxylate superplasticizers (PCEs) with different side-chain densities, main chain polymerization degrees, and side-chain lengths were designed and synthesized using a novel highly active ethylene glycol mono vinyl ether polyethylene glycol as the ether monomer. The influence of polycarboxylate ether on the rheological properties, interface adsorption, and hydration characteristics in cement paste was investigated through characterization of charge density, rheological properties, adsorption behavior, and hydration heat. The results indicate that the adsorption process of PCE on cement particles is spontaneous physical adsorption, and the hydration kinetics fitting reveals that the geometric crystal growth exponent n is in the range of 1–2, with needle-like and lamellar hydration products formed. With a decrease in side-chain density, the broadening of molecular weight distribution and the increase of charge density accelerate the flow of slurry, reduces saturation adsorption, and delays cement hydration. A decrease in main chain polymerization degree results in a downward trend in molecular weight and charge density, leading to larger molecular conformations, reduced slurry flow, decreased saturation adsorption, and delayed cement hydration. As the side-chain length of PCE (molecular weight) increases, the charge density decreases, and the molecular conformation exhibits a compact structure with reduced slurry flow, decreased saturation adsorption, and delayed cement hydration. In cases of low side-chain density, short side chains, and low molecular weight, enhanced adsorption capacity and faster adsorption rates are observed, resulting in the lower viscosity and a delay in the cement hydration process

Beclin1 Controls the Levels of p53 by Regulating the Deubiquitination Activity of USP10 and USP13

Autophagy is an important intracellular catabolic mechanism that mediates the degradation of cytoplasmic proteins and organelles. We report a potent small molecule inhibitor of autophagy named “spautin-1” for specific and potent autophagy inhibitor-1. Spautin-1 promotes the degradation of Vps34 PI3 kinase complexes by inhibiting two ubiquitin-specific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes. Beclin1 is a tumor suppressor and frequently monoallelically lost in human cancers. Interestingly, Beclin1 also controls the protein stabilities of USP10 and USP13 by regulating their deubiquitinating activities. Since USP10 mediates the deubiquitination of p53, regulating deubiquitination activity of USP10 and USP13 by Beclin1 provides a mechanism for Beclin1 to control the levels of p53. Our study provides a molecular mechanism involving protein deubiquitination that connects two important tumor suppressors, p53 and Beclin1, and a potent small molecule inhibitor of autophagy as a possible lead compound for developing anticancer drugs

Toll-Like Receptor 9 Is Required for Opioid-Induced Microglia Apoptosis

Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects beyond addiction. However, the underlying mechanism by which microglia in response to opioids remains largely unknown. Here we show that morphine induces the expression of Toll-like receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, TLR9 deficiency significantly inhibited morphine-induced apoptosis in microglia. Similar results were obtained when endogenous TLR9 expression was suppressed by the TLR9 inhibitor CpGODN. Inhibition of p38 MAPK by its specific inhibitor SB203580 attenuated morphine-induced microglia apoptosis in wild type microglia. Morphine caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type microglia, but not in TLR9 deficient microglia. In addition, morphine treatment failed to induce an increased levels of phosphorylated p38 MAPK and MAP kinase kinase 3/6 (MKK3/6), the upstream MAPK kinase of p38 MAPK, in either TLR9 deficient or µ-opioid receptor (µOR) deficient primary microglia, suggesting an involvement of MAPK and µOR in morphine-mediated TLR9 signaling. Moreover, morphine-induced TLR9 expression and microglia apoptosis appears to require μOR. Collectively, these results reveal that opioids prime microglia to undergo apoptosis through TLR9 and µOR as well. Taken together, our data suggest that inhibition of TLR9 and/or blockage of µOR is capable of preventing opioid-induced brain damage