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Objective: To investigate the relationship between immunohistochemical characteristics and recurrence after complete remission (CR) with fertility preservation treatment in patients with endometrial cancer (EC) and endometrial atypical hyperplasia (AH). Methods: The clinical data and immunohistochemical results of 53 patients with EC and 68 patients with AH admitted to Peking University People's Hospital from January 2010 to January 2021 were retrospectively analyzed. Patients were divided into two groups according to whether recurrence after complete remission (CR): group 1: recurrence after CR; group 2: no recurrence after CR, for statistical analysis. Results: (1) The expression rate of ER in group 1 was lower than that in group 2, (P < 0.05). The expression rate of Ki-67 in group 1 was significantly higher than that in group 2, (P < 0.01). The expression rates of PR, P16, P53, and PTEN were not significantly different between the two groups (P > 0.05); (2) combination index ER/ Ki-67 row ROC curve analysis, there was a significant difference (P < 0.01), the best cut-off value was 3.55, sensitivity 0.730, specificity 1.000, Youden index 0.730. The 3-year RFS of high rate patients was 100%, and that of low rate patients was 42.3%, P < 0.01. Conclusions: The expression rate of Ki-67 is of great significance in predicting the recurrence of EC after fertility preservation therapy. The best cut-off value of combination index ER/ Ki-67 (3.55) was better than a single immunohistochemical marker in predicting recurrence of EC after fertility preservation treatment. [ABSTRACT FROM AUTHOR]

Metallic glass offers several advantages, including high strength, corrosion resistance, and low coercivity. In precision machining fields like optical devices, medical devices, and micro-electromechanical systems, Ti-based metallic glass offers more advantages than Fe- and Zr-based metallic glass. However, its current machinability poses a challenge in meeting the requirements of precision metallic glass parts. To obtain the best machining performance, a thermophysical model of the EDM drilling process was established to simulate the temperature distribution on the surface of metal glass workpiece during EDM drilling. In addition, a new systematic method is utilized to calculate the characteristics of important machining holes, such as inlet and outlet overcut and inlet and outlet edge deviation. In this investigation, the maximum relative overcut and edge deviation are 8.59% and 7.23%, respectively, relative to the electrode radius. To improve the machining quality and machining stability, the slit width should be kept at an ideal value. Therefore, the recommended discharge current is 4–5 A, pulse duration is 50 μ s, and pulse duty ratio is 0.2 - 0.3 when EDM drilling of amorphous alloy. Based on this, the EDM drilling analysis method by numerical and experimental investigation for titanium-based metallic glass is put forward, which provides scientific theoretical guidance for the EDM of drilling it. [ABSTRACT FROM AUTHOR]

We present a novel workflow for forecasting production in unconventional reservoirs using reduced-order models and machine-learning. Our physics-informed machine-learning workflow addresses the challenges to real-time reservoir management in unconventionals, namely the lack of data (i.e., the time-frame for which the wells have been producing), and the significant computational expense of high-fidelity modeling. We do this by applying the machine-learning paradigm of transfer learning, where we combine fast, but less accurate reduced-order models with slow, but accurate high-fidelity models. We use the Patzek model (Proc Natl Acad Sci 11:19731–19736, https://doi.org/10.1073/pnas.1313380110, 2013) as the reduced-order model to generate synthetic production data and supplement this data with synthetic production data obtained from high-fidelity discrete fracture network simulations of the site of interest. Our results demonstrate that training with low-fidelity models is not sufficient for accurate forecasting, but transfer learning is able to augment the knowledge and perform well once trained with the small set of results from the high-fidelity model. Such a physics-informed machine-learning (PIML) workflow, grounded in physics, is a viable candidate for real-time history matching and production forecasting in a fractured shale gas reservoir. [ABSTRACT FROM AUTHOR]

Two Co–Cr–O spinel catalysts with different stoichiometry were synthesized and characterized by X-ray diffraction, X-ray photoelectron spectroscopy, N2 physisorption and temperature-programmed reduction in H2. Excess Co in Co1.5Cr1.5O4 existed as Co3+ that substituted for Cr3+ in the octahedral sites of the spinel lattice. High temperature treatment of the spinel catalysts in H2 resulted in stepwise reduction of Co3+ to Co2+ and eventually to Co metal. Both CoCr2O4 and Co1.5Cr1.5O4 catalysts were active and structurally stable in ethylene steam reforming under differential reaction conditions at 873 K, with the areal reforming rate over Co1.5Cr1.5O4 being one order-of-magnitude greater than that over CoCr2O4. The steady state reforming rate after oxidation was comparable to that over the fresh catalyst for both CoCr2O4 and Co1.5Cr1.5O4, indicating the stability of the spinel structure against reduction under steam reforming conditions. [ABSTRACT FROM AUTHOR]

The complete genome of a bear picornavirus 1 (BePV-1) in the viscera of an Asian black bear (Ursus thibetanus) from China was characterized using viral metagenomics and RT-PCR/Sanger sequencing. The genome of BePV1 is 6703 nt long, contains a type-IV IRES 5'UTR with the '8-like' motif, encodes a 2053-aa-long polyprotein showing a 3-4-4 organization pattern and two 2A genes. BePV-1 showed the highest overall genome nucleotide sequence identity of 71.7% to a picornavirus genome from an Arctic ringed seal (Phoca hispida) from Canada, classified as a member of the species Aquamavirus A, currently the only one in the genus Aquamavirus. Phylogenetic and genetic distance analyses of P1 and 3D indicated that Asian bear picornavirus (aquamavirus B) represents the second sequenced member of the genus Aquamavirus. [ABSTRACT FROM AUTHOR]

The Ras-like GTPases RalA and RalB are important drivers of tumour growth and metastasis. Chemicals that block Ral function would be valuable as research tools and for cancer therapeutics. Here we used protein structure analysis and virtual screening to identify drug-like molecules that bind to a site on the GDP-bound form of Ral. The compounds RBC6, RBC8 and RBC10 inhibited the binding of Ral to its effector RALBP1, as well as inhibiting Ral-mediated cell spreading of murine embryonic fibroblasts and anchorage-independent growth of human cancer cell lines. The binding of the RBC8 derivative BQU57 to RalB was confirmed by isothermal titration calorimetry, surface plasmon resonance and 1H-15N transverse relaxation-optimized spectroscopy (TROSY) NMR spectroscopy. RBC8 and BQU57 show selectivity for Ral relative to the GTPases Ras and RhoA and inhibit tumour xenograft growth to a similar extent to the depletion of Ral using RNA interference. Our results show the utility of structure-based discovery for the development of therapeutics for Ral-dependent cancers. [ABSTRACT FROM AUTHOR]

The factors that determine the transcription-regulating sequence (TRS) activity of porcine reproductive and respiratory syndrome virus (PRRSV) remain largely unclear. In this study, the effect of mutagenesis of conserved C nucleotides at positions 5 and 6 in the leader TRS (TRS-L) and/or canonical body TRS7 (TRS-B) on the synthesis of subgenomic (sg) mRNA and virus infectivity was investigated in the context of a type 2 PRRSV infectious cDNA clone. The results showed that a double C mutation in the leader TRS completely abolished sg mRNAs synthesis and virus infectivity, but a single C mutation did not. A single C or double C mutation in TRS-B or/and TRS-B impaired or abolished the corresponding sg mRNA synthesis. Introduction of identical mutations in the leader and body TRSs partially restored sg mRNA7.1 and/or sg mRNA7.2 transcription, indicating that the base-pairing interaction between sense TRS-L and cTRS-B is a crucial factor influencing sg mRNA synthesis. Analysis of the mRNA leader-body junctions of mutants provided evidence for a mechanism of discontinuous minus-strand transcription. This study also showed that mutational inactivation of TRS-B or TRS-B did not affect the production of infectious progeny virus, and the sg mRNA formed from each of them could express N protein. However, TRS-B plays more important roles than TRS-B in maintaining the growth characteristic of type 2 PRRSV. These results provide more insight into the molecular mechanism of genome expression and subgenomic mRNA transcription of PRRSV. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) can impact viral infections by binding to sequences with partial complementarity on viral RNA transcripts, usually resulting in the repression of virus replication. In the present study, we identified a potential binding site for miR-130 in the 5′ untranslated region (bps 155-162) of the porcine reproductive and respiratory syndrome virus (PRRSV) genome. We found that the delivery of multiple miR-130 family mimics, especially miR-130b, resulted in inhibition of PRRSV replication in vitro. miR-130 was effective in inhibiting the replication of multiple type 2 PRRSV strains, but not against vSHE, a classical type 1 strain. miR-130 over-expression did not induce IFN-α or TNF-α expression in either uninfected or PRRSV-infected porcine alveolar macrophages. Results from luciferase reporter assays indicated that miR-130 directly targeted the PRRSV 5′ UTR. Intranasal inoculation of piglets with miR-130b exhibited antiviral activity in vivo and partially protected piglets from an otherwise lethal challenge with HP-PRRSV strain vJX143. Overall, these results demonstrate the importance of the miR-130 family in modulating PRRSV replication and also provide a scientific basis for using cellular miRNAs in anti-PRRSV therapies. [ABSTRACT FROM AUTHOR]