PHGDH Is Upregulated at Translational Level and Implicated in Platin-Resistant in Ovarian Cancer Cells

BackgroundPlatinum-based chemotherapy is the first line option for ovarian cancer. The development of resistance to such chemotherapy results in treatment failure, while the underlying mechanisms are poorly understood.MethodsClinical samples were collected from Shengjing Hospital of China Medical University. MTT assay was used to see the proliferation and chemoresistance of ovarian cancer cells. Transwell migration and Matrigel invasion assays was used to see the invasion ability of ovarian cancer cells. In addition, polysome profiling and tissue microarray and immunohistochemical staining were also used. The statistical significance of the difference was analyzed by ANOVA and post hoc Dunnett’s test.ResultsPHGDH is the first enzyme responsible for serine biosynthesis pathway. The current study demonstrated that PHGDH is upregulated in platin-resistant ovarian cancer cells and tissues at the protein level. Importantly, knockdown of PHGDH suppressed, while overexpression of PHGDH increased the survival upon cisplatin exposure, invasiveness and spheroid formation of ovarian cancer cells. The current study demonstrated that PHGDH translation was upregulated in platin-resistant ovarian cancer. In addition, our study provided evidence that LncRNA RMRP (RNA Component of Mitochondrial RNA Processing Endoribonuclease) was upregulated in platin-resistant ovarian cancer, which promoted enrichment of RNA binding protein DDX3X (DEAD-Box Helicase 3 X-Linked) on the PHGDH mRNA to promote its translation.ConclusionCollectively, the current study described that PHGDH was upregulated and conferred resistance of ovarian cancer cells to cisplatin, suggesting that cisplatin resistance could be overcome by targeting PHGDH. Our study also provided evidence that differential PHGDH protein expression was defined by its translation, and RNA binding protein DDX3X and LncRNA RMRP are regulators of its translation

Entanglement in spin-1/2 dimerized Heisenberg systems

We study entanglement in dimerized Heisenberg systems. In particular, we give exact results of ground-state pairwise entanglement for the four-qubit model by identifying a Z_2 symmetry. Although the entanglements cannot identify the critical point of the system, the mean entanglement of nearest-neighbor qubits really does, namely, it reaches a maximum at the critical point.Comment: Four pages, three figures, accepted in Communications in Theoretical Physic

N-(Ferrocenylmethyl)­dodecan-1-amine

The title compound, [Fe(C5H5)(C18H32N)], was synthesized by the amination of ferrocenecarbaldehyde. In the complex, the two cyclo­penta­dienyl (Cp) rings are almost parallel with a dihedral angle of 1.36 (8)°, and are separated by a centroid–centroid distance of 3.299 (2) Å. In the crystal, adjacent mol­ecules are linked into a one-dimensional supra­molecular structure via weak C—H⋯π inter­actions between the Cp ring H atom and the Cp ring

Rare Earth Eu Doped PtRu/C Catalysts and Their Properties for Methanol Electrooxidation

Commercially available PtRu/C catalyst was doped with Eu by chemical reduction and sintering, resulting in PtRuEux/C catalysts with different Eu contents. The catalysts were characterized by transmission electron microscopy (TEM), energy dispersive X-ray (EDX) spectroscopy, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Results showed that Eu doping did not change the average size of the PtRu/C catalysts (ca 3 nm), and their surfaces were modified by both Eu metal and oxide. Cyclic voltammetry and chronoamperometry demonstrated that the activity of the PtRuEux/C catalysts was higher than that of commercial PtRu/C for methanol electrooxidation. Among the PtRuEux/C catalysts, PtRuEu0.3/C exhibited the best performance. The electrocatalytic oxidation of methanol on the catalyst was further investigated by in situ Fourier transform infrared (FTIR) spectroscopy at molecular level. Results indicated that the adsorbed species derived from the dissociative adsorption of methanol on the catalysts were linear. bonded CO (COL). Eu doping decreased the oxidation potential of COL and thus significantly enhanced the activity of the catalysts and their tolerance to CO.National Natural Science Foundation of China [20833005, 20828005]; Scientific Research Foundation, Ministry of Education ; Opening Foundation of the State Key Laboratory for Physical Chemistry of Solid Surface of Xiamen University ; Innovation Project of Guangxi Graduate Education, Chin

Abstract Syntax Tree for Programming Language Understanding and Representation: How Far Are We?

Programming language understanding and representation (a.k.a code representation learning) has always been a hot and challenging task in software engineering. It aims to apply deep learning techniques to produce numerical representations of the source code features while preserving its semantics. These representations can be used for facilitating subsequent code-related tasks. The abstract syntax tree (AST), a fundamental code feature, illustrates the syntactic information of the source code and has been widely used in code representation learning. However, there is still a lack of systematic and quantitative evaluation of how well AST-based code representation facilitates subsequent code-related tasks. In this paper, we first conduct a comprehensive empirical study to explore the effectiveness of the AST-based code representation in facilitating follow-up code-related tasks. To do so, we compare the performance of models trained with code token sequence (Token for short) based code representation and AST-based code representation on three popular types of code-related tasks. Surprisingly, the overall quantitative statistical results demonstrate that models trained with AST-based code representation consistently perform worse across all three tasks compared to models trained with Token-based code representation. Our further quantitative analysis reveals that models trained with AST-based code representation outperform models trained with Token-based code representation in certain subsets of samples across all three tasks. We also conduct comprehensive experiments to evaluate and reveal the impact of the choice of AST parsing/preprocessing/encoding methods on AST-based code representation and subsequent code-related tasks. Our study provides future researchers with detailed guidance on how to select solutions at each stage to fully exploit AST.Comment: submitted to ACM Transactions on Software Engineering and Methodology. arXiv admin note: text overlap with arXiv:2103.10668 by other author

Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in Aβ1–42 Induced Alzheimer’s Disease Model Rats

There is increasing evidence indicating that inflammation represents a key pathological component of Alzheimer’s disease (AD). A possible factor that may contribute to this process is netrin-1, a neuronal guidance molecule. This molecule has been shown to exert an unexpected immunomodulatory function. However, the potential changes and correlations of netrin-1 with T helper 17/regulatory T cells (Th17/Tregs) as related to inflammation in AD has yet to be examined. In this study, netrin-1 and Th17/Tregs balance were investigated, and the relationship among netrin-1, Th17/Tregs and cognitive function were analyzed in a rat model of AD. In this model, a bilateral intracerebroventricular administration of Amyloid β1-42 (Aβ1–42) was used to produce spatial learning and memory deficits, as well as increased neuronal apoptosis, which were detected 7 days after injection for AD7d group and 14 days for AD14d group. Netrin-1 concentrations were significantly down regulated in both serum and cerebrospinal fluid (CSF) of these AD rats, effects which were strongly correlated with cognitive deficits. Increased levels of interleukin (IL)-17 and deceased IL-10 were observed in both the circulation and CSF and were also correlated with the percent of time spent in the target quadrant of AD in these rats. These changes resulted in netrin-1 concentrations being negatively correlated with IL-17 but positively correlated with IL-10 concentrations in the serum and CSF. We also found that the Th17/Tregs balance was disrupted in these AD rats. Collectively, these findings reveal that the reduction in netrin-1 and the correlated disruption of Th17/Tregs balance in AD rats may diminish the immunosuppressive effect of netrin-1 on Th17/Tregs in AD pathogenesis

Radiated tumor cell-derived microparticles effectively kill stem-like tumor cells by increasing reactive oxygen species

Stem-like tumor cells (SLTCs) are thought to be the cellular entity responsible for clinical recurrence and subsequent metastasis. Inhibiting or killing SLTCs can effectively reduce recurrence and metastasis, yet little has been done to clear SLTCs because they are usually resistant to chemotherapy, radiotherapy, and even immunotherapy. In this study, we established SLTCs by low-serum culture and confirmed that the low-serum-cultured tumor cells were in a quiescent state and resistant to chemotherapy, showing features of SLTCs, consistent with the reported data. We demonstrated that SLTCs had high levels of reactive oxygen species (ROS). Based on the finding that radiated tumor cell-derived microparticles (RT-MPs) contained ROS, we used RT-MPs to kill SLTCs. We found that RT-MPs could further increase ROS levels and kill SLTCs in vivo and in vitro partially by ROS carried by the RT-MPs themselves, providing a new method for eliminating SLTCs