Enantioselective propargylic amination and related tandem sequences to α-tertiary ethynylamines and azacycles.

Chiral α-tertiary amines and related azacycles are sought-after compounds for drug development. Despite progress in the catalytic asymmetric construction of aza-quaternary stereocentres, enantioselective synthesis of multifunctional α-tertiary amines remains underdeveloped. Enantioenriched α-disubstituted α-ethynylamines are attractive synthons for constructing chiral α-tertiary amines and azacycles, but methods for their catalytic enantioselective synthesis need to be expanded. Here we describe an enantioselective asymmetric Cu(I)-catalysed propargylic amination (ACPA) of simple ketone-derived propargylic carbonates to give both α-dialkylated and α-alkyl-α-aryl α-tertiary ethynylamines. Sterically confined pyridinebisoxazoline (PYBOX) ligands, with a C4 shielding group and relaying groups, play a key role in achieving excellent enantioselectivity. The syntheses of quaternary 2,5-dihydropyrroles, dihydroquinines, dihydrobenzoquinolines and dihydroquinolino[1,2-α]quinolines are reported, and the synthetic value is further demonstrated by the enantioselective catalytic total synthesis of a selective multi-target ß-secretase inhibitor. Enantioselective Cu-catalysed propargylic substitutions with O- and C-centred nucleophiles are also realized, further demonstrating the potential of the PYBOX ligand.

SLFN11 promotes clear cell renal cell carcinoma progression via the PI3K/AKT signaling pathway.

SLFN11 is abnormally expressed and associated with survival outcomes in various human cancers. However, the role of SLFN11 in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the clinical value and potential functions of SLFN11 in ccRCC. Comprehensive bioinformatics analyses were performed using online databases. Quantitative real-time PCR (qPCR) and western blotting were used to validate the expression data. CCK8, flow cytometry analysis, and EdU staining were performed to determine the level of cell proliferation. Flow cytometry analysis was also used to detect cell apoptosis. Wound-healing assay and Transwell assays were performed to assess cell migration and invasion capability, respectively. SLFN11 was overexpressed and was an independent prognostic factor in ccRCC. SLFN11 knockdown inhibited cell proliferation, migration, and invasion and promoted apoptosis. Functional and pathway enrichment analyses suggested that SLFN11 may have an impact on tumorigenesis in ccRCC through regulation of the inflammatory response, the PI3K/AKT signaling pathway and other effectors. Furthermore, SLFN11 knockdown inhibited the phosphorylation of the PI3K/AKT signaling pathway and could be activated by 740 Y-P. Finally, we demonstrated that miR-183 may specifically target SLFN11, and miR-183 expression was correlated with predicted survival. SLFN11 may play a critical role in ccRCC progression and may serve as a novel prognostic biomarker in ccRCC.

Combining BERT Model with Semi-Supervised Incremental Learning for Heterogeneous Knowledge Fusion of High-Speed Railway On-Board System.

On-board system fault knowledge base (KB) is a collection of fault causes, maintenance methods, and interrelationships among on-board modules and components of high-speed railways, which plays a crucial role in knowledge-driven dynamic operation and maintenance (O&M) decisions for on-board systems. To solve the problem of multi-source heterogeneity of on-board system O&M data, an entity matching (EM) approach using the BERT model and semi-supervised incremental learning is proposed. The heterogeneous knowledge fusion task is formulated as a pairwise binary classification task of entities in the knowledge units. Firstly, the deep semantic features of fault knowledge units are obtained by BERT. We also investigate the effectiveness of knowledge unit features extracted from different hidden layers of the model on heterogeneous knowledge fusion during model fine-tuning. To further improve the utilization of unlabeled test samples, a semi-supervised incremental learning strategy based on pseudo labels is devised. By selecting entity pairs with high confidence to generate pseudo labels, the label sample set is expanded to realize incremental learning and enhance the knowledge fusion ability of the model. Furthermore, the model's robustness is strengthened by embedding-based adversarial training in the fine-tuning stage. Based on the on-board system's O&M data, this paper constructs the fault KB and compares the model with other solutions developed for related matching tasks, which verifies the effectiveness of this model in the heterogeneous knowledge fusion task of the on-board system.

Compound heterozygous LPIN2 pathogenic variants in a patient with Majeed syndrome with recurrent fever and severe neutropenia: case report.

BACKGROUND: Majeed syndrome is a rare, autosomal recessive autoinflammatory disorder first described in 1989. The syndrome starts during infancy with recurrent relapses of osteomyelitis typically associated with fever, congenital dyserythropoietic anemia (CDA), and often neutrophilic dermatosis. Mutations in the LPIN2 gene located on the short arm of chromosome 18 have been identified as being responsible for Majeed syndrome. CASE PRESENTATION: We report an 8-month-old boy, who presented with recurrent fever, mild to moderate anemia, and severe neutropenia. Erythrocyte sedimentation rate and C-reactive protein were elevated. Molecular testing identified a paternal splicing donor site variant c.2327 + 1G > C and a maternal frameshift variant c.1691_1694delGAGA (Arg564Lysfs*3) in LPIN2. CONCLUSIONS: Only a few cases with LPIN2 mutation have been reported, mainly in the Middle East with homozygous variants. Our patient exhibited a mild clinical phenotype and severe neutropenia, different from previous reports.

Detailed structure information a highly thermostable Tb-cluster that based on a prodrug ligand of 2,4,5-trifluoro-3-methoxybenzoic acid.

In this brief data article, we present the precise structural information, PARD data and thermographic analysis of the Tb-cluster. Detailed structure, luminescence and detecting properties were discussed in our previous study (Zhao et al., 2017) [1]. The data includes the coordination modes of ligand, PXRD patterns of these Ln-MOFs, thermostability, detailed bond lengths and bond angles of the Tb-cluster.

Structural data of structure variation and luminescence of 3D, 2D and 1D lanthanide coordination polymers with 1,3-adamantanediacetic acid.

In this data article, we report the structure, Fourier transform infrared spectroscopy(FT-IR), powder X-ray diffraction (PARD), luminescence decay, thermogravimetric analysis (TGA) and UV-vis data of three series Ln-MOFs. Detailed structure and luminescence properties were discussed in our previous study (Zhao et al., 2018) [1]. The data includes the structure patterns of ligand H2ADA, FT-IR, PXRD and thermostability of Ln-MOFs in the air, detailed structure information for these structures are listed in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7.

Utrecht Interstitial Applicator Shifts and DVH Parameter Changes in 3D CT-based HDR Brachytherapy of Cervical Cancer.

BACKGROUND: For brachytherapy of cervical cancer, applicator shifts can not be avoided. The present investigation concerned Utrecht interstitial applicator shifts and their effects on organ movement and DVH parameters during 3D CT-based HDR brachytherapy of cervical cancer. MATERIALS AND METHODS: After the applicator being implanted, CT imaging was achieved for oncologist contouring CTVhr, CTVir, and OAR, including bladder, rectum, sigmoid colon and small intestines. After the treatment, CT imaging was repeated to determine applicator shifts and OARs movements. Two CT images were matched by pelvic structures. In both imaging results, we defined the tandem by the tip and the base as the marker point, and evaluated applicator shift, including X, Y and Z. Based on the repeated CT imaging, oncologist contoured the target volume and OARs again. We combined the treatment plan with the repeated CT imaging and evaluated the change range for the doses of CTVhr D90, D2cc of OARs. RESULTS: The average applicator shift was -0.16 mm to 0.10 mm for X, 1.49 mm to 2.14 mm for Y, and 1.9 mm to 2.3 mm for Z. The change of average physical doses and EQD2 values in Gyα/ß range for CTVhr D90 decreased by 2.55 % and 3.5 %, bladder D2cc decreased by 5.94 % and 8.77 %, rectum D2cc decreased by 2.94 % and 4 %, sigmoid colon D2cc decreased by 3.38 % and 3.72 %, and small intestines D2cc increased by 3.72 % and 10.94 %. CONCLUSIONS: Applicator shifts and DVH parameter changes induced the total dose inaccurately and could not be ignored. The doses of target volume and OARs varied inevitably.