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Poly(ADP-ribose)polymerase (PARP) is a significant therapeutic target for the treatment of numerous human diseases. Olaparib has been approved as a PARP inhibitor. In this paper, a series of new compounds were designed and synthesized with Olaparib as the lead compound. In order to evaluate the inhibitory activities against PARP1 of the synthesized compounds, in vitro PARP1 inhibition assay and intracellular PARylation assay were conducted. The results showed that the inhibitory activities of the derivatives were related to the type of substituent and the length of alkyl chain connecting the aromatic ring. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT)-based assay also proved that these compounds demonstrating strong inhibition to PARP1 also have high anti-proliferative activities against BRCA2-deficient cell line (Capan-1). Analysis of the entire results suggest that compound 23 with desirable inhibitory efficiency may hold promise for further in vivo exploration of PARP inhibition.

High-energy–density lithium-ion batteries (LIBs) that can be safely fast-charged are desirable for electric vehicles. However, sub-optimal lithiation potential and low capacity of commonly used LIBs anode cause safety issues and low energy density. Here we hypothesize that a cobalt vanadate oxide, Co2VO4, can be attractive anode material for fast-charging LIBs due to its high capacity (~ 1000 mAh g−1) and safe lithiation potential (~ 0.65 V vs. Li+/Li). The Li+ diffusion coefficient of Co2VO4 is evaluated by theoretical calculation to be as high as 3.15 × 10–10 cm2 s−1, proving Co2VO4 a promising anode in fast-charging LIBs. A hexagonal porous Co2VO4 nanodisk (PCVO ND) structure is designed accordingly, featuring a high specific surface area of 74.57 m2 g−1 and numerous pores with a pore size of 14 nm. This unique structure succeeds in enhancing Li+ and electron transfer, leading to superior fast-charging performance than current commercial anodes. As a result, the PCVO ND shows a high initial reversible capacity of 911.0 mAh g−1 at 0.4 C, excellent fast-charging capacity (344.3 mAh g−1 at 10 C for 1000 cycles), outstanding long-term cycling stability (only 0.024% capacity loss per cycle at 10 C for 1000 cycles), confirming the commercial feasibility of PCVO ND in fast-charging LIBs. Highlights: 1 The Li+ diffusion coefficient of Co2VO4 is evaluated by theoretical calculation to be as high as 3.15 × 10–10 cm2 s−1, theoretically proving Co2VO4 a promising anode in fast-charging lithium-ion batteries.2 A hexagonal porous Co2VO4 nanodisk (PCVO ND) structure is designed, featuring a high specific surface area of 74.57 m2 g−1 and numerous pores with a pore size of 14 nm.3 The PCVO ND shows excellent fast-charging performance (a high average capacity of 344.3 mAh g−1 at 10 C for 1000 cycles with only 0.024% capacity loss per cycle for 1000 cycles).

The Li+ diffusion coefficient of Co2VO4 is evaluated by theoretical calculation to be as high as 3.15 × 10–10 cm2 s−1, theoretically proving Co2VO4 a promising anode in fast-charging lithium-ion batteries.A hexagonal porous Co2VO4 nanodisk (PCVO ND) structure is designed, featuring a high specific surface area of 74.57 m2 g−1 and numerous pores with a pore size of 14 nm.The PCVO ND shows excellent fast-charging performance (a high average capacity of 344.3 mAh g−1 at 10 C for 1000 cycles with only 0.024% capacity loss per cycle for 1000 cycles). Supplementary Information The online version contains supplementary material available at 10.1007/s40820-021-00758-5., High-energy–density lithium-ion batteries (LIBs) that can be safely fast-charged are desirable for electric vehicles. However, sub-optimal lithiation potential and low capacity of commonly used LIBs anode cause safety issues and low energy density. Here we hypothesize that a cobalt vanadate oxide, Co2VO4, can be attractive anode material for fast-charging LIBs due to its high capacity (~ 1000 mAh g−1) and safe lithiation potential (~ 0.65 V vs. Li+/Li). The Li+ diffusion coefficient of Co2VO4 is evaluated by theoretical calculation to be as high as 3.15 × 10–10 cm2 s−1, proving Co2VO4 a promising anode in fast-charging LIBs. A hexagonal porous Co2VO4 nanodisk (PCVO ND) structure is designed accordingly, featuring a high specific surface area of 74.57 m2 g−1 and numerous pores with a pore size of 14 nm. This unique structure succeeds in enhancing Li+ and electron transfer, leading to superior fast-charging performance than current commercial anodes. As a result, the PCVO ND shows a high initial reversible capacity of 911.0 mAh g−1 at 0.4 C, excellent fast-charging capacity (344.3 mAh g−1 at 10 C for 1000 cycles), outstanding long-term cycling stability (only 0.024% capacity loss per cycle at 10 C for 1000 cycles), confirming the commercial feasibility of PCVO ND in fast-charging LIBs. Supplementary Information The online version contains supplementary material available at 10.1007/s40820-021-00758-5.

Silicon/carbon (Si/C) composite has been proven to be an effective method of enhancing the electrochemical performance of Si-based anodes for lithium-ion batteries (LIBs). However, the practical application of Si/C materials in LIBs is difficult because of the weak interaction between Si and C. In this study, we applied two-step diazotization reactions to modify graphite nanosheets (GNs) and Si nanoparticles (Si NPs), yielding a stable Si&ndash, Ar&ndash, GNs composite. Owing to aryl (Ar) group bonding, Si NPs were dispersed well on the GNs. The as-prepared Si&ndash, GNs composite delivered an initial reversible capacity of 1174.7 mAh&middot, g&minus, 1 at a current density of 100 mAh&middot, 1. Moreover, capacity remained at 727.3 mAh&middot, 1 after 100 cycles, showing improved cycling performance. This synthesis strategy can be extended to prepare other Si/C anode materials of LIBs.

A series of compounds following the lead compounds including deferasirox and tacrine were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease (AD). In vitro studies showed that most synthesized compounds exhibited good multifunctional activities in inhibiting acetylcholinesterase (bAChE), and chelating metal ions. Especially, compound TDe demonstrated significant metal chelating property, a moderate acetylcholinesterase (AChE) inhibitory activity and an antioxidant activity. Results from the molecular modeling indicated that TD compounds were mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of TcAChE. Moreover, TDe showed a low cytotoxicity but a good protective activity against the injury caused by H2O2. These results suggest that TD compounds might be considered as attractive multi-target cholinesterase inhibitor and will play important roles in the treatment of AD.

Mechanical and metallurgical properties of a 27mm thick Grade X80 steel plate and its UOE pipe are described in this paper. The steel is economically designed for its chemical compositions. Steel plates were produced by Thermal-mechanical processing (TMCP) with attentive reduction control during hot rolling stage. The microstructure is composed of multi-phases in which polygonal ferrite and granular bainite are the principal constituents. Line pipes of 1219mm outer diameter, which has strain based design for long distance natural gas transportation over the permafrost and seismic areas, were manufactured by the UOE process under a 0.8% expanding ratio on the pipe. Mechanical properties of the pipe and in the girth weld joints comply well with the pipeline construction requirement. Precipitation behaviors were analyzed in the steel materials, and a strengthening contribution at about 45.6 MPa is disclosed. Dislocation hardening in the pipe base materials after the simulating coating gives rise to 44.9 MPa.

Background Conventional prenatal screening tests, such as maternal serum tests and ultrasound scan, have limited resolution and accuracy. Methods We developed an advanced noninvasive prenatal diagnosis method based on massively parallel sequencing. The Noninvasive Fetal Trisomy (NIFTY) test, combines an optimized Student’s t-test with a locally weighted polynomial regression and binary hypotheses. We applied the NIFTY test to 903 pregnancies and compared the diagnostic results with those of full karyotyping. Results 16 of 16 trisomy 21, 12 of 12 trisomy 18, two of two trisomy 13, three of four 45, X, one of one XYY and two of two XXY abnormalities were correctly identified. But one false positive case of trisomy 18 and one false negative case of 45, X were observed. The test performed with 100% sensitivity and 99.9% specificity for autosomal aneuploidies and 85.7% sensitivity and 99.9% specificity for sex chromosomal aneuploidies. Compared with three previously reported z-score approaches with/without GC-bias removal and with internal control, the NIFTY test was more accurate and robust for the detection of both autosomal and sex chromosomal aneuploidies in fetuses. Conclusion Our study demonstrates a powerful and reliable methodology for noninvasive prenatal diagnosis.

Isodicentric chromosome 18 [idic(18)] is rare structural aberration. We report on a prenatal case described by conventional and molecular cytogenetic analyses. The sonography at 24 weeks of gestation revealed multiple fetal anomalies; radial aplasia and ventricular septal defect were significant features. Routine karyotyping showed a derivative chromosome replacing one normal chromosome 18. The parental karyotypes were normal, indicating that the derivative chromosome was de novo. Array comparative genomic hybridization (array-CGH) revealed 18p11.21→qter duplication and 18p11.21→pter deletion for genomic DNA of the fetus. The breakpoint was located at 18p11.21 (between 12104527 bp and 12145199 bp from the telomere of 18p). Thus, the derivative chromosome was ascertained as idic(18)(qter→p11.21::p11.21→qter). Fluorescent in situ hybridization (FISH) confirmed that the derivative chromosome was idic(18). Our report describes a rare isodicentric chromosome 18 and demonstrates that array-CGH is a useful complementary tool to cytogenetic analysis for reliable identifying derivative chromosome.

The acrofacial dysostoses (AFDs) are a heterogeneous group of disorders involving craniofacial dysostosis and limb anomalies. Depending on the type of limb defects, two major groups have been defined: Nager syndrome with predominant preaxial anomalies and Miller syndrome with postaxial malformations. Genomic copy number variation, a common type of genomic variability, can influence gene expression by disrupting coding sequences, perturbing long-range gene regulation, or altering gene dosage, and these effects could contribute to phenotypic variations or disease risk. We present a distinct AFD case with mandibulofacial dysostosis, microtia and limb malformations but without limb defects, which may represent a new form of AFD. To investigate the etiology of the phenotype, whole genomic high-resolution array comparative genomic hybridization analysis was carried out, revealing two cryptic duplications, 1p36.33 and 1q21.3-q22 duplications. Two genes, VWA1 and PYGO2, contained in the two duplications, respectively, are likely to be the candidate genes for the phenotype of our patient.