Publications by authors named "Wenwei Zhang"

99 Publications

stLFRsv: A Germline Structural Variant Analysis Pipeline Using Co-barcoded Reads.

Front Genet 2021 18;12:636239. Epub 2021 Mar 18.

BGI-Shenzhen, Shenzhen, China.

Co-barcoded reads originating from long DNA fragments (mean length >30 kbp) maintain both single base level accuracy and long-range genomic information. We propose a pipeline, stLFRsv, to detect structural variation using co-barcoded reads. stLFRsv identifies abnormal large gaps between co-barcoded reads to detect potential breakpoints and reconstruct complex structural variants (SVs). Haplotype phasing by co-barcoded reads increases the signal to noise ratio, and barcode sharing profiles are used to filter out false positives. We integrate the short read SV caller smoove for smaller variants with stLFRsv. The integrated pipeline was evaluated on the well-characterized genome HG002/NA24385, and 74.5% precision and a 22.4% recall rate were obtained for deletions. stLFRsv revealed some large variants not included in the benchmark set that were verified by long reads or assembly. For the HG001/NA12878 genome, stLFRsv also achieved the best performance for both resource usage and the detection of large variants. Our work indicates that co-barcoded read technology has the potential to improve genome completeness.
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http://dx.doi.org/10.3389/fgene.2021.636239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012683PMC
March 2021

Organic-Inorganic Superlattices of Vanadium Oxide@Polyaniline for High-Performance Magnesium-Ion Batteries.

ChemSusChem 2021 Mar 9. Epub 2021 Mar 9.

Hubei Provincial Key Laboratory of Green Materials for Light Industry, School of Materials and Chemical Engineering, Hubei University of Technology, Wuhan, 430068, P.R. China.

Rechargeable magnesium batteries (RMBs) have attracted significant attention owing to the high energy density and economic viability. However, the lack of suitable cathode materials, owing to the high polarizability of divalent Mg-ion and slow Mg-ion diffusion, hinders the development of RMBs. V O is a promising RMBs cathode material, but its limited interlayer spacing is unfavorable for the rapid diffusion of Mg , demonstrating unsatisfactory electrochemical performance. In this study, the superlattices of V O and polyaniline (PANI) with expanded interlayer spacing are assembled as the cathode material for RMBs. The intercalation of PANI in the interlayer region of V O significantly improves the reversible capacities, Mg diffusion kinetics, and cycling performance of the PVO cathode. Furthermore, RMBs with PVO as the cathode and Mg metal as the anode deliver high specific capacities. The introduced polyaniline layer not only expands the interlayer spacing of V O , but also increases the electrical conductivity. Moreover, ex situ XRD characterization indicates that PVO does not undergo obvious phase transformation with the continuous insertion of Mg , which may be ascribed to the π-conjugated chains of PANI that give flexibility to the structure to improve cycling stability. This study demonstrates that designing organic-inorganic superlattices is an efficient strategy for developing high-performance cathode materials for RMBs.
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http://dx.doi.org/10.1002/cssc.202100263DOI Listing
March 2021

Dual regulation of TxNIP by ChREBP and FoxO1 in liver.

iScience 2021 Mar 20;24(3):102218. Epub 2021 Feb 20.

Université de Paris, Institut Cochin, CNRS, INSERM, 75014 Paris, France.

TxNIP (Thioredoxin-interacting protein) is considered as a potential drug target for type 2 diabetes. Although TxNIP expression is correlated with hyperglycemia and glucotoxicity in pancreatic β cells, its regulation in liver cells has been less investigated. In the current study, we aim at providing a better understanding of regulation in hepatocytes in response to physiological stimuli and in the context of hyperglycemia in mice. We focused on regulatory pathways governed by ChREBP (Carbohydrate Responsive Element Binding Protein) and FoxO1 (Forkhead box protein O1), transcription factors that play central roles in mediating the effects of glucose and fasting on gene expression, respectively. Studies using genetically modified mice reveal that hepatic TxNIP is up-regulated by both ChREBP and FoxO1 in liver cells and that its expression strongly correlates with fasting, suggesting a major role for this protein in the physiological adaptation to nutrient restriction.
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http://dx.doi.org/10.1016/j.isci.2021.102218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966993PMC
March 2021

Rice FLOURY SHRUNKEN ENDOSPERM 5 Encodes a Putative Plant Organelle RNA Recognition Protein that Is Required for cis-Splicing of Mitochondrial nad4 Intron 1.

Rice (N Y) 2021 Mar 10;14(1):29. Epub 2021 Mar 10.

State Key Laboratory for Crop Genetics and Germplasm Enhancement, Jiangsu Plant Gene Engineering Research Center, Nanjing Agricultural University, Nanjing, 210095, China.

Background: The sequences of several important mitochondrion-encoded genes involved in respiration in higher plants are interrupted by introns. Many nuclear-encoded factors are involved in splicing these introns, but the mechanisms underlying this splicing remain unknown.

Results: We isolated and characterized a rice mutant named floury shrunken endosperm 5 (fse5). In addition to having floury shrunken endosperm, the fse5 seeds either failed to germinate or produced seedlings which grew slowly and died ultimately. Fse5 encodes a putative plant organelle RNA recognition (PORR) protein targeted to mitochondria. Mutation of Fse5 hindered the splicing of the first intron of nad4, which encodes an essential subunit of mitochondrial NADH dehydrogenase complex I. The assembly and NADH dehydrogenase activity of complex I were subsequently disrupted by this mutation, and the structure of the mitochondria was abnormal in the fse5 mutant. The FSE5 protein was shown to interact with mitochondrial intron splicing factor 68 (MISF68), which is also a splicing factor for nad4 intron 1 identified previously via yeast two-hybrid (Y2H) assays.

Conclusion: Fse5 which encodes a PORR domain-containing protein, is essential for the splicing of nad4 intron 1, and loss of Fse5 function affects seed development and seedling growth.
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http://dx.doi.org/10.1186/s12284-021-00463-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947098PMC
March 2021

Population Bottlenecks and Intra-host Evolution During Human-to-Human Transmission of SARS-CoV-2.

Front Med (Lausanne) 2021 15;8:585358. Epub 2021 Feb 15.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions.
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http://dx.doi.org/10.3389/fmed.2021.585358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917136PMC
February 2021

Clinical evaluation of preoperative embolization, vertebroplasty, and decompression in the treatment of aggressive vertebral hemangiomas.

J Orthop Surg (Hong Kong) 2021 Jan-Apr;29(1):2309499021993997

Department of Spine Surgery, 235960The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.

Objective: To evaluate the efficacy and safety of preoperative embolization and vertebroplasty in the treatment of aggressive hemangioma.

Methods: A retrospective clinical review of patients diagnosed with aggressive vertebral hemangiomas was conducted. All the patients were assigned to three groups according to the treatment strategies: patients in Group A underwent embolization and decompression with internal fixation, patients in Group B underwent vertebroplasty and decompression with internal fixation, patients in Group C received all three treatments. Clinical indexes were compared within three groups.

Results: There were 16 patients received embolization and decompression (Group A), 19 patients underwent decompression with vertebroplasty (Group B) and 16 patients in Group C. The operative duration of patients in group A (198.33 ± 38.43 min) were less than another two groups ( = 0.001). The intraoperative blood loss of patients in group C was 713.33 ± 165.13 mL, which was significantly less than group A and group B ( = 0.045). Patients in group C exhibited the lowest volume of drainage on POD 1 (178.33 ± 66.76 mL), which showed significant difference compared with group A (368.33 ± 191.15 mL, = 0.01). There was no significant difference of preoperative and postoperative VAS and JOA score among three groups, as well as drainage on POD 2, total volume and hospital duration.

Conclusion: Both embolization and vertebroplasty are efficient and safe measures to reduce blood loss in the surgical treatment of aggressive vertebral hemangiomas, combination of all three methods is also competent.
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http://dx.doi.org/10.1177/2309499021993997DOI Listing
March 2021

Comparative performance of the BGI and Illumina sequencing technology for single-cell RNA-sequencing.

NAR Genom Bioinform 2020 Jun 13;2(2):lqaa034. Epub 2020 May 13.

Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.

The libraries generated by high-throughput single cell RNA-sequencing (scRNA-seq) platforms such as the Chromium from 10× Genomics require considerable amounts of sequencing, typically due to the large number of cells. The ability to use these data to address biological questions is directly impacted by the quality of the sequence data. Here we have compared the performance of the Illumina NextSeq 500 and NovaSeq 6000 against the BGI MGISEQ-2000 platform using identical Single Cell 3' libraries consisting of over 70 000 cells generated on the 10× Genomics Chromium platform. Our results demonstrate a highly comparable performance between the NovaSeq 6000 and MGISEQ-2000 in sequencing quality, and the detection of genes, cell barcodes, Unique Molecular Identifiers. The performance of the NextSeq 500 was also similarly comparable to the MGISEQ-2000 based on the same metrics. Data generated by both sequencing platforms yielded similar analytical outcomes for general single-cell analysis. The performance of the NextSeq 500 and MGISEQ-2000 were also comparable for the deconvolution of multiplexed cell pools via variant calling, and detection of guide RNA (gRNA) from a pooled CRISPR single-cell screen. Our study provides a benchmark for high-capacity sequencing platforms applied to high-throughput scRNA-seq libraries.
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http://dx.doi.org/10.1093/nargab/lqaa034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671348PMC
June 2020

An Adaptive EEG Feature Extraction Method Based on Stacked Denoising Autoencoder for Mental Fatigue Connectivity.

Neural Plast 2021 20;2021:3965385. Epub 2021 Jan 20.

School of Mechanical Engineering, Xi'an Jiao Tong University, Xi'an 710049, China.

Mental fatigue is a common psychobiological state elected by prolonged cognitive activities. Although, the performance and the disadvantage of the mental fatigue have been well known, its connectivity among the multiareas of the brain has not been thoroughly studied yet. This is important for the clarification of the mental fatigue mechanism. However, the common method of connectivity analysis based on EEG cannot get rid of the interference from strong noise. In this paper, an adaptive feature extraction model based on stacked denoising autoencoder has been proposed. The signal to noise ratio of the extracted feature has been analyzed. Compared with principal component analysis, the proposed method can significantly improve the signal to noise ratio and suppress the noise interference. The proposed method has been applied on the analysis of mental fatigue connectivity. The causal connectivity among the frontal, motor, parietal, and visual areas under the awake, fatigue, and sleep deprivation conditions has been analyzed, and different patterns of connectivity between conditions have been revealed. The connectivity direction under awake condition and sleep deprivation condition is opposite. Moreover, there is a complex and bidirectional connectivity relationship, from the anterior areas to the posterior areas and from the posterior areas to the anterior areas, under fatigue condition. These results imply that there are different brain patterns on the three conditions. This study provides an effective method for EEG analysis. It may be favorable to disclose the underlying mechanism of mental fatigue by connectivity analysis.
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http://dx.doi.org/10.1155/2021/3965385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843194PMC
January 2021

Novel colorimetric aptasensor based on unmodified gold nanoparticle and ssDNA for rapid and sensitive detection of T-2 toxin.

Food Chem 2021 Jun 19;348:129128. Epub 2021 Jan 19.

College of Food Science and Engineering, Gansu Agricultural University, Lanzhou 730070, China. Electronic address:

A novel colorimetric aptasensor based on unmodified gold nanoparticle (AuNPs) and single-strand DNA (ssDNA) aptamer was developed for the rapid and sensitive detection of T-2 toxin. In the absence of T-2, the AuNPs were wrapped by the aptamer to avoid the salt-induced aggregation and the solution remains red. In the presence of T-2, the aptamer was bound with T-2 and released from the surface of AuNPs, resulting in the aggregation of AuNPs under proper salt solution and the color change from red to purple-blue. The aptasensor exhibited a high sensitivity and selectivity for the detection of T-2. The range of linearity and detection limit were 0.1 ng/mL-5000 ng/mL (0.21435 nM-10717.5 nM) and 57.8 pg/mL (0.124 nM), respectively. The aptasensor developed here was applicable to assay T-2 in wheat and corn samples. These results implied that the colorimetric aptasensor was potentially useful in food detection.
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http://dx.doi.org/10.1016/j.foodchem.2021.129128DOI Listing
June 2021

Adjusting the Valence State of Vanadium in VO (B) by Extracting Oxygen Anions for High-Performance Aqueous Zinc-Ion Batteries.

ChemSusChem 2021 Feb 28;14(3):971-978. Epub 2020 Dec 28.

Hubei Provincial Key Laboratory of Green Materials for Light Industry, School of Materials and Chemical Engineering, Hubei University of Technology, Wuhan, 430068, P. R. China.

VO generally has a higher theoretical capacity and layered structure suitable for the intercalation/extraction of zinc ions. However, Zn ions with high charge density interact with the crystal lattice and limit further improvement in electrochemical performance. Defect engineering is a potential modification method with very promising application prospects, but the established procedures for preparing defects are complicated. In this study, VO (B) with oxygen deficiency is prepared by a simple solution reaction with NaBH . The presence of oxygen deficiencies is confirmed by positron annihilation lifetime spectroscopy, UV/Vis absorbance spectroscopy and others. Owing to the presence of oxygen defects, the aqueous Zn/VO (B) battery exhibits improved specific capacity, excellent reversibility, and structural stability. Ex situ characterization techniques are employed to demonstrate the reversible insertion-extraction mechanism of Zn ions from and into the host material. In addition, the Zn/VO (B) batteries still exhibit considerable electrochemical performance, even with high-loading electrodes (about 4 mg cm ).
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http://dx.doi.org/10.1002/cssc.202002401DOI Listing
February 2021

Simulation and Experimental Study of Dynamical Recrystallization Kinetics of TB8 Titanium Alloys.

Materials (Basel) 2020 Oct 5;13(19). Epub 2020 Oct 5.

Guizhou Key Laboratory of Materials Mechanical Behavior and Microstructure, College of Materials and Metallurgy, Guizhou University, Guiyang 550025, China.

The dynamic recrystallization (DRX) behavior in the hot working of TB8 titanium alloy was studied by using the experiment and finite element simulation (FEM) method. The results showed that the DRX behavior of TB8 titanium alloys was drastically affected by the hot processing parameters. The rising deformation temperature and reducing strain rate led to an augmentation in the grain size (dDRX) and volume fraction (XDRX) of DRX grains. In view of the true stress-strain curves gained from the experiment, the dDRX and XDRX models of DRX grains were constructed. Based on the developed models for DRX of TB8 titanium alloy, the isothermal forging process of the cylindrical samples was simulated by the DEFORM-3D software. The distributions of the effective strain and XDRX for DRX were analyzed. A comparison of the dDRX and XDRX of DRX grains in the central regions of the samples between the experimental and FEM results was performed. A good correlation between the experimental and simulation results was obtained, indicating that the established FEM model presented good prediction capabilities.
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http://dx.doi.org/10.3390/ma13194429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579267PMC
October 2020

A low symmetry cluster meets a low symmetry ligand to sharply boost MOF thermal stability.

Chem Commun (Camb) 2020 Oct 8;56(80):11985-11988. Epub 2020 Sep 8.

State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

A new approach in which a low symmetry cluster meets a low symmetry ligand to sharply boost the thermal stability of a MOF via additional inter-linker interactions is presented for the first time, leading to the successful synthesis of a novel binuclear Co-based MOF, {[Co(L)DMF]·1.5DMF·0.75MeOH·1.5HO} (HL = 5-(pyridin-3-yl) isophthalic acid, NJU-Bai62: NJU-Bai for Nanjing University Bai group), with exceptional thermal stability of up to 450 °C. This work may open up a new avenue for constructing robust MOFs from abundant, unstable, and low symmetry binuclear clusters, which have usually been ignored by most MOF chemists.
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http://dx.doi.org/10.1039/d0cc04543hDOI Listing
October 2020

Cytokines in abdominal exudate and serum predict small bowel obstruction following appendectomy.

ANZ J Surg 2020 10 17;90(10):1991-1996. Epub 2020 Aug 17.

The First Department of General Surgery, Qingdao Municipal Hospital, Qingdao City, China.

Background: This study aimed to investigate the value of inflammatory markers for the prediction of small bowel obstruction (SBO) following appendectomy.

Methods: We included cases of acute appendicitis that underwent laparoscopic appendectomy (LA) in the Qingdao Municipal Hospital between January 2017 and January 2019. The cases were divided into an SBO group and a non-SBO group depending on whether patients had or did not have SBO, and patients were followed up for at least 1 year. The levels of interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α) in abdominal exudate and venous blood were examined using enzyme-linked immunosorbent assay.

Results: After 1 year of follow-up, there were 985 cases in the non-SBO group and 16 cases in the SBO group. The levels of IL-1β, IL-6 and TNF-α in abdominal exudate on post-operative day 1 in the SBO group were 172.5 ± 14.7, 2167.3 ± 372.1 and 253.9 ± 12.9 pg/mL, respectively, which were significantly higher than that in the non-SBO group. The serum levels of IL-1β, IL-6, TNF-α and C-reactive protein (CRP) in the SBO group were significantly higher than that in the non-SBO group before surgery. Post-operatively, the inflammatory markers above decreased significantly and became similar with time in both groups. The logistic regression showed that the levels of peritoneal IL-6, preoperative serum CRP and perforated appendicitis were significant risk factors of SBO. The specificity and sensitivity of peritoneal IL-6 were 0.81 and 0.921, respectively.

Conclusion: The IL-1β, IL-6, TNF-α and CRP in serum and abdominal exudate played an important role in SBO after LA. The peritoneal IL-6 was the most reliable prediction marker for SBO.
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http://dx.doi.org/10.1111/ans.16241DOI Listing
October 2020

DNB-based on-chip motif finding: A high-throughput method to profile different types of protein-DNA interactions.

Sci Adv 2020 Jul 31;6(31):eabb3350. Epub 2020 Jul 31.

BGI-Shenzhen, Shenzhen 518083, China.

Here, we report a sensitive DocMF system that uses next-generation sequencing chips to profile protein-DNA interactions. Using DocMF, we successfully identified a variety of endonuclease recognition sites and the protospacer adjacent motif (PAM) sequences of different CRISPR systems. DocMF can simultaneously screen both 5' and 3' PAMs with high coverage. For SpCas9, we found noncanonical 5'-NAG-3' (~5%) and 5'-NGA-3' (~1.6%), in addition to its common PAMs, 5'-NGG-3' (~89.9%). More relaxed PAM sequences of two uncharacterized Cas endonucleases, VeCas9 and BvCas12a, were extensively characterized using DocMF. Moreover, we observed that dCas9, a DNA binding protein lacking endonuclease activity, preferably bound to the previously reported 5'-NGG-3' sequence. In summary, our studies demonstrate that DocMF is the first tool with the capacity to exhaustively assay both the binding and the cutting properties of different DNA binding proteins.
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http://dx.doi.org/10.1126/sciadv.abb3350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399529PMC
July 2020

Attenuation of Oxidative Injury With Targeted Expression of NADPH Oxidase 2 Short Hairpin RNA Prevents Onset and Maintenance of Electrical Remodeling in the Canine Atrium: A Novel Gene Therapy Approach to Atrial Fibrillation.

Circulation 2020 Sep 20;142(13):1261-1278. Epub 2020 Jul 20.

Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.Y., A.P., J.H., W.Z., J.N., A.B., D.A.J., G.G., T.W., S.B., B.B., B.P.K., R.P., J.A.W., R.A.).

Background: Atrial fibrillation (AF) is the most common heart rhythm disorder in adults and a major cause of stroke. Unfortunately, current treatments of AF are suboptimal because they are not targeted to the molecular mechanisms underlying AF. Using a highly novel gene therapy approach in a canine, rapid atrial pacing model of AF, we demonstrate that NADPH oxidase 2 (NOX2) generated oxidative injury causes upregulation of a constitutively active form of acetylcholine-dependent K current (), called ; this is an important mechanism underlying not only the genesis, but also the perpetuation of electric remodeling in the intact, fibrillating atrium.

Methods: To understand the mechanism by which oxidative injury promotes the genesis and maintenance of AF, we performed targeted injection of NOX2 short hairpin RNA (followed by electroporation to facilitate gene delivery) in atria of healthy dogs followed by rapid atrial pacing. We used in vivo high-density electric mapping, isolation of atrial myocytes, whole-cell patch clamping, in vitro tachypacing of atrial myocytes, lucigenin chemiluminescence assay, immunoblotting, real-time polymerase chain reaction, immunohistochemistry, and Masson trichrome staining.

Results: First, we demonstrate that generation of oxidative injury in atrial myocytes is a frequency-dependent process, with rapid pacing in canine atrial myocytes inducing oxidative injury through the induction of NOX2 and the generation of mitochondrial reactive oxygen species. We show that oxidative injury likely contributes to electric remodeling in AF by upregulating by a mechanism involving frequency-dependent activation of PKC (protein kinase C epsilon). The time to onset of nonsustained AF increased by >5-fold in NOX2 short hairpin RNA-treated dogs. Furthermore, animals treated with NOX2 short hairpin RNA did not develop sustained AF for up to 12 weeks. The electrophysiological mechanism underlying AF prevention was prolongation of atrial effective refractory periods, at least in part attributable to the attenuation of . Attenuated membrane translocation of PKC appeared to be a likely molecular mechanism underlying this beneficial electrophysiological remodeling.

Conclusions: NOX2 oxidative injury (1) underlies the onset, and the maintenance of electric remodeling in AF, as well, and (2) can be successfully prevented with a novel, gene-based approach. Future optimization of this approach may lead to a novel, mechanism-guided therapy for AF.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044127DOI Listing
September 2020

Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage.

Am J Hum Genet 2019 12 31;105(6):1102-1111. Epub 2019 Oct 31.

Centre for Reproductive Medicine, Shandong University, Jinan 250021, China; The Key laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan 250021, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan 250021, China; Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China; Hong Kong Branches of Chinese National Engineering Research Centers - Center for Assisted Reproductive Technology and Reproductive Genetics, Hong Kong, China. Electronic address:

Recurrent miscarriage (RM) affects millions of couples globally, and half of them have no demonstrated etiology. Genome sequencing (GS) is an enhanced and novel cytogenetic tool to define the contribution of chromosomal abnormalities in human diseases. In this study we evaluated its utility in RM-affected couples. We performed low-pass GS retrospectively for 1,090 RM-affected couples, all of whom had routine chromosome analysis. A customized sequencing and interpretation pipeline was developed to identify chromosomal rearrangements and deletions/duplications with confirmation by fluorescence in situ hybridization, chromosomal microarray analysis, and PCR studies. Low-pass GS yielded results in 1,077 of 1,090 couples (98.8%) and detected 127 chromosomal abnormalities in 11.7% (126/1,077) of couples; both members of one couple were identified with inversions. Of the 126 couples, 39.7% (50/126) had received former diagnostic results by karyotyping characteristic of normal human male or female karyotypes. Low-pass GS revealed additional chromosomal abnormalities in 50 (4.0%) couples, including eight with balanced translocations and 42 inversions. Follow-up studies of these couples showed a higher miscarriage/fetal-anomaly rate of 5/10 (50%) compared to 21/93 (22.6%) in couples with normal GS, resulting in a relative risk of 2.2 (95% confidence interval, 1.1 to 4.6). In these couples, this protocol significantly increased the diagnostic yield of chromosomal abnormalities per couple (11.7%) in comparison to chromosome analysis (8.0%, chi-square test p = 0.000751). In summary, low-pass GS identified underlying chromosomal aberrations in 1 in 9 RM-affected couples, enabling identification of a subgroup of couples with increased risk of subsequent miscarriage who would benefit from a personalized intervention.
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http://dx.doi.org/10.1016/j.ajhg.2019.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904795PMC
December 2019

Solvents-Dependent Formation of Three MOFs from the FeO Cluster and 3,3',5,5'-Diphenyltetracarboxylic Acid and Their Selective CO Adsorption.

Inorg Chem 2019 Oct 3;58(20):13836-13842. Epub 2019 Oct 3.

State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering , Nanjing University , Nanjing 210023 , China.

On the basis of the [Fe(μ-O)(COO)] cluster and 3,3',5,5'-diphenyltetracarboxylic acid (HBPTC), three novel metal-organic frameworks (MOFs), NJU-Bai25, NJU-Bai26, and NJU-Bai27 (NJU-Bai for Bai's group at Nanjing University ) with different (4,4,4,6)-, (4,4,4,4,4,6)-, and (4,4,6)-connected nets were obtained in different solvent systems, in which due to the steric hindrance of the coordinated solvents the conformations of BPTC gradually change from the planar to the torsional; thus, the pore sizes of those MOFs were also gradually narrowed. Interestingly, the MOFs show high thermal/chemical stabilities and selective CO adsorption: NJU-Bai27 exhibits larger CO uptake (5.0 and 13.8 wt %) at 298 K under 0.15 and 1 bar, whereas NJU-Bai26 has a higher selectivity for CO/N (366).
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http://dx.doi.org/10.1021/acs.inorgchem.9b01697DOI Listing
October 2019

Region-specific parasympathetic nerve remodeling in the left atrium contributes to creation of a vulnerable substrate for atrial fibrillation.

JCI Insight 2019 10 17;4(20). Epub 2019 Oct 17.

Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Atrial fibrillation (AF) is the most common heart rhythm disorder and a major cause of stroke. Unfortunately, current therapies for AF are suboptimal, largely because the molecular mechanisms underlying AF are poorly understood. Since the autonomic nervous system is thought to increase vulnerability to AF, we used a rapid atrial pacing (RAP) canine model to investigate the anatomic and electrophysiological characteristics of autonomic remodeling in different regions of the left atrium. RAP led to marked hypertrophy of parent nerve bundles in the posterior left atrium (PLA), resulting in a global increase in parasympathetic and sympathetic innervation throughout the left atrium. Parasympathetic fibers were more heterogeneously distributed in the PLA when compared with other left atrial regions; this led to greater fractionation and disorganization of AF electrograms in the PLA. Computational modeling revealed that heterogeneously distributed parasympathetic activity exacerbates sympathetic substrate for wave break and reentry. We further discovered that levels of nerve growth factor (NGF) were greatest in the left atrial appendage (LAA), where AF was most organized. Preferential NGF release by the LAA - likely a direct function of frequency and regularity of atrial stimulation - may have important implications for creation of a vulnerable AF substrate.
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http://dx.doi.org/10.1172/jci.insight.130532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824299PMC
October 2019

Pure-Supramolecular-Linker Approach to Highly Connected Metal-Organic Frameworks for CO Capture.

J Am Chem Soc 2019 Sep 5;141(37):14539-14543. Epub 2019 Sep 5.

State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering , Nanjing University , Nanjing 210023 , China.

A pure-supramolecular-linker (PSL) approach for the formation of metal-organic frameworks (MOFs) was initially given, which was demonstrated by syntheses of two highly connected and isostructural MOFs, {FeO(TPBTM)(Cl)(HO)} (TPBTM = ,',″-tris(isophthalyl)-1,3,5-benzenetricarboxamide) (NJU-Bai52, NJU-Bai for Nanjing University Bai group) and {ScO(TPBTM)(OH)(HO)} (NJU-Bai53). Very interestingly, they exhibit exceptional thermal stability, water stability, and highly selective CO capture properties. In particular, NJU-Bai53 with higher uptakes (2.74 wt % at 0.4 mbar and 298 K, 7.67 wt % at 298 K and 0.15 bar) and higher selectivity may be an excellent candidate for CO capture.
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http://dx.doi.org/10.1021/jacs.9b07422DOI Listing
September 2019

OsPEX5 regulates rice spikelet development through modulating jasmonic acid biosynthesis.

New Phytol 2019 10 29;224(2):712-724. Epub 2019 Jul 29.

National Key Laboratory for Crop Genetics and Germplasm Enhancement, Jiangsu Plant Gene Engineering Research Center, Nanjing Agricultural University, Nanjing, 210095, China.

Spikelet is the primary reproductive structure and a critical determinant of grain yield in rice. The molecular mechanisms regulating rice spikelet development still remain largely unclear. Here, we report that mutations in OsPEX5, which encodes a peroxisomal targeting sequence 1 (PTS1) receptor protein, cause abnormal spikelet morphology. We show that OsPEX5 can physically interact with OsOPR7, an enzyme involved in jasmonic acid (JA) biosynthesis and is required for its import into peroxisome. Similar to Ospex5 mutant, the knockout mutant of OsOPR7 generated via CRISPR-Cas9 technology has reduced levels of endogenous JA and also displays an abnormal spikelet phenotype. Application of exogenous JA can partially rescue the abnormal spikelet phenotype of Ospex5 and Osopr7. Furthermore, we show that OsMYC2 directly binds to the promoters of OsMADS1, OsMADS7 and OsMADS14 to activate their expression, and subsequently regulate spikelet development. Our results suggest that OsPEX5 plays a critical role in regulating spikelet development through mediating peroxisomal import of OsOPR7, therefore providing new insights into regulation of JA biosynthesis in plants and expanding our understanding of the biological role of JA in regulating rice reproduction.
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http://dx.doi.org/10.1111/nph.16037DOI Listing
October 2019

Effects of sweetener sucralose on diet preference, growth performance and hematological and biochemical parameters of weaned piglets.

Asian-Australas J Anim Sci 2019 May 28:802-811. Epub 2019 May 28.

State Key Laboratory of Animal Nutrition, Ministry of Agriculture Feed Centre, China Agricultural University, Beijing 100193, China.

Objective: Two experiments were conducted to investigate the effects of dietary sucralose on diet preference and growth performance of weaned piglets, and a third experiment was a 28-d safety study to examine if high-dose sucralose could affect the health state of weaned piglets.

Methods: In experiment one, 48 piglets had free access to a corn-soybean based diet and the same diet supplemented with 150 mg/kg sucralose for 15 d. In experiment two, 180 piglets were blocked into 5 treatments with 6 replications. They were fed basal diets supplemented with 0, 75, 150, 225, and 300 mg/kg sucralose for 28 days. In experiment three, 108 piglets were randomly assigned to 3 treatments and fed diets supplemented with 0, 150 (suitable level), and 1,500 (ten-fold suitable level) mg/kg sucralose for 28 d.

Results: The experiment 1 showed that piglets preferred (p < 0.05) diets containing sucralose during experimental period. In experiment 2, piglets fed a diet supplemented with 150 mg/kg sucralose had a higher average daily gain (ADG) and average daily feed intake (ADFI) than pigs in the control group and other treatment groups during the experiment period. The concentrations of sucralose over 150 mg/kg may decrease feed intake. However, no difference in feed conversion ratio was observed. In experiment 3, piglets fed diet supplemented with 150 mg/kg sucralose had a higher average daily gain (ADG) and average daily feed intake (ADFI) than that of pigs in the control group and 1500 mg/kg treatment groups during the experiment period. Clinical blood metabolites, organ index and histological morphology were not significantly different between sucralose treatments.

Conclusion: Sucralose can promote feed intake and thereby improve growth performance of weaned piglets. Moreover, inclusion of 1,500 mg/kg sucralose was demonstrated to have no observed adverse effects. Supplementing 150 mg/kg sucralose for weaned piglets is recommended in this study.
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http://dx.doi.org/10.5713/ajas.18.0863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206394PMC
May 2019

Development of coupling controlled polymerizations by adapter-ligation in mate-pair sequencing for detection of various genomic variants in one single assay.

DNA Res 2019 Aug;26(4):313-325

Complete Genomics Inc., San Jose, CA, USA.

The diversity of disease presentations warrants one single assay for detection and delineation of various genomic disorders. Herein, we describe a gel-free and biotin-capture-free mate-pair method through coupling Controlled Polymerizations by Adapter-Ligation (CP-AL). We first demonstrated the feasibility and ease-of-use in monitoring DNA nick translation and primer extension by limiting the nucleotide input. By coupling these two controlled polymerizations by a reported non-conventional adapter-ligation reaction 3' branch ligation, we evidenced that CP-AL significantly increased DNA circularization efficiency (by 4-fold) and was applicable for different sequencing methods but at a faction of current cost. Its advantages were further demonstrated by fully elimination of small-insert-contaminated (by 39.3-fold) with a ∼50% increment of physical coverage, and producing uniform genome/exome coverage and the lowest chimeric rate. It achieved single-nucleotide variants detection with sensitivity and specificity up to 97.3 and 99.7%, respectively, compared with data from small-insert libraries. In addition, this method can provide a comprehensive delineation of structural rearrangements, evidenced by a potential diagnosis in a patient with oligo-atheno-terato-spermia. Moreover, it enables accurate mutation identification by integration of genomic variants from different aberration types. Overall, it provides a potential single-integrated solution for detecting various genomic variants, facilitating a genetic diagnosis in human diseases.
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http://dx.doi.org/10.1093/dnares/dsz011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704401PMC
August 2019

An ATAC-seq atlas of chromatin accessibility in mouse tissues.

Sci Data 2019 May 20;6(1):65. Epub 2019 May 20.

BGI-Shenzhen, Shenzhen, 518083, China.

The Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) is a fundamental epigenomics approach and has been widely used in profiling the chromatin accessibility dynamics in multiple species. A comprehensive reference of ATAC-seq datasets for mammalian tissues is important for the understanding of regulatory specificity and developmental abnormality caused by genetic or environmental alterations. Here, we report an adult mouse ATAC-seq atlas by producing a total of 66 ATAC-seq profiles from 20 primary tissues of both male and female mice. The ATAC-seq read enrichment, fragment size distribution, and reproducibility between replicates demonstrated the high quality of the full dataset. We identified a total of 296,574 accessible elements, of which 26,916 showed tissue-specific accessibility. Further, we identified key transcription factors specific to distinct tissues and found that the enrichment of each motif reflects the developmental similarities across tissues. In summary, our study provides an important resource on the mouse epigenome and will be of great importance to various scientific disciplines such as development, cell reprogramming, and genetic disease.
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http://dx.doi.org/10.1038/s41597-019-0071-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527694PMC
May 2019

Altered DNA methylation of the Y subfamily in schizophrenia and bipolar disorder.

Epigenomics 2019 05 8;11(6):581-586. Epub 2019 May 8.

Department of Medical Genetics, School of Basic Medical Sciences, Guangdong Provincial Key Laboratory of Single Cell Technology & Application, and Key Laboratory of Mental Health of the Ministry of Education, Southern Medical University, Guangzhou, Guangdong, China.

To study DNA methylation patterns of Y subfamilies in schizophrenia (SCZ) and bipolar disorder (BPD). A bisulfite conversion-specific one-label extension method was employed to detect the Y subfamily methylation levels of peripheral blood DNA from 92 SCZ patients, 99 BPD patients and 92 controls. Hypermethylation of the Y A1 and A2 CpG sites in BPD patients and hypomethylation of A3 CpG site in both of BPD and SCZ patients, and opposite age-dependent methylation alterations between SCZ and controls. The differentially altered DNA methylation patterns of the Y families between BPD and SCZ suggest the role of DNA methylation in the pathogenesis of these major psychiatric disorders.
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http://dx.doi.org/10.2217/epi-2018-0139DOI Listing
May 2019

Salvianolic Acid B Inhibits Activation of Human Primary Hepatic Stellate Cells Through Downregulation of the Myocyte Enhancer Factor 2 Signaling Pathway.

Front Pharmacol 2019 11;10:322. Epub 2019 Apr 11.

Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Various isoforms of myocyte enhancer factor 2 (MEF2) have been shown to play a role in the activation of rat hepatic stellate cells (HSCs) in culture. The signals that regulate MEF2 in HSCs are unknown. In addition, whether MEF2s regulate the activation of human HSCs (H-HSCs) is unclear. Here, we studied the expression and function of MEF2s in H-HSCs. Our data showed that the levels of MEF2A, C, and D proteins were high in liver tissues from patients with cirrhosis and increased during culture-induced activation of primary H-HSCs. Exposure of H-HSCs to transforming growth factor beta 1 (TGF-β1) led to a significant increase in MEF2A and C protein levels and enhanced MEF2 activity. Interestingly, TGF-β1 did not further enhance MEF2D levels. Furthermore, TGF-β1 activated p38 mitogen-activated protein kinase (MAPK) and led to increased phosphorylation of MEF2C at its p38 recognition site. Inhibition of p38 MAPK inhibited both TGF-β1- and culture-induced activation of MEF2. The activity of collagen I reporter in H-HSCs was significantly reduced when MEF2A and MEF2C were blocked with overexpression of dominant negative MEF2 mutants. Salvianolic-acid B (SA-B), a water-soluble element of known to have anti-fibrosis effects, attenuated both basal and TGF-β1-induced increased levels of MEF2A and C mRNA and protein. In addition, SA-B inhibited MEF2 activity, which correlated with reduced expression of the HSC activation markers, α-smooth muscle actin (α-SMA), and collagen I. Administration of SA-B reduced MEF2A , which was accompanied by reduced levels of α-SMA in a model of dimethylnitrosamine-induced rat liver fibrosis. We concluded that the MEF2 transcription factor was stimulated by TGF-β1 in H-HSCs. Antagonizing TGF-β1-induced activation of the MEF2 signaling pathway may account in part for the anti-fibrosis effects of SA-B.
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http://dx.doi.org/10.3389/fphar.2019.00322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470251PMC
April 2019

Efficient and unique cobarcoding of second-generation sequencing reads from long DNA molecules enabling cost-effective and accurate sequencing, haplotyping, and de novo assembly.

Genome Res 2019 05 2;29(5):798-808. Epub 2019 Apr 2.

BGI-Shenzhen, Shenzhen 518083, China.

Here, we describe single-tube long fragment read (stLFR), a technology that enables sequencing of data from long DNA molecules using economical second-generation sequencing technology. It is based on adding the same barcode sequence to subfragments of the original long DNA molecule (DNA cobarcoding). To achieve this efficiently, stLFR uses the surface of microbeads to create millions of miniaturized barcoding reactions in a single tube. Using a combinatorial process, up to 3.6 billion unique barcode sequences were generated on beads, enabling practically nonredundant cobarcoding with 50 million barcodes per sample. Using stLFR, we demonstrate efficient unique cobarcoding of more than 8 million 20- to 300-kb genomic DNA fragments. Analysis of the human genome NA12878 with stLFR demonstrated high-quality variant calling and phase block lengths up to N50 34 Mb. We also demonstrate detection of complex structural variants and complete diploid de novo assembly of NA12878. These analyses were all performed using single stLFR libraries, and their construction did not significantly add to the time or cost of whole-genome sequencing (WGS) library preparation. stLFR represents an easily automatable solution that enables high-quality sequencing, phasing, SV detection, scaffolding, cost-effective diploid de novo genome assembly, and other long DNA sequencing applications.
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http://dx.doi.org/10.1101/gr.245126.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499310PMC
May 2019

A new massively parallel nanoball sequencing platform for whole exome research.

BMC Bioinformatics 2019 Mar 25;20(1):153. Epub 2019 Mar 25.

BGI-Genomics, BGI-Shenzhen, Shenzhen, 518083, China.

Background: Whole exome sequencing (WES) has been widely used in human genetics research. BGISEQ-500 is a recently established next-generation sequencing platform. However, the performance of BGISEQ-500 on WES is not well studied. In this study, we evaluated the performance of BGISEQ-500 on WES by side-to-side comparison with Hiseq4000, on well-characterized human sample NA12878.

Results: BGISEQ demonstrated similarly high reproducibility as Hiseq for variation detection. Also, the SNVs from BGISEQ data is highly consistent with Hiseq results (concordance 96.5%~ 97%). Variation detection accuracy was subsequently evaluated with data from the genome in a bottle project as the benchmark. Both platforms showed similar sensitivity and precision in SNV detection. While in indel detection, BGISEQ showed slightly higher sensitivity and lower precision. The impact of sequence depth and read length on variation detection accuracy was further analyzed, and showed that variation detection sensitivity still increasing when the sequence depth is larger than 100x, and the impact of read length is minor when using 100x data.

Conclusions: This study suggested that BGISEQ-500 is a qualified sequencing platform for WES.
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http://dx.doi.org/10.1186/s12859-019-2751-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434795PMC
March 2019

Reliable multiplex sequencing with rare index mis-assignment on DNB-based NGS platform.

BMC Genomics 2019 Mar 13;20(1):215. Epub 2019 Mar 13.

Complete Genomics Inc., 2904 Orchard Pkwy, San Jose, California, 95134, USA.

Background: Massively-parallel-sequencing, coupled with sample multiplexing, has made genetic tests broadly affordable. However, intractable index mis-assignments (commonly exceeds 1%) were repeatedly reported on some widely used sequencing platforms.

Results: Here, we investigated this quality issue on BGI sequencers using three library preparation methods: whole genome sequencing (WGS) with PCR, PCR-free WGS, and two-step targeted PCR. BGI's sequencers utilize a unique DNA nanoball (DNB) technology which uses rolling circle replication for DNA-nanoball preparation; this linear amplification is PCR free and can avoid error accumulation. We demonstrated that single index mis-assignment from free indexed oligos occurs at a rate of one in 36 million reads, suggesting virtually no index hopping during DNB creation and arraying. Furthermore, the DNB-based NGS libraries have achieved an unprecedentedly low sample-to-sample mis-assignment rate of 0.0001 to 0.0004% under recommended procedures.

Conclusions: Single indexing with DNB technology provides a simple but effective method for sensitive genetic assays with large sample numbers.
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http://dx.doi.org/10.1186/s12864-019-5569-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416933PMC
March 2019

The first chromosome-level genome for a marine mammal as a resource to study ecology and evolution.

Mol Ecol Resour 2019 Jul 9;19(4):944-956. Epub 2019 May 9.

BGI-Qingdao, BGI-Shenzhen, Qingdao, Shandong Province, China.

Marine mammals are important models for studying convergent evolution and aquatic adaption, and thus reference genomes of marine mammals can provide evolutionary insights. Here, we present the first chromosome-level marine mammal genome assembly based on the data generated by the BGISEQ-500 platform, for a stranded female sperm whale (Physeter macrocephalus). Using this reference genome, we performed chromosome evolution analysis of the sperm whale, including constructing ancestral chromosomes, identifying chromosome rearrangement events and comparing with cattle chromosomes, which provides a resource for exploring marine mammal adaptation and speciation. We detected a high proportion of long interspersed nuclear elements and expanded gene families, and contraction of major histocompatibility complex region genes which were specific to sperm whale. Using comparisons with sheep and cattle, we analysed positively selected genes to identify gene pathways that may be related to adaptation to the marine environment. Further, we identified possible convergent evolution in aquatic mammals by testing for positively selected genes across three orders of marine mammals. In addition, we used publicly available resequencing data to confirm a rapid decline in global population size in the Pliocene to Pleistocene transition. This study sheds light on the chromosome evolution and genetic mechanisms underpinning sperm whale adaptations, providing valuable resources for future comparative genomics.
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http://dx.doi.org/10.1111/1755-0998.13003DOI Listing
July 2019

Stable Amide-Functionalized Metal-Organic Framework with Highly Selective CO Adsorption.

Inorg Chem 2019 Feb 31;58(4):2729-2735. Epub 2019 Jan 31.

State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering , Nanjing University , Nanjing 210023 , China.

A new amide-functionalized metal-organic framework (AFMOF) with the combined feature of highly selective CO adsorption and high thermal and chemical stability, [Sc(μ-O)(L)(HO)Cl] [NJU-Bai49; NJU-Bai for Nanjing University Bai's group, HL = 5-(3,5-dicarboxybenzamido)isophthalic acid], was synthesized that exhibits 4.5 wt % CO uptake at 298 K and 0.15 bar and the highest selectivity for CO/N (166.7) among all AFMOFs. Grand canonical Monte Carlo simulations further indicate that both the decorated amide group and the open metal site act as CO binding sites, which may contribute to its highly selective CO uptake.
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http://dx.doi.org/10.1021/acs.inorgchem.8b03308DOI Listing
February 2019