Publications by authors named "Boyang Li"

69 Publications

Acid-Tolerant Sulfate Tetrahedral Cages from Anion-Coordination-Driven Assembly.

Chemistry 2021 Oct 22. Epub 2021 Oct 22.

Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, 710069, P. R. China.

Supramolecular cages have been constructed by anion-coordination-driven assembly (ACDA) in recent years and have shown unique host-guest interactions. However, most of the reported cages are made of the phosphate ion (PO ); other anions have rarely been explored. Here we show for the first time that the sulfate ion (SO ) is also able to form the A L tetrahedral motif with tris-bis(urea) ligands, but this is dependent on the stoichiometry of the sulfate ion (in solution). Notably, the sulfate cages display enhanced resistance for both Brønsted (pH as low as 4.3 in acetone containing 15 % water) and Lewis acids (metal complexes) compared to the corresponding phosphate cages, and thus could find applications where an acidic (proton or metals) environment is required.
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http://dx.doi.org/10.1002/chem.202103671DOI Listing
October 2021

The Epithelial-Stromal Microenvironment in Early Colonic Neoplasia.

Mol Cancer Res 2021 Oct 20. Epub 2021 Oct 20.

Center for Molecular Oncology, University of Connecticut School of Medicine, Farmington, Connecticut.

Stromal cells play a central role in promoting the progression of colorectal cancer. Here, we analyze molecular changes within the epithelial and stromal compartments of dysplastic aberrant crypt foci (ACF) formed in the ascending colon, where rapidly developing interval cancers occur. We found strong activation of numerous neutrophil/monocyte chemokines, consistent with localized inflammation. The data also indicated a decrease in interferon signaling and cell-based immunity. The immune checkpoint and T-cell exhaustion gene was one of the most significantly upregulated genes, which was accompanied by a decrease in cytotoxic T-cell effector gene expression. In addition, expression was strongly upregulated in the stroma and downregulated in the epithelium, consistent with diverse changes in senescence-associated signaling on the two tissue compartments. IMPLICATIONS: Decreased CD8 T-cell infiltration within proximal colon ACF occurs within the context of a robust inflammatory response and potential stromal cell senescence, thus providing new insight into potential promotional drivers for tumors in the proximal colon.
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http://dx.doi.org/10.1158/1541-7786.MCR-21-0202DOI Listing
October 2021

Atomic Structure Evolution of Pt-Co Binary Catalysts: Single Metal Sites versus Intermetallic Nanocrystals.

Adv Mater 2021 Oct 4:e2106371. Epub 2021 Oct 4.

Center for Functional Nanomaterials, Brookhaven National Laboratory, Upton, NY, 11973, USA.

Due to their exceptional catalytic properties for the oxygen reduction reaction (ORR) and other crucial electrochemical reactions, PtCo intermetallic nanoparticle (NP) and single atomic (SA) Pt metal site catalysts have received considerable attention. However, their formation mechanisms at the atomic level during high-temperature annealing processes remain elusive. Here, the thermally driven structure evolution of Pt-Co binary catalyst systems is investigated using advanced in situ electron microscopy, including PtCo intermetallic alloys and single Pt/Co metal sites. The pre-doping of CoN sites in carbon supports and the initial Pt NP sizes play essential roles in forming either Pt Co intermetallics or single Pt/Co metal sites. Importantly, the initial Pt NP loadings against the carbon support are critical to whether alloying to L1 -ordered Pt Co NPs or atomizing to SA Pt sites at high temperatures. High Pt NP loadings (e.g., 20%) tend to lead to the formation of highly ordered Pt Co intermetallic NPs with excellent activity and enhanced stability toward the ORR. In contrast, at a relatively low Pt loading (<6 wt%), the formation of single Pt sites in the form of PtC N is thermodynamically favorable, in which a synergy between the PtC N and the CoN sites could enhance the catalytic activity for the ORR, but showing insufficient stability.
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http://dx.doi.org/10.1002/adma.202106371DOI Listing
October 2021

Construction of a sandwich-like [email protected]@mSiO catalyst for one-pot cascade reductive amination of nitrobenzene with benzaldehyde.

J Colloid Interface Sci 2022 Jan 16;606(Pt 2):1524-1533. Epub 2021 Aug 16.

State Key Laboratory of Applied Organic Chemistry, Laboratory of Special Function Materials and Structure Design of the Ministry of Education, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China. Electronic address:

Heterogeneous noble metal-based catalysts with stable, precise structures and high catalytic performance are of great research interest for sustainable catalysis. Herein, we designed the novel sandwich-like metal-organic-framework composite nanocatalyst [email protected]@mSiO using [email protected] as the core, and mesoporous SiO as the shell. The obtained [email protected]@mSiO catalyst shows a well-defined structure and interface, and the protection of the mSiO shell can efficiently prevent Pt NPs from aggregating and leaching in the reaction process. In the one-pot cascade reaction of nitroarenes and aromatic aldehydes to secondary amines, [email protected]@mSiO shows excellent catalytic performance due to acid catalytic sites provided by UiO-66-NH and Pt hydrogenation catalytic sites. Furthermore, the porous structure of the [email protected]@mSiO catalyst also enhances reactant diffusion and improves the reaction efficiency. This work provides a new avenue to meticulously design well-defined nanocatalysts with superior catalytic performance and stability for challenging reactions.
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http://dx.doi.org/10.1016/j.jcis.2021.08.081DOI Listing
January 2022

Facile preparation of ultrafine Pd nanoparticles anchored on covalent triazine frameworks catalysts for efficient N-alkylation.

J Colloid Interface Sci 2022 Jan 13;606(Pt 2):1340-1351. Epub 2021 Aug 13.

State Key Laboratory of Applied Organic Chemistry, Laboratory of Special Function Materials and Structure Design of the Ministry of Education, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China. Electronic address:

The fabrication of stable and efficient catalysts for green and economic catalytic transformation is significant. Here, highly stable covalent triazine frameworks (CTF-1) were used as the supporting material for anchoring ultrafine Pd nanoparticles (NPs) via a facile impregnation process and a one-pot calcination-reduction strategy. The widespread dispersion of ultrafine Pd NPs was a result of the abundant high nitrogen-content triazine groups of CTF-1 that endowed the catalyst [email protected] with high catalytic activity. The catalytic performance of [email protected] was demonstrated by the one-pot N-alkylation of benzaldehyde with aniline (or nitrobenzene) under mild reaction conditions, and [email protected] exhibited a wide range of general applicability for N-alkylation reactions. The reaction mechanism for the N-alkylation reaction was also studied in detail. In addition, the [email protected] catalyst exhibited high thermal and chemical stability, maintaining good catalytic efficiency after multiple reaction cycles. This study provides new insights for the fabrication of organic supporting materials with highly dispersed active catalytic sites that can lead to excellent catalytic performance for efficient, economical, and green reactions.
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http://dx.doi.org/10.1016/j.jcis.2021.08.059DOI Listing
January 2022

SUPERGNOVA: local genetic correlation analysis reveals heterogeneous etiologic sharing of complex traits.

Genome Biol 2021 09 7;22(1):262. Epub 2021 Sep 7.

Department of Biostatistics, Yale School of Public Health, 60 College Street, New Haven, CT, 06520, USA.

Local genetic correlation quantifies the genetic similarity of complex traits in specific genomic regions. However, accurate estimation of local genetic correlation remains challenging, due to linkage disequilibrium in local genomic regions and sample overlap across studies. We introduce SUPERGNOVA, a statistical framework to estimate local genetic correlations using summary statistics from genome-wide association studies. We demonstrate that SUPERGNOVA outperforms existing methods through simulations and analyses of 30 complex traits. In particular, we show that the positive yet paradoxical genetic correlation between autism spectrum disorder and cognitive performance could be explained by two etiologically distinct genetic signatures with bidirectional local genetic correlations.
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http://dx.doi.org/10.1186/s13059-021-02478-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422619PMC
September 2021

Association between service scope of primary care facilities and patient outcomes: a retrospective study in rural Guizhou, China.

BMC Health Serv Res 2021 Aug 28;21(1):885. Epub 2021 Aug 28.

School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Background: Extending service scope of primary care facilities (PCFs) has been widely concerned in China. However, no current data about association between service scope of PCFs with patient outcomes are available. This study aims to investigate association between service scope of PCFs and patient outcomes.

Methods: A multistage, stratified clustered sampling method was used to collect information about service scope of PCFs from rural Guizhou, China. Claim data of 299,633 inpatient cases covered by 64 PCFs were derived from local information system of New Rural Cooperation Medical Scheme. Service scope of PCFs was collected with self-administrated questionnaires. Primary outcomes were (1) level of inpatient institutions, (2) length of stay, (3) per capita total health cost, (4) per capita out-of-pocket cost, (5) reimbursement ratio, (6) 30-day readmission. A total of 64 PCFs were categorized into five groups per facility-level service scope scores. Generalized linear regression models, logistic regression model, and ordinal regression model were conducted to identify association between service scope of PCFs and patient outcomes.

Results: On average, the median service scope score of PCFs was 20, with wide variation across PCFs. After controlling for demographic and clinical characteristics, patients living in communities with PCFs of greatest service scope (Quintile V vs. I) tended to have smaller rates of admission by county-level hospitals (-6.2 % [-6.5 %, -5.9 %], city-level hospitals (-1.9 % [-2.0 %, -1.8 %]), and provincial hospitals (-2.1 % [-2.2 %, -2.0 %]), smaller rate of 30-day readmission (-0.5 % [-0.7 %, -0.2 %]), less total health cost (-201.8 [-257.9, -145.8]) and out-of-pocket cost (-210.2 [-237.2, -183.2]), and greater reimbursement ratio (2.3 % [1.9 %, 2.8 %]) than their counterparts from communities with PCFs of least service scope.

Conclusions: Service scope of PCFs varied a lot in rural Guizhou, China. Greater service scope was associated with a reduction in secondary and tertiary hospital admission, reduced total cost and out-of-pocket cost, and 30-day readmission and increased reimbursement ratio. These results raised concerns about access to care for patients discharged from hospitals, which suggests potential opportunities for cost savings and improvement of quality of care. However, further evidence is warranted to investigate whether extending service scope of PCFs is cost-effective and sustainable.
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http://dx.doi.org/10.1186/s12913-021-06877-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400844PMC
August 2021

Atomically Dispersed Co Clusters Anchored on N-doped Carbon Nanotubes for Efficient Dehydrogenation of Alcohols and Subsequent Conversion to Carboxylic Acids.

ChemSusChem 2021 Oct 20;14(20):4536-4545. Epub 2021 Sep 20.

State Key Laboratory of Applied Organic Chemistry, Laboratory of Special Function Materials and Structure Design of the Ministry of Education College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China.

The catalytic dehydrogenation of readily available alcohols to high value-added carbonyl compounds is a research hotspot with scientific significance. Most of the current research about this reaction is performed with noble metal-based homogeneous catalysts of high price and poor reusability. Herein, highly dispersed Co-cluster-decorated N-doped carbon nanotubes (Co/N-CNTs) were fabricated via a facile strategy and used for the dehydrogenation of alcohols with high efficiency. Various characterization techniques confirmed the presence of metallic Co clusters with almost atomic dispersion, and the N-doped carbon supports also enhanced the catalytic activity of Co clusters in the dehydrogenation reaction. Aldehydes as dehydrogenation products were further transformed in situ to carboxylic acids through a Cannizzaro-type pathway under alkaline conditions. The reaction pathway of the dehydrogenation of alcohols was clearly confirmed by theoretical calculations. This work should provide an effective and simple approach for the accurate design and synthesis of small Co-clusters catalysts for the efficient dehydrogenation-based transformation of alcohols to carboxylic acids under mild reaction conditions.
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http://dx.doi.org/10.1002/cssc.202101330DOI Listing
October 2021

A Facile and In-situ Methanol-mediated Fabrication of Low Pd Loading, High-efficiency and Size-selectivity [email protected] Hydrogenation Catalyst.

Chem Asian J 2021 Oct 19;16(19):2952-2957. Epub 2021 Aug 19.

College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China.

In-situ encapsulation of tiny and well-dispersed Pd nanoparticles (Pd NPs) in zeolitic imidazolate frameworks (ZIFs) was firstly achieved using a one-pot and facile methanol-mediated growth approach, in which methanol served as both solvent and a mild reductant. The microstructure, morphology, crystallinity, porosity as well as evolution process of the catalysts were determined by TEM, XRD, N adsorption and UV-vis spectra. Due to the complete encapsulation of such Pd NPs combined with ultrahigh surface area and uniform microporous structure of ZIF-8, the resulting [email protected] min nanocomposite exhibited more superior catalytic activity for olefins hydrogenation with TOF of 7436 h and excellent size selectivity than previously reported catalysts. Furthermore, the catalyst displays excellent recyclability for 1-octene hydrogenation and without any loss of the Pd active species.
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http://dx.doi.org/10.1002/asia.202100740DOI Listing
October 2021

Dual-Doping and Synergism toward High-Performance Seawater Electrolysis.

Adv Mater 2021 Aug 8;33(33):e2101425. Epub 2021 Jul 8.

NanoScience Technology Center, Department of Materials Science and Engineering, Department of Chemistry, Renewable Energy and Chemical Transformation Cluster, University of Central Florida, Orlando, FL, 32826, USA.

Hydrogen (H ) production from direct seawater electrolysis is an economically appealing yet fundamentally and technically challenging approach to harvest clean energy. The current seawater electrolysis technology is significantly hindered by the poor stability and low selectivity of the oxygen evolution reaction (OER) due to the competition with chlorine evolution reaction in practical application. Herein, iron and phosphor dual-doped nickel selenide nanoporous films (Fe,P-NiSe NFs) are rationally designed as bifunctional catalysts for high-efficiency direct seawater electrolysis. The doping of Fe cation increases the selectivity and Faraday efficiency (FE) of the OER. While the doping of P anions improves the electronic conductivity and prevents the dissolution of selenide by forming a passivation layer containing P-O species. The Fe-dopant is identified as the primary active site for the hydrogen evolution reaction, and meanwhile, stimulates the adjacent Ni atoms as active centers for the OER. The experimental analyses and theoretical calculations provide an insightful understanding of the roles of dual-dopants in boosting seawater electrolysis. As a result, a current density of 0.8 A cm is archived at 1.8 V with high OER selectivity and long-term stability for over 200 h, which surpasses the benchmarking platinum-group-metals-free electrolyzers.
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http://dx.doi.org/10.1002/adma.202101425DOI Listing
August 2021

DIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease.

JAMA Neurol 2021 Aug;78(8):993-1003

Yale Center for Genome Analysis, West Haven, Connecticut.

Importance: Moyamoya disease (MMD), a progressive vasculopathy leading to narrowing and ultimate occlusion of the intracranial internal carotid arteries, is a cause of childhood stroke. The cause of MMD is poorly understood, but genetic factors play a role. Several familial forms of MMD have been identified, but the cause of most cases remains elusive, especially among non-East Asian individuals.

Objective: To assess whether ultrarare de novo and rare, damaging transmitted variants with large effect sizes are associated with MMD risk.

Design, Setting, And Participants: A genetic association study was conducted using whole-exome sequencing case-parent MMD trios in a small discovery cohort collected over 3.5 years (2016-2019); data were analyzed in 2020. Medical records from US hospitals spanning a range of 1 month to 1.5 years were reviewed for phenotyping. Exomes from a larger validation cohort were analyzed to identify additional rare, large-effect variants in the top candidate gene. Participants included patients with MMD and, when available, their parents. All participants who met criteria and were presented with the option to join the study agreed to do so; none were excluded. Twenty-four probands (22 trios and 2 singletons) composed the discovery cohort, and 84 probands (29 trios and 55 singletons) composed the validation cohort.

Main Outcomes And Measures: Gene variants were identified and filtered using stringent criteria. Enrichment and case-control tests assessed gene-level variant burden. In silico modeling estimated the probability of variant association with protein structure. Integrative genomics assessed expression patterns of MMD risk genes derived from single-cell RNA sequencing data of human and mouse brain tissue.

Results: Of the 24 patients in the discovery cohort, 14 (58.3%) were men and 18 (75.0%) were of European ancestry. Three of 24 discovery cohort probands contained 2 do novo (1-tailed Poisson P = 1.1 × 10-6) and 1 rare, transmitted damaging variant (12.5% of cases) in DIAPH1 (mammalian diaphanous-1), a key regulator of actin remodeling in vascular cells and platelets. Four additional ultrarare damaging heterozygous DIAPH1 variants (3 unphased) were identified in 3 other patients in an 84-proband validation cohort (73.8% female, 77.4% European). All 6 patients were non-East Asian. Compound heterozygous variants were identified in ena/vasodilator-stimulated phosphoproteinlike protein EVL, a mammalian diaphanous-1 interactor that regulates actin polymerization. DIAPH1 and EVL mutant probands had severe, bilateral MMD associated with transfusion-dependent thrombocytopenia. DIAPH1 and other MMD risk genes are enriched in mural cells of midgestational human brain. The DIAPH1 coexpression network converges in vascular cell actin cytoskeleton regulatory pathways.

Conclusions And Relevance: These findings provide the largest collection to date of non-East Asian individuals with sporadic MMD harboring pathogenic variants in the same gene. The results suggest that DIAPH1 is a novel MMD risk gene and impaired vascular cell actin remodeling in MMD pathogenesis, with diagnostic and therapeutic ramifications.
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http://dx.doi.org/10.1001/jamaneurol.2021.1681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204259PMC
August 2021

Single-cell RNA sequencing of human femoral head .

Aging (Albany NY) 2021 06 10;13(11):15595-15619. Epub 2021 Jun 10.

Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science, Central South University, Yuelu, Changsha 410013, China.

The homeostasis of bone metabolism depends on the coupling and precise regulation of various types of cells in bone tissue. However, the communication and interaction between bone tissue cells at the single-cell level remains poorly understood. Thus, we performed single-cell RNA sequencing (scRNA-seq) on the primary human femoral head tissue cells (FHTCs). Nine cell types were identified in 26,574 primary human FHTCs, including granulocytes, T cells, monocytes, B cells, red blood cells, osteoblastic lineage cells, endothelial cells, endothelial progenitor cells (EPCs) and plasmacytoid dendritic cells. We identified () and () as novel bone metabolism-related genes. Additionally, we found that several subtypes of monocytes, T cells and B cells were related to bone metabolism. Cell-cell communication analysis showed that collagen, chemokine, transforming growth factor and their ligands have significant roles in the crosstalks between FHTCs. In particular, EPCs communicated with osteoblastic lineage cells closely via the "COL2A1-ITGB1" interaction pair. Collectively, this study provided an initial characterization of the cellular composition of the human FHTCs and the complex crosstalks between them at the single-cell level. It is a unique starting resource for in-depth insights into bone metabolism.
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http://dx.doi.org/10.18632/aging.203124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221309PMC
June 2021

Narcissistic self-sorting in anion-coordination-driven assemblies.

Chem Commun (Camb) 2021 Jun 26;57(49):6078-6081. Epub 2021 May 26.

Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710069, China.

Three tris-bis(urea) ligands with triphenylamine-based C-symmetric spacers were synthesized, which assembled with sulfate or phosphate to form anionic AL pinwheel helices (A = anion and L = ligand) and AL tetrahedra, respectively. Interestingly, narcissistic self-sorting was observed in both structures from the mixture of the ligands, wherein each assembly contains only one type of ligand with no detectable mixed-ligand product as confirmed by the NMR and MS studies.
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http://dx.doi.org/10.1039/d1cc01652kDOI Listing
June 2021

Detection of deep myometrial invasion in endometrial cancer MR imaging based on multi-feature fusion and probabilistic support vector machine ensemble.

Comput Biol Med 2021 07 11;134:104487. Epub 2021 May 11.

School of Optical-Electrical and Computer Engineering, University of Shanghai for Science and Technology, Shanghai, China.

The depth of myometrial invasion affects the treatment and prognosis of patients with endometrial cancer (EC), conventionally evaluated using MR imaging (MRI). However, only a few computer-aided diagnosis methods have been reported for identifying deep myometrial invasion (DMI) using MRI. Moreover, these existing methods exhibit relatively unsatisfactory sensitivity and specificity. This study proposes a novel computerized method to facilitate the accurate detection of DMI on MRI. This method requires only the corpus uteri region provided by humans or computers instead of the tumor region. We also propose a geometric feature called LS to describe the irregularity of the tissue structure inside the corpus uteri triggered by EC, which has not been leveraged for the DMI prediction model in other studies. Texture features are extracted and then automatically selected by recursive feature elimination. Utilizing a feature fusion strategy of strong and weak features devised in this study, multiple probabilistic support vector machines incorporate LS and texture features, which are then merged to form the ensemble model EPSVM. The model performance is evaluated via leave-one-out cross-validation. We make the following comparisons, EPSVM versus the commonly used classifiers such as random forest, logistic regression, and naive Bayes; EPSVM versus the models using LS or texture features alone. The results show that EPSVM attains an accuracy, sensitivity, specificity, and F1 score of 93.7%, 94.7%, 93.3%, and 87.8%, all of which are higher than those of the commonly used classifiers and the models using LS or texture features alone. Compared with the methods in existing studies, EPSVM exhibits high performance in terms of both sensitivity and specificity. Moreover, LS can achieve an accuracy, sensitivity, and specificity of 89.9%, 89.5%, and 90.0%. Thus, the devised geometric feature LS is significant for DMI detection. The fusion of LS and texture features in the proposed EPSVM can provide more reliable prediction. The computer-aided classification based on the proposed method can assist radiologists in accurately identifying DMI on MRI.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104487DOI Listing
July 2021

Calcium-dependent cytosolic phospholipase A activation is implicated in neuroinflammation and oxidative stress associated with ApoE4.

Mol Neurodegener 2021 04 16;16(1):26. Epub 2021 Apr 16.

Departments of Medicine and Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Background: Apolipoprotein E4 (APOE4) is associated with a greater response to neuroinflammation and the risk of developing late-onset Alzheimer's disease (AD), but the mechanisms for this association are not clear. The activation of calcium-dependent cytosolic phospholipase A (cPLA2) is involved in inflammatory signaling and is elevated within the plaques of AD brains. The relation between APOE4 genotype and cPLA2 activity is not known.

Methods: Mouse primary astrocytes, mouse and human brain samples differing by APOE genotypes were collected for measuring cPLA2 expression, phosphorylation, and activity in relation to measures of inflammation and oxidative stress.

Results: Greater cPLA2 phosphorylation, cPLA2 activity and leukotriene B (LTB4) levels were identified in ApoE4 compared to ApoE3 in primary astrocytes, brains of ApoE-targeted replacement (ApoE-TR) mice, and in human brain homogenates from the inferior frontal cortex of patients with AD carrying APOE3/E4 compared to APOE3/E3. Greater cPLA2 phosphorylation was also observed in human postmortem frontal cortical synaptosomes and primary astrocytes after treatment with recombinant ApoE4 ex vivo. In ApoE4 astrocytes, the greater levels of LTB4, reactive oxygen species (ROS), and inducible nitric oxide synthase (iNOS) were reduced after cPLA2 inhibition.

Conclusions: Our findings implicate greater activation of cPLA2 signaling system with APOE4, which could represent a potential drug target for mitigating the increased neuroinflammation with APOE4 and AD.
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http://dx.doi.org/10.1186/s13024-021-00438-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052701PMC
April 2021

The impact of removing former drinkers from genome-wide association studies of AUDIT-C.

Addiction 2021 11 6;116(11):3044-3054. Epub 2021 May 6.

Yale University School of Public Health, New Haven, CT, USA.

Background And Aims: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire screens for harmful drinking using a 12-month timeframe. A score of 0 is assigned to individuals who report abstaining from alcohol in the past year. However, many middle-age individuals reporting current abstinence are former drinkers (FDs). Because FDs may be more genetically prone to harmful alcohol use than lifelong abstainers (LAs) and are often combined with LAs, we evaluated the impact of differentiating them on the identification of genetic association.

Design And Setting: The United Kingdom Biobank (UKBB) includes AUDIT-C and alcohol drinker status.

Participants: 131 510 Europeans, including 5135 FDs.

Measurements: We compared three genome-wide association (GWAS) analyses to explore the effects of removing FDs: the full AUDIT-C data, AUDIT-C data without FDs, and data from a random sample numerically matched to the data without FDs. Because prior studies show a consistent association of the ADH1B polymorphism rs1229984 with both alcohol consumption and alcohol use disorder, we compared allele frequencies for rs1229984 stratified by AUDIT-C value and FD versus LA status. Additionally, we calculated polygenic risk scores (PRS) of related diseases.

Findings: The rs1229984 allele frequencies among FDs were numerically comparable to those with high AUDIT-C scores and very different from those of LAs. Removing FDs from GWAS yielded a stronger association with rs1229984 (P value after removal: 1.9 × 10 vs 1.7 × 10 and 2.5 × 10 ), more statistically significant single nucleotide polymorphisms (SNPs) (after removal: 11 vs 9 and 8), and genomic loci (after removal: 11 vs 9 and 7). Additional independent SNPs were identified after removal of FDs: rs2817866 (PTGER3), rs7105867 (ANO3), and rs17601612 (DRD2). For PRS of alcohol use disorder and major depressive disorder, there are statistically significant differences between FDs and LAs.

Conclusions: Differentiating between former drinkers and lifelong abstainers can improve Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) genome-wide association results.
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http://dx.doi.org/10.1111/add.15511DOI Listing
November 2021

Potential-Dependent Mechanistic Study of Ethanol Electro-oxidation on Palladium.

ACS Appl Mater Interfaces 2021 Apr 31;13(14):16602-16610. Epub 2021 Mar 31.

Institute of Fuel Cells, School of Mechanical Engineering, MOE Key Laboratory of Power & Machinery Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.

We herein used the density functional theory (DFT) method and the implicit continuum solvation model to study the potential-dependent mechanism of ethanol oxidation reaction (EOR) on palladium (Pd). Energy evolutions of the EOR on low-index Pd surfaces, including (111), (110), and (100), were obtained as a function of the electrode potential. Moreover, the onset potentials for key intermediates and products were calculated. In addition, the potential range for adsorbed ethanol as the most stable adsorption state for proceeding the EOR was determined to be between 0.15 and 0.78 V via the calculated Pourbaix diagrams when considering hydrogen underpotential deposition and Pd(II) oxide formation as competing reactions. Specifically, the behavior of Pd(111) as the dominating facet decided the overall activity of the EOR with onset potentials to acidic acid/acetate at 0.40 V, to carbon dioxide at 0.71 V, and to oxide formation at 0.78 V. Pd(110) was predicted to exhibit the optimal activity toward the EOR with the lowest onset potentials to both the first dehydrogenation process and carbon dioxide at 0.08 and 0.60 V, respectively. A computational potential-dependent mechanism of the EOR was proposed, which agrees well with the experimental curve of linear sweeping voltammetry on the commercial Pd/C electrocatalyst. Our study suggests that targeted control of products can be tuned with proper overpotential and thus provides a foundation for the future development of EOR electrocatalysts.
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http://dx.doi.org/10.1021/acsami.1c04513DOI Listing
April 2021

Promoting Atomically Dispersed MnN Sites Sulfur Doping for Oxygen Reduction: Unveiling Intrinsic Activity and Degradation in Fuel Cells.

ACS Nano 2021 Apr 31;15(4):6886-6899. Epub 2021 Mar 31.

Giner Inc., Newton, Massachusetts 02466, United States.

Carbon supported and nitrogen coordinated single Mn site (Mn-N-C) catalysts are the most desirable platinum group metal (PGM)-free cathode catalysts for proton-exchange membrane fuel cells (PEMFCs) due to their insignificant Fenton reactions ( Fe), earth abundances ( Co), and encouraging activity and stability. However, current Mn-N-C catalysts suffer from high overpotential due to low intrinsic activity and less dense MnN sites. Herein, we present a sulfur-doped Mn-N-C catalyst (Mn-N-C-S) synthesized through an effective adsorption-pyrolysis process. Using electron microscopy and X-ray absorption spectroscopy (XAS) techniques, we verify the uniform dispersion of MnN sites and confirm the effect of S doping on the Mn-N coordination. The Mn-N-C-S catalyst exhibits a favorable oxygen reduction reaction (ORR) activity in acidic media relative to the S-free Mn-N-C catalyst. The corresponding membrane electrode assembly (MEA) generates enhanced performance with a peak power density of 500 mW cm under a realistic H/air environment. The constant voltage tests of fuel cells confirm the much-enhanced stability of the Mn-N-C-S catalyst compared to the Fe-N-C and Fe-N-C-S catalysts. The electron microscopy and Fourier transform XAS analyses provide insights into catalyst degradation associated with Mn oxidation and agglomeration. The theoretical calculation elucidates that the promoted ORR activity is mainly attributed to the spatial effect stemmed from the repulsive interaction between the ORR intermediates and adjacent S dopants.
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http://dx.doi.org/10.1021/acsnano.0c10637DOI Listing
April 2021

Learning-Based Autonomous UAV System for Electrical and Mechanical (E&M) Device Inspection.

Sensors (Basel) 2021 Feb 16;21(4). Epub 2021 Feb 16.

Interdisciplinary Division of Aeronautical and Aviation Engineering, The Hong Kong Polytechnic University, Kowloon 999077, Hong Kong.

The inspection of electrical and mechanical (E&M) devices using unmanned aerial vehicles (UAVs) has become an increasingly popular choice in the last decade due to their flexibility and mobility. UAVs have the potential to reduce human involvement in visual inspection tasks, which could increase efficiency and reduce risks. This paper presents a UAV system for autonomously performing E&M device inspection. The proposed system relies on learning-based detection for perception, multi-sensor fusion for localization, and path planning for fully autonomous inspection. The perception method utilizes semantic and spatial information generated by a 2-D object detector. The information is then fused with depth measurements for object state estimation. No prior knowledge about the location and category of the target device is needed. The system design is validated by flight experiments using a quadrotor platform. The result shows that the proposed UAV system enables the inspection mission autonomously and ensures a stable and collision-free flight.
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http://dx.doi.org/10.3390/s21041385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922194PMC
February 2021

Fine-Tuning the Spring-Like Motion of an Anion-Based Triple Helicate by Tetraalkylammonium Guests.

Angew Chem Int Ed Engl 2021 Apr 10;60(17):9389-9394. Epub 2021 Mar 10.

Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, 710069, China.

Supramolecular springs are a class of molecular devices that may provide implications to the macroscopic spring behavior from the molecular level. Helical structures are suitable molecular springs because the specific twisting of the helical strands can cause spring-like (extension-contraction) movement along the axis upon external stimuli. Herein we report an anion-based triple-helicate spring, which can undergo reversible contraction-extension motion through introduction and removal of tetraalkylammonium cations, including TMA and analogous irregular tetrahedral cations bearing different alkyl chains, while the relative orientation of the two phosphate ions changes to facilitate guest inclusion. Notably, the degree of contraction (shortening of the helical pitch) can be fine-tuned by varying the shape and size of guest cation. However, with the larger cations (TEA , TPA and TBA ), the meso-helicate configuration is obtained, which interconverts with the helicate by addition/removal of TMA ion.
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http://dx.doi.org/10.1002/anie.202100294DOI Listing
April 2021

Targeting eIF4F translation initiation complex with SBI-756 sensitises B lymphoma cells to venetoclax.

Br J Cancer 2021 03 14;124(6):1098-1109. Epub 2020 Dec 14.

Department of Molecular Biology & Biochemistry, University of California, Irvine, CA, 92697, USA.

Background: The BCL2 inhibitor venetoclax has shown efficacy in several hematologic malignancies, with the greatest response rates in indolent blood cancers such as chronic lymphocytic leukaemia. There is a lower response rate to venetoclax monotherapy in diffuse large B-cell lymphoma (DLBCL).

Methods: We tested inhibitors of cap-dependent mRNA translation for the ability to sensitise DLBCL and mantle cell lymphoma (MCL) cells to apoptosis by venetoclax. We compared the mTOR kinase inhibitor (TOR-KI) MLN0128 with SBI-756, a compound targeting eukaryotic translation initiation factor 4G1 (eIF4G1), a scaffolding protein in the eIF4F complex.

Results: Treatment of DLBCL and MCL cells with SBI-756 synergised with venetoclax to induce apoptosis in vitro, and enhanced venetoclax efficacy in vivo. SBI-756 prevented eIF4E-eIF4G1 association and cap-dependent translation without affecting mTOR substrate phosphorylation. In TOR-KI-resistant DLBCL cells lacking eIF4E binding protein-1, SBI-756 still sensitised to venetoclax. SBI-756 selectively reduced translation of mRNAs encoding ribosomal proteins and translation factors, leading to a reduction in protein synthesis rates in sensitive cells. When normal lymphocytes were treated with SBI-756, only B cells had reduced viability, and this correlated with reduced protein synthesis.

Conclusions: Our data highlight a novel combination for treatment of aggressive lymphomas, and establishes its efficacy and selectivity using preclinical models.
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http://dx.doi.org/10.1038/s41416-020-01205-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960756PMC
March 2021

MNL-Network: A Multi-Scale Non-local Network for Epilepsy Detection From EEG Signals.

Front Neurosci 2020 17;14:870. Epub 2020 Nov 17.

Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Epilepsy is a prevalent neurological disorder that threatens human health in the world. The most commonly used method to detect epilepsy is using the electroencephalogram (EEG). However, epilepsy detection from the EEG is time-consuming and error-prone work because of the varying levels of experience we find in physicians. To tackle this challenge, in this paper, we propose a multi-scale non-local (MNL) network to achieve automatic EEG signal detection. Our MNL-Network is based on 1D convolution neural network involving two specific layers to improve the classification performance. One layer is named the signal pooling layer which incorporates three different sizes of 1D max-pooling layers to learn the multi-scale features from the EEG signal. The other one is called a multi-scale non-local layer, which calculates the correlation of different multi-scale extracted features and outputs the correlative encoded features to further enhance the classification performance. To evaluate the effectiveness of our model, we conduct experiments on the Bonn dataset. The experimental results demonstrate that our MNL-Network could achieve competitive results in the EEG classification task.
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http://dx.doi.org/10.3389/fnins.2020.00870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705239PMC
November 2020

Multiple Transformations among Anion-based AL Assemblies: Bicapped Trigonal Antiprism AL, Tetrahedron AL, and Triple Helicate AL (A = Anion).

J Am Chem Soc 2020 12 3;142(50):21160-21168. Epub 2020 Dec 3.

Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710069, China.

The construction of sophisticated, high-nuclearity polyhedral cages is an attractive yet challenging task in supramolecular chemistry. Herein we report the anion-coordination-driven assembly (ACDA) of a series of AL architectures ("A" denotes anion, L is ligand, = 1, 2, 4) with a biphenylene-spaced -(urea) ligand including triple helicate AL (), tetrahedron AL (), and the octanuclear, bicapped trigonal antiprism (or parallelepiped) AL (). Among them, is held by 96 hydrogen bonds, the largest number ever reported in a discrete polyhedron, and encapsulates multiple guests (three tetramethylammonium cations) in three compartments. Remarkably, multiple reversible transformations of these dynamic assemblies have been realized by alternation of the template guest, solvent, and concentration. Furthermore, a chiral ligand () with carbon stereocenters at both termini of the -(urea) backbone was designed and assembled with phosphate to form the enantio-pure triple helicate or tetrahedron. The chiral amplification effect in the tetrahedral complex is significantly larger than that in the triple helicate as a function of the point chirality.
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http://dx.doi.org/10.1021/jacs.0c10346DOI Listing
December 2020

Genome-Wide Association Studies of Schizophrenia and Bipolar Disorder in a Diverse Cohort of US Veterans.

Schizophr Bull 2021 03;47(2):517-529

Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY.

Background: Schizophrenia (SCZ) and bipolar disorder (BIP) are debilitating neuropsychiatric disorders, collectively affecting 2% of the world's population. Recognizing the major impact of these psychiatric disorders on the psychosocial function of more than 200 000 US Veterans, the Department of Veterans Affairs (VA) recently completed genotyping of more than 8000 veterans with SCZ and BIP in the Cooperative Studies Program (CSP) #572.

Methods: We performed genome-wide association studies (GWAS) in CSP #572 and benchmarked the predictive value of polygenic risk scores (PRS) constructed from published findings. We combined our results with available summary statistics from several recent GWAS, realizing the largest and most diverse studies of these disorders to date.

Results: Our primary GWAS uncovered new associations between CHD7 variants and SCZ, and novel BIP associations with variants in Sortilin Related VPS10 Domain Containing Receptor 3 (SORCS3) and downstream of PCDH11X. Combining our results with published summary statistics for SCZ yielded 39 novel susceptibility loci including CRHR1, and we identified 10 additional findings for BIP (28 326 cases and 90 570 controls). PRS trained on published GWAS were significantly associated with case-control status among European American (P < 10-30) and African American (P < .0005) participants in CSP #572.

Conclusions: We have demonstrated that published findings for SCZ and BIP are robustly generalizable to a diverse cohort of US veterans. Leveraging available summary statistics from GWAS of global populations, we report 52 new susceptibility loci and improved fine-mapping resolution for dozens of previously reported associations.
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http://dx.doi.org/10.1093/schbul/sbaa133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965063PMC
March 2021

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia.

iScience 2020 Oct 11;23(10):101552. Epub 2020 Sep 11.

Yale Center for Genome Analysis, West Haven, CT, USA.

Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated mutation (p.Cys188Trp) in the GABA receptor Cl channel γ-1 subunit () exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na and Ca channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca channel Ca3.2 (). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis.
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http://dx.doi.org/10.1016/j.isci.2020.101552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554653PMC
October 2020

Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals.

Nat Commun 2020 10 20;11(1):5302. Epub 2020 Oct 20.

Yale School of Medicine, New Haven, CT, 06511, USA.

Here we report a large genome-wide association study (GWAS) for longitudinal smoking phenotypes in 286,118 individuals from the Million Veteran Program (MVP) where we identified 18 loci for smoking trajectory of current versus never in European Americans, one locus in African Americans, and one in Hispanic Americans. Functional annotations prioritized several dozen genes where significant loci co-localized with either expression quantitative trait loci or chromatin interactions. The smoking trajectories were genetically correlated with 209 complex traits, for 33 of which smoking was either a causal or a consequential factor. We also performed European-ancestry meta-analyses for smoking status in the MVP and GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) (N = 842,717) and identified 99 loci for smoking initiation and 13 loci for smoking cessation. Overall, this large GWAS of longitudinal smoking phenotype in multiple populations, combined with a meta-GWAS for smoking status, adds new insights into the genetic vulnerability for smoking behavior.
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http://dx.doi.org/10.1038/s41467-020-18489-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598939PMC
October 2020

Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus.

Nat Med 2020 11 19;26(11):1754-1765. Epub 2020 Oct 19.

Departments of Neurosurgery, Engineering Science & Mechanics, and Physics; Center for Neural Engineering and Infectious Disease Dynamics, The Pennsylvania State University, University Park, PA, USA.

Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to ~22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH.
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http://dx.doi.org/10.1038/s41591-020-1090-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871900PMC
November 2020

An Actuator Allocation Method for a Variable-Pitch Propeller System of Quadrotor-based UAVs.

Sensors (Basel) 2020 Oct 2;20(19). Epub 2020 Oct 2.

Interdisciplinary Division of Aeronautical and Aviation Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong.

This paper presents a control allocation method for enhancing the attitude following performance and the energy efficiency of a variable-pitch propeller (VPP) system on quadrotor-based unmanned aerial vehicles. The VPP system was modeled according to the blade element momentum (BEM) theory, and an actuator allocation method was developed with the aim of enhancing the attitude control and energy performance. A simulation environment was built to validate the VPP system by creating a thrust and moment database from the experiments. A four-motor variable-pitch quadrotor was built for verifying the proposed method. The control allocation method was firstly verified in a simulation environment, and was then implemented in a flight controller for indoor flight experiments. The simulation results show the proposed control allocation method greatly improves the yaw following performance. The experimental results demonstrate a difference in the energy consumption through various pitch angles, as well as a reduction in energy consumption, by applying this VPP system.
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http://dx.doi.org/10.3390/s20195651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582693PMC
October 2020

Mutations disrupting neuritogenesis genes confer risk for cerebral palsy.

Nat Genet 2020 10 28;52(10):1046-1056. Epub 2020 Sep 28.

Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance. We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that the RHOB mutation enhances active-state Rho effector binding while the FBXO31 mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.
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http://dx.doi.org/10.1038/s41588-020-0695-1DOI Listing
October 2020
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