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1.
Hum Cell ; 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34628623

RESUMO

The immune context of the tumor microenvironment (TME) is critical for effective immunotherapy. Nonetheless, DNA-based biomarkers for the immune-sensitive TME and the identification of immune checkpoint inhibitor (ICI) responders are under-explored. This study aims to comprehensively landscape the homologous recombination deficiency (HRD) score, an emerging hallmark for tumor genome instability that triggers immune responsiveness across major cancer types, and to unveil their link to the TME and immunotherapeutic response. The HRD-associated genomic scars were characterized in 9088 tumor samples across 32 cancer types from TCGA. We evaluated the HRD score's performance in classifying ICI responders using an independent breast cancer cohort (GSE87049) and 11 in vivo murine mammary tumor models treated with anti-PD1/CTLA4 regimen (GSE124821). This study revealed a broad association between HRD-high genotype and neoantigenesis in the major cancer types including bladder cancer, breast cancer, head and neck squamous carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, ovarian cancer, and sarcoma. Tumors with high HRD score bears increased leukocyte infiltration and lymphocyte fraction and demonstrated immune-sensitive microenvironment. The tumor immune dysfunction and exclusion (TIDE) model further confirmed HRD score-high genotype as a potential predictor for ICI immunotherapy responders in breast cancer. In conclusion, tumors with high HRD score exhibit an immune-sensitive TME. The HRD-high genotype is a promising marker for identifying ICI therapy responders among breast cancer patients.

2.
J Org Chem ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623805

RESUMO

A novel visible-light-induced coupling-cyclization of ortho-alkynylaryl vinylethers with arylsulfonyl azides has been described. This transformation provided a concise approach to access C3-exocyclic C═C bond/C2-alkylsulfone-tethered benzofurans via a solvent-leveraged carbosulfonylation and [2 + 2 + 3] cyclization. Primary mechanistic studies demonstrated that THF belongs to a crucial H atom source.

3.
Inorg Chem ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528788

RESUMO

A new alkali metal-rare earth metal anhydrous sulfate, KTb(SO4)2 (KTSO), was synthesized by a hydrothermal method. It crystallized in the non-centrosymmetric (NCS) orthorhombic space group P212121 with cell parameters a = 5.43950(10), b = 8.8579(3), c = 13.3962(4), Z = 2. Its structure is composed of [KO11], [TbO8], and [SO4] groups, which are interconnected to constitute a one-dimensional (1D) chain, and then further linked to construct a three-dimensional (3D) network structure through [SO4] units. The results of the powder frequency doubling test show that KTb(SO4)2 has a phase-matching second-order nonlinear optical effect of 0.3 times that of KH2PO4 (KDP). The measured birefringence of the crystal (0.01) agrees well with the calculated value (0.019). Meanwhile, its infrared and ultraviolet spectrum and thermal properties were studied, respectively. Its optical properties and band gap structure are studied by theoretical calculation. This work provides a NCS structure of anhydrous sulfates and offers guidance for further exploration of new anhydrous sulfates.

4.
J Clin Anesth ; 75: 110489, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481363

RESUMO

STUDY OBJECTIVE: A lateral mini-thoracotomy approach to cardiac surgery causes severe and complicated postoperative pain compared to the sternotomy approach. In this study we assessed the benefits and risks of intermittent bolus erector spinae plane block (ESPB) via a catheter for patients who underwent cardiac surgery through a lateral mini-thoracotomy. DESIGN: A propensity score-matched retrospective cohort study. SETTING: University hospital. PATIENTS: 452 consecutive patients that underwent cardiac surgery through a lateral mini-thoracotomy from 2018 to 2020. INTERVENTIONS: Patients who received intermittent bolus ESPB through a catheter for 3 days (ESPB group, n = 93) were compared with patients who did not receive any regional anesthesia (Control group, n = 174) after propensity score matching. MEASUREMENTS: The primary endpoint was postoperative in-hospital cumulative opioid consumption (calculated as oral morphine milligram equivalents, MME). The secondary outcomes were intraoperative sufentanil doses, therapeutic use of antiemetic, pulmonary infection (assessed using a modified clinical pulmonary infection score, CPIS), durations of ICU and hospital stays, and ESPB related/unrelated complications. MAIN RESULTS: There is a lower oral MME in the ESPB group, 266 ± 126 mg in the ESPB group vs. 346 ± 105 mg in the control group (95% CI -113 to -46; P < 0.01). Fewer patients received therapeutic antiemetic agents in the ESPB group (30% vs. 42%, odds ratio 0.58; 95% CI 0.34 to 0.99; P = 0.04). The modified CPIS in the ESPB group is lower: 1.4 ± 0.9 vs. 2.0 ± 1.0 (95% CI -0.9 to -0.3; P < 0.01) on postoperative day 1; 1.6 ± 0.9 vs. 2.0 ± 0.9 (95% CI -0.7 to -0.2; P < 0.01) on postoperative day 2. The observed complications associated with ESPB include pneumothorax (1%), staxis around stomas (5%), hypotension (1%), catheter displacement (3%), and catheter obstruction (2%). None of the patients had any adverse outcomes. CONCLUSION: Intermittent bolus ESPB is relatively safe and correlated with a reduction in the use of opioids and antiemetics for cardiac surgery through a lateral mini-thoracotomy.

5.
Int J Biol Macromol ; 190: 463-473, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34506859

RESUMO

Xanthine oxidase (XO) plays a vital role in inducing hyperuricemia and increasing the level of superoxide free radicals in blood, and is proved as an important target for gout. Chrysoeriol (CHE) is a natural flavone with potent XO inhibitory activity (IC50 = 2.487 ± 0.213 µM), however, the mechanism of interaction is still unclear. Therefore, a comprehensive analysis of the interaction between CHE and XO was accomplished by enzyme kinetics, isothermal titration calorimetry (ITC), multi-spectroscopic methods, molecular simulation and ADMET. The results showed that CHE acted as a rapid reversible and competitive-type XO inhibitor and its binding to XO was driven by hydrogen bonding and hydrophobic interaction. Moreover, CHE exhibited a strong fluorescence quenching effect through a static quenching procedure and induced conformational changes of XO. Its binding pattern with XO was revealed by docking study and the binding affinity to XO was enhanced by the interactions with key amino acid residues in the active pocket of XO. Further, CHE showed good stability and pharmacokinetic behavior properties in molecule dynamic simulation and ADMET prediction. Overall, this study shed some light on the mechanism of interaction between CHE and XO, also provided some valuable information concerning the future therapeutic application of CHE as natural XO inhibitor.

6.
Microvasc Res ; 139: 104252, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34520772

RESUMO

Soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating antiangiogenic protein, is involved in the pathogenesis of atherosclerosis (AS), and the underlying mechanism is still unclear. Here, we attempted to investigate the mechanism of action of sFlt-1 in AS. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low density lipoprotein (ox-LDL) to induce cell injury. ox-LDL treatment increased LC3-II/LC3-I ratio, Beclin-1 expression and GFP-LC3 puncta in HUVECs, suggesting that ox-LDL may induce autophagic flux impairment in HUVECs. ox-LDL-treated HUVECs displayed a decrease of sFlt-1 levels. Moreover, ox-LDL treatment reduced cell proliferation and elevated apoptosis in HUVECs, which was abrogated by sFlt-1 overexpression. Up-regulation of sFlt-1 repressed the activity of PI3K/AKT/mTOR signaling pathway and enhanced autophagy in HUVECs following ox-LDL treatment. Additionally, sFlt-1 overexpression-mediated increase of autophagy in ox-LDL-treated HUVECs was abolished by 3-methyladenine (autophagy inhibitor). 3-methyladenine abrogated the impact of sFlt-1 overexpression on proliferation and apoptosis in ox-LDL-treated HUVECs. This work confirmed that overexpression of sFlt-1 activated autophagy by repressing PI3K/Akt/mTOR signaling pathway, and thus alleviated ox-LDL-induced injury of HUVECs. Therefore, this study suggests that sFlt-1 may be a potential target for AS treatment.

7.
Adv Mater ; : e2101466, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34480371

RESUMO

2D carbon nitride nanosheets have attracted ever-increasing interest in photocatalysis due to their unique structural advantages. However, the nanosheets synthesized by the traditional methods, such as post oxidation and liquid exfoliation, have suffered from in-plane disorder with abundant structural defects, which seriously counteracts their structural benefits for photocatalysis. Herein, it is demonstrated that polymer carbon nitride nanosheets with in-plane highly ordered structure (PCNNs-IHO) can be successfully prepared by on-surface polymerization of melamine on NaCl crystal surface at elevated temperatures. The NaCl crystals with relative high surface energy not only facilitate the adsorption and activation of melamine to undergo condensation reaction, but also function as unique substrates to orientate the assembly of 2D nanosheet structure. In addition, NaCl also acts as a reactant to provide Na+ doping into carbon nitride matrix, affording PCNNs-IHO with robust structural base sites. Benefiting from this structural basicity, PCNNs-IHO exhibits superior photocatalytic performance toward CH3 SH mineralization under visible light irradiation.

8.
Org Lett ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34397220

RESUMO

An unprecedented Pd/Rh cooperatively catalyzed arylalkynylation of alkynylsilanes was developed to merge an alkynylidene moiety with benzosilacycle. These silaarenes possess a particular aggregation-induced emission behavior. Mechanistic investigations demonstrate that the relay trimetallic transmetalation plays a pivotal role in governing this transformation.

9.
ChemSusChem ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34323383

RESUMO

A two-dimensional electron-rich fused-ring moiety (ClBDSe) based on benzo[1,2-b:4,5-b']diselenophene is synthesized. Three copolymers (PBDT-Se, PBDSe-T, and PBDSe-Se) are obtained by manipulating the connection types and number of selenophene units on the conjugated main chains with two 2D fused-ring units and two different π-bridges, respectively. In comparison with PBDT-Se and PBDSe-Se, PBDSe-T with benzo[1,2-b:4,5-b']diselenophene unit and thiophene π-bridge exhibits the deepest HOMO energy level and the strongest crystallinity in neat films. The PBDSe-T:Y6 blend film exhibits the best absorption complementarity, the most distinctive face-on orientation with proper phase separation, the highest carrier mobilities, and the lowest charge recombination among three blend films. Finally, the PBDSe-T:Y6-based device delivers an impressive power conversion efficiency (PCE) of 14.50 %, which is higher than those of PBDT-Se:Y6 and PBDSe-Se:Y6. Moreover, a decent open-circuit voltage (Voc ) of 0.89 V with a remarkably small energy loss of 0.44 eV is achieved for PBDSe-T:Y6. The efficiency of 14.50 % is the highest value for selenophene-containing copolymer-based binary organic solar cells (OSCs). This study provides evidence that introduction of 2D-benzo[1,2-b:4,5-b']diselenophene as a fused electron-rich unit with π-bridging into copolymeric donors is a valid strategy for providing high Voc and excellent PCE simultaneously in selenophene-based OSCs.

10.
IEEE Trans Med Imaging ; PP2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34255626

RESUMO

In this paper, we discuss the design study for a brain SPECT imaging system, referred to as the HelmetSPECT system, based on a spherical synthetic compound-eye (SCE) gamma camera design. The design utilizes a large number ( 500) of semiconductor detector modules, each coupled to an aperture with a very narrow opening for high-resolution SPECT imaging applications. In this study, we demonstrate that this novel system design could provide an excellent spatial resolution, a very high sensitivity, and a rich angular sampling without scanning motion over a clinically relevant field-of-view (FOV). These properties make the proposed HelmetSPECT system attractive for dynamic imaging of epileptic patients during seizures. In ictal SPECT, there is typically no prior information on where the seizures would happen, and both the imaging resolution and quantitative accuracy of the dynamic SPECT images would provide critical information for staging the seizures outbreak and refining the plans for subsequent surgical intervention. We report the performance evaluation and comparison among similar system geometries using non-conventional apertures, such as micro-ring and micro-slit, and traditional lofthole apertures. We demonstrate that the combination of ultrahigh-resolution imaging detectors, the SCE gamma camera design, and the micro-ring and micro-slit apertures would offer an interesting approach for the future ultrahigh-resolution clinical SPECT imaging systems without sacrificing system sensitivity and FOV.

11.
Nat Commun ; 12(1): 3304, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083532

RESUMO

Sila-molecules have recently attracted attention due to their promising applications in medical and industrial fields. Compared with all-carbon parent compounds, the different covalent radius and electronegativity of silicon from carbon generally endow the corresponding sila-analogs with unique biological activity and physicochemical properties. Vinylsilanes feature both silyl-hyperconjugation effect and versatile reactivities, developing vinylsilane-based Smiles rearrangement will therefore provide an efficient platform to assemble complex silacycles. Here we report a practical Ir(III)-catalyzed cycloaromatization of ortho-alkynylaryl vinylsilanes with arylsulfonyl azides for delivering naphthyl-fused benzosiloles under visible-light photoredox conditions. The combination of experiments and density functional theory (DFT) energy profiles reveals the reaction mechanism involving α-silyl radical Smiles rearrangement.

12.
Opt Express ; 29(11): 16904-16913, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34154243

RESUMO

Ultratrace molecular detections are vital for precancer diagnosis, forensic analysis, and food safety. Superhydrophobic (SH) surface-enhanced Raman scattering (SERS) sensors are regarded as an ideal approach to improve detection performance by concentrating analyte molecules within a small volume. However, due to the low adhesion of SH surfaces, the analyte droplet is prone to rolling, making it hard to deposit molecules on a predetermined position. Furthermore, the sediment with a very small area on the SH-SERS surface is difficult to be captured even with a Raman microscope. In this study, femtosecond laser fabricated hybrid SH/hydrophobic (SH/HB) surfaces are successfully applied to realize a rapid and highly sensitive SERS detection. By modulating dual surface structures and wetting behaviors, the analyte molecules can be enriched at the edge of HB pattern. This improves the convenience and speed of Raman test. On a hybrid SH/HB SERS substrate with a circular HB pattern at 300-µm-diameter, a femtomolar level (10-14 M) of rhodamine 6G can be detected by using analyte volumes of just 5 µL. The SERS enhancement factor can reach 5.7×108 and a good uniformity with a relative standard deviation of 6.98% is achieved. Our results indicate that the laser fabrication of hybrid SERS sensor offers an efficient and cost-effective approach for ultratrace molecular detection.

13.
Dalton Trans ; 50(22): 7563-7570, 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-33978025

RESUMO

Three new organic-inorganic hybrid perovskite (OIHP) halides, [N(CH3)4]HgCl0.63Br2.37 (I), [N(CH3)4]HgBrI2 (II) and [N(CH3)4]HgCl0.45I2.55 (III), were synthesized by a hydrothermal reaction. They feature different crystal structures, in which both II and III are isomorphic and contain a one-dimensional chain with organic cation [N(CH3)4]+ interspersed in the space, whereas II has a similar one-dimensional chain but significantly different spatial arrangement due to the enhanced hydrogen bond interaction. The experimental results show that the divergent second-order nonlinear optical (NLO) effect from Br(Cl) to I and the arrangement of anion groups change dramatically from the presence of hydrogen bonds to the absence of hydrogen bonds, leading to a sharply increased NLO response of II and III (18 and 25 times that of I) compared with that of I. Moreover, the phase matching ability disappeared and the band gap decreased significantly. Meanwhile, a high temperature phase transition was observed in II and III, which is rare in common OIHPs. All these results indicate that the regulation of halogen bonds plays a crucial role in the structural and property mutations of OIHP halides.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34051037

RESUMO

A dissymmetric backbone and selenophene substitution on the central core was used for the synthesis of symmetric or dissymmetric A-DA'D-A type non-fullerene small molecular acceptors (NF-SMAs) with different numbers of selenophene. From S-YSS-Cl to A-WSSe-Cl and to S-WSeSe-Cl, a gradually red-shifted absorption and a gradually larger electron mobility and crystallinity in neat thin film was observed. A-WSSe-Cl and S-WSeSe-Cl exhibit stronger and tighter intermolecular π-π stacking interactions, extra S⋅⋅⋅N non-covalent intermolecular interactions from central benzothiadiazole, better ordered 3D interpenetrating charge-transfer networks in comparison with thiophene-based S-YSS-Cl. The dissymmetric A-WSSe-Cl-based device has a PCE of 17.51 %, which is the highest value for selenophene-based NF-SMAs in binary polymer solar cells. The combination of dissymmetric core and precise replacement of selenophene on the central core is effective to improve Jsc and FF without sacrificing Voc .

15.
Org Lett ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33955759

RESUMO

A Rh(III)-catalyzed Csp2-Csp3 σ-bond carbenoid functionalization of α-(2-indolyl)alcohols with acceptor/acceptor diazo compounds has been developed. This transformation provides an efficient strategy to assemble stable C2-enolated indole skeletons via Csp2-Csp3 σ-bond cleavage.

16.
J Hematol Oncol ; 14(1): 60, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849617

RESUMO

BACKGROUND: Both aberrant alternative splicing and m6A methylation play complicated roles in the development of pancreatic cancer (PC), while the relationship between these two RNA modifications remains unclear. METHODS: RNA sequencing (RNA-seq) was performed using 15 pairs of pancreatic ductal adenocarcinoma (PDAC) tissues and corresponding normal tissues, and Cdc2-like kinases 1 (CLK1) was identified as a significantly upregulated alternative splicing related gene. Real-time quantitative PCR (qPCR) and western blotting were applied to determine the CLK1 levels. The prognostic value of CLK1 was elucidated by Immunohistochemistry (IHC) analyses in two independent PDAC cohorts. The functional characterizations and mechanistic insights of CLK1 in PDAC growth and metastasis were evaluated with PDAC cell lines and nude mice. SR-like splicing factors5250-Ser (SRSF5250-Ser) was identified as an important target phosphorylation site by phosphorylation mass spectrometry. Through transcriptome sequencing, Methyltransferase-like 14exon10 (METTL14exon10) and Cyclin L2exon6.3 skipping were identified as key alternative splicing events regulated by the CLK1-SRSF5 axis. RIP assays, RNA-pulldown and CLIP-qPCR were performed to confirm molecular interactions and the precise binding sites. The roles of the shift of METTL14exon 10 and Cyclin L2exon6.3 skipping were surveyed. RESULTS: CLK1 expression was significantly increased in PDAC tissues at both the mRNA and protein levels. High CLK1 expression was associated with poor prognosis. Elevated CLK1 expression promoted growth and metastasis of PC cells in vitro and in vivo. Mechanistically, CLK1 enhanced phosphorylation on SRSF5250-Ser, which inhibited METTL14exon10 skipping while promoted Cyclin L2exon6.3 skipping. In addition, aberrant METTL14exon 10 skipping enhanced the N6-methyladenosine modification level and metastasis, while aberrant Cyclin L2exon6.3 promoted proliferation of PDAC cells. CONCLUSIONS: The CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2, which promotes growth and metastasis and regulates m6A methylation of PDAC cells. This study suggests the potential prognostic value and therapeutic targeting of this pathway in PDAC patients.


Assuntos
Ciclinas/metabolismo , Éxons , Metiltransferases/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Fatores de Processamento de Serina-Arginina/metabolismo , Fatores de Transcrição/metabolismo , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Ciclinas/genética , Feminino , Células HEK293 , Xenoenxertos , Humanos , Masculino , Metiltransferases/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Fatores de Processamento de Serina-Arginina/genética , Fatores de Transcrição/genética
17.
Inorg Chem ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33887916

RESUMO

A new hybrid compound [N(CH3)4]2HgBr2I2, obtained by a hydrothermal reaction, crystallized in the noncentrosymmetric space group P212121. Its structure contains an isolated asymmetric [HgBr2I2]2- tetrahedron with net polarization, connected by hydrogen bonds to form pseudo-one-dimensional chain structures. Moreover, its optical band gap, nonlinear optical (NLO) property, fluorescence property, and thermal property were characterized in detail. A rare high-temperature phase transition was observed in the compound. In addition, theoretical calculations were performed to elaborate the relation between electronic state, band structure, and their nonlinear optical response. These results indicate that [N(CH3)4]2HgBr2I2 is a new potential candidate for future photoelectronic applications in fluorescence and nonlinear optics.

18.
Am J Hum Genet ; 108(4): 632-655, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33770506

RESUMO

The development of polygenic risk scores (PRSs) has proved useful to stratify the general European population into different risk groups. However, PRSs are less accurate in non-European populations due to genetic differences across different populations. To improve the prediction accuracy in non-European populations, we propose a cross-population analysis framework for PRS construction with both individual-level (XPA) and summary-level (XPASS) GWAS data. By leveraging trans-ancestry genetic correlation, our methods can borrow information from the Biobank-scale European population data to improve risk prediction in the non-European populations. Our framework can also incorporate population-specific effects to further improve construction of PRS. With innovations in data structure and algorithm design, our methods provide a substantial saving in computational time and memory usage. Through comprehensive simulation studies, we show that our framework provides accurate, efficient, and robust PRS construction across a range of genetic architectures. In a Chinese cohort, our methods achieved 7.3%-198.0% accuracy gain for height and 19.5%-313.3% accuracy gain for body mass index (BMI) in terms of predictive R2 compared to existing PRS approaches. We also show that XPA and XPASS can achieve substantial improvement for construction of height PRSs in the African population, suggesting the generality of our framework across global populations.


Assuntos
Estatura/genética , Índice de Massa Corporal , Simulação por Computador , Modelos Genéticos , Herança Multifatorial/genética , África/etnologia , Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Asiático/genética , China/etnologia , Bases de Dados Factuais , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise de Componente Principal , Tamanho da Amostra , Reino Unido
19.
Sci Adv ; 7(11)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33712470

RESUMO

Metal-ceramic interfaces are scientifically interesting and technologically important. However, the transition of chemical bonding character from a metal to a nonoxide ceramic is not well understood. The effects of solute segregation and interfacial structural transitions are even more elusive. In this study, aberration-corrected electron microscopy is combined with atomic-resolution energy-dispersive x-ray and electron energy loss spectroscopy to investigate Ti-, V-, and Cr-segregated WC-Co interfaces as model systems. The experiments reveal the general anisotropic formation of reconstructed trilayer-like superstructures with segregant-specific compositional profiles that facilitate the transition from covalent to metallic electronic structures. Density functional theory calculations confirm the gradual increasing metallicity from WC to Co in the interfacial trilayers via increasing metallic solute concentration. This study uncovers unprecedented details of the sophisticated interfacial superstructures at metal-ceramic interfaces. It sheds light on how a metal transits to a ceramic at a "general" interface with strong segregation.

20.
Methods Mol Biol ; 2212: 93-103, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33733352

RESUMO

Transcriptome-wide association studies (TWASs) integrate expression quantitative trait loci (eQTLs) studies with genome-wide association studies (GWASs) to prioritize candidate target genes for complex traits. TWASs have become increasingly popular. They have been used to analyze many complex traits with expression profiles from different tissues, successfully enhancing the discovery of genetic risk loci for complex traits. Though conceptually straightforward, some steps are required to perform the TWAS properly. Here we provide a step-by-step guide to integrate eQTL data with both GWAS individual-level data and GWAS summary statistics from complex traits.


Assuntos
Epistasia Genética , Testes Genéticos/métodos , Modelos Genéticos , Herança Multifatorial , Software , Transcriptoma , Genoma Humano , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Incerteza
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