Additional file 1 of Genome-wide association study identifies new loci associated with noise-induced tinnitus in Chinese populations

Additional file 1: Supplementary Figure 1. The principal components analyses (PCA) of the population in the discovery stage in this study and reference populations from the 1,000 Genomes Project. Supplementary Figure 2. The genotypes of rs2846071 are significantly associated with the expression levels of WNT11 in several types of brain tissues from GTEx. Supplementary Figure 3. Colocalization analyses of the association signals from GWAS and brain eQTL data at the 11q13.5 and 12p13.31 loci. Supplementary Figure 4. Chromatin state segmentations for rs1800692 and rs4149570 using the ENCODE data. Supplementary Figure 5. The genotypes of rs4149577 are significantly associated with the expression levels of TNFRSF1A in several types of brain tissue from GTEx. Supplementary Figure 6. Proxy plots for 11q13.5 and 12p13.31 regions in Chinese Han Chinese and European populations. Supplementary Figure 7. Linkage disequilibrium plots for 11q13.5 and 12p13.31 regions in Chinese Han Chinese and European populations. Supplementary Figure 8. Power to detect the genetic effects of rs2846071 and rs4149577. Supplementary Table 1. Summary of the case/control populations used in this study. Supplementary Table 2. Summary of the genotyped and imputed SNPs in the discovery stage. Supplementary Table 3. Summary of the SNPs that have been reported to be associated with tinnitus in previous studies. Supplementary Table 4. Summary of the top 22 SNPs in the discovery stage. Supplementary Table 5. Primers used for SNPs genotyping in the replication stage. Supplementary Table 6. Summary of the association results in the replication stage. Supplementary Table 7. Stratification analyses of rs2846071 and rs4149577 by age. Supplementary Table 8. The predicted functional relevance of rs2846071, rs4149577 and the other SNPs in strong or moderate LD with them. Supplementary Table 9. Pathway analyses based on i-GSEA4GWAS. Supplementary Table 10. The allele and genotype frequencies of rs2846071 and rs4149577 in different populations

Palladium-Catalyzed Asymmetric Intramolecular Dearomative Heck Annulation of Aryl Halides to Furnish Indolines

An unprecedented Pd-catalyzed asymmetric intramolecular cascade cyclization of aryl halides with readily available arylboronic acids proceeds through a Heck-type dearomative cyclization terminated with arylation in the presence of Pd2(dba)3 (10 mol %), Cu2O (5 mol %), and Cs2CO3 (2.0 equiv) in 1,2-dichloroethane (1.0 mL) at 100 °C for 15 h in air using BINOL-based phosphoramidite as the chiral ligand. This dearomative Heck protocol, which tolerates a broad variety of functional groups, is amenable to the generation of optically active indoline derivatives bearing all-carbon quaternary stereogenic centers in one step in moderate to excellent yields, with excellent diastereoselectivities (>20:1) and enantioselectivities (up to >99% ee). It is worth mentioning that no decrease in the enantiopurity of the indoline derivatives was observed during the synthetic transformations of the products

Palladium-Catalyzed Asymmetric Intramolecular Dearomative Heck Annulation of Aryl Halides to Furnish Indolines

An unprecedented Pd-catalyzed asymmetric intramolecular cascade cyclization of aryl halides with readily available arylboronic acids proceeds through a Heck-type dearomative cyclization terminated with arylation in the presence of Pd2(dba)3 (10 mol %), Cu2O (5 mol %), and Cs2CO3 (2.0 equiv) in 1,2-dichloroethane (1.0 mL) at 100 °C for 15 h in air using BINOL-based phosphoramidite as the chiral ligand. This dearomative Heck protocol, which tolerates a broad variety of functional groups, is amenable to the generation of optically active indoline derivatives bearing all-carbon quaternary stereogenic centers in one step in moderate to excellent yields, with excellent diastereoselectivities (>20:1) and enantioselectivities (up to >99% ee). It is worth mentioning that no decrease in the enantiopurity of the indoline derivatives was observed during the synthetic transformations of the products

Role of Daucosterol Linoleate on Breast Cancer: Studies on Apoptosis and Metastasis

The antitumor property of steroids in sweet potato (Ipomoea batatas L.) remains poorly understood. Herein, we investigated the anticancer effect on breast carcinoma of daucosterol linoleate (DL), a steroid isolated from sweet potato. DL inhibited the cell viability of estrogen receptor (ER)-positive MCF-7 breast cancer cells at an IC50 value of 53.27 ± 9.02 μg/mL, while the effect was modest in ER-negative MDA-MB-231 breast cancer cells. Flow cytometry indicated that the DL-induced apoptosis in MCF-7 cells is dose-dependent. However, DL inhibited tumor growth and tumor weight at 100 mg/kg in MCF-7 xenograft nude mice. DL diminished the expression of Bcl-xl, Bcl-2, and XIAP, while increasing Bax, Bad, and activated caspase-dependent apoptosis in tumor tissues. Furthermore, DL inactivated the upstream Pi3k/Akt/NF-κB pathway. In the 4T1 spontaneous metastasis model, DL blocked metastasis progression, decreased the number of visible metastasis foci and inhibited metastasis size distribution in lung tissue. Further studies showed that DL suppressed VEGF, MMP 2, and MMP 9 expression in both tumor and lung tissues. From these results, we can assume that DL is a potential adjuvant therapy for ER-positive breast cancer patients

Single Copper Atom Photocatalyst Powers an Integrated Catalytic Cascade for Drug-Resistant Bacteria Elimination

To address the issue posed by drug-resistant bacteria and inspired by natural antimicrobial enzymes, we report the atomically doped copper on guanine-derived nanosheets (G–Cu) that possess the integrated catalytic cascade property of glucose oxidase and peroxidase, yielding free radicals to eliminate drug-resistant bacteria upon light irradiation. Density functional theory calculations demonstrate that copper could notably promote oxygen activation and H2O2 splitting on the G–Cu complexes. Further all-atom simulation and experimental data indicate that the lysis of bacteria is mainly induced by cell membrane damage and the elevation of intracellular reactive oxygen species. Lastly, the G–Cu complexes efficiently eliminate the staphylococci in the infected wounds and accelerate their closure in a murine model, with negligible side effects on the normal tissues. Therefore, our G–Cu complexes may provide an efficient nonantibiotic alternative to the current treatments for bacterial infections

Lipid Prodrug Nanoassemblies via Dynamic Covalent Boronates

Prodrug nanoassemblies combine the advantages of prodrug and nanomedicines, offering great potential in targeting the lesion sites and specific on-demand drug release, maximizing the therapeutic performance while minimizing their side effects. However, there is still lacking a facile pathway to prepare the lipid prodrug nanoassemblies (LPNAs). Herein, we report the LPNAs via the dynamic covalent boronate between catechol and boronic acid. The resulting LPNAs possess properties like drug loading in a dynamic covalent manner, charge reversal in an acidic microenvironment, and specific drug release at an acidic and/or oxidative microenvironment. Our methodology enables the encapsulation and delivery of three model drugs: ciprofloxacin, bortezomib, and miconazole. Moreover, the LPNAs are often more efficient in eradicating pathogens or cancer cells than their free counterparts, both in vitro and in vivo. Together, our LPNAs with intriguing properties may boost the development of drug delivery and facilitate their clinical applications

Facilitating Catalytic Purification of Auto-Exhaust Carbon Particles via the Fe₂O₃{113} Facet-dependent Effect in Pt/Fe₂O₃ Catalysts

The purification efficiency of auto-exhaust carbon particles in the catalytic aftertreatment system of vehicle exhaust is strongly dependent on the interface nanostructure between the noble metal component and oxide supports. Herein, we have elaborately synthesized the catalysts (Pt/Fe2O3-R) of Pt nanoparticles decorated on the hexagonal bipyramid α-Fe2O3 nanocrystals with co-exposed twelve {113} and six {104} facets. The area ratios (R) of co-exposed {113} to {104} facets in α-Fe2O3 nanocrystals were adjusted by the fluoride ion concentration in the hydrothermal method. The strong Pt–Fe2O3{113} facet interaction boosts the formation of coordination unsaturated ferric sites for enhancing adsorption/activation of O2 and NO. Pt/Fe2O3-R catalysts exhibited the Fe2O3{113} facet-dependent performance during catalytic purification of soot particles in the presence of H2O. Among the catalysts, the Pt/Fe2O3-19 catalyst exhibits the highest catalytic activities (T50 = 365 °C, TOF = 0.13 h–1), the lowest apparent activation energy (69 kJ mol–1), and excellent catalytic stability during soot purification. Combined with the results of characterizations and density functional theory calculations, the catalytic mechanism is proposed: the active sites located at the Pt–Fe2O3{113} interface can boost the key step of NO oxidation to NO2. The crystal facet engineering is an effective strategy to obtain efficient catalysts for soot purification in practical applications

Recent Progress on Density Functional Theory Calculations for Catalytic Control of Air Pollution

With the urgent demand for environmental protection and sustainable development, the field of environmental catalysis has received increasing attention. The further development of environmental catalysis is limited by the understanding of reaction processes at the atomic and molecular levels. It has become a research tendency to apply theoretical calculations to assist research in the field of air pollution control. Density functional theory (DFT) calculations have been utilized to research the surface structural characteristics of catalysts, explore the mechanisms of catalytic reactions, and design suitable catalysts for environmental catalysis applications. This Review provides an overview of the basic approach of DFT calculations. Specific applications of DFT in environmental catalysis, focusing on oxide catalysts, are extensively explored, including CO oxidation, volatile organic compound (VOC) oxidation, NOx reduction, soot oxidation, and other reactions. Finally, we point out the challenges associated with DFT and potential future prospects in the battle to control air pollution. This Review paves the way for the further design of efficient and stable catalytic materials

Additional file 1 of The A-to-I editing of KPC1 promotes intrahepatic cholangiocarcinoma by attenuating proteasomal processing of NF-κB1 p105 to p50

Additional file 1: Supplementary file 1