To date, most genome-wide association studies (GWAS) and studies of fine-scale population structure have been conducted primarily on Europeans. Han Chinese, the largest ethnic group in the world, composing 20% of the entire global human population, is largely underrepresented in such studies. A well-recognized challenge is the fact that population structure can cause spurious associations in GWAS. In this study, we examined population substructures in a diverse set of over 1700 Han Chinese samples collected from 26 regions across China, each genotyped at approximately 160K single-nucleotide polymorphisms (SNPs). Our results showed that the Han Chinese population is intricately substructured, with the main observed clusters corresponding roughly to northern Han, central Han, and southern Han. However, simulated case-control studies showed that genetic differentiation among these clusters, although very small (F(ST) = 0.0002 approximately 0.0009), is sufficient to lead to an inflated rate of false-positive results even when the sample size is moderate. The top two SNPs with the greatest frequency differences between the northern Han and southern Han clusters (F(ST) > 0.06) were found in the FADS2 gene, which associates with the fatty acid composition in phospholipids, and in the HLA complex P5 gene (HCP5), which associates with HIV infection, psoriasis, and psoriatic arthritis. Ingenuity Pathway Analysis (IPA) showed that most differentiated genes among clusters are involved in cardiac arteriopathy (p < 10(-101)). These signals indicating significant differences among Han Chinese subpopulations should be carefully explained in case they are also detected in association studies, especially when sample sources are diverse.
Poly(vinylcaprolactam) (PVCL)-based biodegradable microgels were prepared for the biomedical application as drug delivery system via precipitation polymerization, where N,N-bis(acryloyl) cystamine (BAC) served as cross-linker, methacrylic acid (MAA) and polyethylene glycol (PEG) methyl ether methacrylate acted as comonomers. The microgels with excellent stability had distinct temperature sensitivity as largely observed in the case of PVCL-based particles and their volume phase transition temperature (VPTT) shifted to higher temperature with increasing MAA content and ambient pH. In the presence of reducing agent glutathione (GSH) or dithiothreitol (DTT), the microgels could be degraded into individual linear polymer chains by the cleavage of the disulfide linkages coming from the cross-linker BAC. The microgels could effectively encapsulate Doxorubicin (DOX) inside and presented stimuli-triggered drug release in acidic or reducing environment. The results of the cytotoxicity assays further demonstrated that the blank microgels were nontoxic to normal cells while DOX-loaded microgels presented efficient antitumor activity to HeLa cells.
In this work, core-shell-shell-structured boronic acid-functionalized magnetic composite microspheres Fe3O4@SiO2@poly (methyl methacrylate-co-4-vinylphenylbornoic acid) (Fe3O4@SiO2@P(MMA-co-VPBA)) with a uniform size and fine morphology were synthesized. Here, Fe3O4 magnetic particles were prepared by a solvothermal reaction, whereas the Fe3O4@SiO2 microspheres with a core-shell structure were obtained by a sol-gel process. 3-(Trimethoxysilyl) propyl methacrylate (MPS)-modified Fe3O4@SiO2 was used as the seed in the emulsion polymerization of MMA and VPBA to form the core-shell-shell-structured magnetic composite microspheres. As the boronic acid groups on the surface of Fe3O4@SiO2@P(MMA-co-VPBA) could form tight yet reversible covalent bonds with the cis-1,2-diols groups of glycoproteins, the magnetic composite microspheres were applied to enrich a standard glycoprotein, horseradish peroxidase (HRP), and the results demonstrated that the composite microspheres have a higher affinity for the glycoproteins in the presence of the nonglycoprotein bovine serum albumin (BSA) over HRP. Additionally, different monomer mole ratios of MMA/VPBA were studied, and the results implied that using MMA as the major monomer could reduce the amount of VPBA with a similar glycoprotein enrichment efficiency but a lower cost.
The development of theranostic systems capable of diagnosis, therapy, and target specificity is considerably significant for accomplishing personalized medicine. Here, a multifunctional rattle-type nanoparticle (MRTN) as an effective biological bimodal imaging and tumor-targeting delivery system is fabricated, and an enhanced loading ability of hydrophobic anticancer drug (paclitaxel) is also realized. The rattle structure with hydrophobic Fe3 O4 as the inner core and mesoporous silica as the shell is obtained by one-step templates removal process, and the size of interstitial hollow space can be easily adjusted. The Fe3 O4 core with hydrophobic poly(tert-butyl acrylate) (PTBA) chains on the surface is not only used as a magnetic resonance imaging (MRI) agent, but contributes to improving hydrophobic drug loading amount. Transferrin (Tf) and a near-infrared fluorescent dye (Cy 7) are successfully modified on the surface of the nanorattle to increase the ability of near-infrared fluorescence (NIRF) imaging and tumor-targeting specificity. In vivo studies show the selective accumulation of MRTN in tumor tissues by Tf-receptor-mediated endocytosis. More importantly, paclitaxel-loaded MRTN shows sustained release character and higher cytotoxicity than the free paclitaxel. This theranostic nanoparticle as an effective MRI/NIRF bimodal imaging probe and drug delivery system shows great potential in cancer diagnosis and therapy.
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