Accurate age estimation from blood samples of Han Chinese individuals using eight high-performance age-related CpG sites.

Age-related CpG sites (AR-CpGs) are currently the most promising biomarkers for forensic age estimation. In our previous studies, we first validated the age correlation of seven reported AR-CpGs in blood samples of Chinese Han population. Subsequently, we screened some good age predictors from blood samples of Chinese Han population, and built pyrosequencing-based age prediction models. However, it is still important to select a set of high-performance AR-CpGs in a specific racial group and establish a simple and efficient method for accurate age estimation for forensic purpose. In this study, eight AR-CpGs, namely chr6: 11,044,628 (ELOVL2), cg06639320 (FHL2), chr1: 207,823,723 (C1orf132), cg19283806 (CCDC102B), cg14361627 (KLF14), cg17740900 (SYNE2), cg07553761 (TRIM59), and cg26947034, were selected based on our previous studies, and a multiplex methylation SNaPshot assay was developed to investigate DNA methylation levels at these AR-CpGs in 529 blood samples (aged 2-82 years) from Han Chinese population. All selected CpG sites showed strong age correlation with the correlation coefficient (r) from 0.8363 to 0.9251. Multiple linear regression (MLR) and support vector regression (SVR) age prediction models were simultaneously established to fit change characteristics of DNA methylation levels of eight AR-CpGs with the age in 374 donors' blood samples. The MLR model enabled age prediction with R2 = 0.923, mean absolute error (MAE) = 3.52, while the SVR model enabled age prediction with R2 = 0.935, MAE = 2.88. One hundred fifty-five independent samples were used as a validation set to test the two models' performance, and the prediction MAE for the validation set was 3.71 and 3.34 for the MLR and SVR models, respectively. For the MLR and SVR models, the correct prediction rate at ± 5 years reached a high level of 79.35% and 83.23%, respectively. In general, these statistical parameters indicated that the SVR model outperformed the MLR model in age prediction of the Han Chinese population. In addition, our method provides sufficient sensitivity in forensic applications and allows for 100% efficiency when examining bloodstains kept in room conditions for up to 43 days. These results indicate that our multiplex methylation SNaPshot assay is a reliable, effective, and accurate method for age prediction in blood samples from the Chinese Han population.

Mutation analysis of 28 autosomal short tandem repeats in the Chinese Han population.

Short tandem repeats (STRs) have been extensively used in forensic genetics. However, according to previous studies, the mutation rates of STRs are relatively high and are affected by many factors. Therefore, it is important to analyze STR mutations and determine the influence of underlying factors on STR mutation rates. Mutation rates of 28 autosomal STRs were determined from 8708 paternity testing cases in the Chinese Han population, and the relationships between STR mutation rates and population, sex, age, allele length and heterozygosity were investigated. A total of 279 mutations were observed at 27 loci in a total of 233,530 meiosis cases, including 273 (97.8%) one-step, 5 (1.8%) two-step and 1 (0.4%) three-step mutations. The overall average mutation rate was 1.19 × 10-3 (95% CI 1.06 × 10-3 - 1.34 × 10-3) ranging from 0 (TPOX) to 2.79 × 10-3 (D13S325). Mutation rate comparisons revealed statistically significant differences at several STRs among populations. Paternal mutations occurred more frequently than maternal mutations, at a ratio of 6.04:1, and the mutation rate tended to increase with paternal age. Moreover, our study revealed a bias towards contraction mutations for long alleles and expansion mutations for short alleles. No obvious bias was observed in the overall mutation direction. In addition, STR loci with higher expected heterozygosity (Hexp) tended to have higher mutation rates. This work revealed the relationships between STR mutation rates and several influencing factors, providing useful data and information for further research on STR mutations in forensic genetics.

Genetic analysis of 32 InDels in four ethnic minorities from Chinese Xinjiang.

The present study used the previously constructed 32-plex InDels panel to investigated the genetic diversity of four ethnic minorities (Hui, Mongol, Uygur and Kazakh) from Xinjiang, and analyzed the genetic relationships between the four populations and 27 reference populations. No significant deviations were observed from the Hardy-Weinberg equilibrium (HWE) at the 32 InDels for each population. The average observed heterozygosity (Hexp), average polymorphic information content (PIC), combined power of discrimination (CPD) and cumulative probability of exclusion (CPE) for the 32 InDels were all higher than the Qiagen Investigator DIPplex kit in the four populations from Xinjiang. The CPD ranged from 0.999999999999903 (Kazakh) to 0.999999999999952 (Hui) and CPE ranged from 0.9971 (Uygur) to 0.9985 (Hui), which indicated that the 32 InDels were capable for individual identification and could be a supplementary tool in paternity test for these populations. Population genetic analysis by the method of analysis of molecular variance (AMOVA), FST, phylogenetic tree, TreeMix-based topology, multi-dimensional scale analysis (MDS), principal components analysis (PCA) and STRUCTURE analysis showed that Xinjiang Hui population has a close relationship with East Asians (EAS), especially Chinese Han, and the populations of Xinjiang Mongol, Uygur and Kazakh showed mixed ancestral components related to EAS and Europeans (EUR).

Computational study on optoelectronic and charge transport properties of diketopyrrolopyrrole-based A-D-A-D-A structure molecules for organic solar cells.

Eight novel diketopyrrolopyrrole (DPP)-based A-D-A-D-A structure molecules were designed for organic solar cells (OSCs) applications. In these molecules, the electron-deficient DPP and dicyanovinyl groups were used as the acceptor groups and different planar electron-rich groups were employed as the donor π-bridges. Applying the B3LYP/6-31G (d,p) and TD-B3LYP/6-31G (d,p) methods, the optoelectronic and charge transport properties were investigated. It turned out that the different π-bridges can tune effectively the frontier molecular orbital energy levels, band gap, and absorption spectra. Furthermore, the different π-bridges also affect the charge transport properties of the designed molecules. Our results suggest that the investigated molecules can serve as donor materials. Additionally, some investigated molecules can also be used as hole and/or electron transport materials for OSCs. Graphical abstract A series of novel A-D-A-D-A molecules are investigated systematically. The optical and electronic properties can be tuned effectively by the π-bridges. All derivatives can be used as donor materials for OSCs. Some designed molecules can be used as hole and/or electron transport materials. The different π-bridges do not significantly affect the stability of the molecules.

Improving optoelectronic and charge transport properties of D-π-D type diketopyrrolopyrrole-pyrene derivatives as multifunctional materials for organic solar cell applications.

A series of novel diketopyrrolopyrrole-pyrene-based molecules were designed for small molecule based organic solar cell (SMOSC) applications. Their electronic and charge transfer properties were investigated by applying the PBE0/6-31G(d,p) method. The absorption spectra were simulated using the TD-PBE0/6-31G(d,p) method. The results showed that the frontier molecular orbital (FMO) energy levels, reorganization energy, the energetic driving force, and absorption spectra can be tuned by the introduction of different aromatic heterocyclic groups to the side of diketopyrrolopyrrole fragments' backbones. Additionally, the designed molecules possess suitable FMOs to match those of typical acceptors PC61BM and PC71BM. Meanwhile, the designed molecules can act as good ambipolar charge transport materials in SMOSC applications. Meanwhile, the electron and hole reorganization energies of the designed molecules are smaller than those of the typical electron and hole transport materials, respectively. Moreover, the differences between electron and hole reorganization energies do not exceed 0.046 eV. Our results suggest that the designed molecules can act as promising candidates for donor and ambipolar charge transport materials in SMOSC applications.

Application of low-tube current with iterative model reconstruction on Philips Brilliance iCT Elite FHD in the accuracy of spinal QCT using a European spine phantom.

BACKGROUND: To investigate the repeatability and accuracy of quantitative CT (QCT) measurement of bone mineral density (BMD) by low-mAs using iterative model reconstruction (IMR) technique based on phantom model. METHODS: European spine phantom (ESP) was selected and measured on the Philips Brilliance iCT Elite FHD machine for 10 times. Data were transmitted to the QCT PRO workstation to measure BMD (mg/cm3) of the ESP (L1, L2, L3). Scanning method: the voltage of X-ray tube is 120 kV, the electric current of X-ray tube output in five respective groups A-E were: 20, 30, 40, 50 and 60 mAs. Reconstruction: all data were reconstructed using filtered back projection (FBP), IR levels of hybrid iterative reconstruction (iDose4, levels 1, 2, 3, 4, 5, 6 were used) and IMR (levels 1, 2, 3 were used). ROIs were placed in the middle of L1, L2 and L3 spine phantom in each group. CT values, noise and contrast-to-noise ratio (CNR) were measured and calculated. One-way analysis of variance (ANOVA) was used to compare BMD values of different mAs and different IMR. RESULTS: Radiation dose [volume CT dose index (CTDIvol) and dose length product (DLP)] was positively correlated with tube current. In L1 with low BMD, different mAs in FBP showed P<0.05, indicating statistically significant BMD in ESP. In other iterative algorithms, different mAs under same iterative algorithms showed P>0.05, indicating no difference in BMD. And P>0.05 was observed among BMD of spine phantom in L1, L2 and L3 under same mAs joined with varied iterative reconstruction. The BMD in L1 varied greatly during FBP reconstruction, and less variation was observed in reconstruction of IMR [1] and IMR [2]. The BMD of L2 changed more during FBP reconstruction, where less was observed in IMR [2]. The BMD of L3 varied greatly during FBP reconstruction, and was less varied in all levels of iDose4 and reconstruction of IMR [2]. In addition, along with continuous mAs incensement, the CNRs in various algorithms continued to increase. Among them, CNR with the FBP algorithm is the lowest, and CNR of the IMR [3] algorithm is the highest. CONCLUSIONS: Repeated measurements of BMD with QCT in the ESP multicenter showed that BMD changes in L1-L3 are the least varied at IMR [2] algorithm. It is recommended to scan at 120 kV with 20 mAs combined with IMR [2] algorithm. In this way, the BMD of spine by QCT could be accurately measured, while radiation dosage significantly reduced and imaging quality improved at the same time.

An ultrasmall and metabolizable PEGylated NaGdF4:Dy nanoprobe for high-performance T(1)/T(2)-weighted MR and CT multimodal imaging.

Lanthanide-based multimodal probes with high sensitivity, simple synthesis strategy, and good biocompatibility promise new applications for clinical diagnosis. However, today's challenge is not only to develop high-performance multimodal probes for more accurate and reliable diagnosis, but also to understand the fate of these probes in vivo. In this context, a novel PEGylated Dy-doped NaGdF4 nanoprobe (PEG-NaGdF4:Dy) was designed and fabricated as a T1/T2-weighted MRI/CT imaging agent. This nanoprobe has a distinct longitudinal relaxivity (r1 = 5.17 mM(-1) s(-1)), relatively high transverse relaxivity (r2 = 10.64 mM(-1) s(-1)), and exhibits strong X-ray attenuation properties (44.70 HU L g(-1)) in vitro. Furthermore, T1/T2-weighted MRI/CT imaging in vivo confirmed that this PEG-NaGdF4:Dy nanoprobe could lead to a significant contrast enhancement effect on liver, spleen and kidney at 24 h post injection. The MTT assay, histological analysis, and biodistribution investigation demonstrated that this multifunctional nanoprobe possessed relatively low cytotoxicity, negligible tissue damage and could be completely excreted out of the body of mice as time prolonged. Therefore, the present PEG-NaGdF4:Dy nanoprobe has the potential for the development of multifunctional T1/T2-weighted MRI/CT imaging to provide more comprehensive and accurate diagnosis information.

Ultrasmall biomolecule-anchored hybrid GdVO4 nanophosphors as a metabolizable multimodal bioimaging contrast agent.

Multimodal molecular imaging has recently attracted much attention on disease diagnostics by taking advantage of individual imaging modalities. Herein, we have demonstrated a new paradigm for multimodal bioimaging based on amino acids-anchored ultrasmall lanthanide-doped GdVO4 nanoprobes. On the merit of special metal-cation complexation and abundant functional groups, these amino acids-anchored nanoprobes showed high colloidal stability and excellent dispersibility. Additionally, due to typical paramagnetic behaviour, high X-ray mass absorption coefficient and strong fluorescence, these nanoprobes would provide a unique opportunity to develop multifunctional probes for MRI, CT and luminescence imaging. More importantly, the small size and biomolecular coatings endow the nanoprobes with effective metabolisability and high biocompatibility. With the superior stability, high biocompatibility, effective metabolisability and excellent contrast performance, amino acids-capped GdVO4:Eu(3+) nanocastings are a promising candidate as multimodal contrast agents and would bring more opportunities for biological and medical applications with further modifications.

Facile fabrication of single-phase multifunctional BaGdF5 nanospheres as drug carriers.

Multifunctional BaGdF5 nanospheres with mesoporous, luminescent, and magnetic properties have been successfully synthesized with the assistance of trisodium citrate by a hydrothermal method. The mesoporous structure is revealed by scanning electron microscope and transmission electron microscope images as well as N2 adsorption-desorption isotherm. The as-synthesized BaGdF5 nanospheres exhibit an intense broad bluish emission (centered at 450 nm) under the excitation of 390 nm, which might originate from the CO2·(-) radical-related defect produced by Cit(3-) groups. It is also shown that these BaGdF5 nanospheres brightened the T1-weighted images, suggesting that they could act as T1 contrast agents for magnetic resonance imaging. Using metformin hydrochloride as the model drug, the luminescent porous spheres show good drug storage/release capability. Furthermore, the emission intensity varies as a function of the cumulative drug release, making the drug-carrying system easily trackable and monitorable by detecting the luminescence intensity. Additionally, the paramagnetic property, originating from the unpaired electrons of Gd(3+) ions, opens the possibility of directing the magnetic targeted carrier to the pathological site by magnetic field gradient.

In vivo near-infrared photothermal therapy and computed tomography imaging of cancer cells using novel tungsten-based theranostic probe.

Photothermal therapy, as a physical therapeutic technique to kill cancer, has generated a great deal of interest. Photothermal agents hence play a critical role in this modern therapy. We report the use of transition metal oxides as photothermal agents based on PEGylated WO3-x nanoparticles. The well-prepared nanoparticles presented effective results during photothermal therapy both in vitro and in vivo by using near-IR laser irradiation (980 nm, 0.5 W cm(-2)). The tumor cells were effectively damaged using low power density during a short irradiation time without destroying healthy tissues. In vitro results of photothermal therapy with PEGylated WO3-x nanoparticles proved to be effective on 4T1 murine breast cancer cells via a confocal microscopy method and MTT assay. In vivo results were further confirmed by hematoxylin and eosin (H & E) histological staining. Additionally, PEGylated WO3-x nanoparticles were shown to be effective as a CT imaging contrast agent on a tumor-bearing mouse model. Our results suggest that this generation of PEGylated WO3-x nanoparticles can potentially be used in oncological CT imaging and photothermal therapy.

Anti-biofouling polymer-decorated lutetium-based nanoparticulate contrast agents for in vivo high-resolution trimodal imaging.

Nanomaterials have gained considerable attention and interest in the development of novel and high-resolution contrast agents for medical diagnosis and prognosis in clinic. A classical urea-based homogeneous precipitation route that combines the merits of in situ thermal decomposition and surface modification is introduced to construct polyethylene glycol molecule (PEG)-decorated hybrid lutetium oxide nanoparticles (PEG-UCNPs). By utilizing the admirable optical and magnetic properties of the yielded PEG-UCNPs, in vivo up-conversion luminescence and T1 -enhanced magnetic resonance imaging of small animals are conducted, revealing obvious signals after subcutaneous and intravenous injection, respectively. Due to the strong X-ray absorption and high atomic number of lanthanide elements, X-ray computed-tomography imaging based on PEG-UCNPs is then designed and carried out, achieving excellent imaging outcome in animal experiments. This is the first example of the usage of hybrid lutetium oxide nanoparticles as effective nanoprobes. Furthermore, biodistribution, clearance route, as well as long-term toxicity are investigated in detail after intravenous injection in a murine model, indicating the overall safety of PEG-UCNPs. Compared with previous lanthanide fluorides, our nanoprobes exhibit more advantages, such as facile construction process and nearly total excretion from the animal body within a month. Taken together, these results promise the use of PEG-UCNPs as a safe and efficient nanoparticulate contrast agent for potential application in multimodal imaging.