Genetic epidemiology of thalassemia in couples of childbearing age: over 6 years of a thalassemia intervention project.

BACKGROUND: Shenzhen is one of the most populated metropolises in southern China where thalassemia is highly prevalent. The prevention of thalassemia inheritance is an ambition of child-bearing couples. METHODS AND RESULTS: A total of 22,098 peripheral blood samples were collected from 11,049 potentially at-risk couples of childbearing age from Shenzhen. Thalassemia mutations were determined by PCR-based flow-through hybridization. The results identified 45.02% of the participants (9948 out of 22,098) as harboring globin gene mutations, distributed into 18 α-thalassemia alleles detected in 71.48% (7111 out of 9948) and 15 ß-thalassemia alleles detected in 32.68% (3252 out of 9948) of all mutant individuals, among which 415 individuals carried both α- and ß-thalassemia alleles. The most frequent phenotypes for α-globin variations were --SEA/αα (63.37%), -α3.7/αα (18.66%), and -α4.2/αα (7.31%), and those for ß-globin variations were ß41-42/ßN (34.96%), ß654/ßN (28.11%), and ß17/ßN (13.84%). A total of 970 high-risk couples who could possibly give birth to offspring with thalassemia intermedia or major were identified. In addition, the hematological indices were compared among thalassemia genotypes. Significant differences in MCH, MCV, Hb A, and Hb A2 levels among α-thalassemia minor (α+), trait (α0), and intermediate phenotypes (P < 0.05) and between ßE/ßN and the other ß-thalassemia phenotypes (P < 0.05) were found. Moreover, GAP-PCR and next-generation sequencing further identified 42 rare mutations, 13 of which were first reported in the Chinese population. A novel mutation in the ß-globin gene (HBB: c.246 C > A (rs145669504)) was also discovered. CONCLUSIONS: This study presented a comprehensive analysis of thalassemia variations in a population from Shenzhen and may offer valuable insights for thalassemia control and intervention strategies in this area.

The role of the core microorganisms in the microbial interactions in activated sludge.

In order to gain a deeper understanding of the microbial interactions in wastewater treatment plants (WWTPs) in China and clarify the role of the core community in the microbial interactions in activated sludge (AS), this study used a molecular ecological network approach based on random matrix theory to construct co-occurrence networks of the core microorganisms (CoreN), the whole AS community (WholeN) and the microbial communities without the core microorganisms (OtherN), respectively. It was shown that the WholeN had more complex and tighter connections compared with the OtherN, because of its higher total number of nodes, higher average clustering coefficient, and shorter average geodesic distance. The proportions of positive links in the CoreN, WholeN and OtherN were gradually decreased, indicating that the core microorganisms promoted cooperation between AS microorganisms. Moreover, higher robustness after random removal of 50% of the nodes of the WholeN (0.2836 ± 0.0311) was observed than the robustness of the OtherN (0.1152 ± 0.0263). In addition, the vulnerability of OtherN (0.0514) is significantly higher than WholeN (0.0225). Meanwhile, the average ratio of negative/positive cohesion, was significantly decreased when the core microorganisms were removed. These results demonstrated that core community could strengthen the stability of the ecological network in AS. By discerning the key factors affecting ecological network, AS temperature was observed to have a strong correlation with all three networks. Moreover, pollutants in wastewater shown stronger correlations with the CoreN and WholeN, supporting the point that core community play a critical role in pollutant removal in WWTPs to a certain extent.

Thermodiffusion of ions in nanoconfined aqueous electrolytes.

Understanding of thermal effects on ion transport in porous media is very important for environmental applications. The movement of ions along a temperature gradient is named thermophoresis or thermodiffusion. In nanoporous media, where the interaction of ions with solid-liquid interfaces has a significant influence on their migration, the theoretical understanding of thermodiffusion is still incomplete. Herein, we present experimental results for the thermodiffusion of cations in saturated nanoporous silica by the through-diffusion method. Both the experimental data and theoretical analysis indicate that the temperature-induced polarization of surface charges strongly influences ionic transport. Stated simply, the electric field in a liquid electrolyte confined in nanopores changes when the applied temperature gradients are altered, thereby affecting the motion of the nanoconfined ionic species. By applying an external temperature field, the gradient of the surface charge density leads to the charged aqueous species exhibiting strong temperature gradient-dependent electrophoretic mobility. When the thickness of the electrical double layer is comparable to the size of the nanopores, the theory used herein indicates that this kind of nonisothermal ionic mobility is up to one order of magnitude larger than classical thermophoretic mobility. This study improves the understanding of the underlying mechanisms that govern the transport of ions in nanoporous media, which could set the stage for diffusional metamaterials induced by specific thermal fields.

Cation Diffusion in Compacted Clay: A Pore-Scale View.

Cation diffusion through compacted clays is of great interest due to its potential for buffer materials for waste disposal. The importance of the electrokinetic effect on cationic tracer diffusion is investigated by using pore-scale simulations to consider the influence from the electrokinetic properties and topology of clays. It is indicated that the normalized volume charge density has a significant impact on the cationic diffusion. In clays with a large normalized volume charge density, the electrical double layer has the major impact on cationic diffusion. When the ion strength of the pore solution is constant, the flux from the electromigration term can be negligible. However, once an ion strength gradient is added, the electromigration process should be considered carefully due to its non-negligible role to balance the alteration of total flux. The present study could help improve the understanding of the transport mechanism of simple cationic tracers in compacted clays.

Pore-scale study of thermal effects on ion diffusion in clay with inhomogeneous surface charge.

A better understanding of thermal effect on ion transport in compacted clay is of great significance to enhance long-term safety of repository for high-level radioactive waste. It was reported that the macroscopic Soret coefficient in clay is five times larger than that in free water, which was ascribed to the electrokinetic effect. By pore-scale simulations using lattice Boltzmann method, it is found that the Soret effect contributes little to the ionic flux changes in clay because the Soret coefficient is still around the value in free water for different external temperature gradients. The essential cause is the inhomogeneous charged liquid-solid interfaces in clays induced by the temperature gradient. This interface effect plays an important role to the significant changes of inner electrical and concentration fields in clay. Therefore the concentration diffusion and electromigration should be responsible for this phenomenon instead of the thermodiffusion (Soret effect). This study may improve the understanding of ion transport in clays driven by multiphysiochemical effects.

Upscaling scheme for long-term ion diffusion in charged porous media.

Description of long-term (over years) ion diffusion at the pore scale is a huge challenge since the characteristic time of diffusion in a typical representative elementary volume is around microseconds, generally ten orders of magnitude lower than the time we were concerned with. This paper presents a numerical upscaling scheme for ion diffusion with electrical double-layer effects (electrodiffusion) considered in charged porous media. After a scaling analysis for the nondimensional governing equations of ion transport at the pore scale, we identify the conditions for decoupling of electrical effect and diffusion, and therefore are able to choose apposite temporal and spatial scales for corresponding directions of the electrodiffusion process. The upscaling scheme is therefore proposed based on a numerical framework for governing equations using a lattice Boltzmann method. The electrical potential or concentration profiles from steady- or unsteady-state electrodiffusion in the long, straight channel, calculated by this upscaling scheme, are compared with the well-meshed full-sized simulations with good agreement. Furthermore, this scheme is used to predict tracer-ion throughdiffusion and outdiffusion in hardened cement pastes. All numerical results show good agreement with the full-sized simulations or experiment data without any fitting parameters. This upscaling scheme bridges the ion diffusion behaviors in different time scales, and may help to improve the understanding of long-term ion transport mechanisms in charged porous media.

Neocarzinostatin-induced Rad51 nuclear focus formation is cell cycle regulated and aberrant in AT cells.

DNA double-stranded breaks are the most detrimental form of DNA damage and, if not repaired properly, may lead to an accumulation of chromosomal aberrations and eventually tumorigenesis. Proteins of the Rad51/Rad52 epitasis group are crucial for the recombinational repair of DNA double-stranded breaks, whereas the Rad50/NBS1/Mre11 nuclease complex is involved in both the recombinational and the end-joining repair of DNA double-stranded breaks. Herein, we demonstrate that the chemotherapeutic enediyne antibiotic neocarzinostatin induced Rad51, but not NBS1, nuclear focus formation in a cell- cycle-dependent manner. Furthermore, neocarzinostatin-induced Rad51 foci formation revealed a slower kinetic change in AT cells, but not in wild-type or NBS cells. In summary, our results suggest that neocarzinostatin induces Rad51 focus formation through an ATM- and cell-cycle-dependent, but NBS1-independent, pathway.