The beta-thalassemia is associated with abnormality in beta-globin gene, leading to imbalanced synthesis of alpha-/beta-globin chains. Consequently, the excessive free alpha-globin chains precipitate to the erythrocyte membrane, resulting in hemolytic anemia. We have explored post-transcriptional strategies aiming at alpha-globin reduction and beta-globin enrichment on beta(654) (Hbb(th-4)/Hbb(+)) mouse, carrying a human splicing-deficient beta-globin allele (Hbb(th-4)). Lentiviral vectors of short hairpin RNA (shRNA) targeting alpha-globin and/or antisense RNA facilitating beta-globin correct splicing were microinjected into beta(654) single-cell embryos. Three transgenic strains were generated, as alpha(i)-Hbb(th-4)/Hbb(+)(shRNA), beta(a)-Hbb(th-4)/Hbb(+)(antisense) and alpha(i)beta(a)-Hbb(th-4)/Hbb(+)(both shRNA and antisense). Without notable abnormalities, all the founders and their offsprings showed sustained amelioration of hematologic parameters, ineffective erythropoiesis and extramedullary hematopoiesis. Augmented effects appeared in alpha(i)beta(a)-Hbb(th-4)/Hbb(+), which correlated with a better-balanced alpha-/beta-globin mRNA level. Among the transgenic mice integrated with shRNA and antisense RNA, one homozygous mouse (Hbb(th-4)/Hbb(th-4)) had been viable, and the 3-week survival rate for heterozygotes (Hbb(th-4)/Hbb(+)) was 97%, compared with 45.4% for untreated. Our data have demonstrated the feasibility of techniques for beta-thalassemia therapy by balancing the synthesis of alpha-/beta-globin chains.
Increasing evidence suggests that circulating endothelial progenitor cells, which are a subpopulation of hematopoietic progenitor CD34(+) cells, play a critical role in neovascularization and tissue repair. We have tested the hypothesis that traumatic brain injury (TBI) could mobilize CD34(+) cells to peripheral blood and brain tissue, a process critical for vascular repair, in a rat model of TBI. Male Wistar rats were subjected to controlled fluid percussion. Blood and brain tissue were collected before and after TBI to measure the levels of CD34(+) cells in peripheral blood and to detect their accumulation in the damaged cerebral tissue. Compared with surgery controls, CD34(+) cells significantly increased in the peripheral blood and accumulated in the brain tissue of TBI rats. Immunohistochemistry detected new vessels with incomplete CD34(+) endothelial-like cell lining and an increased number of microvessels in the injured and surrounding tissue. The results demonstrate a close correlation between an increase in circulating CD34(+) cells in response to traumatic injury and angiogenesis in TBI rat brain. They also suggest that transplantation of CD34(+) cells or augmentation of endogenous CD34(+) cells may be a novel therapeutic approach for patients with TBI.
Integrating solar power utilization systems with coal-fired power units, the solar aided coal-fired power generation (SACPG) shows a significant prospect for the large-scale utilization of solar energy and energy saving of thermal power units. The methods and mechanism of system integration were studied. The parabolic trough solar collectors were used to collect solar energy and the integration scheme of SACPG system was determined considering the matching of working fluid flows and energy flows. The thermodynamic characteristics of solar thermal power generation and their effects on the performance of thermal power units were studied, and based on this the integration and optimization model of system structure and parameters were built up. The integration rules and coupling mechanism of SACPG systems were summarized in accordance with simulation results. The economic analysis of this SACPG system showed that the solar LEC of a typical SACPG system, considering CO 2 avoidance, is 0.098 $/kW·h, lower than that of SEGS, 0.14 $/kW·h. solar thermal power generation, coal-fired power plant, system integration, performance analysis Solar thermal power generation is a promising way for large-scale utilization of solar energy in future [1,2] . Since the 1970s oil crisis, researches on this technology have been progressively done in many developed countries such as USA, Spain and Germany and large fruits have been achieved [3] . However, the commercialization of the solar-only thermal power is hampered due to its higher initial investment and lower system performance. In order to solve these problems, it was proposed in America and Europe in 1990s that the cost of solar thermal power generation can be reduced by promoting the system performance. So the solar-hybrid system, the integration of solar power plants with fossil-fired power units, has become a concern [4] . In 1997, IEA and SolarPACES identified this solar-hybrid system as one of the important goals for short-term and mid-term solar thermal utilization in the 21st Century, according to energy sustainable development roadmap [5,6] .
Fasting is known to have many health benefits such as prolonging lifespan and suppression of tumorigenesis. [1][2][3] In the present study, we systematically evaluated the effects of water-only fasting on metabolic-syndrome and age-related risk markers in 45 normal-weight individuals.As shown, a 4.59 kg reduction in body weight, 9.85 cm reduction in waist circumference, and 1.64 kg/m 2 reduction in body mass index (BMI) were observed during a 5-day water-only fast (Figures 1A-1C). After refeeding for 1 month (day 38), body weight, waist circumference, and BMI were still lower than the baseline level . Blood pressure (BP) significantly declined during water-only fasting with diastolic BP declining more than systolic BP and gradually both increased to the baseline level by 98 d (Figures 1D and 1E). Considering many fasting studies showed diastolic BP reduction did not exceed systolic BP reduction, future studies are needed on water-only fasting and BP reduction. Insulin dropped approximately 2.8-fold lower than the baseline level during water-only fasting (Figure 1F). Insulin-like growth factor 1 (IGF-1) decreased by a total of 26% during water-only fasting and decreased more in females than males (Figure 1G and Table S1). Future studies will address the sexual disparity of IGF-1 reduction during water-only fasting. The number of pan T cells, CD4+T cells, CD8+T cells, and B cells decreased during water-only fasting . In contrast, the frequency of Treg cells significantly increased during fasting and still exceeded the baseline level 3 months after refeeding (Figures 1L and 1M). This is an important benefit, since Treg cells have anti-inflammation effects. 4 With regard to thyroid hormones, T4 increased rapidly during fasting, whereas T3 and TSH decreased (Figures 1N-1P). The decreased level of T3 during water-only fasting is of particularly importance since a low T3 level, without impairing thyroid function, is strongly associated with longevity. 5,6 The present studyThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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