Long-Term Exposure to High Altitude Affects Voluntary Spatial Attention at Early and Late Processing Stages

The neurocognitive basis of the effect of long-term high altitude exposure on voluntary attention is unclear. Using event related potentials, the high altitude group (people born in low altitude but who had lived at high altitude for 3 years) and the low altitude group (living in low altitude only) were investigated using a voluntary spatial attention discrimination task under high and low perceptual load conditions. The high altitude group responded slower than the low altitude group, while bilateral N1 activity was found only in the high altitude group. The P3 amplitude was smaller in the high altitude compared to the low altitude group only under high perceptual load. These results suggest that long-term exposure to high altitudes causes hemispheric compensation during discrimination processes at early processing stages and reduces attentional resources at late processing stages. In addition, the effect of altitude during the late stage is affected by perceptual load

Human Hepatocytes with Drug Metabolic Function Induced from Fibroblasts by Lineage Reprogramming

SummaryObtaining fully functional cell types is a major challenge for drug discovery and regenerative medicine. Currently, a fundamental solution to this key problem is still lacking. Here, we show that functional human induced hepatocytes (hiHeps) can be generated from fibroblasts by overexpressing the hepatic fate conversion factors HNF1A, HNF4A, and HNF6 along with the maturation factors ATF5, PROX1, and CEBPA. hiHeps express a spectrum of phase I and II drug-metabolizing enzymes and phase III drug transporters. Importantly, the metabolic activities of CYP3A4, CYP1A2, CYP2B6, CYP2C9, and CYP2C19 are comparable between hiHeps and freshly isolated primary human hepatocytes. Transplanted hiHeps repopulate up to 30% of the livers of Tet-uPA/Rag2−/−/γc−/− mice and secrete more than 300 μg/ml human ALBUMIN in vivo. Our data demonstrate that human hepatocytes with drug metabolic function can be generated by lineage reprogramming, thus providing a cell resource for pharmaceutical applications

A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts

Terminally differentiated cells can be generated by lineage reprogramming, which is, however, hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and functionally competent human hepatocytes. Fibroblasts were first induced into human hepatic progenitor-like cells (hHPLCs), which could robustly expand in vitro and efficiently engraft in vivo. Moreover, hHPLCs could be efficiently induced into mature human hepatocytes (hiHeps) in vitro, whose molecular identity highly resembles primary human hepatocytes (PHHs). Most importantly, hiHeps could be generated in large quantity and were functionally competent to replace PHHs for drug-metabolism estimation, toxicity prediction and hepatitis B virus infection modeling. Our results highlight the advantages of the progenitor stage for successful lineage reprogramming. This strategy is promising for generating other mature human cell types by lineage reprogramming.</p

Long-term functional maintenance of primary human hepatocytes in vitro

The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.</p

MEF2C Enhances Dopaminergic Neuron Differentiation of Human Embryonic Stem Cells in a Parkinsonian Rat Model

Human embryonic stem cells (hESCs) can potentially differentiate into any cell type, including dopaminergic neurons to treat Parkinson's disease (PD), but hyperproliferation and tumor formation must be avoided. Accordingly, we use myocyte enhancer factor 2C (MEF2C) as a neurogenic and anti-apoptotic transcription factor to generate neurons from hESC-derived neural stem/progenitor cells (NPCs), thus avoiding hyperproliferation. Here, we report that forced expression of constitutively active MEF2C (MEF2CA) generates significantly greater numbers of neurons with dopaminergic properties in vitro. Conversely, RNAi knockdown of MEF2C in NPCs decreases neuronal differentiation and dendritic length. When we inject MEF2CA-programmed NPCs into 6-hydroxydopamine—lesioned Parkinsonian rats in vivo, the transplanted cells survive well, differentiate into tyrosine hydroxylase-positive neurons, and improve behavioral deficits to a significantly greater degree than non-programmed cells. The enriched generation of dopaminergic neuronal lineages from hESCs by forced expression of MEF2CA in the proper context may prove valuable in cell-based therapy for CNS disorders such as PD

Exploring the Relationship between Green Space in a Neighbourhood and Cardiovascular Health in the Winter City of China: A Study Using a Health Survey for Harbin

A severely cold climate has a significant impact on cardiovascular health, involving temperature, air environment, exercise and diet. Existing studies have revealed that green space, as an important health resource, may play a positive role in promoting cardiovascular health through the air environment and exercise. Studies focusing on the correlation between green space and cardiovascular health are rarely carried out in winter cities. The purpose of this paper is to take a winter city in China as an empirical case to explore the correlation between green space in a neighbourhood and cardiovascular health in a representative sample at the neighbourhood level, combining the results with Urban Residential Area Planning and Design Standards (GB50180-2018) in China and the existing research. The results showed that green space characteristics of a neighbourhood were related to cardiovascular disease and some of its risk factors. In neighbourhoods with a Green Space Ratio lower than 28%, residents had a higher risk of physical inactivity, overweight or obesity, hypertension and stroke. In neighbourhoods with a Green View Index lower than 15%, residents had a higher risk of physical inactivity, overweight/obesity, hypertension, dyslipidemia and stroke. A correlation was found between evergreen tree configuration type and the prevalence of overweight/obesity and hypertension. No correlation was found between the type of sports field and cardiovascular disease and its risk factors, except for hypertension. Residents&rsquo; cardiovascular health scores also showed significant differences among neighbourhoods with different green space characteristics. Intervention efforts may benefit from emphasising the importance of improving the Green Space Ratio and Green View Index effectively in a neighbourhood to reduce the risk of cardiovascular disease

Control Strategy for Vehicle Inductive Wireless Charging Based on Load Adaptive and Frequency Adjustment

Wireless charging system for electric vehicles is a hot research issue in the world today. Since the existing research on wireless charging is mostly forward-looking aimed at low-power appliances like household appliances, while electric vehicles need a high-power, high-efficiency, and strong coupling wireless charging system. In this paper, we have specifically designed a 6.6 KW wireless charging system for electric vehicles and have proposed a control strategy suitable for electric vehicles according to its power charging characteristics and existing common wired charging protocol. Firstly, the influence of the equivalent load and frequency bifurcation on a wireless charging system is analyzed in this paper. Secondly, an adaptive load control strategy matching the characteristics of the battery, and the charging pile is put forward to meet the constant current and constant voltage charging requirements to improve the system efficiency. In addition, the frequency adjustment control strategy is designed to realize the real-time dynamic optimization of the entire system. It utilizes the improved methods of rapid judgment, variable step length matching and frequency splitting recognition, which are not adopted in early related researches. Finally, the results of 6.6 kW test show that the control strategy works perfectly since system response time can be reduced to less than 1 s, and the overall efficiency of the wireless charging system and the grid power supply module can reach up to 91%