The progress of space science and technology has ushered in a new era for humanity’s exploration of outer space. Recent studies have indicated that the aerospace special environment including microgravity and space radiation poses a significant risk to the health of astronauts, which involves multiple pathophysiological effects on the human body as well on tissues and organs. It has been an important research topic to study the molecular mechanism of body damage and further explore countermeasures against the physiological and pathological changes caused by the space environment. In this study, we used the rat model to study the biological effects of the tissue damage and related molecular pathway under either simulated microgravity or heavy ion radiation or combined stimulation. Our study disclosed that ureaplasma-sensitive amino oxidase (SSAO) upregulation is closely related to the systematic inflammatory response (IL-6, TNF-α) in rats under a simulated aerospace environment. In particular, the space environment leads to significant changes in the level of inflammatory genes in heart tissues, thus altering the expression and activity of SSAO and causing inflammatory responses. The detailed molecular mechanisms have been further validated in the genetic engineering cell line model. Overall, this work clearly shows the biological implication of SSAO upregulation in microgravity and radiation-mediated inflammatory response, providing a scientific basis or potential target for further in-depth investigation of the pathological damage and protection strategy under a space environment.
Autophagy has a significant role in myocardial injury induced by lipopolysaccharide (LPS). Estrogen (E2) has been demonstrated to protect cardiomyocytes against apoptosis; however, it remains to be determined whether it exhibits anti‑autophagic effects. The aim of the present study was to investigate whether estrogen-regulated autophagy attenuates cardiomyocyte injury induced by LPS. The cardiomyocytes of neonatal rats were randomized to the control (Con), LPS and estrogen + LPS groups. The LPS group was treated with 1 µg LPS for 24 h and the estrogen + LPS group was treated with 10‑8 M estrogen 30 min prior to treatment with LPS. Cardiomyocyte autophagy was quantitated by investigating the mRNA and protein level of autophagy‑related genes (Atgs). The mRNA expression of Atg5 and Beclin1 were measured by quantitative polymerase chain reaction and the microtubule‑associated protein light chain 3 (LC3) protein expression was measured by western blot analysis. To demonstrate the cardiomyocyte protection of estrogen, cell vitality and serum lactate dehydrogenase (LDH) levels were measured following LPS treatment. It was identified that LPS induced cardiomyocyte injury, together with the upregulation of Atg5, Beclin1 mRNA and LC3‑II protein. Furthermore, estrogen attenuated the effect of LPS. The present study provides evidence that estrogen has a myocardial protective role against injury induced by LPS by regulating autophagy.
Flow cytometry analysis requires a large amount of isolated, labelled, and purified cells for accurate results. To address the demand for a large quantity of cells prepared in a timely manner, we describe a novel microfluidic trap structure array for on-chip cell labelling, such as intracellular and extracellular labelling, and subsequent washing and release of cells. Each device contains 7×104 trap structures, which made the preparation of large numbers of cells 3×105 possible. The structure has a streamlined shape, which minimizes clogging of cells in capture and release steps. The trap structure arrays are built and tested using leukocytes, with different load flow speeds, incubation times, and release flow speeds. ∼85% of cells are captured independent of the input flow speed. The release efficiency depends on the incubation time, with over ∼80% of captured cells released for up to 20 min incubation, and on-chip labelling and washing with STYO13 are demonstrated. Qualitative models are developed as guidance for designing the proposed trap structure and to explain the increased performance over previous approaches.
Renal ischemia-reperfusion (IR) injury is a therapeutic challenge for surgeons. Sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase that plays a vital role in modulating cellular senescence and aging. In this study, we determined whether SIRT1 upregulation could alleviate renal IR injury and the underlying mechanism.A renal IR model was induced in male C57BL/6 mice. Blood urea nitrogen and serum creatinine were evaluated as markers of kidney function, and renal injury was assessed by pathological examination. The inflammatory milieu was analyzed by real-time RT-PCR and myeloperoxidase immunofluorescence assays. Western blotting was used to quantify SIRT1 protein expression, endoplasmic reticulum stress, and autophagy.SIRT1 was upregulated in renal tissue after IR. Blood analysis and histopathologic examination demonstrated that SIRT1 preserved renal function and reduced renal damage. Further evaluation illustrated that IR induced autophagy and endoplasmic reticulum stress, while SIRT1 upregulation reduced endoplasmic reticulum stress-mediated autophagy levels.SIRT1 upregulation protects the kidney against IR-induced injury by inhibiting endoplasmic reticulum stress-mediated autophagy.
Radiotherapy to treat brain tumors can potentially harm the central nervous system (CNS). The radiation stimulates a series of immune responses in both the CNS as well as peripheral immune system. To date, studies have mostly focused on the changes occurring in the immune response within the CNS. In this study, we investigated the effect of γ-ray-induced CNS injury on the peripheral immune response using a cell co-culture model and a whole-brain irradiation (WBI) rat model. Nerve cells (SH-SY5Y and U87 MG cells) were γ-ray irradiated, then culture media of the irradiated cells (conditioned media) was used to culture immune cells (THP-1 cells or Jurkat cells). Analyses were performed based on the response of immune cells in conditioned media. Sprague-Dawley rats received WBI at different doses, and were fed for one week to one month postirradiation. Spleen and peripheral blood were then isolated and analyzed. We observed that the number of monocytes in peripheral blood, and the level of NK cells and NKT cells in spleen increased after CNS injury. However, the level of T cells in spleen did not change and the level of B cells in the spleen decreased after γ-ray-induced CNS injury. These findings indicate that CNS injury caused by ionizing radiation induces a series of changes in the peripheral immune system.
Objective
To analyze the language function impairment differences between the two steps from the form to sound processing and from the sound to meaning processing for pseudo-words reading in Alzheimer’s disease(AD).
Methods
The pseudo-words reading test consists two parts: pseudo-true words and pseudo-pseudo words. Each part had 10 words. All of the 20 words were presented randomly. Correct reading presents the processing of from form to sound, and correct judging presents the processing of from sound to meaning. Each correct respond get 1 score, otherwise get 0. Each part had a total score of 20.
Results
The pseudo-words reading test was performed to 41 mild AD participants with Mini-mental State Examination (MMSE) average scores of (21.06±2.86), and 135 normal controls with MMSE average scores of (28.08±1.52). The two groups were matched in age, gender and education. For all of the mild AD group and normal control group, there was no significant difference between reading score and judging score in either pseudo-true words or pseudo-pseudo words (P>0.05). Comparing with mild AD group and normal control group, there was no significant difference in reading score in either pseudo-true words or pseudo-pseudo words (P>0.05). For judging score, there was significant difference in pseudo-true words (P 0.05).
Conclusion
Understanding real syllable is impaired in patients with mild AD.
Key words:
Pseudo-words; Reading; Alzheimer’s disease
Chemical-mechanical planarization (CMP) and other manufacturing steps in very deep-submicron VLSI have varying effects on device and interconnect features, depending on the local layout density. To improve manufacturability and performance predictability, area fill features are inserted into the layout to improve uniformity with respect to density criteria. However, the performance impact of area fill insertion is not considered by any fill method in the literature. In this paper, we first review and develop estimates for capacitance and timing overhead of area fill insertions. We then give the first formulations of the Performance Impact Limited Fill (PIL-Fill) problem with the objective of either minimizing total delay impact (MDFC) or maximizing the minimum slack of all nets (MSFC), subject to inserting a given prescribed amount of fill. For the MDFC PIL-Fill problem, we describe three practical solution approaches based on Integer Linear Programming (ILP-I and ILP-II) and the Greedy method. For the MSFC PIL-Fill problem, we describe an iterated greedy method that integrates call to an industry static timing analysis tool. We test our methods on layout testcases obtained from industry. Compared with the normal fill method [3], our ILP-II method for MDFC PIL-Fill problem achieves between 25-% and 90% reduction in terms of total weighted edge delay (roughly, a measure of sum of node slacks) impact while maintaining identical quality of the layout density control; and our iterated greedy method for MSFC PIL-Fill problem also shows significant advantage with respect to the minimum slack of nets on post-fill layout.
Abstract Background The blood–cerebrospinal fluid barrier (BCSFB) comprises the choroid plexus epithelia. It is important for brain development, maintenance, function, and especially for maintaining immune homeostasis in the cerebrospinal fluid (CSF). Although previous studies have shown that the peripheral immune function of the body is impaired upon exposure to microgravity, no studies have reported changes in immune cells and cytokines in the CSF that reflect neuroimmune status. The purpose of this study is to investigate the alterations in cerebrospinal fluid (CSF) immune homeostasis induced by microgravity and its mechanisms. This research is expected to provide basic data for brain protection of astronauts during spaceflight. Methods The proportions of immune cells in the CSF and peripheral blood (PB) of SMG rats were analyzed using flow cytometry. Immune function was evaluated by measuring cytokine concentrations using the Luminex method. The histomorphology and ultrastructure of the choroid plexus epithelia were determined. The concentrations of intercellular junction proteins in choroid plexus epithelial cells, including vascular endothelial‐cadherin (VE‐cadherin), zonula occludens 1 (ZO‐1), Claudin‐1 and occludin, were detected using western blotting and immunofluorescence staining to characterize BCSFB injury. Results We found that SMG caused significant changes in the proportion of CD4 and CD8 T cells in the CSF and a significant increase in the levels of cytokines (GRO/KC, IL‐18, MCP‐1, and RANTES). In the PB, there was a significant decrease in the proportion of T cells and NKT cells and a significant increase in cytokine levels (GRO/KC, IL‐18, MCP‐1, and TNF‐α). Additionally, we observed that the trends in immune markers in the PB and CSF were synchronized within specific SMG durations, suggesting that longer SMG periods (≥21 days) have a more pronounced impact on immune markers. Furthermore, 21d‐SMG resulted in ultrastructural disruption and downregulated expression of intercellular junction proteins in rat choroid plexus epithelial cells. Conclusions We found that SMG disrupts the BCSFB and affects the CSF immune homeostasis. This study provides new insights into the health protection of astronauts during spaceflight.
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