Search

Feng Pan,1,* Ai-Ting Lu,1,2,* Xiaowei Mao,1,* Yefeng Chen,3 Yizhuo Zhao,1 Baohui Han1 1Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Nursing, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Respiratory Medicine, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang, 312000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baohui Han; Yizhuo ZhaoDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaEmail 18930858216@163.com; zhyz920916@126.comBackground: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a valuable tool for diagnosing pulmonary disease due to its efficiency and safety. We retrospectively analyzed patients with mediastinal masses who underwent diagnostic EBUS-TBNA at Shanghai Chest Hospital, and evaluated the clinical accuracy of EBUS-TBNA in the diagnosis mediastinal masses.Method: From 2009 and 2014, patients who received EBUS-TBNA to diagnose a isolated mediastinal mass were enrolled. Clinical follow-up was performed to ascertain the patient’s final diagnosis.Results: Forty-six patients were enrolled in this study. Thirty-seven were diagnosed with an oncologic disease, 3 were diagnosed with a mediastinal infection, and 2 were found to have a mediastinal goiter. The overall sensitivity, specificity, positive predictive value, negative predictive value, diagnostic yield was 63.6%, 100%, 100%, 42.9%, and 71.4%, respectively.Conclusion: EBUS-TBNA is a safe and effective means of diagnosing mediastinal masses.Keywords: EBUS-TBNA, mediastinum, diagnosis

Cerebral amyloid angiopathy (CAA) is a vascular lesion associated with Alzheimer's disease (AD) present in up to 95% of AD patients and produces MRI-detectable microbleeds in many of these patients. It is possible that CAA-related microbleeding is a source of pathological iron in the AD brain. Because the homeostasis of copper, iron, and zinc are so intimately linked, we determined whether CAA contributes to changes in the brain levels of these metals. We obtained brain tissue from AD patients with severe CAA to compare to AD patients without evidence of vascular amyloid-β. Patients with severe CAA had significantly higher non-heme iron levels. Histologically, iron was deposited in the walls of large CAA-affected vessels. Zinc levels were significantly elevated in grey matter in both the CAA and non-CAA AD tissue, but no vascular staining was noted in CAA cases. Copper levels were decreased in both CAA and non-CAA AD tissues and copper was found to be prominently deposited on the vasculature in CAA. Together, these findings demonstrate that CAA is a significant variable affecting transition metals in AD. [ABSTRACT FROM AUTHOR]

Prolonged spaceflight can induce physiologic and pathologic abnormalities in the central nervous system (CNS). Our knowledge of the adaptive and/or detrimental effects of spaceflight on the structure and function of the nervous system is limited. Substantial effort has been devoted to identifying and developing reliable indicators to characterize and predict CNS injury and dysfunction associated with prolonged exposure to major components of the space environment including microgravity, physiological/psychological stress, and radiation from galactic cosmic rays (GCR) and solar particle events (SPEs) outside of low earth orbit (LEO). The blood-brain barrier (BBB) is a semi-permeable membrane that is essential to maintain homeostasis of the brain microenvironment. Oxidative stress or other environmental stressors may disrupt BBB integrity and increase permeability leading to immune cell infiltration and undesirable neuroinflammation. The focus of this review article is on BBB damage associated with spaceflight and space radiation in rodent and human studies. We will highlight potential biomarkers for this damage, including site-specific and circulating neuroinflammatory factors, BBB structural and brain parenchyma proteins, and neuroimaging tools for BBB damage evaluation. These knowledge will help to understand the risks associated with space travel and are also critical for novel countermeasure development to mitigate the space flight risk to astronaut performances., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Committee on Space Research (COSPAR). Published by Elsevier B.V. All rights reserved.)

The number of long duration human spaceflights has increased substantially over the past 15 years, leading to the discovery of numerous effects on the CNS. Microgravity results in headward fluid shifts, ventricular expansion, an upward shift of the brain within the skull, and remodelling of grey and white matter. The fluid changes are correlated with changes to perivascular space and spaceflight associated neuro-ocular syndrome. Microgravity alters the vestibular processing of head tilt and results in reduced tactile and proprioceptive inputs during spaceflight. Sensory adaptation is reflected in postflight effects, evident as transient sensorimotor impairment. Another major concern is that galactic cosmic radiation, which spacefarers will be exposed to when going beyond the magnetosphere around Earth, might have a negative effect on CNS function. Research with rodents points to the potential disruptive effects of space radiation on blood-brain barrier integrity and brain structures. More work is needed to understand and mitigate these effects on the CNS before humans travel to Mars, as the flight durations will be longer than anyone has previously experienced., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: To compare the effects of 2 Hz continuous wave and 2 Hz/100 Hz dilatational wave setting in electroacupuncture(EA) on ovulation frequency, hormone levels, body fat parameters, quality of life and depression-anxiety level in polycystic ovary syndrome (PCOS) patients with abdominal obesity., Methods: PCOS patients with abdominal obesity were randomly divided into low-frequency group ( n =29) and dilatational wave group ( n =29). Patients in both groups were treated with "Tongtiaodaimai" (regulating Dai Meridian) acupuncture therapy, and EA was applied to bilateral Daimai (GB26), Tianshu (ST25), Shenshu (BL23) and Ciliao (BL32). The low-frequency group received EA using a continuous wave at a frequency of 2 Hz, while the dilatational wave group received dilatational wave at a frequency of 2 Hz/100 Hz. Both groups received treatment for 30 min each time, 3 times per week for 12 consecutive weeks. Ovulation frequency was calculated according to the ovulation cycle. The contents of serum anti-Mullerian hormone (AMH) and sex hormone binding globulin (SHBG) were detected with electrochemiluminescence method. Body weight (BW) and waist circumference (WC) were measured, and body mass index (BMI) and waist-height ratio (WHtR) were calculated. PCOS questionnaire (Chi-PCOSQ), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were evaluated., Results: Compared with before treatment, both the low-frequency group and the dilatational wave group showed an increase in ovulation frequency ( P <0.01, P <0.05), and a decrease in BW, BMI, WC, WHtR, and SDS score ( P <0.01, P <0.05)；the dilatational wave group showed decreased serum AMH contents ( P <0.05) and increased serum SHBG contents ( P <0.05), the scores related to acne, fatigue, and dysmenorrhea in the Chi-PCOSQ increased ( P <0.01, P <0.05). Compared with the low-frequency group, the dilatational wave group showed a reduction ( P <0.05) in WC after treatment., Conclusions: 2 Hz/100 Hz dilatational wave EA is equally effective as 2 Hz low-frequency EA in improving ovulation frequency. In terms of reducing WC in abdominal obesity type PCOS patients, 2 Hz/100 Hz dilatational wave EA is superior to 2 Hz low-frequency EA. 2 Hz/100 Hz dilatational wave EA can decrease serum AMH, increase serum SHBG, and improve symptoms of acne, fatigue, and dysmenorrhea.

Biomarkers, ranging from molecules to behavior, can be used to identify thresholds beyond which performance of mission tasks may be compromised and could potentially trigger the activation of countermeasures. Identification of homologous brain regions and/or neural circuits related to operational performance may allow for translational studies between species. Three discussion groups were directed to use operationally relevant performance tasks as a driver when identifying biomarkers and brain regions or circuits for selected constructs. Here we summarize small-group discussions in tables of circuits and biomarkers categorized by (a) sensorimotor, (b) behavioral medicine and (c) integrated approaches (e.g., physiological responses). In total, hundreds of biomarkers have been identified and are summarized herein by the respective group leads. We hope the meeting proceedings become a rich resource for NASA's Human Research Program (HRP) and the community of researchers.

Botrytis cinerea causes gray mold in many fruit and vegetable crops. We previously found that Seselin (SL) displayed antifungal activity against B. cinerea (EC 50 = 6.1 μg·mL -1 ), and this study investigated the effects of Ca 2+ and the Ca 2+ /CN signaling pathway on its antifungal activity against B. cinerea . The results indicated that exogenous Ca 2+ , Cyclosporine A, and Verapamil reduced the sensitivity of SL against B. cinerea ; SL significantly reduced the intracellular Ca 2+ concentration in the hyphae; the sensitivity of strains Δ bcCCH 1 and Δ bcMID 1 to SL were significantly increased; and the expressions of CCH 1, MID 1, CNA , PMC 1, and PMR 1 genes of the Ca 2+ /CN signaling pathway were significantly downregulated by SL treatment. Hence, SL is a potential compound for developing fungicides against B. cinerea . SL dramatically reduces intracellular Ca 2+ concentration and disturbs Ca 2+ homeostasis, leading to cell death. The Ca 2+ /CN signaling pathway plays an important role in the antifungal activity of SL against B. cinerea .

Purpose: Astronauts on missions beyond low Earth orbit will be exposed to galactic cosmic radiation, and there is concern about potential adverse cardiovascular effects. Most of the research to identify cardiovascular risk of space radiation has been performed in rodent models. To aid in the translation of research results to humans, the current study identified long-term effects of high-energy charged particle irradiation on cardiovascular function and structure in a larger non-rodent animal model., Materials and Methods: At the age of 12 months, male New Zealand white rabbits were exposed to whole-body protons (250 MeV) or oxygen ions ( 16 O, 600 MeV/n) at a dose of 0 or 0.5 Gy and were followed for 12 months after irradiation. Ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 10- and 12-months post-irradiation. At 12 months after irradiation, blood cell counts and blood chemistry values were assessed, and cardiac tissue and aorta were collected for histological as well as molecular and biochemical analyses. Plasma was used for metabolomic analysis and to quantify common markers of cardiac injury., Results: A small but significant decrease in the percentage of circulating lymphocytes and an increase in neutrophil percentage was seen 12 months after 0.5 Gy protons, while 16 O exposure resulted in an increase in monocyte percentage. Markers of cardiac injury, cardiac troponin I (cTnI) and N-Terminal pro-B-type Natriuretic Peptide were modestly increased in the proton group, and cTnI was also increased after 16 O. On the other hand, metabolomics on plasma at 12 months revealed no changes. Both types of irradiation demonstrated alterations in cardiac mitochondrial morphology and an increase in left ventricular protein levels of inflammatory cell marker CD68. However, changes in cardiac function were only mild., Conclusion: Low dose charged particle irradiation caused mild long-term changes in inflammatory markers, cardiac function, and structure in the rabbit heart, in line with previous studies in mouse and rat models., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2023 The Committee on Space Research (COSPAR). Published by Elsevier B.V. All rights reserved.)

Background: Botrytis cinerea causes grey mould and is one of the most destructive fungal pathogens affecting important fruit and vegetable crops. In preliminary studies, we found that disenecioyl-cis-khellactone (DK) had strong antifungal activity against several fungi species including B. cinerea [half maximal effective concentration (EC 50 ) = 11.0 μg mL -1 ]. In this study, we aimed to further evaluate the antifungal activity of DK against B. cinerea and determine the role of calcium ion/calcineurin (Ca 2+ /CN) signalling pathway on its antifungal effect., Results: DK was effective against B. cinerea in both in vitro and in vivo assays. Exogenous Ca 2+ reduced the antifungal activity of DK. The combination of DK and cyclosporine A (CsA) did not exhibit an additive effect against B. cinerea. In contrast to CsA, DK reduced the intracellular Ca 2+ concentration in B. cinerea. DK bound to calcineurin A (cnA) and up-regulated the expression of PMC1 and PMR1 genes. Moreover, DK sensitivity of △bccnA significantly decreased compared with that of Bc05.10 strain., Conclusion: DK is a promising lead compound for developing fungicides against B. cinerea. The Ca 2+ /CN signalling pathway plays a crucial role in the DK antifungal activity, and cnA is one of the targets of DK against B. cinerea. DK directly reacts with cnA, which up-regulates the transcription of Ca 2+ /CN-dependent target genes PMC1 and PMR1, decreasing the intracellular Ca 2+ concentration and disturbing the intracellular Ca 2+ balance, leading to cell death. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

The space environment includes unique hazards like radiation and microgravity which can adversely affect biological systems. We assessed a multi-omics NASA GeneLab dataset where mice were hindlimb unloaded and/or gamma irradiated for 21 days followed by retinal analysis at 7 days, 1 month or 4 months post-exposure. We compared time-matched epigenomic and transcriptomic retinal profiles resulting in a total of 4178 differentially methylated loci or regions, and 457 differentially expressed genes. Highest correlation in methylation difference was seen across different conditions at the same time point. Nucleotide metabolism biological processes were enriched in all groups with activation at 1 month and suppression at 7 days and 4 months. Genes and processes related to Notch and Wnt signaling showed alterations 4 months post-exposure. A total of 23 genes showed significant changes in methylation and expression compared to unexposed controls, including genes involved in retinal function and inflammatory response. This multi-omics analysis interrogates the epigenomic and transcriptomic impacts of radiation and hindlimb unloading on the retina in isolation and in combination and highlights important molecular mechanisms at different post-exposure stages., (© 2022. The Author(s).)

It has been proposed that neuroinflammatory response plays an important role in the neurovascular remodeling in the brain after stress. The goal of the present study was to characterize changes in the gene expression profiles associated with neuroinflammation, neuronal function, metabolism and stress in mouse brain tissue. Ten-week old male C57BL/6 mice were launched to the International Space Station (ISS) on SpaceX-12 for a 35-day mission. Within 38 ± 4 h of splashdown, mice were returned to Earth alive. Brain tissues were collected for analysis. A novel digital color-coded barcode counting technology (NanoString TM ) was used to evaluate gene expression profiles in the spaceflight mouse brain. A set of 54 differently expressed genes (p < 0.05) significantly segregates the habitat ground control (GC) group from flight (FLT) group. Many pathways associated with cellular stress, inflammation, apoptosis, and metabolism were significantly altered by flight conditions. A decrease in the expression of genes important for oligodendrocyte differentiation and myelin sheath maintenance was observed. Moreover, mRNA expression of many genes related to anti-viral signaling, reactive oxygen species (ROS) generation, and bacterial immune response were significantly downregulated. Here we report that significantly altered immune reactions may be closely associated with spaceflight-induced stress responses and have an impact on the neuronal function., (© 2022. The Author(s).)

Alpha(α)Klotho, a soluble transmembrane protein, facilitates calcium-phosphorus homeostasis through feedback between bone and kidney and is a potential systemic biomarker for bone-kidney health during spaceflight. We determined if: (1) plasma αKlotho was reduced after both spaceflight aboard the ISS and hindlimb unloading (HU); and (2) deficiency could be reversed with exercise. Both spaceflight and HU lowered circulating plasma αKlotho: plasma αKlotho recovered with exercise after HU., (© 2022. The Author(s).)

This study aims to summarize the research hotspots of Hedysari Radix and predict the research trend with bibliometric methods, which is expected to serve as a reference for future research. CiteSpace V 5.8.R2 was employed for visualization of the number, authors, author affiliations, journals, funds, and keywords of the Chinese and English articles on Hedysari Radix in China National Knowledge Infrastructure(CNKI) and Web of Science(WOS) from 2001 to 2021. A total of 693 Chinese articles and 167 English articles were finally included. According to the knowledge map, most of the articles were from China and the authors from China had a close cooperation with the related institutions in the United States and Australia. Gansu University of Chinese Medicine(288) and Lanzhou University(151) respectively came out on top of the author affiliations in the number of Chinese and English articles. The journals were mainly about Chinese medicine, mainly including Chinese Journal of Information on Traditional Chinese Medicine and Evidence-based Complementary and Alternative Medicine. Papers(191 in Chinese and 60 in English) funded by National Natural Science Foundation of China were the most. Keyword analysis suggested that the main research directions were pharmacological action and mechanism, component analysis, content determination, and industrialization of medicinal materials of Hedysari Radix and that the research hotspots were the prevention and treatment of diabetes and its complications, tumors, myocardial injury, liver fibrosis and other diseases with active components such as polysaccharides, ultrafiltrate, formononetin, and calycosin. The targets, signaling pathways, and genes related to the anti-tumor, heart protection, prevention and treatment of diabetes and its complications, and regulation of immunity should be further studied.

A LC-Q-Orbitrap HRMS analytical method for both qualitative screening and quantitative determination of 90 synthetic dyes including ten groups of isomers in foods has been established. An in-house synthetic dyes database and characteristic ions were also developed. Based on Q-Orbitrap HRMS, mass spectrum and fragmentation patterns of synthetic dyes were studied, which indicated that double charged ions were usually the main precursor ions. Matrix effects were successfully eliminated by the C 18 d-SPE clean-up coupled with dilute and shoot approach with methanol-water (1:4, v/v) in 100-fold. For most of the compounds, mean recoveries were satisfactory between 70% and 120% with RSD < 20% at three spiked level in the range of 0.025-1.0 mg/kg. The screening detection limits ranged from 0.025 - 1.0 mg/kg. Method validation showed that the established method was efficient, rapid and high-throughput, which has been successfully applied to the monitoring of these water-soluble synthetic dyes in foods., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

There are serious concerns about possible late radiation damage to ocular tissue from prolonged space radiation exposure, and occupational and medical procedures. This study aimed to investigate the effects of whole-body high-energy proton exposure at a single dose on apoptosis, oxidative stress, and blood-retina barrier (BRB) integrity in the retina and optic nerve head (ONH) region and to compare these radiation-induced effects with those produced by fractionated dose. Six-month-old C57BL/6 male mice were either sham irradiated or received whole-body high energy proton irradiation at an acute single dose of 0.5 Gy or 12 equal dose fractions for a total dose of 0.5 Gy over twenty-five days. At four months following irradiation, mice were euthanized and ocular tissues were collected for histochemical analysis. Significant increases in the number of apoptotic cells were documented in the mouse retinas and ONHs that received proton radiation with a single or fractionated dose ( p < 0.05). Immunochemical analysis revealed enhanced immunoreactivity for oxidative biomarker, 4-hydroxynonenal (4-HNE) in the retina and ONH following single or fractionated protons with more pronounced changes observed with a single dose of 0.5 Gy. BRB integrity was also evaluated with biomarkers of aquaporin-4 (AQP-4), a water channel protein, a tight junction (TJ) protein, Zonula occludens-1 (ZO-1), and an adhesion molecule, the platelet endothelial cell adhesion molecule-1 (PECAM-1). A significantly increased expression of AQP-4 was observed in the retina following a single dose exposure compared to controls. There was also a significant increase in the expression of PECAM-1 and a decrease in the expression of ZO-1 in the retina. These changes give a strong indication of disturbance to BRB integrity in the retina. Interestingly, there was very limited immunoreactivity of AQP-4 and ZO-1 seen in the ONH region, pointing to possible lack of BRB properties as previously reported. Our data demonstrated that exposure to proton radiation of 0.5 Gy induced oxidative stress-associated apoptosis in the retina and ONH, and changes in BRB integrity in the retina. Our study also revealed the differences in BRB biomarker distribution between these two regions. In response to radiation insults, the cellular response in the retina and ONH may be differentially regulated in acute or hyperfractionated dose schedules.

Objective: To observe the effect of conventional acupuncture combined with row-like puncture at sternocleidomastoid on peripheral facial palsy at recovery stage., Methods: A total of 60 patients with peripheral facial palsy at recovery stage were randomized into an observation group and a control group, 30 cases in each one. Acupuncture was applied at affected Cuanzhu (BL 2), Yangbai (GB 14), Sibai (ST 2), Quanliao (SI 18), Jiache (ST 6), Dicang (ST 4), Hegu (LI 4), Taichong (LR 3) and Zusanli (ST 36) in the control group. On the basis of the treatment in the control group, row-like puncture was applied at sternocleidomastoid (1 needle was punctured at muscle origin and insertion respectively, 3 to 4 needles were row-like punctured at the connection line of muscle origin and insertion). The treatment was given once a day, 5 times were as one course, with 2-day interval, totally 4 courses were required in the both groups. The house-brackmann (H-B) facial nerve function grade, facial nerve function rating system-dynamic view rating scale score and facial disability index (FDI) scale score [including scores of FDI physical function (FDIp) and FDI social life function (FDIs)] before and after treatment were observed, and the clinical efficacy was evaluated in the two groups., Results: After treatment, the H-B facial nerve function grades were improved compared before treatment in the both groups ( P <0.05), and that in the observation group was superior to the control group ( P <0.05). After treatment, the scores of dynamic view rating scale and FDIp were increased ( P <0.05), FDIs scores were decreased compared before treatment in the both groups ( P <0.05); compared with the control group, the scores of dynamic view rating scale and FDIp were increased ( P <0.05), FDIs score was decreased in the observation group ( P <0.05). The total effective rate was 93.3% (28/30) in the observation group, which was superior to 73.3% (22/30) in the control group ( P <0.05)., Conclusion: Compared with conventional acupuncture, combination therapy with row-like puncture at sternocleidomastoid can improve the therapeutic effect of peripheral facial palsy at recovery stage.

Using a ground-based model to simulate spaceflight [21-days of single-housed, hindlimb unloading (HLU) combined with continuous low-dose gamma irradiation (LDR, total dose of 0.04 Gy)], an in-depth survey of the immune and hematological systems of mice at 7-days post-exposure was performed. Collected blood was profiled with a hematology analyzer and spleens were analyzed by whole transcriptome shotgun sequencing (RNA-sequencing). The results revealed negligible differences in immune differentials. However, hematological system analyses of whole blood indicated large disparities in red blood cell differentials and morphology, suggestive of anemia. Murine Reactome networks indicated majority of spleen cells displayed differentially expressed genes (DEG) involved in signal transduction, metabolism, cell cycle, chromatin organization, and DNA repair. Although immune differentials were not changed, DEG analysis of the spleen revealed expression profiles associated with inflammation and dysregulated immune function persist to 1-week post-simulated spaceflight. Additionally, specific regulation pathways associated with human blood disease gene orthologs, such as blood pressure regulation, transforming growth factor-β receptor signaling, and B cell differentiation were noted. Collectively, this study revealed differential immune and hematological outcomes 1-week post-simulated spaceflight conditions, suggesting recovery from spaceflight is an unremitting process.

Reduced knee weight-bearing from prescription or sedentary lifestyles are associated with cartilage degradation; effects on the meniscus are unclear. Rodents exposed to spaceflight or hind limb unloading (HLU) represent unique opportunities to evaluate this question. This study evaluated arthritic changes in the medial knee compartment that bears the highest loads across the knee after actual and simulated spaceflight, and recovery with subsequent full weight-bearing. Cartilage and meniscal degradation in mice were measured via microCT, histology, and proteomics and/or biochemically after: (1) ~ 35 days on the International Space Station (ISS); (2) 13-days aboard the Space Shuttle Atlantis; or (3) 30 days of HLU, followed by a 49-day weight-bearing readaptation with/without exercise. Cartilage degradation post-ISS and HLU occurred at similar spatial locations, the tibial-femoral cartilage-cartilage contact point, with meniscal volume decline. Cartilage and meniscal glycosaminoglycan content were decreased in unloaded mice, with elevated catabolic enzymes (e.g., matrix metalloproteinases), and elevated oxidative stress and catabolic molecular pathway responses in menisci. After the 13-day Shuttle flight, meniscal degradation was observed. During readaptation, recovery of cartilage volume and thickness occurred with exercise. Reduced weight-bearing from either spaceflight or HLU induced an arthritic phenotype in cartilage and menisci, and exercise promoted recovery.

Astronauts exhibit an assortment of clinical abnormalities in their eyes during long-duration spaceflight. The purpose of this study was to determine whether spaceflight induces epigenomic and transcriptomic reprogramming in the retina or alters the epigenetic clock. The mice were flown for 37 days in animal enclosure modules on the International Space Station; ground-based control animals were maintained under similar housing conditions. Mouse retinas were isolated and both DNA methylome and transcriptome were determined by deep sequencing. We found that a large number of genes were differentially methylated with spaceflight, whereas there were fewer differentially expressed genes at the transcriptome level. Several biological pathways involved in retinal diseases such as macular degeneration were significantly altered. Our results indicated that spaceflight decelerated the retinal epigenetic clock. This study demonstrates that spaceflight impacts the retina at the epigenomic and transcriptomic levels, and such changes could be involved in the etiology of eye-related disorders among astronauts., (© The Author(s) 2021. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University.)

We detected some serious inaccuracies and mistakes. Therefore, the article "Long non-coding RNA LINP1 promotes the malignant progression of prostate cancer by regulating p53, by H.-F. Wu, L.-G. Ren, J.-Q. Xiao, Y. Zhang, X.-W. Mao, L.-F. Zhou, published in Eur Rev Med Pharmacol Sci 2018; 22 (14): 4467-4476-DOI: 10.26355/eurrev&#95;201807&#95;15498-PMID: 30058678" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/15498.

Both microgravity and radiation exposure in the spaceflight environment have been identified as hazards to astronaut health and performance. Substantial study has been focused on understanding the biology and risks associated with prolonged exposure to microgravity, and the hazards presented by radiation from galactic cosmic rays (GCR) and solar particle events (SPEs) outside of low earth orbit (LEO). To date, the majority of the ground-based analogues (e.g., rodent or cell culture studies) that investigate the biology of and risks associated with spaceflight hazards will focus on an individual hazard in isolation. However, astronauts will face these challenges simultaneously Combined hazard studies are necessary for understanding the risks astronauts face as they travel outside of LEO, and are also critical for countermeasure development. The focus of this review is to describe biologic and functional outcomes from ground-based analogue models for microgravity and radiation, specifically highlighting the combined effects of radiation and reduced weight-bearing from rodent ground-based tail suspension via hind limb unloading (HLU) and partial weight-bearing (PWB) models, although in vitro and spaceflight results are discussed as appropriate. The review focuses on the skeletal, ocular, central nervous system (CNS), cardiovascular, and stem cells responses.

Many factors contribute to the health risks encountered by astronauts on missions outside Earth's atmosphere. Spaceflight-induced potential adverse neurovascular damage and late neurodegeneration are a chief concern. The goal of the present study was to characterize the effects of spaceflight on oxidative damage in the mouse brain and its impact on blood-brain barrier (BBB) integrity. Ten-week-old male C57BL/6 mice were launched to the International Space Station (ISS) for 35 days as part of Space-X 12 mission. Ground control (GC) mice were maintained on Earth in flight hardware cages. Within 38 ± 4 hours after returning from the ISS, mice were euthanized and brain tissues were collected for analysis. Quantitative assessment of brain tissue demonstrated that spaceflight caused an up to 2.2-fold increase in apoptosis in the hippocampus compared to the control group. Immunohistochemical analysis of the mouse brain revealed an increased expression of aquaporin4 (AQP4) in the flight hippocampus compared to the controls. There was also a significant increase in the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) and a decrease in the expression of the BBB-related tight junction protein, Zonula occludens-1 (ZO-1). These results indicate a disturbance of BBB integrity. Quantitative proteomic analysis showed significant alterations in pathways responsible for neurovascular integrity, mitochondrial function, neuronal structure, protein/organelle transport, and metabolism in the brain after spaceflight. Changes in pathways associated with adhesion and molecular remodeling were also documented. These data indicate that long-term spaceflight may have pathological and functional consequences associated with neurovascular damage and late neurodegeneration., (© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Reports show that prolonged exposure to a spaceflight environment produces morphologic and functional ophthalmic changes in astronauts during and after an International Space Station (ISS) mission. However, the underlying mechanisms of these spaceflight-induced changes are currently unknown. The purpose of the present study was to determine the impact of the spaceflight environment on ocular structures by evaluating the thickness of the mouse retina, the retinal pigment epithelium (RPE), the choroid and the sclera layer using micro-CT imaging. Ten-week-old C57BL/6 male mice were housed aboard the ISS for a 35-day mission and then returned to Earth alive for tissue analysis. For comparison, ground control (GC) mice on Earth were maintained in identical environmental conditions and hardware. Ocular tissue samples were collected for micro-CT analysis within 38(±4) hours after splashdown. The images of the cross-section of the retina, the RPE, the choroid, and the sclera layer of the fixed eye was recorded in an axial and sagittal view using a micro-CT imaging acquisition method. The micro-CT analysis showed that the cross-section areas of the retina, RPE, and choroid layer thickness were changed in spaceflight samples compared to GC, with spaceflight samples showing significantly thinner cross-sections and layers compared to controls. The findings from this study indicate that micro-CT evaluation is a sensitive and reliable method to characterize ocular structure changes. These results are expected to improve the understanding of the impact of environmental stress on global ocular structures.

Purpose: Studies are required to determine whether exposures to radiation encountered during manned missions in deep space may have adverse effects on the cardiovascular system. Most of the prior studies on effects of simulated space radiation on the heart and vasculature have been performed in mouse models. To provide data from a second animal species, two studies were performed to assess effects of high-energy charged particle radiation on the heart and abdominal aorta in a rat model., Materials and Methods: In study A, male Long Evans rats were exposed to whole-body protons (250 MeV, 0.5 Gy) or oxygen ions ( 16 O, 600 MeV/n, 0.5 Gy), and ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 3, 5, 9 and 12 months after radiation, followed by tissue collection at 12 months. In study B, male Long Evans rats were exposed to 16 O (1 GeV/n, 0.01-0.25 Gy), and hearts collected at 6 to 7 and 12 months for histology and western-blots., Results: Both protons (250 MeV) and 16 O (600 MeV/n) caused a decrease in left ventricular posterior wall thickness at 3-5 months, but did not change echocardiographic measures of cardiac function. In Pulsed-wave Doppler assessment of the abdominal aorta, an increase was seen in mean velocity, peak velocity, and velocity time integral at 12 months after 16 O (600 MeV/n), suggesting a change in vascular function. There were no significant changes in histopathology or histological quantification of total collagens in heart or aorta. On the other hand, an increase was seen in a 75 kDa peptide of collagen type III in the left ventricle of rats exposed to protons (250 MeV) and 16 O (600 MeV/n and 1 GeV/n), suggesting that radiation caused remodeling of existing collagens in the heart. 16 O (600 MeV/n and 1 GeV/n) caused increases in left ventricular protein levels of immune cell markers CD2, CD4, CD8, and CD68., Conclusion: A single low dose of whole body protons or 16 O in male Long Evans rats did not change cardiac function or induce gross pathological changes in the heart or aorta, but induced mild changes in vascular function and remodeling of existing collagens in the heart. Altogether, studies in prior mouse models and the current work in rats indicate minor changes in cardiac function and structure after a low dose of single-ion radiation., Competing Interests: Declaration of Competing Interests. The authors report no conflicts of interest., (Copyright © 2020 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.)

Introduction: Mild cognitive impairment (MCI) is considered the intermediate phase between normal age-related cognitive decline and dementia. Moxibustion has gained increased popularity for the management of MCI in China.This study aimed to evaluate the effects and safety of moxibustion on symptoms of MCI., Methods and Analysis: Four English databases and six Chinese databases will be searched from their inception to October 2019: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, China National Knowledge Infrastructure, Chongqing VIP Chinese Science and Technology Periodical Database, Wanfang Database, SinoMed, China Doctoral Dissertations Full-text Database and the China Master's Theses Full-text Database. Only clinical randomised controlled trials and the first period in randomised cross-over trial related to moxibustion for MCI will be included. The primary outcomes include the improvement of cognitive function, as measured by validated assessment tools. The secondary outcomes include changes in the activity of daily living scale, effective rate and the incidences of adverse events. The selection of studies, data extraction and risk of bias assessment will be carried out by two independent reviewers. Review Manager V.5.3 software will be used for statistical analyses. Heterogeneity test, data synthesis and subgroup analysis will be performed if necessary. The risk of bias of included studies will be assessed by the Cochrane Handbook risk of bias tool. Evidence quality will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation system., Ethics and Dissemination: Ethics approval is not required as no private information from individuals are collected. The results will be published in a peer-reviewed journal or disseminated in relevant conferences., Trial Registration Number: CRD42018112657., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Simultaneous determination of multiclass illegal dyes possessing different chemical properties is difficult. By using LC-MS/MS via negative/positive ion switching mode, an efficient and fast multi-residual method for simultaneous determination of multiclass 52 illegal dyes with different acidic-basic properties in foodstuffs was developed and validated during one single run, including 23 fat-soluble neutral azo dyes, 8 acidic sulfonated azo dyes, 12 triphenylmethane basic dyes, three basic indole dyes, three xanthene dyes, one quinoline dye, and two anthraquinones dyes. The illegal dyes were extracted with methanol-acetonitrile and further purified with d-SPE procedure to reduce interference. Sample dilution with 100-fold was used for the elimination of matrix effects of the quantitation of LC-MS/MS analysis. Validation data showed the good recoveries in the range of 71.2-111.2%, with relative standard deviations less than 20%, suggesting the developed method is suitable for the identification and quantitation of multiclass illegal dyes at trace levels in foods., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The long-term adaptations to microgravity and other spaceflight challenges within the confines of a spacecraft, and readaptations to weight-bearing upon reaching a destination, are unclear. While post-flight gait change in astronauts have been well documented and reflect multi-system deficits, no data from rodents have been collected. Thus, the purpose of this study was to evaluate gait changes in response to spaceflight. A prospective collection of gait data was collected on 3 groups of mice: those who spent~35 days in orbit (FLIGHT) aboard the International Space Station (ISS); a ground-based control with the same habitat conditions as ISS (Ground Control; GC); and a vivarium control with typical rodent housing conditions (VIV). Pre-flight and post-flight gait measurements were conducted utilizing an optimized and portable gait analysis system (DigiGait, Mouse Specifics, Inc). The total data acquisition time for gait patterns of FLIGHT and control mice was 1.5-5 min/mouse, allowing all 20 mice per group to be assessed in less than an hour. Patterns of longitudinal gait changes were observed in the hind limbs and the forelimbs of the FLIGHT mice after ~35 days in orbit; few differences were observed in gait characteristics within the GC and VIV controls from the initial to the final gait assessment, and between groups. For FLIGHT mice, 12 out of 18 of the evaluated gait characteristics in the hind limbs were significantly changed, including: stride width variability; stride length and variance; stride, swing, and stance duration; paw angle and area at peak stance; and step angle, among others. Gait characteristics that decreased included stride frequency, and others. Moreover, numerous forelimb gait characteristics in the FLIGHT mice were changed at post-flight measures relative to pre-flight. This rapid DigiGait gait measurement tool and customized spaceflight protocol is useful for providing preliminary insight into how spaceflight could affect multiple systems in rodents in which deficits are reflected by altered gait characteristics., Competing Interests: Declaration of Competing Interest Tom Hampton is the CEO of Mouse Specifics., (Copyright © 2019 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.)

Objectives: Virus infection is underevaluated in older adults with severe acute respiratory infections (SARIs). We aimed to evaluate the clinical impact of combining point-of-care molecular viral test and serum procalcitonin (PCT) level for antibiotic stewardship in the emergency department (ED)., Design: A prospective twin-center cohort study was conducted between January 2017 and March 2018., Setting and Participants: Older adult patients who presented to the ED with SARIs received a rapid molecular test for 17 respiratory viruses and a PCT test., Measures: To evaluate the clinical impact, we compared the outcomes of SARI patients between the experimental cohort and a propensity score-matched historical cohort. The primary outcome was the proportion of antibiotics discontinuation or de-escalation in the ED. The secondary outcomes included duration of intravenous antibiotics, length of hospital stay, and mortality., Results: A total of 676 patients were included, of which 169 patients were in the experimental group and 507 patients were in the control group. More than one-fourth (27.9%) of the patients in the experimental group tested positive for virus. Compared with controls, the experimental group had a significantly higher proportion of antibiotics discontinuation or de-escalation in the ED (26.0% vs 16.1%, P = .007), neuraminidase inhibitor uses (8.9% vs 0.6%, P < .001), and shorter duration of intravenous antibiotics (10.0 vs 14.5 days, P < .001)., Conclusions and Implications: Combining rapid viral surveillance and PCT test is a useful strategy for early detection of potential viral epidemics and antibiotic stewardship. Clustered viral respiratory infections in a nursing home is common. Patients transferred from nursing homes to ED may benefit from this approach., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Extended spaceflight has been shown to adversely affect astronaut visual acuity. The purpose of this study was to determine whether spaceflight alters gene expression profiles and induces oxidative damage in the retina. Ten week old adult C57BL/6 male mice were flown aboard the ISS for 35 days and returned to Earth alive. Ground control mice were maintained on Earth under identical environmental conditions. Within 38 (+/-4) hours after splashdown, mice ocular tissues were collected for analysis. RNA sequencing detected 600 differentially expressed genes (DEGs) in murine spaceflight retinas, which were enriched for genes related to visual perception, the phototransduction pathway, and numerous retina and photoreceptor phenotype categories. Twelve DEGs were associated with retinitis pigmentosa, characterized by dystrophy of the photoreceptor layer rods and cones. Differentially expressed transcription factors indicated changes in chromatin structure, offering clues to the observed phenotypic changes. Immunofluorescence assays showed degradation of cone photoreceptors and increased retinal oxidative stress. Total retinal, retinal pigment epithelium, and choroid layer thickness were significantly lower after spaceflight. These results indicate that retinal performance may decrease over extended periods of spaceflight and cause visual impairment.

The purpose of the current study was to characterize the effects of simulated microgravity and radiation-induced changes in retina and retinal vasculature, and to assess the accompanying early changes in immune cells and hematological parameters. To better understand the effects of spaceflight, we used a combination of treatments designed to simulate both the radiation and low-gravity aspects of space conditions. To simulate the broad energy spectrum of a large solar particle event (SPE) and galactic cosmic ray (GCR) radiation, male C57BL/6J mice were exposed to whole-body irradiation using fully modulated beams of 150-MeV protons containing particles of energy from 0 to 150 MeV and a uniform dose-vs.-depth profile. The mice were also hindlimb-unloaded (HLU) by tail suspension. Mice were unloaded for 7 days, exposed to 50 cGy, unloaded for an additional 7 days and then sacrificed for tissue isolation at days 4 and 30 after the combined treatments. Increases in the number of apoptotic cells were observed in the endothelial cells of mice that received radiation alone or with HLU compared to controls at both days 4 and 30 ( P < 0.05). Endothelial nitric oxide synthase (eNOS) levels were significantly elevated in the retina after irradiation only or combined with HLU compared to controls at the 30-day time point ( P < 0.05). The most robust changes were observed in the combination group, suggesting a synergistic response to radiation and unloading. For hematopoietic parameters, our analysis indicated the main effects for time and radiation at day 4 after treatments (day 11 postirradiation) ( P < 0.05), but a smaller influence of HLU for both white blood cell and lymphocyte counts. The group treated with both radiation and HLU showed greater than 50% reduction in lymphocyte counts compared to controls. Radiation-dependent differences were also noted in specific lymphocyte subpopulations (T, B, natural killer cells). This study shows indications of an early effect of low-dose radiation and spaceflight conditions on retina and immune populations.

Spaceflight poses many challenges for humans. Ground-based analogs typically focus on single parameters of spaceflight and their associated acute effects. This study assesses the long-term transcriptional effects following single and combination spaceflight analog conditions using the mouse model: simulated microgravity via hindlimb unloading (HLU) and/or low-dose γ-ray irradiation (LDR) for 21 days, followed by 4 months of readaptation. Changes in gene expression and epigenetic modifications in brain samples during readaptation were analyzed by whole transcriptome shotgun sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS). The results showed minimal gene expression and cytosine methylation alterations at 4 months readaptation within single treatment conditions of HLU or LDR. In contrast, following combined HLU+LDR, gene expression and promoter methylation analyses showed multiple altered pathways involved in neurogenesis and neuroplasticity, the regulation of neuropeptides, and cellular signaling. In brief, neurological readaptation following combined chronic LDR and HLU is a dynamic process that involves pathways that regulate neuronal function and structure and may lead to late onset neurological sequelae.

Safe use of retinal imaging with two-photon excitation in human eyes is crucial, as the effects of ultrashort pulsed lasers on the retina are relatively unknown. At the time of the study, the laser safety standards were inadequate due to the lack of biological data. This article addresses the feasibility of two-photon retinal imaging with respect to laser safety. In this study, rat retinas were evaluated at various laser exposure levels and with different laser parameters to determine the effects of laser-induced optical damage. The results were experimentally verified using confocal reflectance imaging, two-photon fluorescein angiography, immunohistochemistry, and correlated to the IEC 60825-1 laser safety standard., Competing Interests: The authors declare that there are no conflicts of interest related to this article.

The health risks associated with spaceflight-induced ocular structural and functional damage has become a recent concern for NASA. The goal of the present study was to characterize the effects of spaceflight and reentry to 1 g on the structure and integrity of the retina and blood-retinal barrier (BRB) in the eye. To investigate possible mechanisms, changes in protein expression profiles were examined in mouse ocular tissue after spaceflight. Ten week old male C57BL/6 mice were launched to the International Space Station (ISS) on Space-X 12 at the Kennedy Space Center (KSC) on August, 2017. After a 35-day mission, mice were returned to Earth alive. Within 38 +/- 4 hours of splashdown, mice were euthanized and ocular tissues were collected for analysis. Ground control (GC) and vivarium control mice were maintained on Earth in flight hardware or normal vivarium cages respectively. Repeated intraocular pressure (IOP) measurements were performed before the flight launch and re-measured before the mice were euthanized after splashdown. IOP was significantly lower in post-flight measurements compared to that of pre-flight (14.4-19.3 mmHg vs 16.3-20.3 mmHg) (p < 0.05) for the left eye. Flight group had significant apoptosis in the retina and retinal vascular endothelial cells compared to control groups (p < 0.05). Immunohistochemical analysis of the retina revealed that an increased expression of aquaporin-4 (AQP-4) in the flight mice compared to controls gave strong indication of disturbance of BRB integrity. There were also a significant increase in the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) and a decrease in the expression of the BRB-related tight junction protein, Zonula occludens-1 (ZO-1). Proteomic analysis showed that many key proteins and pathways responsible for cell death, cell cycle, immune response, mitochondrial function and metabolic stress were significantly altered in the flight mice compared to ground control animals. These data indicate a complex cellular response that may alter retina structure and BRB integrity following long-term spaceflight.

Sclerotinia sclerotiorum is a necrotrophic and filamentous fungus with a broad host range. Fluazinam is a pyridinamine fungicide with a broad spectrum of antifungal activity and had a strong inhibition effect on mycelial growth of S. sclerotiorum populations. But the impact of fluazinam on morphological and physiological characteristics of S. sclerotiorum is little known. In this study, the EC 50 values of fluazinam to three strains of S. sclerotiorum (CZ17S, YZ55S and SA42S) were 0.0084, 0.007, 0.0065 μg/ml respectively. After fluazinam treatment, hyphae of S. sclerotiorum became thinner, hyphal offshoot of top increased, the distance between one septum and another became shorter, cell membrane permeability increased markedly, exopolysaccharide (EPS) content and oxalic acid content decreased significantly, peroxidase (POD) activity increased significantly and mycelial respiration was inhibited. While the number and dry weight of sclerotia, glycerol content in the mycelia did not significantly change. In protective activity assay on detached rapeseed leaves, application of fluazinam at 40 μg/ml and 80 μg/ml, the control efficacy reached to 41.4% and 100%, respectively. In curative activity assay, application of fluazinam at 100 μg/ml, the control efficacy reached to 61.09%. In the same concentration, protective activity of fluazinam against S. sclerotiorum was higher than curative activity. These results will contribute to us on evaluating the potential of the fungicide fluazinam for management of Sclerotinia stem rot and understanding the mode of action of fluazinam against S. sclerotiorum., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: Astronauts traveling beyond low-Earth orbit will be exposed to high linear-energy transfer charged particles. Because there is concern about the adverse effects of space radiation on the cardiovascular system, this study assessed cardiac function and structure and immune cell infiltration in a mouse model of charged-particle irradiation., Materials and Methods: Male C57BL/6 J mice were exposed to oxygen ions ( 16 O, 600 MeV/n at 0.25-0.26 Gy/min to a total dose of 0, 0.05, 0.1, 0.25, or 1 Gy), protons (150 MeV, 0.35-0.55 Gy/min to 0, 0.5, or 1 Gy), or protons (150 MeV, 0.5 Gy) followed by 16 O (600 MeV/n, 0.1 Gy). Separate groups of mice received 137 Cs γ-rays (1 Gy/min to 0, 0.5, 1, or 3 Gy) as a reference. Cardiac function and blood velocity were measured with ultrasonography at 3, 5, 7, and 9 months after irradiation. At 2 weeks, 3 months, and 9 months, cardiac tissue was collected to assess apoptosis, tissue remodeling, and markers of immune cells., Results: Ejection fraction and fractional shortening decreased at 3 and 7 months after 16 O. These parameters did not change in mice exposed to γ-rays, protons, or protons followed by 16 O. Each of the radiation exposures caused only small increases in cleaved caspase-3 and numbers of apoptotic nuclei. Changes in the levels of α-smooth muscle cell actin and a 75-kDa peptide of collagen type III in the left ventricle suggested tissue remodeling, but there was no significant change in total collagen deposition at 2 weeks, 3 months, and 9 months. Increases in protein amounts of cluster of differentiation (CD)2, CD68, and CD45 as measured with immunoblots at 2 weeks, 3 months, and 9 months after exposure to protons or 16 O alone suggested immune cell infiltration. For type III collagen, CD2 and CD68, the efficacy in inducing protein abundance of CD2, CD68, and CD45 was 16 O > protons > γ-rays > protons followed by 16 O., Conclusions: Low-dose, high-energy charged-particle irradiation caused mild changes in cardiac function and tissue remodeling in the mouse., (Copyright © 2019 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.)

There is evidence that spaceflight poses acute and late risks to the central nervous system. To explore possible mechanisms, the proteomic changes following spaceflight in mouse brain were characterized. Space Shuttle Atlantis (STS-135) was launched from the Kennedy Space Center (KSC) on a 13-day mission. Within 3⁻5 h after landing, brain tissue was collected to evaluate protein expression profiles using quantitative proteomic analysis. Our results showed that there were 26 proteins that were significantly altered after spaceflight in the gray and/or white matter. While there was no overlap between the white and gray matter in terms of individual proteins, there was overlap in terms of function, synaptic plasticity, vesical activity, protein/organelle transport, and metabolism. Our data demonstrate that exposure to the spaceflight environment induces significant changes in protein expression related to neuronal structure and metabolic function. This might lead to a significant impact on brain structural and functional integrity that could affect the outcome of space missions.

Objective: This study aimed to assess the association of circular RNA (circRNA) ciRS-7 expression with clinicopathological characteristics and prognosis of non-small cell lung cancer (NSCLC) patients, and to investigate its effect on cells proliferation as well as apoptosis in NSCLC., Patients and Methods: 132 patients with primary NSCLC who received surgical resection were recruited in this retrospective study. All patients' tumor tissue and paired adjacent tissue were collected for circRNA ciRS-7 expression detection by RT-qPCR. Disease-free survival (DFS) and overall survival (OS) were calculated. CCK-8 and Annexin-V/propidium iodide (AV/PI) assays were performed to detect cells proliferation and apoptosis in A549 cells after circRNA ciRS-7 inhibition plasmid transfection., Results: CircRNA ciRS-7 expression in tumor tissue was elevated compared to paired adjacent tissue, and positively correlated with tumor size, lymph node metastasis and tumor node metastasis (TNM) stages. K-M curves illustrated that circRNA ciRS-7 high expression was correlated with both shorter DFS and OS, and multivariate Cox's proportional hazards regression analysis showed that circRNA ciRS-7 high expression was an independent factor for predicting unfavorable DFS and OS. Cells methods revealed that circRNA ciRS-7 expression was elevated in NSCLC cell lines (A549, PC9, NCI-H1299 and NCI-H1650) compared to normal lung epithelial cells (DEAS-2B), and the inhibition of circRNA ciRS-7 expression reduced cells proliferation and promoted cells apoptosis in A549 cells., Conclusions: CircRNA ciRS-7 overexpression is associated with advanced disease and poor prognosis in NSCLC patients, and the down-regulation of circRNA ciRS-7 inhibits tumor cells proliferation as well as improves cells apoptosis.

Background: In this study, we investigated the clinical significance of endobronchial ultrasound elastography for differentiating malignant and benign intrathoracic lymph nodes., Methods: A meta-analysis was performed to evaluate the sensitivity and specificity of endobronchial ultrasound elastography in diagnosing intrathoracic lymph nodes. Publications before October 1, 2017, were included for analysis. Sensitivity, specificity, and other variables were pooled using the bivariate mixed-effects regression model., Results: Seven studies met the inclusion criteria and were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio was 0.93 (95% confidence interval [CI], 0.85 to 0.97), 0.85 (95% CI, 0.78 to 0.90), 6.3 (95% CI, 4.2 to 9.2), 0.08 (95% CI, 0.04 to 0.18), and 74 (95% CI, 33 to 168), respectively. The summary receiver operating characteristic curve was 0.93 (95% CI, 0.91 to 0.95)., Conclusions: The results revealed endobronchial ultrasound elastography is a new technique with high sensitivity and specificity. It has a fine performance in diagnosing intrathoracic lymph nodes., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Astronauts are reported to have experienced some impairment in visual acuity during their mission on the International Space Station (ISS) and after they returned to Earth. There is emerging evidence that changes in vision may involve alterations in ocular structure and function. To investigate possible mechanisms, changes in protein expression profiles and oxidative stress-associated apoptosis were examined in mouse ocular tissue after spaceflight. Nine-week-old male C57BL/6 mice ( n = 12) were launched from the Kennedy Space Center on a SpaceX rocket to the ISS for a 35-day mission. The animals were housed in the mouse Habitat Cage Unit (HCU) in the Japan Aerospace Exploration Agency (JAXA) "Kibo" facility on the ISS. The flight mice lived either under an ambient microgravity condition (µg) or in a centrifugal habitat unit that produced 1 g artificial gravity (µg + 1 g ). Habitat control (HC) and vivarium control mice lived on Earth in HCUs or normal vivarium cages, respectively. Quantitative assessment of ocular tissue demonstrated that the µg group induced significant apoptosis in the retina vascular endothelial cells compared to all other groups ( p < 0.05) that was 64% greater than that in the HC group. Proteomic analysis showed that many key pathways responsible for cell death, cell repair, inflammation, and metabolic stress were significantly altered in µg mice compared to HC animals. Additionally, there were more significant changes in regulated protein expression in the µg group relative to that in the µg + 1 g group. These data provide evidence that spaceflight induces retinal apoptosis of vascular endothelial cells and changes in retinal protein expression related to cellular structure, immune response and metabolic function, and that artificial gravity (AG) provides some protection against these changes. These retinal cellular responses may affect blood⁻retinal barrier (BRB) integrity, visual acuity, and impact the potential risk of developing late retinal degeneration.

There is concern that degradation of vision as a result of space flight may compromise both mission goals and long-term quality of life after space travel. The visual disturbances may be due to a combination of intracerebral pressure changes and exposure to ionizing radiation. The retina and the retinal vasculature play important roles in vision, yet have not been studied extensively in relationship to space travel and space radiation. The goal of the current study was to characterize oxidative damage and apoptosis in retinal endothelial cells after whole-body gamma-ray, proton and oxygen ( 16 O) ion radiation exposure at 0.1 to 1 Gy. Six-month-old male C57Bl/6J mice were whole-body irradiated with 600 MeV/n 16 O ions (0, 0.1, 0.25, 1 Gy), solar particle event (SPE)-like protons (0, 0.1, 0.25, 0.5 Gy) or 60 Co gamma rays (0, 0.1, 0.25, 0.5 Gy). Eyes were isolated for examining endothelial nitric oxide synthase (eNOS) expression and characterization of apoptosis in retina and retinal endothelial cells at two weeks postirradiation. The expression of eNOS was significantly increased in the retina after proton and 16 O ion exposure. 16 O ions induced over twofold increase in eNOS expression compared to proton exposure at two weeks postirradiation ( P < 0.05). TUNEL assays showed dose-dependent increases in apoptosis in the retina after irradiation. Low doses of 16 O ions elicited apoptosis in the mouse retinal endothelial cells with the most robust changes observed after 0.1 Gy irradiation ( P < 0.05) compared to controls. Data also showed that 16 O ions induced a higher frequency of apoptosis in retinal endothelial cells compared to protons ( P < 0.05). In summary, our study revealed that exposure to low-dose ionizing radiation induced oxidative damage and apoptosis in the retina. Significant changes in retinal endothelial cells occur at doses as low as 0.1 Gy. There were significant differences in the responses of endothelial cells among the radiation types examined here.

Objective: We aim to investigate the expression of long non-coding RNA-LINP1 (lncRNA LINP1) in prostate cancer (PCa) and its potential mechanism., Patients and Methods: The expression of lncRNA LINP1 in 74 pairs of PCa and normal tissues were detected by quantitative Real-time polymerase chain reaction (qRT-PCR); the relationship between its expression and the pathological features and prognosis of PCa was also analyzed. The expression of lncRNA LINP1 in the PCa cell line was verified by qRT-PCR. Knockdown of LINP1 was constructed by transfection of small interfering RNA (siRNA) in two PCa cell lines (Lncap and PC-3). The biological function of LINP1 was evaluated by cell counting kit-8 (CCK-8) assay, colony formation assay, migration and invasion assay, respectively. Finally, the potential mechanism of LINP1 was explored by Western blot and qRT-PCR., Results: qRT-PCR results showed a higher expression of LINP1 in PCa than that of normal tissues. Compared with PCa patients with a lower expression of LINP1, those with higher expression had a higher tumor stage, lymphatic metastasis and distant metastasis rate, and lower overall survival rate. Proliferation, invasion and metastasis in cells transfected with si-LINP1 were remarkably decreased than those transfected with negative control (si-NC). Moreover, the expressions of the key proteins in the p53 signaling pathway, including p53, PTEN, Akt and CDK2 were remarkably decreased in cells after knockdown of LINP1. In addition, a negative correlation between LINP1 and p53 was confirmed by rescue experiments., Conclusions: Up-regulated LINP1 in PCa was correlated with a higher PCa stage, lymphatic metastasis, distant metastasis, and worse prognosis. Furthermore, LINP1 could promote the proliferative, migratory and invasive abilities of PCa by regulating the p53-signaling pathway.