Publications by authors named "Xiaowei Song"

196 Publications

Strengths and challenges of longitudinal non-human primate neuroimaging.

Neuroimage 2021 Mar 29:118009. Epub 2021 Mar 29.

Biosciences Institute & Centre for Behaviour and Evolution, Faculty of Medical Sciences, Newcastle University, United Kingdom. Electronic address:

Longitudinal non-human primate neuroimaging has the potential to greatly enhance our understanding of primate brain structure and function. Here we describe its specific strengths, compared to both cross-sectional non-human primate neuroimaging and longitudinal human neuroimaging, but also its associated challenges. We elaborate on factors guiding the use of different analytical tools, subject-specific versus age-specific templates for analyses, and issues related to statistical power.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118009DOI Listing
March 2021

Toward improved homecare of frail older adults: A focus group study synthesizing patient and caregiver perspectives.

Aging Med (Milton) 2021 Mar 21;4(1):4-11. Epub 2021 Jan 21.

Health Sciences and Innovation Surrey Memorial Hospital Fraser Health Surrey British Columbia Canada.

Background: Adopting a better understanding of how both older adults and health care providers view the community management of frailty is necessary for improving home health, especially facing the coronavirus disease 2019 (COVID-19) pandemic. We conducted a qualitative focus group study to assess how both older adults and health care providers view frailty and virtual health care in home health.

Methods: Two focus groups enrolled home-living older adults and health care professionals, respectively (n = 15). Questions targeting the use of virtual / telehealth technologies in-home care for frail older adults were administered at audio-recorded group interviews. Transcribed discussions were coded and analyzed using NVivo software.

Results: The older adult group emphasized the autonomy related to increasing frailty and social isolation and the need for transparent dissemination of health care planning. They were optimistic about remote technology-based supports and suggested that telehealth / health-monitoring/tracking were in high demand. Health care professionals emphasized the importance of a holistic biopsychosocial approach to frailty management. They highlighted the need for standardized early assessment and management of frailty.

Conclusions: The integrated perspectives provided an updated understanding of what older adults and practitioners value in home-living supports. This knowledge is helpful to advancing virtual home care, providing better care for frail individuals with complex health care needs.
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http://dx.doi.org/10.1002/agm2.12144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954833PMC
March 2021

Contextual Processing and the Impacts of Aging and Neurodegeneration: A Scoping Review.

Clin Interv Aging 2021 24;16:345-361. Epub 2021 Feb 24.

Clinical Research Centre, Surrey Memorial Hospital, Fraser Health Authority, Surrey, BC, Canada.

Contextual processing (or context processing; CP) is an integral component of cognition. CP allows people to manage their thoughts and actions by adjusting to surroundings. CP involves the formation of an internal representation of context in relation to the environment, maintenance of this information over a period of time, and the updating of mental representations to reflect changes in the environment. Each of these functions can be affected by aging and associated conditions. Here, we introduced contextual processing research and summarized the literature studying the impact of normal aging and neurodegeneration-related cognitive decline on CP. Through searching the PubMed, PsycINFO, and Google Scholar databases, 23 studies were retrieved that focused on the impact of aging, mild cogniitve impairment (MCI), Alzheimer's disease (AD), and Parkinson's disease (PD) on CP. Results indicated that CP is particularly vulnerable to aging and neurodegeneration. Older adults had a delayed onset and reduced amplitude of electrophysiological response to information detection, comparison, and execution. MCI patients demonstrated clear signs of impaired CP compared to normal aging. The only study on AD suggested a decreased proactive control in AD participants in maintaining contextual information, but seemingly intact reactive control. Studies on PD restricted to non-demented older participants, who showed limited ability to use contextual information in cognitive and motor processes, exhibiting impaired reactive control but more or less intact proactive control. These data suggest that the decline in CP with age is further impacted by accelerated aging and neurodegeneration, providing insights for improving intervention strategies. This review highlights the need for increased attention to research this important but understudied field.
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http://dx.doi.org/10.2147/CIA.S287619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917362PMC
February 2021

Functional MRI evaluation of the effect of carotid artery stenting: a case study demonstrating cognitive improvement.

Acta Radiol Open 2021 Feb 10;10(2):2058460120988822. Epub 2021 Feb 10.

Health Sciences and Innovation, Surrey Memorial Hospital, Fraser Health Authority, British Columbia, Canada.

Background: The narrowing of the carotid arteries with plaque formation represents a major risk factor for ischemic stroke and cognitive impairments. Carotid angioplasty and stenting is a standard clinical treatment to reduce stroke risk. The cognitive effect of carotid angioplasty and stenting remains largely unknown.

Purpose: This study aims to provide direct evidence of possible effects of carotid angioplasty and stenting on cognition, using task-phase functional magnetic resonance imaging.

Material And Methods: This study received harmonized institutional ethics board approval (Grant number REB ID =H18-02495/FHREB 2018-058). Two patients had MRI scans pre-carotid angioplasty and stenting and two-month post-carotid angioplasty and stenting. Case 1 had severe (>95%) flow-limiting stenosis in the right carotid artery. Case 2 had 70% non-flow limiting stenosis in the left carotid artery. At each scan, patients completed two functional magnetic resonance imaging sessions while performing a working memory task. Accuracy, reaction time, and brain activation were analyzed for each patient for possible pre-post carotid angioplasty and stenting changes.

Results: Case 1 showed increased activation in the right (treated-side) frontal and temporal lobes post-carotid angioplasty and stenting; associated with improvements in accuracy (from 58% to 74%) and task completion rate (from 17% to 72%). Case 2 completed the tasks pre- and post-carotid angioplasty and stenting with >90% accuracy, while decreased functional magnetic resonance imaging activation in the contralateral (untreated) hemisphere and mildly increased activation in the left (treated -side) anterior circulation territory were observed post-carotid angioplasty and stenting.

Conclusion: These cases provided the first task-phase functional magnetic resonance imaging data demonstrating that carotid angioplasty and stenting improved cognitive function in the re-perfused vascular territory. The finding supports the role of carotid angioplasty and stenting in improving cognitive performance beyond reducing stroke risk.
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http://dx.doi.org/10.1177/2058460120988822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878956PMC
February 2021

The quinazoline derivative, 04NB-03, induces cell cycle arrest and apoptosis in hepatocellular carcinoma cells in a reactive oxygen species-dependent manner.

Chem Biol Interact 2021 Apr 12;338:109371. Epub 2021 Feb 12.

Guangzhou Jinan Biomedicine Research and Development Center, Key Laboratory of Bioengineering Medicine of Guangdong Province, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China; Key Laboratory of Virology of Guangzhou, Jinan University, Guangzhou, 510632, China. Electronic address:

Hepatocellular carcinoma (HCC) is one of the most deadly malignancies worldwide. However, current therapeutic drugs for HCC are far from satisfactory. Thus, the development of new drugs is urgently needed. In this study, we identified a novel quinazoline derivative, 04NB-03, with potent anti-HCC activities both in vitro and in vivo. 04NB-03 effectively suppressed the viability and proliferation of HCC cells. It induced both cell cycle arrest at the G2/M phase and apoptosis in concentration- and time-dependent manners. Moreover, 04NB-03 treatment significantly reduced xenograft tumor growth without notable toxic effects. Mechanistically, 04NB-03 induced endogenous reactive oxygen species (ROS) accumulation in concentration- and time-dependent manners. Scavenging the ROS reversed 04NB-03-induced cell cycle arrest and apoptosis. Taken together, these results indicate that the quinazoline derivative, 04NB-03, inhibits the growth of HCC cells through the induction of cell cycle arrest and apoptosis in an ROS-dependent manner. 04NB-03 is, therefore, a potential small molecule candidate for the development of antitumor drugs targeting HCC.
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http://dx.doi.org/10.1016/j.cbi.2021.109371DOI Listing
April 2021

A large genome with chromosome-scale assembly sheds light on the evolutionary success of a true toad (Bufo gargarizans).

Mol Ecol Resour 2021 May 8;21(4):1256-1273. Epub 2021 Feb 8.

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.

We present a high-quality genome assembly for the Asiatic toad (Bufo gargarizans) and explore the evolution of several large gene families in amphibians. With a large genome assembly size of 4.55 Gb, the chromosome-scale assembly includes 747 scaffolds with an N50 of 539.8 Mb and 1.79% gaps. Long terminal repeats (LTRs) constitute a high proportion of the genome and their expansion is a key contributor to the inflated genome size in this species. This is very different from other small amphibian genomes, but similar to that of the enormous axolotl genome. The genome retains a large number of duplicated genes, with tandem (TD) and proximal duplications (PD) the predominant mode of duplication. A total of 122 gene families have undergone significant expansion and were mainly enriched in sensory perception of smell and bitter taste. The CYP2C subfamily, which plays an important role in metabolic detoxification, specifically expanded via TD and PD in the Asiatic toad and the cane toad (true toads). Most of Na /K -ATPase genes experienced accelerated evolution along Bufonid lineages and two amino acid sites involving toad-toxin resistance were found to experience positive selection. We also revealed a dynamic evolution of olfactory and vomeronasal receptor gene families which was likely driven by the water-to-land transition. The high-quality genome of the Asiatic toad will provide a solid foundation to understand the genetic basis of its many biological processes.
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http://dx.doi.org/10.1111/1755-0998.13319DOI Listing
May 2021

miR-214 Attenuates Aortic Valve Calcification by Regulating Osteogenic Differentiation of Valvular Interstitial Cells.

Mol Ther Nucleic Acids 2020 Dec 15;22:971-980. Epub 2020 Oct 15.

Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.

Calcific aortic valve disease (CAVD) is a common heart valve disease in aging populations, and aberrant osteogenic differentiation of valvular interstitial cells (VICs) plays a critical role in the pathogenesis of ectopic ossification of the aortic valve. miR-214 has been validated to be involved in the osteogenesis process. Here, we aim to investigate the role and mechanism of miR-214 in CAVD progression. miR-214 expression was significantly downregulated in CAVD aortic valve leaflets, accompanied by upregulation of osteogenic markers. Overexpression of miR-214 suppressed osteogenic differentiation of VICs, while silencing the expression of miR-214 promoted this function. miR-214 directly targeted ATF4 and Sp7 to modulate osteoblastic differentiation of VICs, which was proved by dual luciferase reporter assay and rescue experiment. miR-214 knockout rats exhibited higher mean transvalvular velocity and gradient. The expression of osteogenic markers in aortic valve leaflets of miR-214 knockout rats was upregulated compared to that of the wild-type group. Taken together, our study showed that miR-214 inhibited aortic valve calcification via regulating osteogenic differentiation of VICs by directly targeting ATF4 and Sp7, indicating that miR-214 may act as a profound candidate of targeting therapy for CAVD.
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http://dx.doi.org/10.1016/j.omtn.2020.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679242PMC
December 2020

Coulometry-assisted quantitation in spray ionization mass spectrometry.

J Mass Spectrom 2020 Jul 19;56(4):e4628. Epub 2020 Jul 19.

Department of Chemistry, Fudan University, Shanghai, 200438, China.

The concentration of target analyte in a mixture can be quantified by combining coulometric measurements with spray ionization mass spectrometry. A three-electrode system screen printed on the polymer support acts both as the coulometry platform for electrochemical oxidation and the sample loading tip for spray ionization. After loading a droplet of the analyte solution onto the tip, two steps were taken to implement quantitation. First, the electrochemical oxidation potential was optimized with cyclic voltammetry followed by coulometric measurements to calculate the amount of oxidized analyte under a constant low voltage within a fixed period of time (5 s). Then, a high voltage (+4.5 kV) was applied to the tip to trigger spray ionization for measuring the oxidation yield from the native analyte ion and its oxidized product ion intensities by mass spectrometry. The analyte's native concentration is quantified by dividing the oxidized product's concentration (based on Coulomb's law) and the oxidation yield (estimated from mass spectrometry [MS] assuming that the parent and oxidation product have nearly the same ionization efficiencies). The workflow has an advantage in being free of any standard for constructing the quantitation curve. Several model compounds (tyrosine, dopamine, and angiotensin II) were selected for method validation. It was demonstrated that this strategy was feasible with an accuracy of ~15% for a wide coverage of different species including endogenous metabolites and peptides. As an example of its possible practical use, it was initially employed to make a bilirubin assay in urine.
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http://dx.doi.org/10.1002/jms.4628DOI Listing
July 2020

White Matter Neuroplasticity: Motor Learning Activates the Internal Capsule and Reduces Hemodynamic Response Variability.

Front Hum Neurosci 2020 26;14:509258. Epub 2020 Oct 26.

Simon Fraser University ImageTech Lab, Health Science and Innovation, Surrey Memorial Hospital, Fraser Health, Surrey, BC, Canada.

Numerous studies have noted the importance of white matter changes in motor learning, but existing literature only focuses on structural and microstructural MRI changes, as there are limited tools available for investigations of white matter function. One method that has gained recent prominence is the application of blood oxygen level dependent (BOLD) fMRI to white matter, with high-field scanners now being able to better detect the smaller hemodynamic changes present in this tissue type compared to those in the gray matter. However, fMRI techniques have yet to be applied to investigations of neuroplastic change with motor learning in white matter. White matter function represents an unexplored component of neuroplasticity and is essential for gaining a complete understanding of learning-based changes occurring throughout the whole brain. Twelve healthy, right-handed participants completed fine motor and gross motor tasks with both hands, using an MRI compatible computer mouse. Using a crossover design along with a prior analysis approach to establish WM activation, participants received a baseline scan followed by 2 weeks of training, returning for a midpoint and endpoint scan. The motor tasks were designed to be selectively difficult for the left hand, leading to a training effect only in that condition. Analysis targeted the comparison and detection of training-associated right vs left hand changes. A statistically significant improvement in motor task score was only noted for the left-hand motor condition. A corresponding change in the temporal characteristics of the white matter hemodynamic response was shown within only the right corticospinal tract. The hemodynamic response exhibited a reduction in the dispersion characteristics after the training period. To our knowledge, this is the first report of MRI detectable functional neuroplasticity in white matter, suggesting that modifications in temporal characteristics of white matter hemodynamics may underlie functional neuroplasticity in this tissue.
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http://dx.doi.org/10.3389/fnhum.2020.509258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649291PMC
October 2020

A fast and fully-automated deep-learning approach for accurate hemorrhage segmentation and volume quantification in non-contrast whole-head CT.

Sci Rep 2020 11 9;10(1):19389. Epub 2020 Nov 9.

Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.

This project aimed to develop and evaluate a fast and fully-automated deep-learning method applying convolutional neural networks with deep supervision (CNN-DS) for accurate hematoma segmentation and volume quantification in computed tomography (CT) scans. Non-contrast whole-head CT scans of 55 patients with hemorrhagic stroke were used. Individual scans were standardized to 64 axial slices of 128 × 128 voxels. Each voxel was annotated independently by experienced raters, generating a binary label of hematoma versus normal brain tissue based on majority voting. The dataset was split randomly into training (n = 45) and testing (n = 10) subsets. A CNN-DS model was built applying the training data and examined using the testing data. Performance of the CNN-DS solution was compared with three previously established methods. The CNN-DS achieved a Dice coefficient score of 0.84 ± 0.06 and recall of 0.83 ± 0.07, higher than patch-wise U-Net (< 0.76). CNN-DS average running time of 0.74 ± 0.07 s was faster than PItcHPERFeCT (> 1412 s) and slice-based U-Net (> 12 s). Comparable interrater agreement rates were observed between "method-human" vs. "human-human" (Cohen's kappa coefficients > 0.82). The fully automated CNN-DS approach demonstrated expert-level accuracy in fast segmentation and quantification of hematoma, substantially improving over previous methods. Further research is warranted to test the CNN-DS solution as a software tool in clinical settings for effective stroke management.
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http://dx.doi.org/10.1038/s41598-020-76459-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652921PMC
November 2020

Identification of White Matter Lesions in Patients With Acute Ischemic Lesions Using U-net.

Front Neurol 2020 30;11:1008. Epub 2020 Sep 30.

Department of Biomedical Engineering, Center for Biomedical Imaging Research, School of Medicine, Tsinghua University, Beijing, China.

White matter lesions (WML) have been proved to be significantly associated with many brain diseases. Precise evaluation of burden of WML at early stage could provide insights in the prognosis and assist in intervention. However, acute ischemic lesions (AIL) exhibit hyperintensities on FLAIR images either, and are detected by diffusion weighted imaging (DWI). It is challenging to identify and segment WML in the patients with WML and AIL. Convolutional neural network (CNN) based architecture has been validated as an efficient tool for automatic segmentation. This study aimed to evaluate the performance of U-net in evaluation of WML in the patients with WML and AIL. A total of 208 cases from Chinese Atherosclerosis Risk Evaluation (CARE II) study were recruited in the present study. All subjects underwent imaging of FLAIR and DWI on 3.0 Tesla scanners. The contours of WML delineated by the observer and its scores rated by the observer were considered as gold standard. Among all 208 cases, 108 were randomly selected as train set, and the remaining 100 cases were used as test set. The performance of lesion segmentation toolbox (LST) and three U-net models were evaluated on three levels: pixel, lesion, and subject levels. The performance of all methods in WML identification and segmentation was also evaluated among the cases with different lesion volumes and between the cases with and without AIL. All U-net models outperformed LST on pixel, lesion, and subject levels, while no differences were found among three U-net models. All segmentation methods performed best in the cases with WML volume (WMLV) > 20 ml but worst in those with WMLV < 5 ml. In addition, all methods showed similar performance between the cases with and without AIL. The scores determined by U-net exhibited a strong correlation with the gold standard (all Spearman correlation coefficients >0.89, ICCs >0.88, -values <0.001). U-net performs well on identification and segmentation of WML in the patients with WML and AIL. The performance of U-net is validated by a dataset of multicenter study. Our results indicate that U-net has an advantage in assessing the burden of WML in the patients suffered from both WML and AIL.
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http://dx.doi.org/10.3389/fneur.2020.01008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554526PMC
September 2020

Sorption and desorption of petroleum hydrocarbons on biodegradable and nondegradable microplastics.

Chemosphere 2020 Oct 11:128553. Epub 2020 Oct 11.

Center for Environmental Metrology, National Institute of Metrology, PR, China. Electronic address:

Both biodegradable and nondegradable plastics are widely used. However, their interactions with petroleum hydrocarbons (PHs) have not been sufficiently studied. In this study, a type of biodegradable [polylactic acid (PLA)] and five types of nondegradable microplastics [polyamide (PA), polyethylene (PE), polyethylene terephthalate (PET), polystyrene (PS), and polyvinyl chloride (PVC)] were selected to investigate the sorption and desorption mechanisms of PHs. The sorption kinetics of the six types of microplastics followed a pseudo-second-order kinetics model (R ranged from 0.956 to 0.999) and indicated that chemical sorption dominated the sorption process. The key rate-controlling steps of the sorption of PHs on microplastics were intraparticle diffusion and liquid film diffusion. The sorption capacity of PHs on microplastics followed the order of PA > PE > PS > PET > PLA > PVC. The difference in sorption capacity might be due to the crystallinity, and rubber or glass state of the microplastics. In addition, all types of microplastics exhibited reversible sorption without noticeable desorption hysteresis. No obvious differences were observed in the sorption and desorption of PHs between biodegradable and nondegradable microplastics. Both biodegradable and nondegradable microplastics could sorb/desorb PHs and serve as transportation vectors.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128553DOI Listing
October 2020

Long-Term Cocaine Self-administration Produces Structural Brain Changes That Correlate With Altered Cognition.

Biol Psychiatry 2021 Feb 18;89(4):376-385. Epub 2020 Aug 18.

Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland. Electronic address:

Background: An enduring question from cross-sectional clinical studies is whether the structural and functional differences often observed between cocaine users and healthy control subjects result from a history of drug use or instead reflect preexisting differences. To assess causality from drug exposure, true predrug baseline imaging and neurocognitive assessments are needed.

Methods: We addressed this fundamental question of causality using longitudinal anatomical magnetic resonance imaging and neurocognitive assessments in rhesus macaques. Cognitive tasks employed were stimulus reversal learning as a measure of cognitive flexibility/inhibitory control and delayed match to sample as a measure of visual working memory. Time points examined were before and following 12 months of chronic cocaine (n = 8) or water (n = 6) self-administration. A magnetic resonance imaging-only time point was also obtained following 2 years of forced abstinence.

Results: We identified localized patterns of gray matter density (GMD) changes that were largely concordant with cross-sectional clinical studies. These included decreases in orbitofrontal cortex, insula, amygdala, and temporal cortex. There was also a prominent increase in GMD in the caudate putamen. GMD decreases were significantly correlated with cognitive impairments across individuals only in select cortical regions. Following abstinence, changes in GMD in some regions, including the orbitofrontal cortex, insula, and amygdala, were persistent and thus may play an important role in risk of relapse following extended abstinence.

Conclusions: Cocaine use is causal in producing regional changes in GMD, and those changes appear to drive cognitive impairments.
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http://dx.doi.org/10.1016/j.biopsych.2020.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855373PMC
February 2021

Landscape of associations between long non-coding RNAs and infiltrating immune cells in liver hepatocellular carcinoma.

J Cell Mol Med 2020 10 10;24(19):11243-11253. Epub 2020 Sep 10.

Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Liver hepatocellular carcinoma (LIHC) can be detected by the immune system; however, it acquires features for evasion of immune surveillance during its origin and development. Long non-coding RNAs (lncRNAs) are critical as immune regulators in cancers; nevertheless, the biological functions and mechanisms of lncRNAs in evasion of immune system by LIHC remain unclear. In this study, an integrated and computational approach was developed to identify immune-related lncRNAs and to divide LIHC patients into diverse immune-related risk groups based on the expression profiles of coding genes and lncRNAs. LIHC-specific genes and lncRNAs in 17 immune cell populations were identified and analysed. Gene and lncRNA co-expressing networks for diverse immune cell populations were constructed and analysed. Some imported immune-related lncRNAs, such as MIR9-3HG, were also identified. The LIHC patients comprised three different groups based on immune-related risk. LIHC patients possessing a greater diversity of immune cell populations had better survival prognosis. The collective data are evidence of a credible computational model that can prioritize novel immune-related lncRNAs and depict the atlas of immune-related lncRNAs in LIHC. These findings will further the understanding of lncRNA function and advance the identification of immunotherapy targets in LIHC.
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http://dx.doi.org/10.1111/jcmm.15690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576285PMC
October 2020

BRE Promotes Esophageal Squamous Cell Carcinoma Growth by Activating AKT Signaling.

Front Oncol 2020 11;10:1407. Epub 2020 Aug 11.

Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China.

Brain and reproductive organ-expressed protein (BRE) is aberrantly expressed in multiple cancers; however, its expression pattern in human esophageal squamous cell carcinoma (ESCC) and its role in ESCC progression remain unclear. In this study, we aimed to investigate the expression pattern of BRE in human ESCC and its role in ESCC progression. BRE was overexpressed in ESCC tissues compared with that in the adjacent non-tumor tissues. Forced expression of BRE was sufficient to enhance ESCC cell growth by promoting cell cycle progression and anti-apoptosis. Silencing of BRE suppressed these malignant phenotypes of ESCC cells. Mechanistic evaluation revealed that BRE overexpression activated the phosphorylation of AKT, and inhibition of the AKT pathway by MK2206 decreased the BRE-induced cell growth and apoptotic resistance in ESCC cells, highlighting the critical role of AKT signaling in mediating the effects of BRE. Moreover, the effects of BRE on ESCC cell growth and AKT activation were verified in a xenograft model . The present results show that BRE is overexpressed in ESCC tissues and contributes to the growth of ESCC cells by activating AKT signaling both and and provide insight into the role of BRE in AKT signaling and ESCC pathogenesis.
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http://dx.doi.org/10.3389/fonc.2020.01407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431625PMC
August 2020

A novel quinolinylmethyl substituted ethylenediamine compound exerts anti-cancer effects via stimulating the accumulation of reactive oxygen species and NO in hepatocellular carcinoma cells.

Eur J Pharmacol 2020 Oct 22;885:173497. Epub 2020 Aug 22.

Guangzhou Jinan Biomedicine Research and Development Center, Key Laboratory of Bioengineering Medicine of Guangdong Province, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China. Electronic address:

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Owing to the limitations in the current therapeutic strategies for treating HCC, development of novel chemotherapeutic drugs is urgently needed. In the present study, we found that QQM, a newly-synthesized quinolinylmethyl substituted ethylenediamine compound, exhibited anti-HCC effects both in vitro and in vivo. QQM inhibited HCC cell growth and induced G0/G1-phase cell cycle arrest and apoptosis in a dose-dependent manner. Our results showed that QQM acted by significantly increasing intracellular reactive oxygen species in HCC cells, which led to cell apoptosis and growth inhibition. Furthermore, QQM treatment resulted in an accumulation of reactive nitric oxide (NO) in HCC cells, and introduction of a NO scavenger, carboxy-PTIO, largely attenuated QQM-induced cytotoxicity. Finally, we found that QQM inhibited growth and induced apoptosis of HCC xenograft tumors in vivo. Taken together, our results indicated that QQM exerted anti-HCC effects by inducing reactive oxygen species and NO accumulation in HCC cells. Thus, QQM exhibits the qualities of a novel, promising anti-tumor candidate for the treatment of HCC.
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http://dx.doi.org/10.1016/j.ejphar.2020.173497DOI Listing
October 2020

Roles of long non-coding RNAs and emerging RNA-binding proteins in innate antiviral responses.

Theranostics 2020 23;10(20):9407-9424. Epub 2020 Jul 23.

Guangzhou Jinan Biomedicine Research and Development Center, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China.

The diseases caused by viruses posed a great challenge to human health, the development of which was driven by the imbalanced host immune response. Host innate immunity is an evolutionary old defense system that is critical for the elimination of the virus. The overactive innate immune response also leads to inflammatory autoimmune diseases, which require precise control of innate antiviral response for maintaining immune homeostasis. Mounting long non-coding RNAs (lncRNAs) transcribed from the mammalian genome are key regulators of innate antiviral response, functions of which greatly depend on their protein interactors, including classical RNA-binding proteins (RBPs) and the unconventional proteins without classical RNA binding domains. In particular, several emerging RBPs, such as mA machinery components, TRIM family members, and even the DNA binding factors recognized traditionally, function in innate antiviral response. In this review, we highlight recent progress in the regulation of type I interferon signaling-based antiviral responses by lncRNAs and emerging RBPs as well as their mechanism of actions. We then posed the future perspective toward the role of lncRNA-RBP interaction networks in innate antiviral response and discussed the promising and challenges of lncRNA-based drug development as well as the technical bottleneck in studying lncRNA-protein interactions. Our review provides a comprehensive understanding of lncRNA and emerging RBPs in the innate antiviral immune response.
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http://dx.doi.org/10.7150/thno.48520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415804PMC
July 2020

Dysregulation of cofilin-1 activity-the missing link between herpes simplex virus type-1 infection and Alzheimer's disease.

Crit Rev Microbiol 2020 Aug 25;46(4):381-396. Epub 2020 Jul 25.

Guangzhou Jinan Biomedicine Research and Development Center, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, PR China.

Alzheimer's disease (AD) is a multifactorial disease triggered by environmental factors in combination with genetic predisposition. Infectious agents, in particular herpes simplex virus type 1 (HSV-1), are gradually being recognised as important factors affecting the development of AD. However, the mechanism linking HSV-1 and AD remains unknown. Of note, HSV-1 manipulates the activity of cofilin-1 to ensure their efficient infection in neuron cells. Cofilin-1, the main regulator of actin cytoskeleton reorganization, is implicating for the plastic of dendritic spines and axon regeneration of neuronal cells. Moreover, dysfunction of cofilin-1 is observed in most AD patients, as well as in mice with AD and ageing. Further, inhibition of cofilin-1 activity ameliorates the host cognitive impairment in an animal model of AD. Together, dysregulation of cofilin-1 led by HSV-1 infection is a potential link between HSV-1 and AD. Herein, we critically summarize the role of cofilin-1-mediated actin dynamics in both HSV-1 infection and AD, respectively. We also propose several hypotheses regarding the connecting roles of cofilin-1 dysregulation in HSV-1 infection and AD. Our review provides a foundation for future studies targeting individuals carrying HSV-1 in combination with cofilin-1 to promote a more individualised approach for treatment and prevention of AD.
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http://dx.doi.org/10.1080/1040841X.2020.1794789DOI Listing
August 2020

Distinct spatiotemporal imaging of femtosecond surface plasmon polaritons assisted with the opening of the two-color quantum pathway effect.

Opt Express 2020 Jun;28(13):19023-19033

Accurately capturing the spatiotemporal information of surface plasmon polaritons (SPPs) is the basis for expanding SPP applications. Here, we report spatio-temporal evolution imaging of femtosecond SPPs launched from a rectangular trench in silver film with a 400-nm light pulse assisted femtosecond laser interferometric time-resolved (ITR) photoemission electron microscopy. It is found that introducing the 400nm light pulse in the spatially separated near-infrared (NIR) laser pump-probe ITR scheme enables distinct spatiotemporal imaging of the femtosecond SPPs with a weak probe pulse in the ITR scheme, which is free from the risk of sample damage due to the required high monochromatic field for a clear photoelectron image as well as the entangled interference fringe (between the SPPs and probe pulse) in the usual spatially overlapped pump-probe ITR scheme. The demonstrated great improvement of the visibility of the SPPs spatiotemporal image with an additional 400nm light pulse scheme facilitates further analysis of the femtosecond SPPs, and carrier wavelength (785nm), group velocity (0.94C) and phase velocity (0.98C) of SPPs are extracted from the distinct spatio-temporal evolution images of SPPs. Furthermore, the modulation of photoemission induced by the quantum pathway interference effect in the 400nm-assisted scheme is proposed to play a major role in the distinct visualization for SPPs. The probabilities of electrons in different quantum pathways are obtained quantitatively through fitting the experimental results with the quantum pathway interference model. The probability that electrons emit through the quantum pathway allows us to quantitatively analyze the contribution to electron emission from the different quantum pathways. These findings pave a way for the spatiotemporal imaging of the near-infrared light-induced SPPs, such as the communication wave band using PEEM.
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http://dx.doi.org/10.1364/OE.397526DOI Listing
June 2020

A comprehensive investigation of the mRNA and protein level of ACE2, the putative receptor of SARS-CoV-2, in human tissues and blood cells.

Int J Med Sci 2020 18;17(11):1522-1531. Epub 2020 Jun 18.

Guangzhou Jinan Biomedicine Research and Development Center, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, PR China.

The outbreak of pneumonia caused by SARS-CoV-2 posed a great threat to global human health, which urgently requires us to understand comprehensively the mechanism of SARS-CoV-2 infection. Angiotensin-converting enzyme 2 (ACE2) was identified as a functional receptor for SARS-CoV-2, distribution of which may indicate the risk of different human organs vulnerable to SARS-CoV-2 infection. Previous studies investigating the distribution of ACE2 mRNA in human tissues only involved a limited size of the samples and a lack of determination for ACE2 protein. Given the heterogeneity among humans, the datasets covering more tissues with a larger size of samples should be analyzed. Indeed, ACE2 is a membrane and secreted protein, while the expression of ACE2 in blood and common blood cells remains unknown. Herein, the proteomic data in HIPED and the antibody-based immunochemistry result in HPA were collected to analyze the distribution of ACE2 protein in human tissues. The bulk RNA-seq profiles from three separate public datasets including HPA tissue Atlas, GTEx, and FANTOM5 CAGE were also obtained to determine the expression of ACE2 in human tissues. Moreover, the abundance of ACE2 in human blood and blood cells was determined by analyzing the data in the PeptideAtlas and the HPA Blood Atlas. We found that the mRNA expression cannot reflect the abundance of ACE2 factor due to the strong differences between mRNA and protein quantities of ACE2 within and across tissues. Our results suggested that ACE2 protein is mainly expressed in the small intestine, kidney, gallbladder, and testis, while the abundance of which in brain-associated tissues and blood common cells is low. HIPED revealed enrichment of ACE2 protein in the placenta and ovary despite a low mRNA level. Further, human secretome shows that the average concentration of ACE2 protein in the plasma of males is higher than those in females. Our research will be beneficial for understanding the transmission routes and sex-based differences in susceptibility of SARS-CoV-2 infection.
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http://dx.doi.org/10.7150/ijms.46695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359402PMC
July 2020

Oral squamous cell carcinoma diagnosed from saliva metabolic profiling.

Proc Natl Acad Sci U S A 2020 07 29;117(28):16167-16173. Epub 2020 Jun 29.

Department of Chemistry, Fudan University, 200438 Shanghai, China;

Saliva is a noninvasive biofluid that can contain metabolite signatures of oral squamous cell carcinoma (OSCC). Conductive polymer spray ionization mass spectrometry (CPSI-MS) is employed to record a wide range of metabolite species within a few seconds, making this technique appealing as a point-of-care method for the early detection of OSCC. Saliva samples from 373 volunteers, 124 who are healthy, 124 who have premalignant lesions, and 125 who are OSCC patients, were collected for discovering and validating dysregulated metabolites and determining altered metabolic pathways. Metabolite markers were reconfirmed at the primary tissue level by desorption electrospray ionization MS imaging (DESI-MSI), demonstrating the reliability of diagnoses based on saliva metabolomics. With the aid of machine learning (ML), OSCC and premalignant lesions can be distinguished from the normal physical condition in real time with an accuracy of 86.7%, on a person by person basis. These results suggest that the combination of CPSI-MS and ML is a feasible tool for accurate, automated diagnosis of OSCC in clinical practice.
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http://dx.doi.org/10.1073/pnas.2001395117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368296PMC
July 2020

Hsa_Circ_0007841 Enhances Multiple Myeloma Chemotherapy Resistance Through Upregulating ABCG2.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820928371

Department of Nephrology, The First People's Hospital of Jingmen, Hubei, China.

The current researches have reported that circular RNA is an important regulatory factor in the progression of various human disease. However, the function and mechanism of most circular RNAs remain unknown in cancers including multiple myeloma. Our study has confirmed that hsa_circ_0007841 is up regulated in U266 doxorubicin resistant cells (U266R) and 8226 doxorubicin resistant cells (8226R) compared to U266 parent cells (U266P) and 8226 parent cells (8226P). Silence of hsa_circ_0007841 in U266R and 8226R could reduce the half-maximal inhibitory concentration which indicated reduction in chemoresistance. In doxorubicin resistant cells, the messenger RNA and protein level of ATP-binding cassette transporters G2 increased. Silence of hsa_circ_0007841 in drug resistant cells could decrease both the messenger RNA and protein levels of ATP-binding cassette transporters G2; reexpression of hsa_circ_0007841 could block the reduction. However, overexpression of hsa_circ_0007841 could effectively upregulate the ATP-binding cassette transporters G2 messenger RNA and protein level. Inhibition of ATP-binding cassette transporters G2 could block hsa_circ_0007841 overexpression induced chemoresistance in U266P and 8226P cells. What's more, inhibition of ATP-binding cassette transporters G2 could reduce differences of half-maximal inhibitory concentration between parent cell lines and drug-resistant cell lines. Our data collectively suggest a new model in which hsa_circ_0007841 promotes acquired chemotherapy resistance by upregulating ATP-binding cassette transporters G2 providing a novel molecular basis of chemotherapy in multiple myeloma cancer.
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http://dx.doi.org/10.1177/1533033820928371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307286PMC
January 2021

Early Detection of Alzheimer's Disease Using Magnetic Resonance Imaging: A Novel Approach Combining Convolutional Neural Networks and Ensemble Learning.

Front Neurosci 2020 13;14:259. Epub 2020 May 13.

SFU ImageTech Lab, Surrey Memorial Hospital, Fraser Health, Surrey, BC, Canada.

Early detection is critical for effective management of Alzheimer's disease (AD) and screening for mild cognitive impairment (MCI) is common practice. Among several deep-learning techniques that have been applied to assessing structural brain changes on magnetic resonance imaging (MRI), convolutional neural network (CNN) has gained popularity due to its superb efficiency in automated feature learning with the use of a variety of multilayer perceptrons. Meanwhile, ensemble learning (EL) has shown to be beneficial in the robustness of learning-system performance via integrating multiple models. Here, we proposed a classifier ensemble developed by combining CNN and EL, i.e., the CNN-EL approach, to identify subjects with MCI or AD using MRI: i.e., classification between (1) AD and healthy cognition (HC), (2) MCIc (MCI patients who will convert to AD) and HC, and (3) MCIc and MCInc (MCI patients who will not convert to AD). For each binary classification task, a large number of CNN models were trained applying a set of sagittal, coronal, or transverse MRI slices; these CNN models were then integrated into a single ensemble. Performance of the ensemble was evaluated using stratified fivefold cross-validation method for 10 times. The number of the intersection points determined by the most discriminable slices separating two classes in a binary classification task among the sagittal, coronal, and transverse slice sets, transformed into the standard Montreal Neurological Institute (MNI) space, acted as an indicator to assess the ability of a brain region in which the points were located to classify AD. Thus, the brain regions with most intersection points were considered as those mostly contributing to the early diagnosis of AD. The result revealed an accuracy rate of 0.84 ± 0.05, 0.79 ± 0.04, and 0.62 ± 0.06, respectively, for classifying AD vs. HC, MCIc vs. HC, and MCIc vs. MCInc, comparable to previous reports and a 3D deep learning approach (3D-SENet) based on a more state-of-the-art and popular Squeeze-and-Excitation Networks model using channel attention mechanism. Notably, the intersection points accurately located the medial temporal lobe and several other structures of the limbic system, i.e., brain regions known to be struck early in AD. More interestingly, the classifiers disclosed multiple patterned MRI changes in the brain in AD and MCIc, involving these key regions. These results suggest that as a data-driven method, the combined CNN and EL approach can locate the most discriminable brain regions indicated by the trained ensemble model while the generalization ability of the ensemble model was maximized to successfully capture AD-related brain variations early in the disease process; it can also provide new insights into understanding the complex heterogeneity of whole-brain MRI changes in AD. Further research is needed to examine the clinical implication of the finding, capability of the advocated CNN-EL approach to help understand and evaluate an individual subject's disease status, symptom burden and progress, and the generalizability of the advocated CNN-EL approach to locate the most discriminable brain regions in the detection of other brain disorders such as schizophrenia, autism, and severe depression, in a data-driven way.
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http://dx.doi.org/10.3389/fnins.2020.00259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238823PMC
May 2020

Differential neural processing of spontaneous blinking under visual and auditory sensory environments: An EEG investigation of blink-related oscillations.

Neuroimage 2020 09 15;218:116879. Epub 2020 May 15.

School of Engineering Science, Simon Fraser University, 8888 University Dr, Burnaby, BC, V5A 1S6, Canada; Health Sciences and Innovation, Surrey Memorial Hospital, Fraser Health Authority, 13750 96 Ave, Surrey, BC, V3V 1Z2, Canada; Department of Biomedical Physiology and Kinesiology, Simon Fraser University, 8888 University Dr, Burnaby, BC, V5A 1S6, Canada. Electronic address:

Blink-related oscillations (BROs) are a recently discovered neurophysiological response associated with spontaneous blinking, distinct from the well-known oculomotor and visual suppression effects. BROs strongly activate the bilateral precuneus along with other cortical regions involved in visuospatial processing and associative episodic memory, and are believed to represent environmental monitoring processes that occur following blink-induced visual interruptions. Although these responses have been reported across multiple imaging modalities under both resting and cognitive loading conditions, it is yet unknown whether these responses also exist under external sensory stimulation conditions. To address this, we investigated BRO responses in healthy adults using 64-channel electroencephalography (EEG), while participants underwent passive external auditory and visual stimulation. Our results showed that BRO responses are present under both auditory and visual stimulation conditions (p ​< ​0.05), with similar temporal and spectral features compared to rest. However, visual stimulation did result in decreased BRO amplitude compared to auditory and resting conditions (p ​< ​0.05), suggesting decreased neuronal resources for processing blink-related information in the visual but not auditory environment. There were also additional pre-blink spectral changes in the visual condition compared to rest (p ​< ​0.05), which suggest that passive visual stimulation induces neural preparatory processes occurring in anticipation of the upcoming blink event. Together, these findings provide new and compelling evidence that blink-related neural processes are modulated not only by the internal cognitive loading due to simultaneous task demands, but also by competing external sensory requirements. This highlights the link between blinking and cognition, and further demonstrates the importance of BROs as a new window into brain function.
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http://dx.doi.org/10.1016/j.neuroimage.2020.116879DOI Listing
September 2020

Molecular Expansion for Constructing Porous Organic Polymers with High Surface Areas and Well-Defined Nanopores.

Angew Chem Int Ed Engl 2020 Oct 8;59(44):19487-19493. Epub 2020 Jun 8.

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore.

Construction of porous organic polymers (POPs) with high surface areas, well-defined nanopores, and excellent stability remains extremely challenging because of the unmanageable reaction process. Until now, only a few reported POPs have Brunauer-Emmett-Teller (BET) surface areas (S ) exceeding 3000 m  g . Herein, we demonstrate a molecular expansion strategy to integrate high surface areas, large nanopore sizes, and outstanding stability into POPs. A series of hyper-crosslinked conjugated polymers (HCCPs) with exceptional porosity are synthesized through this strategy. Specially, HCCP-6 and HCCP-11 exhibit the highest surface areas (S >3000 m  g ) and excellent total pore volumes (up to 3.98 cm  g ) among these HCCPs. They present decent total CH storage capacities of 491 and 421 mg g at 80 bar and 298 K, respectively. Meanwhile, they are highly stable in harsh environments. The facile and general molecular expansion strategy would lead to improved synthetic routes of POPs for desired functions.
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http://dx.doi.org/10.1002/anie.202002702DOI Listing
October 2020

Incremental value of plaque enhancement in predicting stroke recurrence in symptomatic intracranial atherosclerosis.

Neuroradiology 2020 Sep 17;62(9):1123-1131. Epub 2020 Apr 17.

Department of Neurology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, No.168 of Litang Road, Changping District, Beijing, 102218, China.

Purpose: To investigate the association between plaque enhancement and stroke recurrence in subjects with intracranial atherosclerosis.

Methods: Ischemic stroke patients with symptomatic intracranial atherosclerosis were prospectively included and followed in a comprehensive stroke center. Pre- and post-contrast vessel wall images were used to evaluate plaque enhancement. Other established suggestive imaging markers were also acquired simultaneously. Univariate- and multivariate-adjusted Cox proportional hazard regression models were used to determine the association between plaque enhancement and stroke recurrence. Finally, receiver operating characteristic (ROC) curves were used to demonstrate the predictive value of different imaging markers.

Results: Of the 60 subjects included, 12 (20.0%) patients presented with ipsilateral stroke recurrence during the median 12-month follow-up. Cox proportional hazard regression models indicated that plaque enhancement was an independent risk factor associated with stroke recurrence after adjusted covariates, with a hazard ratio (HR) of 14.24 and 95% confidence interval (95% CI) (1.21, 168.11), p = 0.04. In addition, border zone infarction was also statistically significant in predicting stroke recurrence in multi-variable regression (HR = 3.80; 95% CI = 1.04, 13.80; p = 0.04). Collateral status was in marginal significance (HR = 0.25; 95% CI = 0.06, 1.08; p = 0.06). ROC analysis indicated that the area under the curve and 95% CI to identify stroke recurrence are 0.67 (0.51, 0.82) for plaque enhancement and 0.71 (0.54, 0.88) for infarction pattern and collateral status and may increase to 0.82 (0.70, 0.93) by combining the three markers above.

Conclusion: Plaque enhancement is independently associated with stroke recurrence in subjects with intracranial atherosclerosis and has added value to hemodynamic indicators in predicting stroke recurrence.
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http://dx.doi.org/10.1007/s00234-020-02418-8DOI Listing
September 2020

A Computerized Frailty Assessment Tool at Points-of-Care: Development of a Standalone Electronic Comprehensive Geriatric Assessment/Frailty Index (eFI-CGA).

Front Public Health 2020 31;8:89. Epub 2020 Mar 31.

Health Sciences and Innovation, Surrey Memorial Hospital, Surrey, BC, Canada.

Frailty is characterized by loss of biological reserves and is associated with an increased risk of adverse health outcomes. Frailty can be operationalized using a Frailty Index (FI) based on the accumulation of health deficits; items under health evaluation in the well-established Comprehensive Geriatric Assessment (CGA) have been used to generate an FI-CGA. Traditionally, constructing the FI-CGA has relied on paper-based recording and manual data processing. As this can be time-consuming and error-prone, it limits widespread uptake of this proven type of frailty assessment. Here, we report the development of an electronic tool, the eFI-CGA, for use on personal computers by frontline healthcare providers, to collect CGA data and automate FI-CFA calculation. The ultimate goal is to support early identification and management of frailty at points-of-care, and make uptake in Electronic Medical Records (EMR) feasible and transparent. An electronic CGA (eCGA) form was implemented to operate on Microsoft's WinForms platform and coded using C# programming language. Users complete the eCGA form, from which items under the CGA evaluation are automatically retrieved and processed to output an eFI-CGA score. A user-friendly interface and secured data saving methods were implemented. The software was debugged and tested using systematically designed simulation data, addressing different logic, syntax, and application errors, and then tested with clinical assessment. The user manual and manual scoring were used as ground truth to compare eFI-CGA input and automated eFI score calculations. Frontline health-provider user feedback was incorporated to improve the end-user experience. The Standalone eFI-CGA software tool was developed and optimized for use on personal computers. The user interface adapted the design of paper-based CGA form to facilitate familiarity for clinical users. Compared to known scores, the software tool generated eFI-CGA scores with 100% accuracy to four decimal places. The eFI-CGA allowed secure data storage and retrieval of multiple types, including user input, completed eCGA form, coded items, and calculated eFI-CGA scores. It also permitted recording of actions requiring clinical follow-up, facilitating care planning. Application bugs were identified and resolved at various stages of the implementation, resulting in efficient system performance. Accurate, robust, and reliable computerized frailty assessments are needed to promote effective frailty assessment and management, as a key tool in health care systems facing up to frailty. Our research has enabled the delivery of the standalone eFI-CGA software technology to empower effective frailty assessment and management by various healthcare providers at points-of-care, facilitating integrated care of older adults.
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http://dx.doi.org/10.3389/fpubh.2020.00089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137764PMC
March 2020

Correction to: Anti-HSV-1 activity of Aspergillipeptide D, a cyclic pentapeptide isolated from fungus Aspergillus sp. SCSIO 41501.

Virol J 2020 Apr 1;17(1):45. Epub 2020 Apr 1.

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou, 510301, Guangdong, China.

Following publication of the original article [1], we have been notified that there is a typo in the title of this article.
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http://dx.doi.org/10.1186/s12985-020-01322-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110650PMC
April 2020

Single-cell RNA-sequencing analysis identifies host long noncoding RNA MAMDC2-AS1 as a co-factor for HSV-1 nuclear transport.

Int J Biol Sci 2020 5;16(9):1586-1603. Epub 2020 Mar 5.

College of Life science and Technology, Guangzhou Jinan Biomedicine Research and Development Center, Jinan University, Guangzhou 510632, PR China.

Herpes simplex virus (HSV) type 1 (HSV-1) infection exhibited high heterogeneity at individual cells level, including the different gene expression patterns and varying amounts of progeny virus. However, the underlying mechanism of such variability remains obscure. The importance of host long noncoding RNAs (lncRNAs) in virus infection had been recognized, while the contribution of lncRNAs to the heterogeneous infection remains unknown. Herein, a prior single-cell RNA sequencing data using HSV-1 reporter strain expressing ICP4-YFP was re-analyzed to obtain the differentially expressed lncRNA between the successfully initiated viral gene expression (ICP4-YFP) cells and the aborted infection cells (ICP4-YFP). The ICP4-YFP population show a higher abundance of MAMDC2 antisense 1 (MAMDC2-AS1) lncRNA than ICP4-YFP population. MAMDC2-AS1 silencing reduces the expression of HSV-1 immediate early (IE) genes and limit HSV-1 infection in human host cells. Consistently, ectopic expression of MAMDC2-AS1 enhances HSV-1 IE genes transcription and facilitates the formation of HSV-1-induced plaques. Mechanically, both RNA-pull down and RNA immunoprecipitation assays show that MAMDC2-AS1 interacts with the RNA binding protein heat shock protein 90α (Hsp90α), a molecular chaperone involving in the nuclear import of HSV-1. The MAMDC2-AS1-Hsp90α interaction facilitates the nuclear transport of viral tegument protein VP16, the core factor initiating the expression of HSV-1 IE genes. The transcription factor YY1 mediates the induction of MAMDC2-AS1 upon HSV-1 infection. Our study elucidates the contribution of lncRNA to HSV-1 infection susceptibility in human cells and the role of Hsp90α RNA binding activity in HSV-1 infection.
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http://dx.doi.org/10.7150/ijbs.42556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097924PMC
March 2020

Polarization manipulated femtosecond localized surface plasmon dephasing time in an individual bowtie structure.

Opt Express 2020 Mar;28(7):9310-9319

The performance of plasmon in applications is strongly related to plasmon damping, i.e., a dephasing of the optical polarization associated with the electron oscillation. Accurate measurement, manipulation, and, ultimately, prolongation of the dephasing time are prerequisites to the future development of the application of plasmonics. Here, we studied the dephasing time of different plasmonic hotspots in an individual bowtie structure by time-resolved photoemission electron microscopy and proposed an easy-to-operate method for actively and flexibly controlling the mode-dependent plasmon dephasing time by varying the polarization direction of a femtosecond laser. Experimentally, we achieved a large adjustment of the dephasing time ranging from 7 to 17 fs. In addition, a structural defect was found to drastically extend the plasmon dephasing time. Assisted with the finite-difference time-domain simulation, the underlying physics of the dephasing time extension by the structural defect was given.
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http://dx.doi.org/10.1364/OE.379429DOI Listing
March 2020