Publications by authors named "Ming Fan"

406 Publications

A Sensitive LC-MS/MS Method for the Determination of Afatinib in Human Plasma and Its Application to a Bioequivalence Study.

J Chromatogr Sci 2021 Apr 29. Epub 2021 Apr 29.

BE/Phase I clinical center, The first affiliated hospital of Xiamen university, Xiamen, Fujian 361000, China.

A high performance liquid chromatography-tandem mass spectrometry assay for the determination of afatinib (AFT) in human plasma was established. A simple sample preparation of protein precipitation was used and separation was achieved on a C18 column by the gradient mixture of mobile Phase A of water (containing 0.1% ammonia) and the mobile Phase B of acetonitrile and water (V:V = 95:5, containing 0.2% ammonia). The multiple reaction monitoring mode was used to monitor the precursor-to-production transitions of m/z 486.2 → m/z 371.4 for AFT and m/z 492.2 → m/z 371.3 for AFT-d6 (internal standard) at positive ionization mode. The calibration curve ranged from 0.100 to 25.0 ng·mL-1 and the correlation coefficient was greater than 0.99. The intra- and inter-batch precision was less than or equal to 10.0%. Accuracy determined at four concentrations was in the range of 92.3-103.3%. In summary, our method was sensitive, simple and reliable for the quantification of AFT and was successfully applied to a bioequivalence study.
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http://dx.doi.org/10.1093/chromsci/bmab040DOI Listing
April 2021

Radiomics of Tumor Heterogeneity in Longitudinal Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Predicting Response to Neoadjuvant Chemotherapy in Breast Cancer.

Front Mol Biosci 2021 22;8:622219. Epub 2021 Mar 22.

Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, Hangzhou, China.

Breast tumor morphological and vascular characteristics can be changed during neoadjuvant chemotherapy (NACT). The early changes in tumor heterogeneity can be quantitatively modeled by longitudinal dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which is useful in predicting responses to NACT in breast cancer. In this retrospective analysis, 114 female patients with unilateral unifocal primary breast cancer who received NACT were included in a development ( = 61) dataset and a testing dataset ( = 53). DCE-MRI was performed for each patient before and after treatment (two cycles of NACT) to generate baseline and early follow-up images, respectively. Feature-level changes (delta) of the entire tumor were evaluated by calculating the relative net feature change (deltaRAD) between baseline and follow-up images. The voxel-level change inside the tumor was evaluated, which yielded a Jacobian map by registering the follow-up image to the baseline image. Clinical information and the radiomic features were fused to enhance the predictive performance. The area under the curve (AUC) values were assessed to evaluate the prediction performance. Predictive models using radiomics based on pre- and post-treatment images, Jacobian maps and deltaRAD showed AUC values of 0.568, 0.767, 0.630 and 0.726, respectively. When features from these images were fused, the predictive model generated an AUC value of 0.771. After adding the molecular subtype information in the fused model, the performance was increased to an AUC of 0.809 (sensitivity of 0.826 and specificity of 0.800), which is significantly higher than that of the baseline imaging- and Jacobian map-based predictive models ( = 0.028 and 0.019, respectively). The level of tumor heterogeneity reduction (evaluated by texture feature) is higher in the NACT responders than in the nonresponders. The results suggested that changes in DCE-MRI features that reflect a reduction in tumor heterogeneity following NACT could provide early prediction of breast tumor response. The prediction was improved when the molecular subtype information was combined into the model.
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http://dx.doi.org/10.3389/fmolb.2021.622219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044916PMC
March 2021

[Effects of acute high altitude hypoxia on EEG power in different emotional states].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2020 Nov;36(6):556-561

Zhejiang Sci-Tech University, Hangzhou 310018.

To investigate the effects of acute high altitude hypoxia on EEG power in different emotional states. This study was two-factor within-subject design (2 levels of oxygen environment ×4 levels of emotion type). Twelve male subjects aged between 20 and 25 years old were induced to produce four different types of emotions by emotional picture evoked paradigm: low valence and low arousal(LVLA), high valence and low arousal(HVLA), low valence and high arousal(LVHA), high valence and high arousal(HVHA). Brain Products 32 was used to collect EEG signals under different emotional states. The next day, a constant depressed oxygen chamber was used to simulate a 4 300 m plateau hypoxia environment, and the same group of subjects used the same experimental paradigm to collect EEG signals 10h after hypoxia. The collected EEG signals were analyzed by power spectrum (FFT), and the five frequency bands (Delta, Theta, Alpha, beta, gamma) of the frontal lobe (F3\Fz\F4) were analyzed by variance analysis of two-factor repeated measurements. FFT analysis found that before and after acute hypoxia, the whole brain distribution of alpha wave in four emotional states was mainly concentrated in frontal and parietal leaves; the distribution of alpha wave in the whole brain was the least in relaxed emotional state. The results of the two-factor repeated measurement ANOVA showed that: ①the power of delta\ beta band was significantly affected by the oxygen environment(<0.05), and the power was enhanced under hypoxia. ②The power index of theta\ alpha band showed a significant interaction between the oxygen environment and emotional types(<0.05). Except for the HVLA emotional state, the power of theta alpha band was significantly enhanced under hypoxia. ③ The two factors had no significant influence on the gamma band(>0.05). Under the four kinds of emotional states, the difference of the influence of oxygen environment on brain activity was mainly in the frontal lobe, parietal lobe and part of temporal lobe. Of the four types of emotions, the oxygen environment had the least significant effect on brain activity in HVLA emotional states, while the rest showed significant differences.
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http://dx.doi.org/10.12047/j.cjap.5978.2020.117DOI Listing
November 2020

Perceived health-care quality in China: a comparison of second- and third-tier hospitals.

Int J Qual Health Care 2021 Mar;33(1)

Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, China.

Objectives: To evaluate disparity in service quality between second- and third-tier hospitals and explore factors that affect patients' perception of service quality in China.

Design: Cross sectional study.

Setting: Twelve hospitals in China.

Participants: 5714 patients.

Intervention: None.

Main Outcome Measure: Total score of the SERVQUAL scale and each of its five dimensions.

Results: Patients from third-tier hospitals rated significantly higher scores overall and in all the five dimensions of the SERVQUAL scale. Those with lower education, urban residents and those who had higher degree of life satisfaction and attention paid to health perceived higher service quality. Inpatients perceived higher service quality compared with outpatients.

Conclusion: We found a significant gap in patient's perceived service quality between second- and third-tier hospitals in China. A variety of demographic and personality factors were found to significantly influence patient's perceived service quality.
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http://dx.doi.org/10.1093/intqhc/mzab027DOI Listing
March 2021

The traffic light pilot study: assessing the level of evidence for interventions in obstetrics and gynaecology.

J Obstet Gynaecol 2021 Feb 18:1-4. Epub 2021 Feb 18.

Monash Women's, Monash Health, Clayton, Australia.

Evidence-based medicine tries to support clinicians through research, integrated with clinical skill and patient values. This pilot study aimed to assess appropriateness and level of evidence of current clinical practices, through evaluating availability and quality of guidelines.A prospective observational study in a large tertiary hospital network was performed, sampling diagnostic and therapeutic interventions in obstetrics and gynaecology. Interventions performed were justified against knowledge in the published literature, and guideline recommended practice. We collected 58 patient observations, 40(69%) in obstetrics, 18(31%) in gynaecology. There were local guidelines relevant in 52%, national in 22%, and international guidelines in 12%. In 50 interventions with available guidelines, 54% provided strong and clear recommendations for practice, and were supported by research-based knowledge. Similarly, 66% of encounters were thought to be in concordance with research-based knowledge.There was good concordance between interventions and guideline recommendations. However, half of guidelines reviewed had limited or no knowledge to justify their recommendations.IMPACT STATEMENT Evidence based medicine should aim to improve patient outcomes. However, available trials assessing effectiveness of established practices suggest that they convey little to no benefit to patients. There remains a paucity of evidence for established practices in obstetrics and gynaecology This pilot study assesses the usefulness of interventions in obstetrics and gynaecology and confirms the feasibility of collecting and coding our interventions and clinical practices with a traffic light system. These findings demonstrate the feasibility of our traffic lights grading system within obstetrics and gynaecology. It demonstrates this method is useful to assess what knowledge base is guiding clinical practice, how well practice concords with guidelines and literature, as well as the presence and significance of any gaps in knowledge. These early findings will be used in an expanded study and have implications on the way healthcare effectiveness is evaluated, as well as reducing healthcare expenditure in obstetrics and gynaecology.
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http://dx.doi.org/10.1080/01443615.2020.1845635DOI Listing
February 2021

Any day, split halfway: Flexibility in scheduling high-dose cisplatin-A large retrospective review from a high-volume cancer center.

Int J Cancer 2021 Jul 27;149(1):139-148. Epub 2021 Feb 27.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

High-dose (HD) cisplatin remains the standard of care with chemoradiation for locally advanced oropharyngeal cancer (OPC). Cooperative group trials mandate bolus-HD (100 mg/m  × 1 day, every 3 weeks) cisplatin administration at the beginning of the week to optimize radiosensitization-a requirement which may be unnecessary. This analysis evaluates the impact of chemotherapy administration day of week (DOW) on outcomes. We also report our institutional experience with an alternate dosing schedule, split-HD (50 mg/m  × 2 days, every 3 weeks). We retrospectively reviewed 435 definitive chemoradiation OPC patients from 10 December 2001 to 23 December 2014. Those receiving non-HD cisplatin regimens or induction chemotherapy were excluded. Data collected included DOW, dosing schedule (bolus-HD vs split-HD), smoking, total cumulative dose (TCD), stage, Karnofsky Performance Status, human papillomavirus status and creatinine (baseline, peak and posttreatment baseline). Local failure (LF), regional failure (RF), locoregional failure (LRF), distant metastasis (DM), any failure (AF, either LRF or DM) and overall survival (OS) were calculated from radiation therapy start. Median follow-up was 8.0 years (1.8 months-17.0 years). DOW, dosing schedule and TCD were not associated with any outcomes in univariable or multivariable regression models. There was no statistically significant difference in creatinine or association with TCD in split-HD vs bolus-HD. There was no statistically significant association between DOW and outcomes, suggesting that cisplatin could be administered any day. Split-HD had no observed differences in outcomes, renal toxicity or TCD compared to bolus-HD cisplatin. Our data suggest that there is some flexibility of when and how to give HD cisplatin compared to clinical trial mandates.
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http://dx.doi.org/10.1002/ijc.33518DOI Listing
July 2021

HMD-ARG: hierarchical multi-task deep learning for annotating antibiotic resistance genes.

Microbiome 2021 02 8;9(1):40. Epub 2021 Feb 8.

Computational Bioscience Research Center (CBRC), Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955, Saudi Arabia.

Background: The spread of antibiotic resistance has become one of the most urgent threats to global health, which is estimated to cause 700,000 deaths each year globally. Its surrogates, antibiotic resistance genes (ARGs), are highly transmittable between food, water, animal, and human to mitigate the efficacy of antibiotics. Accurately identifying ARGs is thus an indispensable step to understanding the ecology, and transmission of ARGs between environmental and human-associated reservoirs. Unfortunately, the previous computational methods for identifying ARGs are mostly based on sequence alignment, which cannot identify novel ARGs, and their applications are limited by currently incomplete knowledge about ARGs.

Results: Here, we propose an end-to-end Hierarchical Multi-task Deep learning framework for ARG annotation (HMD-ARG). Taking raw sequence encoding as input, HMD-ARG can identify, without querying against existing sequence databases, multiple ARG properties simultaneously, including if the input protein sequence is an ARG, and if so, what antibiotic family it is resistant to, what resistant mechanism the ARG takes, and if the ARG is an intrinsic one or acquired one. In addition, if the predicted antibiotic family is beta-lactamase, HMD-ARG further predicts the subclass of beta-lactamase that the ARG is resistant to. Comprehensive experiments, including cross-fold validation, third-party dataset validation in human gut microbiota, wet-experimental functional validation, and structural investigation of predicted conserved sites, demonstrate not only the superior performance of our method over the state-of-art methods, but also the effectiveness and robustness of the proposed method.

Conclusions: We propose a hierarchical multi-task method, HMD-ARG, which is based on deep learning and can provide detailed annotations of ARGs from three important aspects: resistant antibiotic class, resistant mechanism, and gene mobility. We believe that HMD-ARG can serve as a powerful tool to identify antibiotic resistance genes and, therefore mitigate their global threat. Our method and the constructed database are available at http://www.cbrc.kaust.edu.sa/HMDARG/ . Video abstract (MP4 50984 kb).
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http://dx.doi.org/10.1186/s40168-021-01002-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871585PMC
February 2021

Serine, glycine and one‑carbon metabolism in cancer (Review).

Int J Oncol 2021 Feb 11;58(2):158-170. Epub 2020 Dec 11.

Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cellular and Molecular Immunology of Henan Province, Institute of Translational Medicine, School of Basic Medicine, Henan University, Kaifeng, Henan 475004, P.R. China.

Serine/glycine biosynthesis and one‑carbon metabolism are crucial in sustaining cancer cell survival and rapid proliferation, and of high clinical relevance. Excessive activation of serine/glycine biosynthesis drives tumorigenesis and provides a single carbon unit for one‑carbon metabolism. One‑carbon metabolism, which is a complex cyclic metabolic network based on the chemical reaction of folate compounds, provides the necessary proteins, nucleic acids, lipids and other biological macromolecules to support tumor growth. Moreover, one‑carbon metabolism also maintains the redox homeostasis of the tumor microenvironment and provides substrates for the methylation reaction. The present study reviews the role of key enzymes with tumor‑promoting functions and important intermediates that are physiologically relevant to tumorigenesis in serine/glycine/one‑carbon metabolism pathways. The related regulatory mechanisms of action of the key enzymes and important intermediates in tumors are also discussed. It is hoped that investigations into these pathways will provide new translational opportunities for human cancer drug development, dietary interventions, and biomarker identification.
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http://dx.doi.org/10.3892/ijo.2020.5158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864012PMC
February 2021

Loss of Wip1 aggravates brain injury after ischaemia/reperfusion by overactivating microglia.

Stroke Vasc Neurol 2021 Jan 15. Epub 2021 Jan 15.

Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.

Background And Purpose: The inflammatory response mediated by microglia/macrophages is closely related to cerebral ischaemia/reperfusion injury. Wild-type p53-induced protein phosphatase 1 (Wip1), a serine/threonine phosphatase, is expressed in various tissues. A growing number of reports have suggested that Wip1 is a negative regulator of inflammation in peripheral tissue; however, its role in the central nervous system (CNS) remains unclear. This study aimed to clarify whether Wip1 can inhibit CNS inflammation by regulating microglia/macrophage functions after ischaemic injury.

Methods: A model of middle cerebral artery occlusion and reperfusion was established in mice. CNS inflammation was simulated by lipopolysaccharide treatment of primary microglia. Laser speckle imaging was used to monitor regional cerebral blood flow. Behavioural outcomes were assessed with a TreadScan gait analysis system. TTC staining was used to evaluate the infarct volume, and western blotting and immunofluorescence staining were applied to detect the phenotypical transformation of microglia. ELISA was performed to detect the levels of inflammatory factors.

Results: Wip1 expression was increased after ischaemia/reperfusion. Wip1-knockout (KO) mice displayed more severe brain injury than wild-type mice, as indicated by aggravated motor dysfunction, greater brain infarct volumes and higher expression of inflammatory cytokines (interleukin-6 and tumour necrosis factor alpha) in the brain. We also found that Wip1 depletion increased microglial/macrophage activation in both in vitro and in vivo models, which all showed activation of microglia/macrophages. Lentivirus- reversed the injury induced by Wip1-KO.

Conclusions: Our results suggest that Wip1 may inhibit neuroinflammation by inhibiting microglial/macrophage activation after brain ischaemia/reperfusion injury.
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http://dx.doi.org/10.1136/svn-2020-000490DOI Listing
January 2021

Transcriptomic analysis identifies organ-specific metastasis genes and pathways across different primary sites.

J Transl Med 2021 01 7;19(1):31. Epub 2021 Jan 7.

Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, Hangzhou, 310000, China.

Background: Metastasis is the most devastating stage of cancer progression and often shows a preference for specific organs.

Methods: To reveal the mechanisms underlying organ-specific metastasis, we systematically analyzed gene expression profiles for three common metastasis sites across all available primary origins. A rank-based method was used to detect differentially expressed genes between metastatic tumor tissues and corresponding control tissues. For each metastasis site, the common differentially expressed genes across all primary origins were identified as organ-specific metastasis genes.

Results: Pathways enriched by these genes reveal an interplay between the molecular characteristics of the cancer cells and those of the target organ. Specifically, the neuroactive ligand-receptor interaction pathway and HIF-1 signaling pathway were found to have prominent roles in adapting to the target organ environment in brain and liver metastases, respectively. Finally, the identified organ-specific metastasis genes and pathways were validated using a primary breast tumor dataset. Survival and cluster analysis showed that organ-specific metastasis genes and pathways tended to be expressed uniquely by a subgroup of patients having metastasis to the target organ, and were associated with the clinical outcome.

Conclusions: Elucidating the genes and pathways underlying organ-specific metastasis may help to identify drug targets and develop treatment strategies to benefit patients.
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http://dx.doi.org/10.1186/s12967-020-02696-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791985PMC
January 2021

Hypoxia Augments Cerebral Inflammation in a Dextran Sulfate Sodium-Induced Colitis Mouse Model.

Front Cell Neurosci 2020 9;14:611764. Epub 2020 Dec 9.

Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing, China.

The importance of hypoxia in the pathophysiology of inflammatory bowel disease (IBD) is increasingly being realized; also, hypoxia seems to be an important accelerator of brain inflammation, as has been reported by our group and others. IBD is a chronic intestinal disorder that leads to the development of inflammation, which is related to brain dysfunction. However, no studies have reported whether hypoxia is associated with IBD-induced neuroinflammation. Therefore, the objective of the present study was to determine whether hypoxia augments cerebral inflammation in a DSS-induced colitis mouse model. The mouse model was developed using 3% DSS for five days combined with exposure to hypoxic conditions (6,000 m) for two days. Mice were randomly divided into four groups: control group, DSS group, hypoxia group, and DSS plus hypoxia group. The results demonstrated that DSS combined with hypoxia resulted in up-regulation of colonic and plasmatic proinflammatory cytokines. Meanwhile, DSS plus hypoxia increased expression of Iba1, which is a marker of activated microglia, accompanied by increased expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the brain. Moreover, the expression of tight junction proteins, such as zonula occludens-1 (ZO-1), occludin, and claudin-5, was markedly downregulated. The current study provides new insight into how hypoxia exposure induces excessive inflammatory responses andpathophysiological consequences in the brain in a DSS-induced colitis model.
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http://dx.doi.org/10.3389/fncel.2020.611764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756107PMC
December 2020

Transferrin receptor 1 plays an important role in muscle development and denervation-induced muscular atrophy.

Neural Regen Res 2021 Jul;16(7):1308-1316

Department of Neurobiology, Beijing Institute of Basic Medical Sciences; Chinese Institute for Brain Research (CIBR), Beijing; Key Laboratory of Neuroregeneration, Coinnovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.

Previous studies demonstrate an accumulation of transferrin and transferrin receptor 1 (TfR1) in regenerating peripheral nerves. However, the expression and function of transferrin and TfR1 in the denervated skeletal muscle remain poorly understood. In this study, a mouse model of denervation was produced by complete tear of the left brachial plexus nerve. RNA-sequencing revealed that transferrin expression in the denervated skeletal muscle was upregulated, while TfR1 expression was downregulated. We also investigated the function of TfR1 during development and in adult skeletal muscles in mice with inducible deletion or loss of TfR1. The ablation of TfR1 in skeletal muscle in early development caused severe muscular atrophy and early death. In comparison, deletion of TfR1 in adult skeletal muscles did not affect survival or glucose metabolism, but caused skeletal muscle atrophy and motor functional impairment, similar to the muscular atrophy phenotype observed after denervation. These findings suggest that TfR1 plays an important role in muscle development and denervation-induced muscular atrophy. This study was approved by the Institutional Animal Care and Use Committee of Beijing Institute of Basic Medical Sciences, China (approval No. SYXK 2017-C023) on June 1, 2018.
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http://dx.doi.org/10.4103/1673-5374.301024DOI Listing
July 2021

A novel low-cost electrode for recording the local field potential of freely moving rat's brain.

Transl Neurosci 2020 5;11(1):96-104. Epub 2020 Jun 5.

Institute of Military Cognition and Brain Sciences, Beijing, P. R. China.

Local field potentials (LFPs) are involved in almost all cognitive activities of animals. Several kinds of recording electrodes are used for recording LFPs in freely moving animals, including commercial and homemade electrodes. However, commercial recording electrodes are expensive, and their relatively fixed size often causes a steric hindrance effect, especially when combining deep brain stimulation (DBS) with LFP recording, which may not always satisfy the aim of researchers. Currently, an increasing number of researchers are designing their own recording electrodes to lower research costs. Nevertheless, there is no simple universal method to produce low-cost recording electrodes with a specific size according to the target brain area. Thus, we developed a simple method for quickly producing low-cost multiple-channel recording electrodes. To inspect the effectiveness of our self-designed electrode, LFPs were recorded in a Parkinson's disease (PD) rat model, and an electrical stimulation electrode was implanted into the subthalamic nucleus to verify the space-saving ability of the self-designed recording electrode. The results showed that <30 min was needed to prepare an electrode and that the electrode materials cost <5 dollars. Further investigations showed that our electrode successfully recorded the beta oscillations (12-40 Hz) in the PD rat model. Thus, this method will greatly reduce the cost of recording electrodes and save time for researchers. Additionally, the small size of the electrode will further facilitate DBS research.
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http://dx.doi.org/10.1515/tnsci-2020-0104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705991PMC
June 2020

Mass Detection and Segmentation in Digital Breast Tomosynthesis Using 3D-Mask Region-Based Convolutional Neural Network: A Comparative Analysis.

Front Mol Biosci 2020 11;7:599333. Epub 2020 Nov 11.

Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, Hangzhou, China.

Digital breast tomosynthesis (DBT) is an emerging breast cancer screening and diagnostic modality that uses quasi-three-dimensional breast images to provide detailed assessments of the dense tissue within the breast. In this study, a framework of a 3D-Mask region-based convolutional neural network (3D-Mask RCNN) computer-aided diagnosis (CAD) system was developed for mass detection and segmentation with a comparative analysis of performance on patient subgroups with different clinicopathological characteristics. To this end, 364 samples of DBT data were used and separated into a training dataset ( = 201) and a testing dataset ( = 163). The detection and segmentation results were evaluated on the testing set and on subgroups of patients with different characteristics, including different age ranges, lesion sizes, histological types, lesion shapes and breast densities. The results of our 3D-Mask RCNN framework were compared with those of the 2D-Mask RCNN and Faster RCNN methods. For lesion-based mass detection, the sensitivity of 3D-Mask RCNN-based CAD was 90% with 0.8 false positives (FPs) per lesion, whereas the sensitivity of the 2D-Mask RCNN- and Faster RCNN-based CAD was 90% at 1.3 and 2.37 FPs/lesion, respectively. For breast-based mass detection, the 3D-Mask RCNN generated a sensitivity of 90% at 0.83 FPs/breast, and this framework is better than the 2D-Mask RCNN and Faster RCNN, which generated a sensitivity of 90% with 1.24 and 2.38 FPs/breast, respectively. Additionally, the 3D-Mask RCNN achieved significantly ( < 0.05) better performance than the 2D methods on subgroups of samples with characteristics of ages ranged from 40 to 49 years, malignant tumors, spiculate and irregular masses and dense breast, respectively. Lesion segmentation using the 3D-Mask RCNN achieved an average precision (AP) of 0.934 and a false negative rate (FNR) of 0.053, which are better than those achieved by the 2D methods. The results suggest that the 3D-Mask RCNN CAD framework has advantages over 2D-based mass detection on both the whole data and subgroups with different characteristics.
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http://dx.doi.org/10.3389/fmolb.2020.599333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686533PMC
November 2020

Close Homolog of L1 Deficiency Exacerbated Intestinal Epithelial Barrier Function in Mouse Model of Dextran Sulfate Sodium-Induced Colitis.

Front Physiol 2020 6;11:584508. Epub 2020 Nov 6.

Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing, China.

The cell adhesion molecule CHL1, which belongs to the immunoglobulin superfamily, functions in a variety of physiological and pathological processes, including neural development, tissue injury, and repair. We previously found that the loss of CHL1 exacerbated the dextran sulfate sodium (DSS)-induced colitis in mice. In the present study, we further addressed the role of CHL1 in mouse model of DSS-induced colitis and its' potential mechanism. Colon tissues were collected from CHL1, CHL1, and CHL1 mice after DSS induction to investigate the effects of CHL1 on the development of colitis. The data showed that CHL1 was expressed in intestine tissue, and expression of CHL1 was increased by DSS-induced inflammation. CHL1 deficiency induced more pronounced colitis features, exacerbated inflammation, and damage to colonic tissues in DSS-induced mice. Moreover, colonic tissues of CHL1 mice showed a marked increase in neutrophil and macrophage infiltration, be accompanied by more severe damage to intestinal epithelial cells and higher fluorescein isothiocyanate (FITC) leakage. Our results revealed deficiency of CHL1 exacerbated DSS-induced colitis, and this pathogenesis was potentially mediated by disruption of intestinal barrier integrity, indicating that CHL1 may be an attractive therapeutic target for inflammatory bowel diseases (IBDs) in mice.
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http://dx.doi.org/10.3389/fphys.2020.584508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677258PMC
November 2020

Multi-stimuli-responsive, liposome-crosslinked poly(ethylene glycol) hydrogels for drug delivery.

J Biomater Sci Polym Ed 2021 Apr 22;32(5):635-656. Epub 2020 Dec 22.

Department of Materials Science and Engineering, University of Delaware, Newark, DE, USA.

The development of hybrid hydrogels has been of great interest over recent decades, especially in the field of biomaterials. Such hydrogels provide various opportunities in tissue engineering, drug delivery, and regenerative medicine due to their ability to mimic cellular environments, sequester and release therapeutic agents, and respond to stimuli. Herein we report the synthesis and characterization of an injectable poly(ethylene glycol) hydrogel crosslinked thiol-maleimide reactions and containing both chemically crosslinked temperature-sensitive liposomes (TSLs) and matrix metalloproteinase-sensitive peptide crosslinks. Rheological studies demonstrate that the hydrogel is mechanically stable and can be synthesized to achieve a range of physically applicable moduli. Experiments characterizing the drug delivery and degradation of these materials indicate that the TSL gel responds to both thermal and enzymatic stimuli in a local environment. Doxorubicin, a widely used anticancer drug, was loaded in the TSLs with a high encapsulation efficiency and the subsequent release was temperature dependent. Finally, TSLs did not compromise viability and proliferation of human and murine fibroblasts, supporting the use of these hydrogel-linked liposomes as a thermo-responsive drug carrier for controlled release.
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http://dx.doi.org/10.1080/09205063.2020.1855392DOI Listing
April 2021

Mosquito-infecting virus Espirito Santo virus inhibits replication and spread of dengue virus.

J Med Virol 2021 06 1;93(6):3362-3373. Epub 2020 Dec 1.

Department of Health Education and Promotion, Environmental Health Sciences Program, College of Health and Human Performance, East Carolina University, Greenville, North Carolina, USA.

The primary vector of dengue virus (DENV) is Aedes aegypti. The mosquito-infecting virus, Espirito Santo virus (ESV), does not infect Vero (mammalian) cells and grows in mosquito (C6/36) cells without cytopathic effects. Effects of ESV infection on replication of DENV were explored in vitro and in vivo, analyzing protein, RNA genome expression, and plaque formation. ESV and DENV simultaneous coinfection did not block protein synthesis from either virus but did result in inhibition of DENV replication in mosquito cells. Furthermore, ESV superinfected with DENV resulted in inhibition of DENV replication and spread in A. aegypti, thus reducing vector competence. Tissue culture experiments on viral kinetics of ESV and DENV coinfection showed that neither virus significantly affects the replication of the other in Vero, HeLa, or HEK cells. Hence, ESV blocks DENV replication in insect cells, but not the mammalian cells evaluated here. Our study provides new insights into ESV-induced suppression of DENV, a globally important pathogen impacting public health.
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http://dx.doi.org/10.1002/jmv.26686DOI Listing
June 2021

Metabolomic-proteomic combination analysis reveals the targets and molecular pathways associated with hydrogen sulfide alleviating NAFLD.

Life Sci 2021 Jan 23;264:118629. Epub 2020 Oct 23.

Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cellular and Molecular Immunology of Henan Province, Institute of Translational Medicine, School of Basic Medicine, Henan University, Kaifeng 475004, China. Electronic address:

Aims: Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide. Exogenous HS has been shown to effectively mitigate NAFLD, although little is known about the underlying targets and molecular mechanisms.

Methods: C57BL/6 mice were fed with normal fat diet (NFD) or high fat diet (HFD) for a total 16 weeks, and HFD-fed mice were treated with saline or NaHS beginning in 12th week. The combination analysis of metabolomics and proteomics of liver tissues was firstly performed to discover the candidate targets and potential molecular pathways involved in HS mitigating the NAFLD.

Key Findings: Compared with NaCl, HS relieved NAFLD by reducing liver weight, body weight and lipid accumulation in liver, and improving liver pathology and serum biochemical parameters. There were 40 overlapping metabolites in the intersection analysis between comparative analysis of HFD + NaCl vs NFD and HFD + NaHS vs HFD + NaCl based on liver metabolomics. Moreover, a total of 58 proteins were obtained whose changes were reversed after treatment with HS. A combined analysis of liver metabolomics and proteomics was then conducted, revealing 8 shared molecular pathways, as well as the enrichment of unsaturated fatty acids. In addition, Plin2 may also be a potential target of HS via the regulation of lipid droplet degradation in alleviating NAFLD.

Significance: We performed the first study combining metabolomics and proteomics to explore the mechanisms behind the alleviation of NAFLD by HS. Our results not only provide evidence that HS alleviates NAFLD but also reveals its possible molecular mechanisms and targets.
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http://dx.doi.org/10.1016/j.lfs.2020.118629DOI Listing
January 2021

Radiogenomic signatures reveal multiscale intratumour heterogeneity associated with biological functions and survival in breast cancer.

Nat Commun 2020 09 25;11(1):4861. Epub 2020 Sep 25.

Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, 310018, Hangzhou, Zhejiang, China.

Advanced tumours are often heterogeneous, consisting of subclones with various genetic alterations and functional roles. The precise molecular features that characterize the contributions of multiscale intratumour heterogeneity to malignant progression, metastasis, and poor survival are largely unknown. Here, we address these challenges in breast cancer by defining the landscape of heterogeneous tumour subclones and their biological functions using radiogenomic signatures. Molecular heterogeneity is identified by a fully unsupervised deconvolution of gene expression data. Relative prevalence of two subclones associated with cell cycle and primary immunodeficiency pathways identifies patients with significantly different survival outcomes. Radiogenomic signatures of imaging scale heterogeneity are extracted and used to classify patients into groups with distinct subclone compositions. Prognostic value is confirmed by survival analysis accounting for clinical variables. These findings provide insight into how a radiogenomic analysis can identify the biological activities of specific subclones that predict prognosis in a noninvasive and clinically relevant manner.
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http://dx.doi.org/10.1038/s41467-020-18703-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519071PMC
September 2020

Dual blockade of CD47 and HER2 eliminates radioresistant breast cancer cells.

Nat Commun 2020 09 14;11(1):4591. Epub 2020 Sep 14.

Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, USA.

Although the efficacy of cancer radiotherapy (RT) can be enhanced by targeted immunotherapy, the immunosuppressive factors induced by radiation on tumor cells remain to be identified. Here, we report that CD47-mediated anti-phagocytosis is concurrently upregulated with HER2 in radioresistant breast cancer (BC) cells and RT-treated mouse syngeneic BC. Co-expression of both receptors is more frequently detected in recurrent BC patients with poor prognosis. CD47 is upregulated preferentially in HER2-expressing cells, and blocking CD47 or HER2 reduces both receptors with diminished clonogenicity and augmented phagocytosis. CRISPR-mediated CD47 and HER2 dual knockouts not only inhibit clonogenicity but also enhance macrophage-mediated attack. Dual antibody of both receptors synergizes with RT in control of syngeneic mouse breast tumor. These results provide the evidence that aggressive behavior of radioresistant BC is caused by CD47-mediated anti-phagocytosis conjugated with HER2-prompted proliferation. Dual blockade of CD47 and HER2 is suggested to eliminate resistant cancer cells in BC radiotherapy.
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http://dx.doi.org/10.1038/s41467-020-18245-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490264PMC
September 2020

Characteristics of CD133-Sustained Chemoresistant Cancer Stem-Like Cells in Human Ovarian Carcinoma.

Int J Mol Sci 2020 Sep 4;21(18). Epub 2020 Sep 4.

Department of Pathology, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.

Cancer stem cells (CSCs) are considered to be the origin of ovarian cancer (OC) development, recurrence, and chemoresistance. We investigated changes in expression levels of the CSC biomarker, cluster of differentiation 133 (CD133), from primary OC cell lines to induction of CSC-spheres in an attempt to explore the mechanisms related to modulation of stemness, drug resistance, and tumorigenesis in CSCs, thus facilitating the search for new therapeutics for OC. The effect of CD133 overexpression on the induction of CSC properties was evaluated by sphere-forming assays, RT-qPCR, flow cytometry, cell viability assays, and in vivo xenograft experiments. Moreover, the potential signaling molecules that participate in CD133 maintenance of stemness were screened by RNA-sequencing. CD133 expression was upregulated during OCSC induction and chemotherapeutic drug treatment over time, which increased the expressions of stemness-related markers (SOX2, OCT4, and Nanog). CD133 overexpression also promoted tumorigenesis in NOD/SCID mice. Several signalings were controlled by CD133 spheres, including extracellular matrix receptor interactions, chemokine signaling, and Wnt signaling, all of which promote cell survival and cell cycle progression. Our findings suggest that CD133 possesses the ability to maintain functional stemness and tumorigenesis of OCSCs by promoting cell survival signaling and may serve as a potential target for stem cell-targeted therapy of OC.
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http://dx.doi.org/10.3390/ijms21186467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554888PMC
September 2020

Loss of O-GlcNAc transferase in neural stem cells impairs corticogenesis.

Biochem Biophys Res Commun 2020 11 4;532(4):541-547. Epub 2020 Sep 4.

Department of Neurobiology, Beijing Institute of Basic Medical Sciences, 100850, Beijing, China; College of Hengyang Medical Sciences, Nanhua University, Hengyang, 421001, Hunan Province, China; Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226019, Jiangsu Province, China; Chinese Institute for Brain Research, 102206, Beijing, China. Electronic address:

The proper development of the cerebral cortex is essential for brain formation and functioning. O-GlcNAcylation, an important posttranslational modification, regulates the pathways critical for neuronal health and the survival of the cerebral cortex in neurodegenerative diseases. However, the role of O-GlcNAcylation in regulating cerebral cortical development at the embryonic and early postnatal (0-21 days) stages is still largely unknown. Here we report that the selective deletion of O-GlcNAc transferase (OGT) in neural stem cells (NSCs) in mice led to a series of severe brain developmental deficits, including dramatic shrinkage of cortical and hippocampal histoarchitecture, widespread neuronal apoptosis, decrease in cell proliferation, induction of endoplasmic reticulum (ER) stress, and inhibition of neuronal dendritic and axonal differentiation. The pathology of corticogenesis deficits caused by OGT deletion may largely rely on complicated biological processes, such as proliferation, apoptosis and differentiation. Our results suggest that dysfunctional O-GlcNAcylation in NSCs may be an important contributor to neurodevelopmental diseases.
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http://dx.doi.org/10.1016/j.bbrc.2020.08.084DOI Listing
November 2020

Oryzias sinensis, a new model organism in the application of eco-toxicity and water quality criteria (WQC).

Chemosphere 2020 Dec 30;261:127813. Epub 2020 Jul 30.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, China. Electronic address:

Fish play an important role as a primary eco-toxicity test organism in environmental hazard assessment. Toxicity data of native species are often sought for use in the derivation of water quality criteria (WQC). The Chinese medaka, Oryzias sinensis, is an endemic species of China. The acute toxicity of 6 chemicals on O. sinensis was tested in this work, and toxicity effect of 10 chemicals to O. sinensis was compared with 4 commonly used species globally. A total of 9 robust interspecies correlation estimation (ICE) models using O. sinensis as the surrogate species were constructed and used to derive predicted no effect concentration and hazardous concentrations of 5% species (HC) values based on species sensitivity distribution. Results showed that the 96 h median lethal concentration of Hg, Cr, linear alkylbenzene sulfonates, triclosan, 3,4-dchloroaniline, sodium chloride to O. sinensis were 0.29, 50, 6.0, 0.63, 9.2 and 14,400 mg/L, respectively. The sensitivity of O. sinensis and other 4 testing organisms were statistically indistinguishable (P > 0.05). No significant difference among HC-ICE, HC-measured and HC from published literatures was identified. All results indicated the O. sinensis is a potential model organism in the application of eco-toxicity and WQC in China and other Asian countries.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127813DOI Listing
December 2020

A Rapid, Accurate and Machine-Agnostic Segmentation and Quantification Method for CT-Based COVID-19 Diagnosis.

IEEE Trans Med Imaging 2020 Aug;39(8):2638-2652

COVID-19 has caused a global pandemic and become the most urgent threat to the entire world. Tremendous efforts and resources have been invested in developing diagnosis, prognosis and treatment strategies to combat the disease. Although nucleic acid detection has been mainly used as the gold standard to confirm this RNA virus-based disease, it has been shown that such a strategy has a high false negative rate, especially for patients in the early stage, and thus CT imaging has been applied as a major diagnostic modality in confirming positive COVID-19. Despite the various, urgent advances in developing artificial intelligence (AI)-based computer-aided systems for CT-based COVID-19 diagnosis, most of the existing methods can only perform classification, whereas the state-of-the-art segmentation method requires a high level of human intervention. In this paper, we propose a fully-automatic, rapid, accurate, and machine-agnostic method that can segment and quantify the infection regions on CT scans from different sources. Our method is founded upon two innovations: 1) the first CT scan simulator for COVID-19, by fitting the dynamic change of real patients' data measured at different time points, which greatly alleviates the data scarcity issue; and 2) a novel deep learning algorithm to solve the large-scene-small-object problem, which decomposes the 3D segmentation problem into three 2D ones, and thus reduces the model complexity by an order of magnitude and, at the same time, significantly improves the segmentation accuracy. Comprehensive experimental results over multi-country, multi-hospital, and multi-machine datasets demonstrate the superior performance of our method over the existing ones and suggest its important application value in combating the disease.
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http://dx.doi.org/10.1109/TMI.2020.3001810DOI Listing
August 2020

Effects on Suxiao Jiuxin Pills in the Treatment of Patients with Acute Coronary Syndrome Undergoing Early Percutaneous Coronary Intervention: A Multicenter Randomized Double-Blind Placebo-Controlled Trial.

J Altern Complement Med 2020 Nov 21;26(11):1055-1063. Epub 2020 Jul 21.

Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Acute coronary syndrome (ACS) is an acute disease with high mortality. Although early percutaneous coronary intervention (PCI) is proved to be the practical approach in treating ACS, the incidence of cardiovascular events is still far from satisfactory. The combination of Suxiao Jiuxin Pill (SJP) and Western medicine is one conventional approach in the treatment of ACS. Many elementary and clinical trials have proved the efficacy and safety in the improvement of cardiocerebral vascular conditions. The aim of this project is to evaluate the safety and efficacy of SJP on ACS with early PCI patients. This is a multicenter randomized, double-blind placebo-controlled trial. Trial registration: ChiCTR-TRC-13003053. Hospitals. A total of 200 ACS with early PCI patients were randomly divided into SJP group ( = 100) and placebo group ( = 100). The SJP group was treated with routine treatment and SJP (taking eight SJP pills orally each time, three times per day). The placebo group was treated with routine treatment along with equal amounts of SJP placebo. The course of treatment was 6 months and a follow-up visit at 12 months. Assessments of major adverse cardiovascular events (MACE), safety assessments, adverse events, left ventricular systolic function (LVEF), Seattle angina questionnaire (SAQ), troponin C (cTNI), C-reactive protein (CRP), fibrinogen (Fib), and cystatin C (cysC). The SJP group had a relatively low incidence of MACE than the placebo ( < 0.05, odds ratio: 1.916, 95% confidence interval [0.999-3.674]). LVEF was significantly higher in the SJP group than the placebo group on the 360-day follow-up ( < 0.01). SJP had a significant increase score in the SAQ subscale of physical limitation, angina frequency, and treatment satisfaction ( < 0.05). There is no significant difference in the cTNI and CRP level between the two groups. The serum concentration of Fib and cysC in the SJP was significantly decreased compared with the placebo ( < 0.05). The numbers of adverse events between the two groups were not statistically different ( > 0.05). SJP is associated with a reduction in MACE, and an improvement of heart function and quality of life in ACS patients with early PCI, and is probably safe to use.
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http://dx.doi.org/10.1089/acm.2020.0014DOI Listing
November 2020

Engineering Chimeric Antigen Receptor T Cells against Immune Checkpoint Inhibitors PD-1/PD-L1 for Treating Pancreatic Cancer.

Mol Ther Oncolytics 2020 Jun 26;17:571-585. Epub 2020 May 26.

School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a 5-year survival rate of 9%. Major obstacles to successful treatment of pancreatic cancer are the immunosuppressive tumor microenvironment (TME) and antigenic complexity or heterogeneity. Programmed death-ligand 1 (PD-L1) is expressed on PDAC and immunosuppressed cells within the TME, providing suitable immunotherapy targets. We applied a chimeric antigen receptor (CAR) strategy to target immune checkpoint programmed death-1 (PD-1)/PD-L1 interactions. Lentiviral vectors were used to express the extracellular domain of human PD-1 (PD-1-CD28-4-1BB activating chimeric receptor [PD1ACR]) or the single-chain variable fragment (scFv) region of anti-PD-L1 (PDL1CAR) that binds to PD-L1, and each was fused to intracellular signaling domains containing CD3 zeta, CD28, and 4-1BB (CD137). Both engineered CAR T cells recognized and eliminated PD-L1-overexpressing CFPAC1 cells efficiently at approximately 80% . Adoptive transfer of both CAR T cells enhanced T cell persistence and induced specific regression of established CFPAC1 cancer by >80% in both xenograft and orthotopic models. Ki67 expression in tumors decreased, whereas proinflammatory cytokines/chemokines increased in CAR T cell-treated mouse sera. PD1ACR and PDL1CAR obtained a similar therapeutic efficacy. Thus, these armed third-generation PD-L1-targeted CAR T cells confer antitumor activity and the ability to combat T cell exhaustion, providing a potentially new and innovative CAR T cell immunotherapy against pancreatic cancers.
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http://dx.doi.org/10.1016/j.omto.2020.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321819PMC
June 2020

Neural progenitor cells-secreted exosomal miR-210 induced by hypoxia influences cell viability.

Neuroreport 2020 08;31(11):798-805

Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences.

Hypoxia as a microenvironment is essential for the development of neural stem/progenitor cells (NSCs/NPCs). Our previous studies showed that mild hypoxia can promote proliferation of NPCs. However, the underlying mechanisms are remaining unknown. In the present study, we explored the impact of hypoxia on miR-210 secretion and its effect on cell viability. We found that short time or long time of hypoxia treatment could increase the expression of miR-210, but also promoted its secretion into the medium. The results of exosomes isolation and quantitative real-time PCR showed that hypoxia increased the levels of miR-210 in the exosome enriched from the medium. In addition, the secreted miR-210 can be absorbed by recipient NPCs. The resutls of cell viability assay showed that low levels of secreted miR-210 slightly increased cell viability of NPCs. In contrast, high levels of secreted miR-210 exhibited an inhibitory effect on cell viability. These effects were blocked by an miR-210-specific inhibitor. Taken together, hypoxia increased secretion of miR-210 in exosomes and exhibited a differential effect on cell viability of recipient NPCs.Video abstract: http:/links.lww.com/WNR/A588.
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http://dx.doi.org/10.1097/WNR.0000000000001490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340230PMC
August 2020

Physiological and iTRAQ-based proteomic analyses reveal the mechanism of pinocembrin against Penicillium italicum through targeting mitochondria.

Pestic Biochem Physiol 2020 Jul 30;167:104534. Epub 2020 Jan 30.

Key Laboratory of Environment Correlative Dietology, Ministry of Education, College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China.

The physiological and iTRAQ-based proteomic analyses were used to reveal the inhibitory roles of pinocembrin on mitochondria of P. italicum and its cell death mechanism. The results show that pinocembrin damages both mitochondrial structure and function. 167 and 807 differentially expressed proteins (DEPs) were detected in P. italicum mycelia after treatment with pinocembrin for 8 h and 24 h respectively, and the DEPs were significantly enriched in the oxidative phosphorylation (OXPHOS) pathway, especially for mitochondrial respiratory chain (MRC) complexes I and V. Furthermore, the expression levels of proteins related to programmed cell death (PCD) were significantly up-regulated in mycelia with Pinocembrin incubation for 24 h. Combined with the results of physio-chemical analysis, the data revealed that pinocembrin targeted MRC complexes I and V, to induce ATP depletion, enhance ROS accumulation, stimulate mitochondrial permeability transition pore (MPTP) opening, accelerate the loss of mitochondrial membrane potential (MMP) and promote cytochrome c release from mitochondria to the cytoplasm, which, as a result, effectively triggered three classical types of PCD pathways in mycelia of P. italicum.
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http://dx.doi.org/10.1016/j.pestbp.2020.01.015DOI Listing
July 2020

Generative adversarial network-based super-resolution of diffusion-weighted imaging: Application to tumour radiomics in breast cancer.

NMR Biomed 2020 08 10;33(8):e4345. Epub 2020 Jun 10.

Institute of Biomedical Engineering and Instrumentation, Hangzhou Dianzi University, Hangzhou, China.

Diffusion-weighted imaging (DWI) is increasingly used to guide the clinical management of patients with breast tumours. However, accurate tumour characterization with DWI and the corresponding apparent diffusion coefficient (ADC) maps are challenging due to their limited resolution. This study aimed to produce super-resolution (SR) ADC images and to assess the clinical utility of these SR images by performing a radiomic analysis for predicting the histologic grade and Ki-67 expression status of breast cancer. To this end, 322 samples of dynamic enhanced magnetic resonance imaging (DCE-MRI) and the corresponding DWI data were collected. A SR generative adversarial (SRGAN) and an enhanced deep SR (EDSR) network along with the bicubic interpolation were utilized to generate SR-ADC images from which radiomic features were extracted. The dataset was randomly separated into a development dataset (n = 222) to establish a deep SR model using DCE-MRI and a validation dataset (n = 100) to improve the resolution of ADC images. This random separation of datasets was performed 10 times, and the results were averaged. The EDSR method was significantly better than the SRGAN and bicubic methods in terms of objective quality criteria. Univariate and multivariate predictive models of radiomic features were established to determine the area under the receiver operating characteristic curve (AUC). Individual features from the tumour SR-ADC images showed a higher performance with the EDSR and SRGAN methods than with the bicubic method and the original images. Multivariate analysis of the collective radiomics showed that the EDSR- and SRGAN-based SR-ADC images performed better than the bicubic method and original images in predicting either Ki-67 expression levels (AUCs of 0.818 and 0.801, respectively) or the tumour grade (AUCs of 0.826 and 0.828, respectively). This work demonstrates that in addition to improving the resolution of ADC images, deep SR networks can also improve tumour image-based diagnosis in breast cancer.
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http://dx.doi.org/10.1002/nbm.4345DOI Listing
August 2020

Is It Worth It? Consequences of Definitive Head and Neck Reirradiation.

Semin Radiat Oncol 2020 Jul;30(3):212-217

Department of Radiation and Cellular Oncology, The University of Chicago Medicine, Chicago, IL. Electronic address:

Locally recurrent head and neck malignancies after definitive radiation or chemoradiation represent challenging clinical scenarios requiring careful consideration of individualized risks and benefits before deciding upon the next best course of therapy. Herein, a case-based approach to personalized decision making highlights the expert opinions of leaders in head and neck oncology. Topics of interest include optimal candidacy for reirradiation or salvage surgical resection, the judicious use of chemotherapy as induction therapy or as a radiosensitizing agent, the incorporation of immunotherapy into the treatment paradigm for locally recurrent disease, and the impact of various treatment modalities on quality of life and functional outcomes. Interestingly, the lack of consensus among the experts on topics as fundamental as the appropriateness of offering reirradiation at all and as nuanced as target volume delineation for the reirradiated field suggests that there is no straightforward approach in this scenario. Common to all opinions is a desire to maximize the therapeutic ratio for a patient potentially facing a grim prognosis, and honest discussions about goals of care and expectations for post-treatment quality of life should be central to the clinical approach to this and similar cases.
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http://dx.doi.org/10.1016/j.semradonc.2020.02.002DOI Listing
July 2020