Publications by authors named "Ying Fan"

478 Publications

NAicotinamide retains Klotho expression and ameliorates rhabdomyolysis-induced acute kidney injury.

Nutrition 2021 Jun 2;91-92:111376. Epub 2021 Jun 2.

Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Electronic address:

Objectives: Acute kidney injury (AKI) is a severe complication of rhabdomyolysis that significantly increases mortality. Unfortunately, the therapeutic approach is limited. Inflammation plays a critical role in the pathogenesis of rhabdomyolysis-induced AKI, which is a potential therapeutic target. Nicotinamide, a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide, has been shown to have potent antiinflammation effects. Klotho is a tubular highly expressed renoprotective protein. Therefore, we explored the effect of nicotinamide on rhabdomyolysis-induced AKI and the underlying mechanisms.

Methods: We intramuscularly injected glycerol to induce rhabdomyolysis, and intraperitoneally administrated nicotinamide to observe the effect on kidney injury. Interleukin-1 beta, tumor necrosis factor alpha, nuclear factor kappa B (NF-κB), and Klotho were determined by Western blot. Chromatin immunoprecipitation was used to assess the interaction of NF-κB, nuclear receptor corepressor, and histone deacetylase 1 with Klotho promoters. Small interfering RNA was used to evaluate the role of Klotho in nicotinamide-related renoprotection.

Results: The results showed that nicotinamide attenuated renal pathologic morphology, kidney functional abnormalities, and kidney inflammatory response in rhabdomyolysis. Moreover, nicotinamide effectively blocked the recruitment of NF-κB, nuclear receptor corepressor, and histone deacetylase 1 to the promoter of Klotho, and preserved Klotho expression. More importantly, the renoprotection effect of nicotinamide was abrogated when Klotho was knocked down by small interfering RNA in rhabdomyolysis mice.

Conclusions: Our study demonstrated that Klotho preservation is essential for the renoprotection effect of nicotinamide, and provides a new preventive strategy for rhabdomyolysis-induced AKI.
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http://dx.doi.org/10.1016/j.nut.2021.111376DOI Listing
June 2021

Effect of Trimethyltin chloride on proliferation and cell cycle of intestinal porcine epithelial cells.

Comp Biochem Physiol C Toxicol Pharmacol 2021 Jul 8;249:109131. Epub 2021 Jul 8.

Department of Basic Veterinary Medicine, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, Hunan, China. Electronic address:

Trimethyltin chloride (TMT) is a highly toxic substance produced by organotin heat stabilizers in the synthesis of polyvinyl chloride (PVC) products. TMT is widely used in industry and agriculture. The aim of this study was to investigate the effects of TMT-induced cytotoxicity in intestinal porcine epithelial cells (IPEC-J2). Our study showed that TMT induced a decline in cell viability of IPEC-J2, caused cell shrinkage and rounded cell morphology, reduced the number of proliferating cells and the expression of proliferating cell nuclear antigen (PCNA), and increased lactate dehydrogenase (LDH) activity in cell supernatants. Simultaneously, TMT lowered the mRNA expression of Cyclin B1, and Cyclin D1, but increased P21 and P27 expression. The cell cycle progression was arrested from the G1 to the S phase. Furthermore, the mRNA expression of Bax/Bcl-2 ratio and the protein expression of cleaved Caspase-9 and cleaved Caspase-3 were significantly increased after TMT treatment, while the ratio of advanced apoptotic cells was elevated. These results indicated that TMT blocked the cell cycle, inhibited IPEC-J2 proliferation, and induced apoptosis.
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http://dx.doi.org/10.1016/j.cbpc.2021.109131DOI Listing
July 2021

Acute-on-chronic Liver Failure in a Patient with : A Case Report.

J Clin Transl Hepatol 2021 Jun 30;9(3):447-451. Epub 2021 Mar 30.

Center of Liver Diseases, Capital Medical University Affiliated to Beijing Ditan Hospital, Beijing, China.

Acute-on-chronic liver failure (ACLF) is a risk factor for fungal infection. Endogenous fungal endophthalmitis is a serious, sight-threatening disease. Common causes include immunocompromised state and intravenous drug use, permitting opportunistic pathogens to reach the eye through the blood stream. We report a case of in a 47 year-old woman who was admitted to our hospital with ACLF and poorly controlled diabetes. In addition, she was treated with glucocorticoids due to severe jaundice. After treatment for ACLF, the patient experienced fever with blurred vision in the left eye and was diagnosed with candidemia, endogenous Candida endophthalmitis in the left eye, and chorioretinitis in the right eye. Systemic and topical antifungal treatment was administered based on the positive test in intraocular fluid using second-generation sequencing. The patient underwent vitrectomy in the left eye and was confirmed in vitreous cultures. Follow-up visit, at 6 weeks after the operation, showed only light perception in the left eye and stable visual acuity in the right eye. Physicians should be aware of endogenous fungal endophthalmitis in patients with ACLF, especially those with infection, a history of glucocorticoid use, and diabetes. A dilated retinal examination should be performed by an ophthalmologist if ACLF patients develop fever and fungal infection.
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http://dx.doi.org/10.14218/JCTH.2020.00092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237134PMC
June 2021

Infusion port level detection for intravenous infusion based on Yolo v3 neural network.

Math Biosci Eng 2021 Apr;18(4):3491-3501

Department of Anesthesiology, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, China.

Purpose: In order to improve the accuracy of liquid level detection in intravenous left auxiliary vein infusion and reduce the pain of patients with blood returning from intravenous infusion, we propose a deep learning based liquid level detection model of infusion levels to facilitate this operation.

Method: We implemented a Yolo v3-based detection model of infusion level images in intravenous infusion, and at the same time, compare it with SURF image processing technique, RCNN, and Fast-RCNN methods.

Results: The model in this paper is better than the comparison algorithm in Intersection over Union (IoU), precision, recall and test time. The liquid level detection model based on Yolo v3 has a precision of 0.9768, a recall rate of 0.9688, an IoU of 0.8943, and a test time of 2.9 s.

Conclusion: The experimental results prove that the liquid level detection method based on deep learning has the characteristics of high accuracy and good real-time performance. This method can play a certain auxiliary role in the hospital environment and improve work efficiency of medical workers.
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http://dx.doi.org/10.3934/mbe.2021175DOI Listing
April 2021

An integrated framework of plant form and function: The belowground perspective.

New Phytol 2021 Jul 1. Epub 2021 Jul 1.

The Root Lab, Center for Tree Science, The Morton Arboretum, Lisle, Illinois, 60515, USA.

Plant trait variation drives plant function, community composition, and ecosystem processes. However, our current understanding of trait variation disproportionately relies on aboveground observations. Here we integrate root traits into the global framework of plant form and function. We developed and tested an overarching conceptual framework that integrates two recently identified root trait gradients with a well-established aboveground plant trait framework. We confronted our novel framework with published relationships between above- and belowground trait analogues and with multivariate analyses of aboveground and belowground traits of 2510 species. Our traits represent the leaf- and root conservation gradients (specific leaf area, leaf and root nitrogen concentration and root tissue density), the root collaboration gradient (root diameter and specific root length), and the plant size gradient (plant height and rooting depth). We found that an integrated, whole-plant trait space required as much as four axes. The two main axes represented the fast-slow 'conservation' gradient on which leaf and fine-root traits were well aligned, and the 'collaboration' gradient in roots. The two additional axes were separate, orthogonal plant size axes for height and rooting depth. This perspective on the multi-dimensional nature of plant trait variation better encompasses plant function and influence on the surrounding environment.
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http://dx.doi.org/10.1111/nph.17590DOI Listing
July 2021

The effects of narrative exposure therapy on COVID-19 patients with post-traumatic stress symptoms: A randomized controlled trial.

J Affect Disord 2021 Jun 17;293:141-147. Epub 2021 Jun 17.

Bachelor of Public health, Wuhan University School of Health Sciences, China.

Background: With the global attack of Coronavirus Disease 2019 (COVID-19), cases with Post-traumatic Stress Disorder (PTSD) have been increasing steadily, which seriously affects the quality of life of patients and as such, seeking effective treatments is an urgent matter. Narrative Exposure Therapy (NET) is a typical cognitive behavioral therapy targeting trauma-related psychological disorders and may be an effective intervention.

Methods: A total of 111 COVID-19 patients near the discharge stage with positive screening results for posttraumatic stress symptoms (PTSS) were randomly assigned (1:1) to either the study group or the control group. The study group received NET and personalized psychological intervention, while the control group only received personalized psychological intervention. PTSS, depression, anxiety and sleep quality were measured pre- and post-intervention to evaluate the effect of NET. This trial was registered with the International Standard Randomized Clinical Trial Registry (No. ChiCTR2000039369).

Results: NET participants showed a significantly greater PTSS reduction in comparison with the control group after the intervention. Improvement in sleep quality, anxiety and depression after the intervention were pronounced but not significantly different between the two treatment groups.

Limitations: The assessors weren't blinded for the convenience of measurement and protection of participants' psychological security.

Conclusions: NET likely had a positive impact on PTSS of COVID-19 patients. Clinical staff should consider applying NET to improve the psychological well-being of patients who have experienced an epidemic such as COVID-19.
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http://dx.doi.org/10.1016/j.jad.2021.06.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234566PMC
June 2021

Macular Vessel Density Changes in Young Adults With High Myopia: A Longitudinal Study.

Front Med (Lausanne) 2021 8;8:648644. Epub 2021 Jun 8.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photo Medicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China.

To characterize the longitudinal changes of macular vessel density in young adults and its associated factors. The right eyes of 309 participants (75 high myopic, 194 mild-to-moderate myopic, and 40 healthy) were followed up for 21 months. OCTA images were acquired at two visits using follow-up scans. Macular vessel density was calculated globally and in the nine early treatment diabetic retinopathy study (ETDRS) subfields of the macula superficial layer. The macular vessel density significantly decreased in young myopes after a 21-month follow up ( < 0.05), with variations among sectors. Compared with healthy eyes, HM group exhibited a faster reduction in global macular vessel density ( = 0.0307) as well as in sectors of inner-inferior (II), inner-temporal (IT), and outer-temporal (OT) (all < 0.05). Multivariate regression analysis showed that longer baseline axial length (AL) was significantly associated with larger reduction of macular vessel density in the inner-inferior, inner-temporal and outer-temporal sectors (all < 0.05). Compared with emmetropes, high myopes presented greater loss of macular vessel density over time in global and in the inner-inferior, inner-temporal and outer-temporal sectors. A longer baseline AL was associated with larger changes of macular vessel density in the inner-inferior, inner-temporal and outer-temporal sectors.
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http://dx.doi.org/10.3389/fmed.2021.648644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217628PMC
June 2021

The role of national carbon pricing in phasing out China's coal power.

iScience 2021 Jun 27;24(6):102655. Epub 2021 May 27.

School of Economics and Management, North China Electric Power University, Beijing, 102206, China.

As the country with the world's largest coal power capacity, China is launching a national carbon market. How the carbon pricing may contribute to phasing out China's coal power is a great concern. We collect full-sample data set of China's 4540 operating coal plant units and develop a stochastic Monte-Carlo financial model to assess the financial sustainability of the plant operation. Although China's coal plants have long residual technical lifetime, their operations are close to the break-even state. Even with low carbon price of 50 CNY/tCO growing at 4%/y and the permits being fully auctioned, the average residual lifetime of all the plants will be reduced by 5.43 years, and the cumulative CO emission from 2020 to 2050 will be reduced by 22.73 billion ton. The spatial disparity in the carbon pricing effect is significant, and the western regions are more vulnerable to the carbon pricing risk than the eastern regions.
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http://dx.doi.org/10.1016/j.isci.2021.102655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193610PMC
June 2021

Transcriptome Profiling Reveals a Novel Mechanism of Antiviral Immunity Upon Sacbrood Virus Infection in Honey Bee Larvae ().

Front Microbiol 2021 2;12:615893. Epub 2021 Jun 2.

Key Laboratory of Pollinating Insect Biology of the Ministry of Agriculture, Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing, China.

The honey bee is one of the most important pollinators in the agricultural system and is responsible for pollinating a third of all food we eat. Sacbrood virus (SBV) is a member of the virus family and affects honey bee larvae and causes particularly devastating disease in the Asian honey bees, . Chinese Sacbrood virus (CSBV) is a geographic strain of SBV identified in China and has resulted in mass death of honey bees in China in recent years. However, the molecular mechanism underlying SBV infection in the Asian honey bee has remained unelucidated. In this present study, we employed high throughput next-generation sequencing technology to study the host transcriptional responses to CSBV infection in larvae, and were able to identify genome-wide differentially expressed genes associated with the viral infection. Our study identified 2,534 differentially expressed genes (DEGs) involved in host innate immunity including Toll and immune deficiency (IMD) pathways, RNA interference (RNAi) pathway, endocytosis, etc. Notably, the expression of genes encoding antimicrobial peptides (, , , and ) and core components of RNAi such as and were found to be significantly upregulated in CSBV infected larvae. Most importantly, the expression of Sirtuin target genes, a family of signaling proteins involved in metabolic regulation, apoptosis, and intracellular signaling was found to be changed, providing the first evidence of the involvement of Sirtuin signaling pathway in insects' immune response to a virus infection. The results obtained from this study provide novel insights into the molecular mechanism and immune responses involved in CSBV infection, which in turn will contribute to the development of diagnostics and treatment for the diseases in honey bees.
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http://dx.doi.org/10.3389/fmicb.2021.615893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208235PMC
June 2021

Forkhead box P1 (Foxp1) in osteoblasts regulates bone mass accrual and adipose tissue energy metabolism.

J Bone Miner Res 2021 Jun 15. Epub 2021 Jun 15.

Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Adiponectin (AdipoQ), a hormone abundantly secreted by adipose tissues, has multiple beneficial functions, including insulin sensitization as well as lipid and glucose metabolism. It has been reported that bone controls energy metabolism through an endocrine-based mechanism. In this study, we observed that bone also acts as an important endocrine source for AdipoQ, and its capacity in osteoblasts is controlled by the forkhead box P1 (FOXP1) transcriptional factor. Deletion of the Foxp1 gene in osteoblasts led to augmentation of AdipoQ levels accompanied by fueled energy expenditure in adipose tissues. In contrast, overexpression of Foxp1 in bones impaired AdipoQ secretion and restrained energy consumption. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis revealed that AdipoQ expression, which increases as a function of bone age, is directly controlled by FOXP1. Our results indicate that bones, especially aged bones, provide an important source of a set of endocrine factors, including AdipoQ, that control body metabolism. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4394DOI Listing
June 2021

Surface-Enhanced Raman Scattering-Active Plasmonic Metal Nanoparticle-Persistent Luminescence Material Composite Films for Multiple Illegal Dye Detection.

Anal Chem 2021 06 14;93(25):8945-8953. Epub 2021 Jun 14.

Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, International Joint Research Center for Photoresponsive Molecules and Materials, School of Chemical and Material Engineering, Jiangnan University, Wuxi, Jiangsu 214122, China.

Uniform two-dimensional plasmonic nanoparticle (NP)-semiconductor composite films could retard the attenuation of electromagnetic evanescent wave and show intensive Raman activity for the multiplex monitoring of hazards in a practical food matrix. Here, an efficient Raman platform is developed by employing a plasmonic nanoparticle (NP)-persistent luminescence material (PLM) composite film. PLM show upconversion photoluminescence (UCPL) properties. The emitted photons are absorbed by plasmonic NPs, which further boost the surface plasmon resonance for the generation of high polarizability and induce strong electromagnetic strength for surface-enhanced Raman scattering (SERS) enhancement. A UCPL-assisted SERS-enhanced mechanism is proposed and verified. A plasmonic NP-PLM film with superior SERS activity and detection capability becomes an alternative candidate for the sensitive and multiple detection of illegal addition of dyes in a food matrix. The proposed UCPL-assisted SERS-enhanced mechanism provides promising future directions to this end to design a next-generation SERS-active plasmonic NP-PLM composite film for the specific detection in complex samples.
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http://dx.doi.org/10.1021/acs.analchem.1c01442DOI Listing
June 2021

R1441G but not G2019S mutation enhances LRRK2 mediated Rab10 phosphorylation in human peripheral blood neutrophils.

Acta Neuropathol 2021 Jun 14. Epub 2021 Jun 14.

Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, DD1 5EH, UK.

Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson's disease (PD) albeit with incomplete and age-dependent penetrance. All pathogenic LRRK2 mutations reside within the two catalytic domains of LRRK2-either in its kinase domain (e.g. G2019S) with modest effect or its ROC-COR GTPase domain (e.g. R1441G/H) with large effect on LRRK2 kinase activity. We have previously reported assays to interrogate LRRK2 kinase pathway activity in human bio-samples measuring phosphorylation of its endogenous substrate Rab10, that mirrors LRRK2 kinase activation status. Here, we isolated neutrophils from fresh peripheral blood from 101 participants including 42 LRRK2 mutation carriers (21 with the G2019S and 21 with the R1441G mutations), 27 patients with idiopathic PD, and 32 controls. Using a dual approach, LRRK2 dependent Rab10 phosphorylation at Threonine 73 (pRab10) was measured by quantitative multiplexed immunoblotting for pRab10/total Rab10 as well as targeted mass-spectrometry for absolute pRab10 occupancy. We found a significant over fourfold increase in pRab10 phosphorylation in carriers of the LRRK2 R1441G mutation irrespective of clinical disease status. The effect of the LRRK2 G2019S mutation did not reach statistical significance. Furthermore, we show that LRRK2 phosphorylation at Serine 935 is not a marker for LRRK2 kinase activity in human neutrophils. When analysing pRab10 phosphorylation in post-mortem brain samples, we observed overall high variability irrespective of clinical and LRRK2 mutation status and attributed this mainly to the adverse effect of the peri- and post-mortem period on the stability of posttranslational modifications such as protein phosphorylation. Overall, in vivo LRRK2 dependent pRab10 phosphorylation in human peripheral blood neutrophils is a specific, robust and promising biomarker for significant LRRK2 kinase hyperactivation, as with the LRRK2 R1441G mutation. Additional readouts and/or assays may be needed to increase sensitivity to detect modest LRRK2 kinase activation, as with the LRRK2 G2019S mutation. Our assays could be useful for patient stratification and target engagement studies for LRRK2 kinase inhibitors.
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http://dx.doi.org/10.1007/s00401-021-02325-zDOI Listing
June 2021

HER2 exon 20 insertion mutations in lung adenocarcinoma with leptomeningeal metastasis: a case report and response to poziotinib.

Ann Palliat Med 2021 May 31. Epub 2021 May 31.

Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (lung and esophagus), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China; Department of Thoracic Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China; Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China; The First Clinical Medical College, Wenzhou Medical University, Wenzhou, China.

Leptomeningeal metastasis (LM) is associated with poor prognosis and represents a terminal event of non-small cell lung cancers (NSCLC). In previous studies, most of LM-patients have detected epidermal growth factor receptor (EGFR) mutation and responded to the third generation of EGFR-tyrosine kinase inhibitor (TKI). This study aimed to report a case of ERBB2 (HER2) exon 20 insertion mutations in the cerebrospinal fluid (CSF) of LM-patient which response to poziotinib. At the beginning, postoperative pathology showed a primary invasive adenocarcinoma with no mutations in EGFR and ROS-1. Pemetrexed plus carboplatin combined with bevacizumab was administered as the first-line followed by bevacizumab alone for continuation maintenance therapy. Targeted therapy and immunotherapy were given after the disease progressed in two months. Subsequently, the patient developed mental symptoms and adenocarcinoma cells were found in the CSF. Next-generation sequencing (NGS) results showed HER2 exon 20 insertion mutations in the primary tissue, CSF and plasma samples. Then, poziotinib was administered and the symptoms improved significantly after 3 days and the progress free survival was nearly 2 months. Therefore, we speculate that the CSF concentration and penetration rate of poziotinib may significantly higher than of other TKIs so that it achieves a higher CSF concentration than standard dosing, and successfully controlled LM. It may provide a new therapeutic option for LM-patient and may be especially who are lung adenocarcinoma with HER2 exon 20 insertion.
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http://dx.doi.org/10.21037/apm-21-213DOI Listing
May 2021

Distinct neural representations of content and ordinal structure in auditory sequence memory.

J Neurosci 2021 Jun 3. Epub 2021 Jun 3.

School of Psychological and Cognitive Sciences, Peking University

Two forms of information - frequency (content) and ordinal position (structure) - have to be stored when retaining a sequence of auditory tones in working memory (WM). However, the neural representations and coding characteristics of content and structure, particularly during WM maintenance, remain elusive. Here, in two electroencephalography (EEG) studies in human participants (both sexes), by transiently perturbing the 'activity-silent' WM retention state and decoding the reactivated WM information, we demonstrate that content and structure are stored in a dissociative manner with distinct characteristics throughout WM process. First, each tone in the sequence is associated with two codes in parallel, characterizing its frequency and ordinal position, respectively. Second, during retention, a structural retrocue successfully reactivates structure but not content, whereas a following white noise triggers content but not structure. Third, structure representation remains stable whereas content code undergoes a dynamic transformation through memory progress. Finally, the noise-triggered content reactivations during retention correlate with subsequent WM behavior. Overall, our results support distinct content and structure representations in auditory WM and provide an efficient approach to access the silently stored WM information in the human brain. The dissociation of content and structure could facilitate efficient memory formation via generalizing stable structure to new auditory contents.In memory experiences, contents do not exist independently but are linked with each other via ordinal structure. For instance, recalling a piece of favorite music relies on correct ordering (sequence structure) of musical tones (content). How are the structure and content for an auditory temporally structured experience maintained in working memory? Here, by employing impulse-response approach and time-resolved representational dissimilarity analysis on human EEG recordings in an auditory working memory task, we reveal that content and structure are stored in a dissociated way, which would facilitate efficient and rapid memory formation through generalizing stable structure knowledge to new auditory inputs.
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http://dx.doi.org/10.1523/JNEUROSCI.0320-21.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287991PMC
June 2021

Ca2+-dependent protein acyltransferase DHHC21 controls activation of CD4+ T cells.

J Cell Sci 2022 03 3;135(5). Epub 2021 Jun 3.

Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

Despite the recognized significance of reversible protein lipidation (S-acylation) for T cell receptor signal transduction, the enzymatic control of this post-translational modification in T cells remains poorly understood. Here, we demonstrate that DHHC21 (also known as ZDHHC21), a member of the DHHC family of mammalian protein acyltransferases, mediates T cell receptor-induced S-acylation of proximal T cell signaling proteins. Using Zdhhc21dep mice, which express a functionally deficient version of DHHC21, we show that DHHC21 is a Ca2+/calmodulin-dependent enzyme critical for activation of naïve CD4+ T cells in response to T cell receptor stimulation. We find that disruption of the Ca2+/calmodulin-binding domain of DHHC21 does not affect thymic T cell development but prevents differentiation of peripheral CD4+ T cells into Th1, Th2 and Th17 effector T helper lineages. Our findings identify DHHC21 as an essential component of the T cell receptor signaling machinery and define a new role for protein acyltransferases in regulation of T cell-mediated immunity.
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http://dx.doi.org/10.1242/jcs.258186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214660PMC
March 2022

Cholesterol gallstones: Focusing on the role of interstitial Cajal-like cells.

World J Clin Cases 2021 May;9(15):3498-3505

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.

Cholesterol gallstone (CG) is a common, frequent biliary system disease in China, with a complex and multifactorial etiology. Declined gallbladder motility reportedly contributes to CG pathogenesis. Furthermore, interstitial Cajal-like cells (ICLCs) are reportedly present in human and guinea pig gallbladder tissue. ICLCs potentially contribute to the regulation of gallbladder motility, and aberrant conditions involving the loss of ICLCs and/or a reduction in its pacing potential and reactivity to cholecystokinin may promote CG pathogenesis. This review discusses the association between ICLCs and CG pathogenesis and provides a basis for further studies on the functions of ICLCs and the etiologies of CG.
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http://dx.doi.org/10.12998/wjcc.v9.i15.3498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130069PMC
May 2021

Risk Factors and Survival of Patients With Liver Metastases at Initial Metastatic Breast Cancer Diagnosis in Han Population.

Front Oncol 2021 11;11:670723. Epub 2021 May 11.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

The risk factors for morbidity and mortality in patients with breast cancer liver metastases (BCLM) upon initial metastatic breast cancer (MBC) diagnosis have not been adequately identified in Han population. Data of 3,161 female patients who were initially diagnosed with MBC from December 1991 to September 2019 and treated in the China National Cancer Center were extracted and a total of 2,263 MBC patients were included in our study, among which 550 patients had liver metastases. Multivariable logistic regression was performed to identify risk factors for the presence of liver metastases at initial MBC diagnosis. Univariable and multivariable Cox proportional hazards regression analyses were conducted to determine prognostic factors for the survival of BCLM patients. Patients with hormone receptor (HR)-negative, human epidermal growth factor receptor 2 (HER2)-positive (35.0% of the entire population) subtype had the highest incidence of liver metastases. stage IV breast cancer, HR-/HER2+ and HR+/HER2+ subtypes were associated with higher odds of liver metastases and patients with lung metastases had lower risk of liver metastases at initial MBC diagnosis. The median overall survival of BCLM patients was 31.4 months and BCLM patients with HR+/HER2- subtype had the longest survival of 38.2 months. Older age, worse performance status, later stage of initial breast cancer, triple-negative subtype and lung metastases were significantly associated with a poorer prognosis in BCLM patients. Our study offers insights into the incidence and prognosis of BCLM patients at initial MBC diagnosis in Han population.
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http://dx.doi.org/10.3389/fonc.2021.670723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147724PMC
May 2021

Pulmonary enteric adenocarcinoma.

Transl Oncol 2021 Aug 14;14(8):101123. Epub 2021 May 14.

The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, PR China; Zhejiang Key Laboratory of Diagnosis & Treatment Technology on Thoracic Oncology (lung and esophagus), Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 310022, PR China; Department of Thoracic Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), 310022, PR China; Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, 310022, PR China. Electronic address:

Pulmonary enteric adenocarcinoma (PEAC) is an exceptionally rare subtype of non-small cell lung cancer (NSCLC). It is characterized by pathological features similar to those of colorectal adenocarcinoma. Most patients with PEAC have almost no special clinical manifestations, and it is often difficult to differentiate from metastatic colorectal adenocarcinoma (MCRC). As a special type of lung adenocarcinoma, PEAC has unique mutation expression and immune characteristics; its mutation profile shows higher Kirsten rat sarcoma viral oncogene (KRAS), human epidermal growth factor receptor-2 (HER2) , DNA mismatch repair(MMR) mutation rates, and much lower epidermal growth factor receptor (EGFR) rate. So in the future, targeted therapy may tend to be a new light in the treatment of PEAC. As for immunohistochemistry (IHC), CDX-2, villin, and CK7 are significantly positive in PEAC. This review focuses on the pathologic features, immunohistochemical examination, mutation analysis, diagnosis, treatment, and prognosis of PEAC.
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http://dx.doi.org/10.1016/j.tranon.2021.101123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141771PMC
August 2021

Imaging Features by Machine Learning for Quantification of Optic Disc Changes and Impact on Choroidal Thickness in Young Myopic Patients.

Front Med (Lausanne) 2021 29;8:657566. Epub 2021 Apr 29.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

To construct quantifiable models of imaging features by machine learning describing early changes of optic disc and peripapillary region, and to explore their performance as early indicators for choroidal thickness (ChT) in young myopic patients. Eight hundred and ninety six subjects were enrolled. Imaging features were extracted from fundus photographs. Macular ChT (mChT) and peripapillary ChT (pChT) were measured on swept-source optical coherence tomography scans. All participants were divided randomly into training (70%) and test (30%) sets. Imaging features correlated with ChT were selected by LASSO regression and combined into new indicators of optic disc (IODs) for mChT (IOD_mChT) and for pChT (IOD_pChT) by multivariate regression models in the training set. The performance of IODs was evaluated in the test set. A significant correlation between IOD_mChT and mChT ( = 0.650, = 0.423, < 0.001) was found in the test set. IOD_mChT was negatively associated with axial length (AL) ( = -0.562, < 0.001) and peripapillary atrophy (PPA) area ( = -0.738, < 0.001) and positively associated with ovality index ( = 0.503, < 0.001) and torsion angle ( = 0.242, < 0.001) in the test set. Every 1 × 10 μm decrease in IOD_mChT was associated with an 8.87 μm decrease in mChT. A significant correlation between IOD_pChT and pChT ( = 0.576, = 0.331, < 0.001) was found in the test set. IOD_pChT was negatively associated with AL ( = -0.478, < 0.001) and PPA area ( = -0.651, < 0.001) and positively associated with ovality index ( = 0.285, < 0.001) and torsion angle ( = 0.180, < 0.001) in the test set. Every 1 × 10 μm decrease in IOD_pChT was associated with a 9.64 μm decrease in pChT. The study introduced a machine learning approach to acquire imaging information of early changes of optic disc and peripapillary region and constructed quantitative models significantly correlated with choroidal thickness. The objective models from fundus photographs represented a new approach that offset limitations of human annotation and could be applied in other areas of fundus diseases.
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http://dx.doi.org/10.3389/fmed.2021.657566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116583PMC
April 2021

Biliary Microbiota in Choledocholithiasis and Correlation With Duodenal Microbiota.

Front Cell Infect Microbiol 2021 29;11:625589. Epub 2021 Apr 29.

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China.

Background: The pathogenesis of choledocholithiasis is closely related to the role of bacteria. However, little is known about the predictive role of bile bacteria in clinical conditions of patients and the compositional and functional characteristics of biliary microbiota in choledocholithiasis.

Methods: To investigate the predictive value of biliary bacteria, clinical data of 488 patients with choledocholithiasis were collected. The predictive value of common bile bacteria to patients' clinical conditions was analyzed by logistic regression. Samples of bile and corresponding duodenal juice from 10 selected patients with choledocholithiasis were obtained, and the composition and function of microbial communities were analyzed based on rRNA sequencing and Tax4Fun.

Results: The clinical conditions of patients with choledocholithiasis, such as recurrence, the severity of acute cholangitis, and duration of hospital stay were closely related to different species of bile bacteria as well as antimicrobial-resistant bacteria. Employing rRNA sequencing, the dominant phyla of biliary and duodenal microbiota were and . The top three core microbiota at the genus level were , and . accounted for the most abundant annotated species in both. Differences in composition between biliary and duodenal microbiota were not significant according to the alpha and beta diversities. Differential abundant features were not found in biliary microbiota indicated by A linear discriminant analysis effective size algorithm. The major pathways identified in biliary and duodenal microbiota were related to membrane transport, translation, replication and repair, carbohydrate and amino acid metabolism. However, no significant difference in those major pathways, as well as antimicrobial-resistance patterns, was observed between biliary and duodenal microbiota.

Conclusion: Our study first demonstrates the predictive contribution of biliary bacteria to the clinical conditions of patients with choledocholithiasis, and then it offers new insights into the compositional and functional features of biliary and duodenal microbiota. Similarities between biliary and duodenal microbiota support the theory of bacterial duodenal-biliary reflux in patients with choledocholithiasis. Meanwhile, when it is impracticable to obtain a bile sample, duodenal juice may be used as an alternative for bacterial culture and susceptibility tests.
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http://dx.doi.org/10.3389/fcimb.2021.625589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116743PMC
July 2021

Regulation of Dynamic Protein S-Acylation.

Front Mol Biosci 2021 26;8:656440. Epub 2021 Apr 26.

Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, United States.

Protein S-acylation is the reversible addition of fatty acids to the cysteine residues of target proteins. It regulates multiple aspects of protein function, including the localization to membranes, intracellular trafficking, protein interactions, protein stability, and protein conformation. This process is regulated by palmitoyl acyltransferases that have the conserved amino acid sequence DHHC at their active site. Although they have conserved catalytic cores, DHHC enzymes vary in their protein substrate selection, lipid substrate preference, and regulatory mechanisms. Alterations in DHHC enzyme function are associated with many human diseases, including cancers and neurological conditions. The removal of fatty acids from acylated cysteine residues is catalyzed by acyl protein thioesterases. Notably, S-acylation is now known to be a highly dynamic process, and plays crucial roles in signaling transduction in various cell types. In this review, we will explore the recent findings on protein S-acylation, the enzymatic regulation of this process, and discuss examples of dynamic S-acylation.
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http://dx.doi.org/10.3389/fmolb.2021.656440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107437PMC
April 2021

Characteristics of Fundal Changes in Fundus Tessellation in Young Adults.

Front Med (Lausanne) 2021 26;8:616249. Epub 2021 Apr 26.

Shanghai Eye Disease Prevention and Treatment Center, Shanghai Eye Hospital, Shanghai, China.

To explore the characteristics and associated factors of fundus tessellation, especially the alternation of choroidal thickness among different degrees of tessellated fundus in young adults. Cross-sectional, population-based study. A total of 796 students were included in the study and underwent comprehensive ophthalmic examinations, including anterior segment examinations and swept-source optical coherence tomography (OCT) measurements. The degree of tessellated fundus was assessed by fundus photographs applying an early treatment of diabetic retinopathy study grid to evaluate the location of fundus tessellation and then divided into five groups. The topographic variation and factors, tilted disc ratio, parapapillary atrophy (PPA), retinal thickness (ReT), choroidal thickness (ChT), and subfoveal scleral thickness (SST) related to tessellated fundus were analyzed. Compared to normal fundus, tessellated fundus had a lower spherical equivalent (SE) ( < 0.0001), worse best-corrected visual acuity (BCVA)( = 0.043), longer axial length (AL) ( < 0.0001), thinner retina ( < 0.0001), thinner ( < 0.0001) choroid, and thinner sclera in center fovea ( = 0.0035). Among all subfields of macular and peripapillary regions, center fovea and macula-papillary region showed the most significant decrease in choroidal thickness. The proportion of fundus tessellation significantly increased with lower body weight index (BMI) ( = 0.0067), longer AL ( < 0.0001), larger PPA( = 0.0058), thinner choroid ( < 0.0001), and thinner sclera ( < 0.0001). Eyes showed more severe myopic morphological alternation with the increasement of proportion of fundus tessellation to the center fovea, including a significant decrease in both choroid and scleral thickness. Choroidal thinning may progress most rapidly in the macula-papillary region as fundus tessellation approaches to the center fovea.
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http://dx.doi.org/10.3389/fmed.2021.616249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107222PMC
April 2021

Correction to: Automatic identification of myopic maculopathy related imaging features in optic disc region via machine learning methods.

J Transl Med 2021 May 11;19(1):203. Epub 2021 May 11.

Department of Preventative Ophthalmology, Shanghai Eye Diseases Prevention and Treatment Center, Shanghai Eye Hospital, No. 380 Kangding Road, Shanghai, 200040, China.

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http://dx.doi.org/10.1186/s12967-021-02874-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114694PMC
May 2021

A review on underwater shockwave processing and its application in food technology.

Crit Rev Food Sci Nutr 2020 Oct 14:1-9. Epub 2020 Oct 14.

Department of Food Science and Human Nutrition, University of Florida, Gainesville, Florida, USA.

Underwater shockwave processing (USP) is a non-thermal food processing method where a high-energy impulse is generated near a food product submerged in a liquid. The resulting shockwave transfers energy to the food, and is used to improve quality, safety, and nutritional aspects. This review presents the origin and evolution of the technology, principles of shockwave generation, mechanism of action, and applications in the food industry. The most common food application of USP is currently meat tenderization, where it is used to improve the sensory characteristics of meat as a value-added process. The use of USP as a pretreatment process has also been investigated to increase the yield and nutritional value of extracted juice and oil via softening of plant tissues. This technique also has an impact on food-borne pathogens and spoilage microorganisms in food, however, it is more effective when combined with other hurdles. Major challenges facing the industrial implementation of underwater shockwave technology include the lack of appropriate packaging materials resistant to the disruptive effects of shockwaves, the capital investment required, and a lack of regulatory information pertaining to USP. So far, most studies of underwater shockwaves on food are at the laboratory scale and validation stage. Further research endeavors and collaboration between food scientists, engineers, and regulators are necessary to scale up this technology to industrial implementation.
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http://dx.doi.org/10.1080/10408398.2020.1832439DOI Listing
October 2020

Automatic identification of myopic maculopathy related imaging features in optic disc region via machine learning methods.

J Transl Med 2021 04 26;19(1):167. Epub 2021 Apr 26.

Department of Preventative Ophthalmology, Shanghai Eye Diseases Prevention and Treatment Center, Shanghai Eye Hospital, No. 380 Kangding Road, Shanghai, 200040, China.

Background: Myopic maculopathy (MM) is the most serious and irreversible complication of pathologic myopia, which is a major cause of visual impairment and blindness. Clinic proposed limited number of factors related to MM. To explore additional features strongly related with MM from optic disc region, we employ a machine learning based radiomics analysis method, which could explore and quantify more hidden or imperceptible MM-related features to the naked eyes and contribute to a more comprehensive understanding of MM and therefore may assist to distinguish the high-risk population in an early stage.

Methods: A total of 457 eyes (313 patients) were enrolled and were divided into severe MM group and without severe MM group. Radiomics analysis was applied to depict features significantly correlated with severe MM from optic disc region. Receiver Operating Characteristic were used to evaluate these features' performance of classifying severe MM.

Results: Eight new MM-related image features were discovered from the optic disc region, which described the shapes, textural patterns and intensity distributions of optic disc region. Compared with clinically reported MM-related features, these newly discovered features exhibited better abilities on severe MM classification. And the mean values of most features were markedly changed between patients with peripapillary diffuse chorioretinal atrophy (PDCA) and macular diffuse chorioretinal atrophy (MDCA).

Conclusions: Machine learning and radiomics method are useful tools for mining more MM-related features from the optic disc region, by which complex or even hidden MM-related features can be discovered and decoded. In this paper, eight new MM-related image features were found, which would be useful for further quantitative study of MM-progression. As a nontrivial byproduct, marked changes between PDCA and MDCA was discovered by both new image features and clinic features.
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http://dx.doi.org/10.1186/s12967-021-02818-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074495PMC
April 2021

Safety and efficacy study of oral metronomic vinorelbine combined with trastuzumab (mNH) in HER2-positive metastatic breast cancer: a phase II trial.

Breast Cancer Res Treat 2021 Jul 25;188(2):441-447. Epub 2021 Apr 25.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No.17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China.

Purpose: We conducted a single-arm prospective phase II trial to evaluate the efficacy and safety of oral metronomic vinorelbine combined with trastuzumab (mNH) in human epidermal growth factor receptor 2-positive (HER2-positive) metastatic breast cancer (MBC) patients.

Methods: HER2-positive MBC patients received oral vinorelbine 40 mg thrice a week and trastuzumab (loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoints were objective response rate (ORR), clinical benefit rate (CBR; CR + PR + SD for ≥ 24 weeks). The secondary endpoints were progression-free survival (PFS), tolerability, and overall survival (OS).

Results: Twenty patients with HER2-positive MBC were enrolled, with a median of 1 prior chemotherapy regimens for MBC. Median age was 61.5 years (95% Confidence Interval (CI) 48.6-63.1). Visceral involvements presented in 14 patients (70.0%). ORR was 20.0%, and CBR was 75% with 4 PR (20.0%) and 11 SD (55.0%). The median PFS (mPFS) and median OS (mOS) were 7.4 months (95% CI 3.2-11.5) and 45.8 months (95%CI: not reached), respectively. The mPFS was 17.7 months (95%CI not reached) and 5.8 months (95%CI 5.6-5.9) in mNH as first-line and ≥ second-line therapy (log rank p = 0.03), respectively. The most common grade 1 adverse events (AEs) included nausea (15%), leukopenia (15%), ALT/AST elevation (15%), diarrhea (10%), and peripheral neuropathy (10%). Grade 2 adverse events included leukopenia (5%) and neutropenia (10%). No grade 3/4 AEs were observed.

Conclusions: Oral metronomic vinorelbine combined with trastuzumab is a well-tolerated and effective anti-tumor regimen for HER2-positive MBC.
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http://dx.doi.org/10.1007/s10549-021-06216-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070982PMC
July 2021

Sustainability and ecological efficiency of low-carbon power system: A concentrating solar power plant in China.

J Environ Manage 2021 Jul 21;290:112659. Epub 2021 Apr 21.

School of Soil and Water Conservation, Beijing Forestry University, Beijing, 100083, China.

Low-carbon power generation has been proposed as the key to address climate change. However, the sustainability and ecological efficiency of the generating plants have not been fully understood. This study applies emergy analysis and systems accounting to a pilot solar power tower plant in China for the first time to elaborate its sustainable and ecological performances. Emergy analysis covers virtually all aspects of sustainability and ecological efficiency by considering different forms of materials inputs, environmental support and human labor on the same unit of "solar joule". The input-output analysis based systems accounting is applied to trace the complete emergy embodied in the supply chain for all product materials of the given plant against the back ground of complex economic network, which improved the accuracy of accounting. This analysis illustrated unexpectedly low sustainability and ecological efficiency of this particular plant compared with the emergy analysis based on the primary materials (steel, iron, cement, etc.). Purchased emergy responses more than 95% of the total and emergy input in the construction phase is more than twice as much as that in the operation phase. Comparisons with other kinds of clean energy technologies indicate previous studies may have overestimated the sustainability and ecological benefits of low-carbon power plants. Thus, it is necessary to establish this kind of unified accounting framework. In addition, sensitivity analysis suggests that strictly controlling monetary costs of purchased inputs, extending service lifetime and improving power generation efficiency can promote higher sustainability and ecological efficiency for solar power tower plants. This study provides a more comprehensive framework for quantitative emergy-based evaluation of the sustainability and ecological efficiency for low-carbon power systems.
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http://dx.doi.org/10.1016/j.jenvman.2021.112659DOI Listing
July 2021

Overexpression of circ_0021739 in Peripheral Blood Mononuclear Cells in Women with Postmenopausal Osteoporosis Is Associated with Reduced Expression of microRNA-194-5p in Osteoclasts.

Med Sci Monit 2021 Apr 20;27:e929170. Epub 2021 Apr 20.

Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland).

BACKGROUND Postmenopausal osteoporosis, a common disease among elderly women, is linked to estrogen deficiency, mechanical loading, and genotype. Circular RNAs (circRNAs) are formed through reverse splicing of the splice donor at the 3' end and the splice accepter at the 5' end in pre-mRNA and have been shown to be involved in the development of multiple diseases. Based on their high sequence conservation and stability, circRNAs may be useful biomarkers in different diseases. However, the roles of circRNAs in postmenopausal osteoporosis remain incompletely understood. MATERIAL AND METHODS Fifty-three postmenopausal women were assigned to either the postmenopausal osteoporosis group (n=28) or the control group (n=25). Reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) analysis was performed to determine the differential expression of circRNAs between the 2 groups. Receiver-operating characteristic (ROC) curve analysis was conducted to evaluate the clinical diagnostic value of circRNA. Prediction of the binding sites between circRNA and miRNAs was conducted using miRanda and RNAhybrid. The function of the circRNA in osteoclastogenesis was determined by circRNA overexpression followed by tartrate-resistant acid phosphatase staining and RT-qPCR analysis. RESULTS Among 4 circRNAs previously identified by RNA-sequencing analysis as differentially expressed in patients with postmenopausal osteoporosis, only hsa_circ_0021739 showed a significant difference in expression between the groups and was downregulated in patients with postmenopausal osteoporosis. The hsa_circ_0021739 expression level was determined to be correlated with the lumbar vertebra, femur, and forearm T-scores. Overexpression of hsa_circ_0021739 decreased the level of hsa-miR-502-5p and inhibited the differentiation of osteoclasts. CONCLUSIONS The circRNA hsa_circ_0021739 is a potential blood biomarker for postmenopausal osteoporosis. In addition, hsa-miR-502-5p is a likely target of hsa_circ_0021739, which acts to regulate the differentiation of osteoclasts.
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http://dx.doi.org/10.12659/MSM.929170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067671PMC
April 2021