Publications by authors named "Jie Yan"

877 Publications

Talin mechanosensitivity is modulated by a direct interaction with cyclin-dependent kinase-1.

J Biol Chem 2021 Jun 9:100837. Epub 2021 Jun 9.

School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK. Electronic address:

Talin (TLN1) is a mechanosensitive component of adhesion complexes that directly couples integrins to the actin cytoskeleton. In response to force, talin undergoes switch-like behavior of its multiple rod domains that modulate interactions with its binding partners. Cyclin-dependent kinase-1 (CDK1) is a key regulator of the cell cycle, exerting its effects through synchronized phosphorylation of a large number of protein targets. CDK1 activity maintains adhesion during interphase, and its inhibition is a prerequisite for the tightly choreographed changes in cell shape and adhesion that are required for successful mitosis. Using a combination of biochemical, structural and cell biological approaches, we demonstrate a direct interaction between talin and CDK1 that occurs at sites of integrin-mediated adhesion. Mutagenesis demonstrated that CDK1 contains a functional talin-binding LD motif, and the binding site within talin was pinpointed to helical bundle R8. Talin also contains a consensus CDK1 phosphorylation motif centered on S1589, a site shown to be phosphorylated by CDK1 in vitro. A phosphomimetic mutant of this site within talin lowered the binding affinity of the cytoskeletal adaptor KANK and weakened the response of this region to force as measured by single molecule stretching, potentially altering downstream mechanotransduction pathways. The direct binding of the master cell cycle regulator CDK1 to the primary integrin effector talin represents a coupling of cell proliferation and cell adhesion machineries, and thereby indicates a mechanism by which the microenvironment can control cell division in multicellular organisms.
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http://dx.doi.org/10.1016/j.jbc.2021.100837DOI Listing
June 2021

Blockade of β-Adrenergic Receptors by Propranolol Disrupts Reconsolidation of Drug Memory and Attenuates Heroin Seeking.

Front Pharmacol 2021 25;12:686845. Epub 2021 May 25.

National Institute on Drug Abuse, Molecular Targets and Medications Discovery Branch, Baltimore, MD, United States.

Persistent traces of drug reward memories contribute to intense craving and often trigger relapse. A number of pharmacological interventions on drug-associated memories have shown significant benefits in relapse prevention at a preclinical level but their translational potential is limited due to deleterious side effects. Propranolol, a non-specific β-adrenergic receptors antagonist, is known for its ability to erase maladaptive memories associated with nicotine or cocaine in rodents and humans. However, little is known about its effect on reconsolidation of heroin memory and heroin seeking. In the present study, rats with a history of intravenous heroin self-administration received the propranolol treatment (10 mg/kg; i.p.) at different time windows with or without CS (conditioned stimulus) exposure. Our results showed that propranolol, when administered immediately after CS exposure but not 6 h later, can significantly attenuate cue-induced and drug-primed reinstatement of heroin seeking, suggesting that propranolol has the ability to disrupt heroin memory and reduce relapse. The propranolol treatment without retrieval of drug memory had no effect on subsequent reinstatement of heroin seeking, suggesting that its interfering effects are retrieval-dependent. Importantly, the effects of propranolol were long lasting as rats showed diminished drug seeking even 28 days after the treatment. Altogether, our study suggests that propranolol can interfere with reconsolidation of heroin memory and reduce subsequent drug seeking, making it an attractive therapeutic candidate for the treatment of opioid addiction and relapse prevention.
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http://dx.doi.org/10.3389/fphar.2021.686845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185332PMC
May 2021

P300-mediated NEDD4 acetylation drives ebolavirus VP40 egress by enhancing NEDD4 ligase activity.

PLoS Pathog 2021 Jun 10;17(6):e1009616. Epub 2021 Jun 10.

State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.

The final stage of Ebola virus (EBOV) replication is budding from host cells, where the matrix protein VP40 is essential for driving this process. Many post-translational modifications such as ubiquitination are involved in VP40 egress, but acetylation has not been studied yet. Here, we characterize NEDD4 is acetylated at a conserved Lys667 mediated by the acetyltransferase P300 which drives VP40 egress process. Importantly, P300-mediated NEDD4 acetylation promotes NEDD4-VP40 interaction which enhances NEDD4 E3 ligase activity and is essential for the activation of VP40 ubiquitination and subsequent egress. Finally, we find that Zaire ebolavirus production is dramatically reduced in P300 knockout cell lines, suggesting that P300-mediated NEDD4 acetylation may have a physiological effect on Ebola virus life cycle. Thus, our study identifies an acetylation-dependent regulatory mechanism that governs VP40 ubiquitination and provides insights into how acetylation controls EBOV VP40 egress.
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http://dx.doi.org/10.1371/journal.ppat.1009616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191996PMC
June 2021

Early Decline of Neuron-Specific Enolase during Neuroblastoma Chemotherapy is a Predictive Factor of Clinical Outcome.

Pediatr Hematol Oncol 2021 Jun 9:1-13. Epub 2021 Jun 9.

Department of Pediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

High risk neuroblastoma (HR-NB) remains one of the most difficult-to-treat pediatric cancers. However, although current risk-stratification is based on multiple pretreatment criteria, HR-NB remains a significant heterogeneity. We examined 60 patients with HR-NB for a median follow-up time of 28 months. We examined the serum neuronspecific enolase (NSE) levels of each chemo cycle, using the survival receiver operating characteristic (survivalROC) method to assess the prognostic power of NSE levels at variant chemo points. We demonstrated that serum NSE was associated with systemic tumor burden. NSE after the third chemo cycle (C3) (C3NSE) was significantly higher in patients who eventually showed cancer relapse or progression. C3NSE had independent prognostic significance for event-free survival (EFS) but not for overall survival (OS) in multivariate cox analysis. SurvivalROC prompted that the C3NSE is a prognostic marker of HR-NB, which had good discrimination for 2- and 3-year EFS with AUC 0.734 and 0.729, respectively. However, its prognositc value for 2- and 3- year OS declined progressively. C3 is the optimal point to predict EFS. Patients whose C3 serum NSE remain at higher level need to undergo more intensive treatment as early as possible to resist recurrence.
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http://dx.doi.org/10.1080/08880018.2021.1894277DOI Listing
June 2021

The complete mitochondrial genome of (Diptera: Muscidae).

Mitochondrial DNA B Resour 2021 May 31;6(6):1757-1758. Epub 2021 May 31.

Department of Forensic Science, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, P. R. China.

(Fabricius, 1794) is closely related to human life in ecological habits, which can lead to health concerns since they feed on various contamination sources. In this study, we first present the mitochondrial genome (mitogenome) of (GenBank No. MT017706). The length of this mitogenome was composed of 15,040 base pairs, including 13 protein-coding genes, two ribosomal RNA, 22 transfer RNA, and an AT-rich region. It consisted of A 39.3%, G 9.1%, C 13.0%, and T 38.6%. The arrangement of the genes was consistent with that of the ancestral metazoan. Furthermore, phylogenetic relationship indicated that was obviously separated from the muscid flies. This study provides useful genetic data in order to further understand the evolutionary relationship of the Muscidae.
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http://dx.doi.org/10.1080/23802359.2020.1820391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168768PMC
May 2021

Analysis of in vitro fertilization/intracytoplasmic sperm injection outcomes in infertile women with a history of thyroid cancer: a retrospective study.

Reprod Biol Endocrinol 2021 Jun 4;19(1):82. Epub 2021 Jun 4.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, 49 North Garden Rd, Beijing, 100191, China.

Background: Recent studies have revealed that women with infertility have a higher risk of thyroid cancer (TC) than fertile women. However, studies on whether a history of thyroid cancer affects clinical outcomes in women who conceive using in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) are scarce. We investigate whether a history of thyroid cancer (TC) affects the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and increases the risk of adverse obstetric outcomes in women with infertility.

Methods: This retrospective study enrolled 384 women with infertility who underwent their first IVF/ICSI treatment at the Peking University Third Hospital between 2010 and 2019. Participants were divided into the TC (64 women with TC history) and control (320 women matched from 85,272 women without thyroid diseases) groups. Controls were individually matched to the TC group according to age, body mass index, concomitant infertility factors, first IVF/ICSI dates, and controlled ovarian stimulation and embryo transfer procedure protocols. IVF/ICSI outcomes, including the numbers of retrieved oocytes and high-grade embryos, clinical pregnancy, miscarriage, preterm delivery, and live birth rates, and adverse obstetric outcome risk were assessed.

Results: The TC group had significantly higher thyroid hormone and lower thyroid-stimulating hormone (TSH) levels than the control group. Despite similar gonadotropin treatment dosage, the TC group had a significantly lower numbers of retrieved oocytes and high-grade embryos than the control group. The occurrence rates of clinical pregnancy, miscarriage, preterm delivery, live births, and adverse obstetric outcomes, including multiple gestation, preterm delivery, gestational diabetes mellitus, gestational hypertension, low birth weight, and large-for-gestational-age infants, were not significantly different between the two groups.

Conclusions: TC history did not affect the pregnancy outcomes or increase the risk of adverse obstetric outcomes after the first IVF/ICSI, but it may decrease the number of retrieved oocytes and high-grade embryos.
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http://dx.doi.org/10.1186/s12958-021-00763-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176716PMC
June 2021

Zeaxanthin promotes browning by enhancing mitochondrial biogenesis through the PKA pathway in 3T3-L1 adipocytes.

Food Funct 2021 May 28. Epub 2021 May 28.

National Engineering Laboratory for Wheat and Corn Deep Processing, Jilin Agricultural University, Changchun, Jilin 130118, China. and College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin 130118, China.

Obesity is closely associated with maintaining mitochondrial homeostasis, and mitochondrial dysfunction can lead to systemic lipid metabolism disorders. Zeaxanthin (ZEA) is a kind of carotenoid with potent antioxidant activity and has been reported to promote mitochondrial biogenesis. Nevertheless, the molecular mechanism has not been explained. In this study, we first discovered that ZEA stimulated 3T3-L1 adipocyte browning by increasing the expression of specific markers (Cd137, Tbx1, Sirt1, Cidea, Ucp1, Tmem26, and Cited1), thereby reducing lipid accumulation. Besides, ZEA promoted mitochondrial biogenesis by increasing the expression of PRDM16, UCP1, NRF2, PGC-1α, and SIRT1. Moreover, the uncoupled oxygen consumption rate (OCR) of protons leaked in 3T3-L1 adipocytes was rapidly increased by ZEA treatment, which improved mitochondrial respiration and energy metabolism. Furthermore, we found that ZEA promotes browning by enhancing mitochondrial biogenesis partly through the protein kinase A (PKA) pathway. This study provided new insight into the promotion of browning and mitochondrial biogenesis by ZEA, suggesting that ZEA probably has potential therapeutic effects on obesity.
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http://dx.doi.org/10.1039/d1fo00524cDOI Listing
May 2021

OP-IVM: Combining In vitro Maturation after Oocyte Retrieval with Gynecological Surgery.

J Vis Exp 2021 May 9(171). Epub 2021 May 9.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital; National Clinical Research Center for Obstetrics and Gynecology; Key Laboratory of Assisted Reproduction, Ministry of Education; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction; Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences;

The use of in vitro maturation (IVM) before gynecological operation (OP-IVM) is an extension of conventional IVM that combines IVM following oocyte retrieval with routine gynecological surgery. OP-IVM is suitable for patients undergoing benign gynecological surgery who have the need for fertility preservation (FP) or infertility treatments such as in vitro fertilization and embryo transfer (IVF-ET). In the operating room, patients undergoing benign gynecological surgery are first anesthetized and receive ultrasound-guided immature follicle aspiration (IMFA) treatment. As the subsequent gynecological surgery is performed, the cumulus-oocyte complexes (COCs) are examined, and the immature COCs are transferred into the IVM medium and cultured for 28-32 hours in the IVF laboratory. After assessment, mature oocytes in the MII stage will be selected and cryopreserved in liquid nitrogen for FP or fertilized by intracytoplasmic sperm injection (ICSI) for IVF-ET. By combining IVM with gynecological surgery, immature oocytes that would have been discarded can be saved and used for assisted reproductive technology (ART). The procedure, significance and critical aspects of OP-IVM are described in this article.
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http://dx.doi.org/10.3791/61647DOI Listing
May 2021

Mild therapeutic hypothermia improves neurological outcomes in a rat model of cardiac arrest.

Brain Res Bull 2021 Aug 19;173:97-107. Epub 2021 May 19.

Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Department of Critical Care Medicine, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. Electronic address:

Cardiac arrest (CA) is the leading cause of death in humans. Research has shown that mild therapeutic hypothermia (MTH) can reduce neurological sequelae and mortality after CA. Nevertheless, the mechanism remains unclear. This study aimed to determine whether MTH promotes neurogenesis, attenuates neuronal damage, and inhibits apoptosis of neurons in rats after CA. Sprague-Dawley rats were divided into the normothermia and mild hypothermia groups. The rats in the normothermia and hypothermia groups were exposed to 2 h of normothermia (36-37℃) and hypothermia (32-33℃), respectively, immediately after resuscitation from 5 min of asphyxial CA. Corresponding control groups not subjected to CA were included. On days 1-6, 5-bromodeoxyuridine (BrdU) 100 mg/kg/day was administered intraperitoneally. The animals were euthanized 1 week after CA. Compared with the normothermia group, the hypothermia group showed a significant increase in the number of doublecortin (DCX) immune-positive cells in the subgranular zone of the hippocampus 1 week after CA. Neurogenesis was assessed using double immunofluorescent labeling of BrdU with neuronal-specific nuclear protein (NeuN)/DCX. There was no marked change in the number of newborn mature (BrdU+-NeuN+) neurons, though there was a significant increase in the number of newborn immature (BrdU+-DCX+) neurons in the hypothermia than in the normothermia group 1 week after CA. Neuronal injury and apoptosis in the CA1 region of the hippocampus, assessed using NeuN immunofluorescence and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays, were significantly reduced in the hypothermia group 1 week after CA. Moreover, mild hypothermia increased the expression of cold-shock protein RNA-binding motif protein 3 (RBM3) in the early stage (24 h/48 h) after CA. These results suggested that mild hypothermia promotes generation of neuronal cells, reduces neuronal injury, and inhibits apoptosis of neurons, which may be related to RBM3 expression.
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http://dx.doi.org/10.1016/j.brainresbull.2021.05.014DOI Listing
August 2021

Effects and satisfaction of dignity therapy among patients with hematologic neoplasms in the Chinese cultural context: a randomized controlled trial.

Support Care Cancer 2021 May 17. Epub 2021 May 17.

The School of Nursing, Fujian Medical University, No. 1 of Xueyuan Road, Shangjie Town, Minhou County, Fuzhou City, Fujian Province, China.

Purpose: To evaluate potential effects and satisfaction of dignity therapy among patients with hematologic neoplasms in the Chinese cultural context.

Methods: Sixty-six patients with hematologic neoplasms were randomly assigned into either a dignity therapy group (N = 32) or control group (N = 34). The primary outcomes were level of hope and spiritual well-being, as measured according to the Herth Hope Index and the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being, at baseline (T0), 1-week follow-up (T1), and 4-week follow-up (T2). Satisfaction with dignity therapy was assessed using a 5-grade marking system at T1.

Results: Among the 66 participants, 61 remained at 1-week follow-up and 57 remained at 4-week follow-up. Group differences were found in the total score and the scores of each dimension of spiritual well-being and level of hope at T1 and T2 (p < 0.05). Interaction effects were statistically significant in terms of spiritual well-being (p < 0.001) and level of hope (p < 0.001). Majority of the patients (93.34%) and family members (96.67%) gave positive evaluations ("very satisfactory" or "relatively satisfactory") for the dignity therapy intervention.

Conclusion: Implementing dignity therapy among patients with hematologic neoplasms in China was associated with good efficacy in improving spiritual well-being and the level of hope in the short term. Difficulties and solutions involved in the implementation of dignity therapy in multiple cultures deserve attention.
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http://dx.doi.org/10.1007/s00520-021-06227-4DOI Listing
May 2021

Structural basis for CD97 recognition of the decay-accelerating factor CD55 suggests mechanosensitive activation of adhesion GPCRs.

J Biol Chem 2021 May 13:100776. Epub 2021 May 13.

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China. Electronic address:

The adhesion G protein-coupled receptor CD97 and its ligand complement decay-accelerating factor CD55 are important binding partners in the human immune system. Dysfunction in this binding has been linked to immune disorders such as multiple sclerosis and rheumatoid arthritis, as well as various cancers. Previous literatures have indicated that the CD97 includes three to five EGF domains at its N-terminus and these EGF domains can bind to the N-terminal SCR domains of CD55. However, the details of this interaction remain elusive, especially why the CD55 binds with the highest affinity to the shortest isoform of CD97 (EGF). Herein, we designed a chimeric expression construct with the EGF domains of CD97 and the SCR domains of CD55 connected by a flexible linker, and determined the complex structure by crystallography. Our data reveal that the two proteins adopt an overall anti-parallel binding mode involving the SCR domains of CD55 and all three EGF domains of CD97. Mutagenesis data confirmed the importance of EGF in the interaction and explained the binding specificity between CD55 and CD97. The architecture of CD55-CD97 binding mode together with kinetics suggest a force-resisting shearing stretch geometry when forces applied to the C-termini of both proteins in the circulating environment. The potential of the CD55-CD97 complex to withstand tensile force may provide a basis for the mechanosensing mechanism for activation of adhesion G protein-coupled receptors.
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http://dx.doi.org/10.1016/j.jbc.2021.100776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191316PMC
May 2021

Hippocampal Interneurons are Required for Trace Eyeblink Conditioning in Mice.

Neurosci Bull 2021 May 15. Epub 2021 May 15.

Experimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University, Chongqing, 400038, China.

While the hippocampus has been implicated in supporting the association among time-separated events, the underlying cellular mechanisms have not been fully clarified. Here, we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning (tEBC) task. We found that the hippocampal interneurons exhibited conditioned stimulus (CS)-evoked sustained activity, which predicted the performance of conditioned eyeblink responses (CRs) in the early acquisition of the tEBC. Consistent with this, greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC. Moreover, optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC. In contrast, suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs. Our findings highlight the role of hippocampal interneurons in the tEBC, and point to a potential cellular mechanism subserving associative learning.
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http://dx.doi.org/10.1007/s12264-021-00700-0DOI Listing
May 2021

Serum Cytokine Profiling Identifies Axl as a New Biomarker Candidate for Active Eosinophilic Granulomatosis With Polyangiitis.

Front Mol Biosci 2021 27;8:653461. Epub 2021 Apr 27.

Department of Pathophysiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, China.

Eosinophilic granulomatosis with polyangiitis (EGPA) prognosis is generally favorable and is treated with combined corticosteroids/immunosuppressor(s) therapy. However, disease flares increase the number of clinical visits. Therefore, discovering new serum biomarkers for early identification of active EGPA is crucial. To identify reliable serum biomarkers to measure EGPA activity. The expression of 160 proteins was compared in sera from 15 inactive and 13 active EGPA patients by antibody-based microarray. Network-based analysis identified patterns in the different groups. Differentially expressed proteins (DEPs) in active disease were identified, and the correlation between their serum levels and clinical parameters was assessed. DEPs were further analyzed for GO enrichment and KEGG pathways. Finally, DEP marker candidates were validated by ELISA and Bio-plex as well as against a second cohort of 22 inactive and 18 active EGPA patients. The active group presented higher peripheral and sputum eosinophil counts, FeNO, and FEV1 (% predicted) ( < 0.05). Network-based analysis showed scattered expression patterns in active subjects, but no significant bias in inactive subjects. Significant differences were observed in serum levels of 19 candidate markers, all of which were higher in active EGPA ( < 0.05). KEGG analysis indicated that DEPs were mainly involved in the MAPK, PI3K-Akt, RAS and Rap1 related pathways. Nine out of 19 candidate markers were positively correlated with peripheral eosinophil counts including FGF-7, SCF, GDNF, β-NGF, IGFBP-4, Axl, PIGF, Insulin, NT-4, ErbB3, OPN and BMP-4 ( = 0.693, = 0.692, = 0.687, = 0.683, = 0.671, = 0.606, = 0.571, = 0.570, = 0.516, respectively; < 0.05), while two, CD14 and MCP-3, were negatively correlated ( = -0.644 and = -0.515; < 0.05). The higher expression of Axl, OPN, HCC-4, GDNF, and MCP-3 in active EGPA subjects was confirmed by ELISA and Custom Multiplex Bio-plex analyses. The serum protein profiles were significantly different between active and inactive EGPA. The expression of the candidate proteins correlated with peripheral blood eosinophil count. Serum Axl, OPN, HCC-4, GDNF, and MCP-3 levels were consistently higher in active EGPA, independent of the assessment methods. Finally, Axl had the largest AUC, indicating that this cytokine may serve as novel biomarker for the diagnosis of active EGPA.
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http://dx.doi.org/10.3389/fmolb.2021.653461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112820PMC
April 2021

Comparative analyses of ACE2 and TMPRSS2 gene: Implications for the risk to which vertebrate animals are susceptible to SARS-CoV-2.

J Med Virol 2021 May 11. Epub 2021 May 11.

Department of Diagnosis, School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Along with the control and prevention of coronavirus disease 2019 transmission, infected animals might have potential to carry the virus to spark new outbreaks. However, very few studies explore the susceptibility of animals to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Viral attachment as a crucial step for cross-species infection requires angiotensin-converting enzyme 2 (ACE2) as a receptor and depends on TMPRSS2 protease activity. Here, we searched the genomes of metazoans from different classes using an extensive BLASTP survey and found ACE2 and TMPRSS2 occur in vertebrates, but some vertebrates lack Tmprss2. We identified 6 amino acids among 25 known human ACE2 residues are highly associated with the binding of ACE2 to SARS-CoV-2 (p value < .01) by Fisher exact test, and following this, calculated the probability of viral attachment within each species by the randomForest function from R randomForest library. Furthermore, we observed that Ace2 selected from seven animals based on the above analysis lack the hydrophobic contacts identified on human ACE2, indicating less affinity of SARS-CoV-2 to Ace2 in animals than humans. Finally, the alignment of 3D structure between human ACE2 and other animals by I-TASSER and TM-align displayed a reasonable structure for viral attachment within these species. Taken together, our data may shed light on the human-to-animal transmission of SARS-CoV-2.
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http://dx.doi.org/10.1002/jmv.27073DOI Listing
May 2021

A Facile Strategy for the High Yielding, Quantitative Conversion of Polyglycol End-Groups to Amines.

Polymers (Basel) 2021 Apr 26;13(9). Epub 2021 Apr 26.

Applied Chemistry and Translational Biomaterials (ACTB) Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia.

Amino end-group functionalised polyglycols are important intermediates in the synthesis of sophisticated polymeric architectures and biomaterials. Herein, we report a facile strategy for the end-group conversion of hydroxyl-terminated polyglycols to amino-terminated polyglycols in high isolated yields and with excellent end-group fidelity. Following traditional conversion of polyglycol hydroxyl end-groups to azides via the corresponding mesylate, reduction with zinc in the presence of ammonium chloride afforded a range of amino end-group functionalised poly(ethylene glycol) and poly(propylene glycol) homopolymers and copolymers with isolated yields of 82-99% and end-group conversions of >99% as determined by NMR spectroscopy and MALDI ToF MS. Furthermore, this process is applicable to a sequential reagent addition approach without intermediate polymer isolation steps with only a slight reduction in yield and end-group conversion (95%). Importantly, a simple work-up procedure provides access to high purity polyglycols without contamination from other reagents.
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http://dx.doi.org/10.3390/polym13091403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123656PMC
April 2021

Impact of thyroid cancer treatment on assisted reproductive technology outcomes in women with infertility.

J Assist Reprod Genet 2021 Apr 26. Epub 2021 Apr 26.

Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, 49 North Garden Rd, Beijing, 100191, China.

Purpose: We investigated the effect of different surgical procedures and radioactive iodine treatment (RAIT) on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and evaluated whether possible risk factors, including age, thyroid-stimulating hormone (TSH) levels, and thyroid antibody positivity, were associated with adverse IVF/ICSI outcomes.

Methods: This retrospective study included 76 women with infertility who had received thyroid cancer (TC) treatment among 137,698 infertile women who underwent IVF/ICSI cycles at the Peking University Third Hospital between 2010 and 2019. Clinical pregnancy and live birth rates were assessed.

Results: We found that the clinical pregnancy and live birth rates in women who underwent partial thyroidectomy were 7- and 6-fold higher, respectively, than those in women who underwent total thyroidectomy. We observed no significant differences in the clinical pregnancy and live birth rates between the RAIT and non-RAIT groups, even after adjusting for age, TSH levels, surgical treatment, and thyroid antibody positivity. Multivariate logistic regression analysis showed that age and TSH levels were not associated with decreased clinical pregnancy and live birth rates. Women with thyroid antibody positivity had significantly lower clinical pregnancy and live birth rates than women without thyroid antibody positivity.

Conclusion: Our study showed lower clinical pregnancy and live birth rates in women who underwent total thyroidectomy than in women who underwent partial thyroidectomy. Thyroid antibody positivity is an important risk factor for adverse IVF/ICSI outcomes in women who have received TC treatment.
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http://dx.doi.org/10.1007/s10815-021-02204-2DOI Listing
April 2021

Disrupting Reconsolidation by Systemic Inhibition of mTOR Kinase via Rapamycin Reduces Cocaine-Seeking Behavior.

Front Pharmacol 2021 9;12:652865. Epub 2021 Apr 9.

Key Laboratory of Molecular Epidemiology of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China.

Drug addiction is considered maladaptive learning, and drug-related memories aroused by the presence of drug related stimuli (drug context or drug-associated cues) promote recurring craving and reinstatement of drug seeking. The mammalian target of rapamycin signaling pathway is involved in reconsolidation of drug memories in conditioned place preference and alcohol self-administration (SA) paradigms. Here, we explored the effect of mTOR inhibition on reconsolidation of addiction memory using cocaine self-administration paradigm. Rats received intravenous cocaine self-administration training for 10 consecutive days, during which a light/tone conditioned stimulus was paired with each cocaine infusion. After acquisition of the stable cocaine self-administration behaviors, rats were subjected to nosepoke extinction (11 days) to extinguish their behaviors, and then received a 15 min retrieval trial with or without the cocaine-paired tone/light cue delivery or without. Immediately or 6 h after the retrieval trial, rapamycin (10 mg/kg) was administered intraperitoneally. Finally, cue-induced reinstatement, cocaine-priming-induced reinstatement and spontaneous recovery of cocaine-seeking behaviors were assessed in rapamycin previously treated animals, respectively. We found that rapamycin treatment immediately after a retrieval trial decreased subsequent reinstatement of cocaine seeking induced by cues or cocaine itself, and these effects lasted at least for 28 days. In contrast, delayed intraperitoneal injection of rapamycin 6 h after retrieval or rapamycin injection without retrieval had no effects on cocaine-seeking behaviors. These findings indicated that mTOR inhibition within the reconsolidation time-window impairs the reconsolidation of cocaine associated memory, reduces cocaine-seeking behavior and prevents relapse, and these effects are retrieval-dependent and temporal-specific.
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http://dx.doi.org/10.3389/fphar.2021.652865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064688PMC
April 2021

The role of cGMP-signalling and calcium-signalling in photoreceptor cell death: perspectives for therapy development.

Pflugers Arch 2021 Apr 16. Epub 2021 Apr 16.

Institute for Ophthalmic Research, University of Tübingen, Elfriede-Aulhorn-Strasse 7, 72076, Tübingen, Germany.

The second messengers, cGMP and Ca, have both been implicated in retinal degeneration; however, it is still unclear which of the two is most relevant for photoreceptor cell death. This problem is exacerbated by the close connections and crosstalk between cGMP-signalling and calcium (Ca)-signalling in photoreceptors. In this review, we summarize key aspects of cGMP-signalling and Ca-signalling relevant for hereditary photoreceptor degeneration. The topics covered include cGMP-signalling targets, the role of Ca permeable channels, relation to energy metabolism, calpain-type proteases, and how the related metabolic processes may trigger and execute photoreceptor cell death. A focus is then put on cGMP-dependent mechanisms and how exceedingly high photoreceptor cGMP levels set in motion cascades of Ca-dependent and independent processes that eventually bring about photoreceptor cell death. Finally, an outlook is given into mutation-independent therapeutic approaches that exploit specific features of cGMP-signalling. Such approaches might be combined with suitable drug delivery systems for translation into clinical applications.
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http://dx.doi.org/10.1007/s00424-021-02556-9DOI Listing
April 2021

Upregulated MicroRNA-483-3p is an Early Event in Pancreatic Ductal Adenocarcinoma (PDAC) and as a Powerful Liquid Biopsy Biomarker in PDAC.

Onco Targets Ther 2021 25;14:2163-2175. Epub 2021 Mar 25.

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.

Background: There is an urgent need for the development of effective noninvasive biomarkers for early pancreatic cancer diagnosis. MicroRNAs (miRNAs) are promising candidates that can be identified in peripheral blood and can act as "liquid biopsy" biomarkers. miR-483-3p is overexpressed in the tumor tissue of pancreatic duct adenocarcinoma, but its potential as noninvasive biomarker remains unknown.

Methods: We conducted locked nucleic acid in situ hybridization (LNA-ISH) for miR-483-3p in archival tissues of 107 patients with PDAC. We also used immunohistochemistry to evaluate SMAD4 expression, the putative miR-483-3p target gene. miR-483-3p expression level was also assessed using quantitative real-time PCR (qRT-PCR) in serum and serum exosome samples from 63 patients with PDAC and 22 healthy individuals.

Results: LNA-ISH showed that miR-483-3p was overexpressed in PDAC and PanIN tissues compared to normal pancreatic duct cells. miR-483-3p expression levels correlated with increases in PanIN lesion grade. miR-483-3p expression negatively correlated with Smad4 expression (γ=-0.770, p<0.0001) in PDAC and PanIN tissues. Circulating miR-483-3p levels were significantly elevated in the serum and serum exosomes of PDAC patients compared to healthy controls (p<0.0001 and p<0.01, respectively). Specifically, serum miR-483-3p levels were able to distinguish patients with early stage (≤2cm) PDAC from healthy controls with an AUC of 0.83 [95% CI, 0.70-0.96]. Higher serum exosomal miR-483-3p levels predicted worse survival in PDAC patients and serum exosomal miR-483-3p also proved to be an independent prognostic factor for PDAC (hazard ratio = 3.307; 95% CI=1.104 to 9.903; p=0.033). In vitro studies also showed that miR-483-3p promoted pancreatic cancer cell migration and invasion.

Conclusion: miR-483-3p overexpression occurs early in PDAC development and is present in premalignant PanIN lesions. Serum miR-483-3p may act as an early PDAC diagnostic biomarker and serum exosomal miR-483-3p may be a PDAC prognostic biomarker.
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http://dx.doi.org/10.2147/OTT.S288936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006761PMC
March 2021

Effects of size, cooperativity, and competitive binding on protein positioning on DNA.

Biophys J 2021 May 23;120(10):2040-2053. Epub 2021 Mar 23.

Mechanobiology InstituteNational University of Singapore, Singapore, Singapore; Department of Physics, National University of Singapore, Singapore, Singapore. Electronic address:

Accurate positioning of proteins on chromosomal DNA is crucial for its proper organization as well as gene transcription regulation. Recent experiments revealed existence of periodic patterns of nucleoprotein complexes on DNA, which frequently cannot be explained by sequence-dependent binding of proteins. Previous theoretical studies suggest that such patterns typically emerge as a result of the proteins' volume-exclusion effect. However, the role of other physical factors in patterns' formation, such as the length of DNA, its sequence heterogeneity, and protein binding cooperativity/binding competition to DNA, remains unclear. To address these less understood yet important aspects, we investigated potential effects of these factors on protein positioning on finite-size DNA by using transfer-matrix calculations. It has been found that upon binding to DNA, proteins form oscillatory patterns that span over the length of up to ∼10 times the size of the protein binding site, with the shape of the patterns being strongly dependent on the length of DNA and the proteins' binding cooperativity to DNA. Furthermore, calculations showed that small variations in the proteins' affinity to DNA due to its sequence heterogeneity do not much change the main geometric characteristics of the observed protein patterns. Finally, competition between two different types of proteins for binding to DNA has been found to lead to formation of highly diverse and complex alternating positioning of the two proteins. Altogether, these results provide new insights into the roles of physicochemical properties of proteins, the DNA length, and DNA-binding competition between proteins in formation of protein positioning patterns on DNA.
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http://dx.doi.org/10.1016/j.bpj.2021.03.016DOI Listing
May 2021

The impact of lockdown policy on depressive symptoms among pregnant women in China: mediating effects of internet use and family support.

Glob Health Res Policy 2021 03 26;6(1):11. Epub 2021 Mar 26.

School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

Background: Although more and more attention has been paid to the psychological consequences of the lockdown policy amongst pregnant women, the underlying mechanism linking the lockdown policy to maternal depression has not been studied in the context of China. This study aimed to explore the association between the lockdown policy and maternal depressive symptoms, and whether such association was mediated by internet use and/or family support.

Methods: This cross-sectional study used multi-stage sampling techniques in central and western China. Data were collected from 1266 pregnant women using a structtured questionnaire that measured internet use, family support, and depressive symptoms. The Patient Health Questionnaire-9 (PHQ-9) was used to measure depressive symptoms. Internet use was measured by length of usage and varierity of purpose for internet use. Family support was measureed by spousal support and parental support. The structural equation modelling was employed to conduct mediation analysis to test the specificity of the hypothetical paths.

Results: Overall, 527 respondents (41.63%) presented depressive symptoms. The lockdown policy was negatively associated with depressive symptoms in pregnant women (β = - 0.925, 95% CI = -1.510, - 0.360). The impact of the lockdown policy on depressive symptoms was partially mediated by internet use (β = 1.589, 95% CI = 0.730, 2.807) and family support (β = - 0.162, 95% CI = - 0.341, - 0.017), accounting for 42.67% of the total effect.

Conclusions: The lockdown policy was generally associated with fewer depressive symptoms in pregnant women. The lockdown policy increased maternal depressive symptoms through increased internet use, but decreased maternal depressive symptoms through enhanced family support. The findings suggest that the psychological consequence of the lockdown policy may vary across different populations, and warrant the need to take into consideration the features of subgroups.
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http://dx.doi.org/10.1186/s41256-021-00193-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994177PMC
March 2021

Value of pretreatment 18F-FDG PET/CT in prognosis and the reflection of tumor burden: a study in pediatric patients with newly diagnosed neuroblastoma.

Int J Med Sci 2021 24;18(8):1857-1865. Epub 2021 Feb 24.

Department of Pediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

Fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT has been commonly used in pediatric patients with newly diagnosed neuroblastoma (NB) for diagnosis. We retrospectively reviewed 40 pediatric patients with newly diagnosed NB who underwent 18F-FDG PET/CT. Clinicopathological factors and metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were evaluated as predictive factors for progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analysis. Spearman rank correlation analyses were used to estimate the correlations between clinical factors and PET findings. The mean follow-up after 18F-FDG-PET/CT was 32.9 months. During the follow-up period 15 (37.5%) patients experienced progression, and 9 (22.5%) died. MTV (P=0.001) and TLG (p=0.004) remained significant predictive factors for tumor progression, along with lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and bone metastasis. Univariate analysis showed that bone metastasis, LDH (>1064 IU/L), NSE (>364.4 ug/L), MTV (>191 cm3) and TLG (>341.41 g) correlated with PFS, and LDH (>1064 IU/L), NSE (>364.4 ug/L) and MTV (>191 cm) correlated with OS (p<0.05). In multivariate analysis, MTV and bone metastasis were independent prognostic factors for PFS (p=0.001 and 0.023, respectively), and MTV remained the only independent prognostic factor for OS (p= 0.004). We also found that there were correlations between semiquantitative PET/CT parameters and clinical features in NB. Our results suggested that 18F-FDG PET/CT was a useful tool to predictive progression and to reflect tumor burden for patients with NB.
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http://dx.doi.org/10.7150/ijms.58263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976578PMC
February 2021

iTRAQ-based proteomic analysis of the rat striatum in response to methamphetamine preconditioning.

Acta Biochim Biophys Sin (Shanghai) 2021 Apr;53(5):636-639

School of Basic Medical Science, Xinjiang Medical University, Urumqi 830001, China.

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http://dx.doi.org/10.1093/abbs/gmab024DOI Listing
April 2021

Mechanical instability of adherens junctions overrides intrinsic quiescence of hair follicle stem cells.

Dev Cell 2021 Mar 15;56(6):761-780.e7. Epub 2021 Mar 15.

Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore 560065, India; Skin Research Institute of Singapore (A∗STAR), Singapore 138648, Singapore. Electronic address:

Vinculin, a mechanotransducer associated with both adherens junctions (AJs) and focal adhesions (FAs), plays a central role in force transmission through cell-cell and cell-substratum contacts. We generated the conditional knockout (cKO) of vinculin in murine skin that results in the loss of bulge stem cell (BuSC) quiescence and promotes continual cycling of the hair follicles. Surprisingly, we find that the AJs in vinculin cKO cells are mechanically weak and impaired in force generation despite increased junctional expression of E-cadherin and α-catenin. Mechanistically, we demonstrate that vinculin functions by keeping α-catenin in a stretched/open conformation, which in turn regulates the retention of YAP1, another potent mechanotransducer and regulator of cell proliferation, at the AJs. Altogether, our data provide mechanistic insights into the hitherto-unexplored regulatory link between the mechanical stability of cell junctions and contact-inhibition-mediated maintenance of BuSC quiescence.
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http://dx.doi.org/10.1016/j.devcel.2021.02.020DOI Listing
March 2021

Identification of lncRNA expression profiles and analysis of ceRNA in the hippocampus of perinatal glyphosate-exposed mice.

Int J Dev Neurosci 2021 Jun 18;81(4):312-323. Epub 2021 Mar 18.

Department of Basic Medicine and Forensic Medicine, Hangzhou Medical College, Hangzhou, P.R. China.

Objective: In order to understand the role of long noncoding RNAs (lncRNAs) played in the mechanisms of glyphosate neurotoxicity in neuronal development.

Methods: Perinatal glyphosate exposure (PGE) mouse model was constructed, and a lncRNA microarray was used to study the lncRNA expression changes in the hippocampus tissue of perinatal glyphosate exposure mice. Then we used GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) databases to analyze the function of the differentially expressed mRNAs and lncRNAs.

Results: LncRNA microarray analysis revealed that 1759 lncRNAs and 759 mRNAs were differentially expressed in the perinatal glyphosate exposure (PGE) mice group (G group) compared with the normal control mice group (C group). The functions of the DEmRNAs are involved in the cellular response to hormone stimulus. The ceRNA analysis showed that some interaction networks existed, including (ENSMUST00000137546, ENSMUST00000160950)/(miR-34a-3p, miR-130a-3p)/(Il12b, Irf1). Further analysis of the target mRNAs of miRNAs indicated that the possible functions involved the neuroactive ligand-receptor interaction and calcium signaling pathway, which are involved in perinatal glyphosate exposure-induced neurotoxicity.

Conclusion: The aberrant expression of lncRNAs is related to the perinatal glyphosate-exposed neurotoxicity. These lncRNAs affect the target gene expression level, might by regulating neuroactive ligand-receptor interactions. The (ENSMUST00000137546, ENSMUST00000160950)/ (miRNA-34a-5p, miR-130a-3p) / mRNAs (e.g., Il12b, Irf1) interaction network may functions in perinatal glyphosate exposure-induced neurotoxicity.
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http://dx.doi.org/10.1002/jdn.10102DOI Listing
June 2021

Validation of a scoring system for prediction of obstetric complications in placenta accreta spectrum disorders.

J Matern Fetal Neonatal Med 2021 Mar 8:1-7. Epub 2021 Mar 8.

Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.

Background: Placenta accreta spectrum (PAS) refers to a spectrum of conditions characterized by the abnormal adherence of the placenta to the implantation site and has been a challenge due to the risk of postpartum hemorrhage, peripartum hysterectomy and maternal mortality. Despite of sonographic findings, no consensus on the prenatal evaluation of PAS has been established yet. We are aiming to establish a scoring system to increase the accuracy of prediction of PAS severity, especially to differentiate placenta percreta and placenta increta.

Methods: We conducted a retrospective study and collected 2,219 cases of placenta increta and placenta percreta obtained from 20 tertiary care centers in China. Demographic information, clinical characteristics, and sonographic findings were collected. Logistic regression analysis was used to determine the risk factors and sonographic features that were significantly associated with a clinical diagnosis of placenta percreta. The formula and subsequent scoring system were generated. This scoring system was then verified in 67 cases of placenta increta or placenta percreta in Peking University First Hospital from 2016 to 2017. Diagnosis of placental invasion was confirmed by surgical findings or histopathologic results. The scoring system was evaluated using a receiver operating characteristic (ROC) curve.

Results: The scoring system combined maternal risk factors and ultrasound features and was then verified in 67 cases. According to ROC curve, the area under the curve (AUC) of our scoring system for prenatal diagnosis of placenta percreta is 0.96 (95%CI, 0.91-1.00,  < .001), for severe postpartum hemorrhage (≥1500 ml) is 0.76 (95%CI, 0.62-0.91,  = .005), for hysterectomy is 0.98 (95%CI, 0.93-1.000,  = .023).

Conclusions: Our scoring system combining maternal risk factors and ultrasound features can improve the predictive accuracy of placenta percreta and obstetric outcomes (severe hemorrhage and hysterectomy).
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http://dx.doi.org/10.1080/14767058.2020.1847077DOI Listing
March 2021

Acute exposure to N-Ethylpentylone induces developmental toxicity and dopaminergic receptor-regulated aberrances in zebrafish larvae.

Toxicol Appl Pharmacol 2021 04 3;417:115477. Epub 2021 Mar 3.

Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, PR China. Electronic address:

N-Ethylpentylone (NEP) is one of the most recent novel stimulants, and there is limited understanding of its toxicity. Here we employed zebrafish model for analyzing the effects of NEP on early embryos and cardiovascular and nervous systems at late developmental stages. We first observed multi-malformations in early embryos and larvae after NEP administration, together with significant deregulations of brain and heart development-associated genes (neurog1, her6, elavl3, nkx2.5, nppa, nppb, tnnt2a) at transcriptional level. Low-dosed NEP treatment induced an anxiety-like phenotype in zebrafish larvae, while higher doses of NEP exerted an inhibitory effect on locomotion and heart rate. Besides, the expression of th (tyrosine hydroxylase) and th2 (tyrosine hydroxylase 2), identifying dopamine (DA) release, were significantly increased during one-hour free swimming after effective low-dosed NEP administration, along with the upregulation of gene fosab and fosb related to stress and anxiety response. D1R antagonist SCH23390 and D2R antagonist sulpiride partially alleviated the aberrances of locomotion and heart rate, indicating dopaminergic receptors were involved in the bidirectional dosage-dependent pattern of NEP-induced performance. Meanwhile, sulpiride offset the upregulated expression of th, th2 and fosab in the group of 1.5 μM NEP, which highlighted the significant role of D2R in NEP-induced locomotive effects. This study systematically described the developmental, neuronal and cardiac toxicity of NEP in zebrafish, and identified the dopaminergic receptors as one of the downstream effectors of NEP administration.
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http://dx.doi.org/10.1016/j.taap.2021.115477DOI Listing
April 2021

Congenital dysfibrinogenemia caused by γAla327Val mutation: structural abnormality of D region.

Hematology 2021 Dec;26(1):305-311

Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China.

Background: : Congenital dysfibrinogenemia (CD) is a coagulation disorder caused by mutations in the fibrinogen genes, which result in abnormal fibrinogen function. However, the precise pathogenesis underlying it remains unclear.

Methods: : In this study, we identified a novel heterozygous mutation in an asymptomatic patient with CD caused by γ Ala327Val mutation. Aimed to investigate the pathogenesis, functional studies of fibrinogen isolated from the proband and her family members were performed, such as coagulation function, fibrinogen aggregation test, and fibrin clot lysis test. Coagulation was monitored using a thromboelastometer, and the fibrin clot network structure was observed by scanning electron microscopy. The effect of the mutation on fibrinogen structure and function was predicted by molecular modeling.

Results: : The fibrinogen activity concentration in patients with CD was significantly lower than that in healthy individuals, indicating that fibrinogen activity was low. Proband's fibrinogen activity concentration was 0.75 g/L(Clauss method) and antigen concentration (immune turbidimetry method) was 1.59 g/L(normal reference range for both parameters: 2.0-4.0 g/L). Thromboelastography showed that the K value of patients with CD was higher than that of healthy individuals and Angle values were decreased, indicating that mutation impaired fibrinogen function. Compared to fibrinogen from healthy individuals, fiber network structure of the proband was loose, pore size was increased, and fiber branch nodes were increased.

Conclusions: : Ala327Val heterozygous missense mutation leads to changes in the structure of fibrinogen D region and impairs the aggregation function of fibrinogen. This mutation is reported here for the first time.
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http://dx.doi.org/10.1080/16078454.2021.1893977DOI Listing
December 2021

The Prognostic Value of Myocardial Injury in COVID-19 Patients and Associated Characteristics.

Res Sq 2021 Feb 19. Epub 2021 Feb 19.

Since December 2019, Coronavirus disease 2019 (COVID-19) has emerged as an international pandemic. COVID-19 patients with myocardial injury might need special attention. However, understanding on this aspect remains unclear. This study aimed to illustrate clinical characteristics and the prognostic value of myocardial injury to COVID-19 patients. This retrospective, single-center study finally included 304 hospitalized COVID-19 cases confirmed by real-time RT-PCR from January 11 to March 25, 2020. Myocardial injury was determined by serum high-sensitivity troponin I (Hs-TnI). The primary endpoint was COVID-19 associated mortality. Of 304 COVID-19 patients (median age, 65 years; 52.6% males), 88 patients (27.3%) died (61 patients with myocardial injury, 27 patients without myocardial injury on admission). COVID-19 patients with myocardial injury had more comorbidities (hypertension, chronic obstructive pulmonary disease, cardiovascular disease, and cerebrovascular disease); lower lymphocyte counts, higher C-reactive protein (CRP, median, 84.9 vs 28.5 mg/L, p<0.001), procalcitonin levels (median, 0.29 vs 0.06 ng/ml, p<0.001), inflammatory and immune response markers; more frequent need for noninvasive ventilation, invasive mechanical ventilation; and was associated with higher mortality incidence (hazard ratio, HR=7.02, 95% confidence interval, CI, 4.45-11.08, p<0.001) than those without myocardial injury. Myocardial injury (HR=4.55, 95% CI, 2.49-8.31, p<0.001), senior age, CRP levels, and novel coronavirus pneumonia (NCP) types on admission were independent predictors to mortality in COVID-19 patients. COVID patients with myocardial injury on admission is associated with more severe clinical presentation and biomarkers. Myocardial injury and higher HsTNI are both strongest independent predictors to COVID related mortality after adjusting confounding factors. In addition, senior age, CRP levels and NCP types are also associated with mortality. Not applicable.
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http://dx.doi.org/10.21203/rs.3.rs-251810/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899459PMC
February 2021

Down-Regulation of CIDEA Promoted Tumor Growth and Contributed to Cisplatin Resistance by Regulating the JNK-p21/Bad Signaling Pathways in Esophageal Squamous Cell Carcinoma.

Front Oncol 2020 3;10:627845. Epub 2021 Feb 3.

Department of Clinical Oncology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with poor prognosis and lack of effective targeted therapies. In this study, we investigated the tumor suppressive role of the cell death inducing DFF like effector A (CIDEA) in ESCC. Firstly, public datasets and ESCC tissue microarray analysis showed that CIDEA was frequently down-regulated at both the mRNA and protein level. This was significantly associated with low differentiation and TNM stage in ESCC, and indicated poor prognosis for ESCC patients. Bisulfite genomic sequencing (BGS) and methylation-specific PCR (MSP) analysis revealed that the down-regulation of CIDEA was associated with hypermethylation of its promoter, which was also correlated with the poor prognosis in ESCC patients. and functional studies demonstrated that CIDEA decreased cell growth, foci formation, DNA replication, and tumorigenesis in nude mice. Further study revealed that, during starvation or cisplatin induced DNA damage, CIDEA facilitated the G1-phase arrest or caspase-dependent mitochondrial apoptosis through the JNK-p21/Bad pathway. Therefore, CIDEA is a novel tumor suppressor gene that plays an important role in the development and progression of ESCC, and may provide a potential therapeutic target for patients with ESCC.
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http://dx.doi.org/10.3389/fonc.2020.627845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888273PMC
February 2021