Publications by authors named "Chun Yang"

986 Publications

Development of an Automatic Column Chromatography Separation Device for Metal Isotope Analysis Based on Droplet Counting.

Anal Chem 2021 May 9. Epub 2021 May 9.

State Key Laboratory of Biogeology and Environmental Geology, China University of Geosciences (Wuhan), Wuhan 430074, China.

A novel, simple, cost-effective, reliable, and practical automatic column chromatography separation device capable of simultaneously purifying samples for radiogenic and non-traditional stable isotope analysis has been developed. The device avoids the use of any pump and features eluent driving by the siphon effect (gravity) and quantitative control by infrared droplet counting. Several factors affecting the control of droplets were investigated, including types and concentrations of eluents and the height of the liquid level. Results showed that accurate dripping of the eluent could be readily achieved by controlling the number of droplets under selected conditions. The separation performance of the device was first demonstrated by the elution of Sr and Cd in synthetic matrix solutions. The recoveries of Sr and Cd samples were better than 87.6 and 95.0%, respectively, and the whole procedure blank was about 0.3 ng for Sr and 0.1 ng for Cd. Finally, the reliability of the device was further validated by the purification of Sr and Cd from different geological reference materials (NIST 2711a, Nod-A-1, BCR-2, and BHVO-2). The determined Cd and Sr isotope values agree well with their reference values within the uncertainty range. All these results clearly demonstrate the reliability and practicability of the proposed device, which provides a promising method for the automated purification of isotope samples.
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http://dx.doi.org/10.1021/acs.analchem.1c00145DOI Listing
May 2021

Porcine and bovine aortic valve comparison for surgical optimization: A fluid-structure interaction modeling study.

Int J Cardiol 2021 Apr 28. Epub 2021 Apr 28.

Department of Cardiac Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Background: Porcine aortic valve (PAV) and bovine aortic valve (BAV) are commonly used in aortic valve replacement (AVR) surgeries. A detailed comparison for their hemodynamic and structural stress/strain performances would help to better understand valve cardiac function and select valve type and size for AVR outcome optimizations.

Methods: Eight fluid-structure interaction models were constructed to compare hemodynamic and stress/strain behaviors of PAV and BAV with 4 sizes (19, 21, 23, and 25 mm). Blood flow velocity, systolic cross-valve pressure gradient (SCVPG), geometric orifice area (GOA), flow shear stresses (FSS), and stress/strain were obtained for comparison.

Results: Compared with PAV, BAV has better hemodynamic performance, with lower maximum flow velocity (7.17%) and pressure (9.82%), smaller pressure gradient (mean and peak SCVPG: 8.92% and 9.28%), larger GOA (9.56%) and lower FSS (6.61%). The averages of the mean and peak net pressure gradient values from 4 BAV models were 8.10% and 8.35% lower than that from PAV models. Larger valve sizes for both PAV and BAV had improved hemodynamic performance. Maximum flow velocity, pressure, mean SCVPG and maximum FSS from 25 mm BAV were 36.80%, 15.81%, 39.05% and 38.83% lower than those from 19 mm BAV. The GOA of PAV and BAV 25 mm Valve were 43.75% and 33.07% larger than 19 mm valves, respectively. BAV has lower stress on the leaflets than PAV.

Conclusions: BAV had better hemodynamic performance and lower leaflets stress than PAV. More patient studies are needed to validate our findings.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.051DOI Listing
April 2021

Pazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3.

Sci Transl Med 2021 Apr;13(591)

Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.

Acute lung injury (ALI) causes high mortality and lacks any pharmacological intervention. Here, we found that pazopanib ameliorated ALI manifestations and reduced mortality in mouse ALI models and reduced edema in human lung transplantation recipients. Pazopanib inhibits mitogen-activated protein kinase kinase kinase 2 (MAP3K2)- and MAP3K3-mediated phosphorylation of NADPH oxidase 2 subunit p47 at Ser to increase reactive oxygen species (ROS) formation in myeloid cells. Genetic inactivation of MAP3K2 and MAP3K3 in myeloid cells or hematopoietic mutation of p47 Ser to alanine attenuated ALI manifestations and abrogates anti-ALI effects of pazopanib. This myeloid MAP3K2/MAP3K3-p47 pathway acted via paracrine HO to enhance pulmonary vasculature integrity and promote lung epithelial cell survival and proliferation, leading to increased pulmonary barrier function and resistance to ALI. Thus, pazopanib has the potential to be effective for treating ALI.
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http://dx.doi.org/10.1126/scitranslmed.abc2499DOI Listing
April 2021

Brain-derived neurotrophic factor: An available biomarker to predict and diagnose sarcopenia in hemodialysis patients?

Geriatr Gerontol Int 2021 Apr 24. Epub 2021 Apr 24.

Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China.

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http://dx.doi.org/10.1111/ggi.14176DOI Listing
April 2021

Optical Coherence Tomography-Based Patient-Specific Residual Multi-Thrombus Coronary Plaque Models with Fluid-Structure Interaction for Better Treatment Decisions: A Biomechanical Modeling Case Study.

J Biomech Eng 2021 Apr 20. Epub 2021 Apr 20.

School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China; Mathematical Sciences Department, Worcester Polytechnic Institute, Worcester, MA 01609, USA.

Intracoronary thrombus from plaque erosion could cause fatal acute coronary syndrome (ACS). A conservative anti-thrombotic therapy has been proposed to treat ACS patients in lieu of stenting. It is speculated that the residual thrombus after aspiration thrombectomy would influence the prognosis of this treatment. However, biomechanical mechanisms affecting intracoronary thrombus remodeling and clinical outcome remain largely unknown. In vivo optical coherence tomography (OCT) data of a coronary plaque with two residual thrombi after anti-thrombotic therapy were acquired from an ACS patient with consent obtained. Three OCT-based FSI models with different thrombus volumes, fluid-only and structure-only models were constructed to simulate and compare the biomechanical interplay among blood flow, residual thrombus and vessel wall mimicking different clinical situations. Our results showed that residual thrombus would decrease coronary volumetric flow rate by 9.3%, but elevate wall shear stress (WSS) by 29.4% and 75.5% at Thrombus 1 & 2, respectively. WSS variations in a cardiac cycle from structure-only model were 12.1% and 13.5% higher at the two thrombus surfaces than those from FSI model. Intracoronary thrombi were subjected to compressive forces indicated by negative thrombus stress. Tandem intracoronary thrombus might influence coronary hemodynamics and solid mechanics differently. Computational modeling could be used to quantify biomechanical conditions under which patients could receive patient-specific treatment plan with optimized outcome after anti-thrombotic therapy. More patient studies with follow-up data are needed to continue the investigation and better understand mechanisms governing thrombus remodeling process.
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http://dx.doi.org/10.1115/1.4050911DOI Listing
April 2021

Taurine reduction associated with heart dysfunction after real-world PM exposure in aged mice.

Sci Total Environ 2021 Apr 5;782:146866. Epub 2021 Apr 5.

Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, School of Environmental Science and Engineering, University of Technology, Guangzhou 510006, PR China; State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China. Electronic address:

Ambient PM has been proved to be an independent risk factor for cardiovascular diseases; however, little information is available on the age-dependent effects of PM on the cardiovascular system and the underlying mechanisms following chronic exposure. In this study, multi-aged mice were exposed to PM via the newly developed real-ambient PM exposure system to investigate age-related effects on the heart after long-term exposure. First, the chemical and physical properties of PM used in the exposure system were analyzed. The heart rate of conscious mice was recorded, and results showed that exposure of aged mice to PM for 26 weeks significantly increased heart rate. Histological analysis and ELISA assays indicated that aged mice were more sensitive to PM exposure in terms of inducing cardiac oxidative stress and inflammation. Furthermore, untargeted metabolomics revealed that taurine was involved with the PM-induced cardiac dysfunction. The reduced taurine concentration in the heart was examined by LC-MS and imaging mass spectrometry; it may be due to the increased p53 expression level, ROS and inflammatory cytokines. These results emphasize the age-dependent effects of PM on the cardiovascular system and suggest that taurine may be the novel cardiac effect target for PM-induced heart dysfunction in the aged.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146866DOI Listing
April 2021

Optotheranostic Nanosystem with Phone Visual Diagnosis and Optogenetic Microbial Therapy for Ulcerative Colitis At-Home Care.

ACS Nano 2021 04 5;15(4):7040-7052. Epub 2021 Apr 5.

School of Life Sciences, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, China.

Ulcerative colitis (UC) is a relapsing disorder characterized by chronic inflammation of the intestinal tract. However, the home care of UC based on remote monitoring, due to the operational complexity and time-consuming procedure, restrain its widespread applications. Here we constructed an optotheranostic nanosystem for self-diagnosis and long-acting mitigations of UC at home. The system included two major modules: (i) A disease prescreening module mediated by smartphone optical sensing. (ii) Disease real-time intervention module mediated by an optogenetic engineered bacteria system. Recombinant Nissle 1917 (EcN) secreted interleukin-10 (IL-10) could downregulate inflammatory cascades and matrix metalloproteinases; it is a candidate for use in the therapeutic intervention of UC. The results showed that the Detector was able to analyze, report, and share the detection results in less than 1 min, and the limit of detection was 15 ng·mL. Besides, the IL-10-secreting EcN treatment suppressed the intestinal inflammatory response in UC mice and protected the intestinal mucosa against injury. The optotheranostic nanosystems enabled solutions to diagnose and treat disease at home, which promotes a mobile health service development.
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http://dx.doi.org/10.1021/acsnano.1c00135DOI Listing
April 2021

Combination of nitrous oxide and the modified inflation-deflation method for identifying the intersegmental plane in segmentectomy: A randomized controlled trial.

Thorac Cancer 2021 May 4;12(9):1398-1406. Epub 2021 Apr 4.

Department of Thoracic Surgery, Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: During thoracoscopic segmentectomy, accurately and rapidly identifying the intersegmental plane (ISP) is of great importance. This study aimed to investigate the effect and safety of a nitrous oxide (N O)/oxygen (O ) inspired mixture on the appearance time of the ISP (T ) via the modified inflation-deflation method.

Methods: A total of 65 participants who underwent segmentectomy were randomized into three groups: 75% N O (n = 24), 50% N O (n = 23) or 0% N O (n = 18). The 75% N O group received a gas mixture of N O/O (Fio = 0.25), the 50% N O group received N O/O (Fio = 0.5), and the 0% N O group received 100% oxygen during lung expansion. The appearance time of satisfactory and ideal planes was recorded. Furthermore, arterial blood gas at breathing room air, one-lung ventilation (OLV) before lung expansion, 5 and 15 min after lung expansion were also recorded.

Results: T was significantly shorter in the 75% N O group (320.2 ± 65.9 s) compared with that of the 50% N O group (552.4 ± 88.9 s, p < 0.001) and the 0% N O group (968.3 ± 85.5 s, p < 0.001), while the 50% N O group was shorter than that of the 0% N O group (p < 0.001). Arterial oxygenation was significantly improved in the 0% N O group only after lung expansion, before which there were no differences in mean PaO values among groups.

Conclusions: The use of N O in the inspired gas mixture during lung expansion is an applicable strategy to rapidly identify the ISP via the modified inflation-deflation method without any adverse effect on OLV related arterial oxygenation during segmentectomy.
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http://dx.doi.org/10.1111/1759-7714.13919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088974PMC
May 2021

Is SARS-CoV-2 vaccination safe and effective for elderly individuals with neurodegenerative diseases?

Expert Rev Vaccines 2021 Apr 12:1-9. Epub 2021 Apr 12.

Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing China.

Introduction: Coronavirus Disease 2019 (COVID-19) poses a substantial threat to the lives of the elderly, especially those with neurodegenerative diseases, and vaccination against viral infections is recognized as an effective measure to reduce mortality. However, elderly patients with neurodegenerative diseases often suffer from abnormal immune function and take multiple medications, which may complicate the role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Currently, there is no expert consensus on whether SARS-CoV-2 vaccines are suitable for patients with neurodegenerative diseases.

Areas Covered: We searched Pubmed to conduct a systematic review of published studies, case reports, reviews, meta-analyses, and expert guidelines on the impact of SARS-CoV-2 on neurodegenerative diseases and the latest developments in COVID-19 vaccines. We also summarized the interaction between vaccines and age-related neurodegenerative diseases. The compatibility of future SARS-CoV-2 vaccines with neurodegenerative diseases is discussed.

Expert Opinion: Vaccines enable the body to produce immunity by activating the body's immune response. The pathogenesis and treatment of neurodegenerative diseases is complex, and these diseases often involve abnormal immune function, which can substantially affect the safety and effectiveness of vaccines. In short, this article provides recommendations for the use of vaccine candidates in patients with neurodegenerative diseases.
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http://dx.doi.org/10.1080/14760584.2021.1911653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054494PMC
April 2021

Revealing consensus gene pathways associated with respiratory functions and disrupted by PM2.5 nitrate exposure at bulk tissue and single cell resolution.

Environ Pollut 2021 Mar 19;280:116951. Epub 2021 Mar 19.

Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China; College of Environmental Science and Engineering, Tongji University, Shanghai, China; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Background: Nitrate is a major pollutant component in ambient PM. It is known that chronic exposure to PM NO damages respiratory functions. We aim to explore the underlying toxicological mechanism at single cell resolution.

Methods: We systematically conducted exposure experiments on forty C57BL/6 mice, assessed respiratory functions, and profiled lung transcriptome. . Afterward, we estimated the cell type compositions from RNA-seq data using deconvolution analysis. The genes and pathways associated with respiratory function and dysregulated by to PM NO exposure were characterized at bulk-tissue and single-cell resolution.

Results: PM NO exposure did not significantly modify the cell type composition in lung, but profoundly altered the gene expression within each cell type. At ambient concentration (22 μg/m), exposure significantly (FDR<10%) altered 95 genes' expression. Among the genes associated with respiratory functions, a large fraction (74.6-91.7%) were significantly perturbed by PM NO exposure. For example, among the 764 genes associated with peak expiratory flow (PEF), 608 (79.6%) were affected by exposure (p = 1.92e-345). Pathways known to play role in lung disease pathogenesis, including circadian rhythms, sphingolipid metabolism, immune response and lysosome, were found significantly associated with respiratory functions and disrupted by PM NO exposure.

Conclusions: This study extended our knowledge of PM NO exposure's effect to the levels of lung gene expression, pathways, lung cell type composition and cell specific transcriptome. At single cell resolution, we provided insights in toxicological mechanism of PM NO exposure and subsequent pulmonary disease risks.
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http://dx.doi.org/10.1016/j.envpol.2021.116951DOI Listing
March 2021

Tendon-to-bone healing after repairing full-thickness rotator cuff tear with a triple-loaded single-row method in young patients.

BMC Musculoskelet Disord 2021 Mar 26;22(1):305. Epub 2021 Mar 26.

Department of Orthopedics, Zhuhai People's hospital, Guangdong Province, Zhuhai City, China.

Background: Arthroscopic repair is recommended for young patients with full-thickness rotator cuff tears (RCTs), but the healing rates have raised concerns. The Southern California Orthopedic Institute (SCOI) row method has been developed based on greater than 3 decades of experience with excellent clinical outcomes; however, studies with a focus on the younger patient population are limited in number. The current study assessed the short-term clinical outcome and the initial tendon-to-bone healing in a young cohort after repair of a full-thickness RCT using the SCOI row method.

Methods: A retrospective cohort study was performed. Patients < 55 years of age who had a full-thickness RCT and underwent an arthroscopic repair using the SCOI row method were reviewed. Clinical outcomes were assessed at baseline, and 3 and 6 months post-operatively. The visual analog scale (VAS), University of California at Los Angeles (UCLA) scale, and Constant-Murley score were completed to assess pain and function. Active range of motion was also examined, including abduction and flexion of the involved shoulder. A preoperative MRI was obtained to assess the condition of the torn tendon, while 3- and 6-month postoperative MRIs were obtained to assess tendon-to-bone healing. Repeated measurement ANOVA and chi-square tests were used as indicated.

Results: Eighty-nine patients (57 males and 32 females) with a mean age of 44.1 ± 8.6 years who met the criteria were included in the study. Compared with baseline, clinical outcomes were significantly improved 3 and 6 months postoperatively based on improvement in the VAS, UCLA score, and Constant-Murley score, as well as range of motion. Greater improvement was also noted at the 6-month postoperative assessment compared to the 3-month postoperative assessment. Three- and six-month postoperative MRIs demonstrated intact repairs in all shoulders and footprint regeneration, which supported satisfactory tendon-to-bone healing. The mean thickness of regeneration tissue was 7.35 ± 0.76 and 7.75 ± 0.79 mm as measured from the 3- and 6-month MRI (P = 0.002). The total satisfactory rate was 93.3 %.

Conclusions: Arthroscopic primary rotator cuff repair of a full-thickness RCT using the SCOI row method in patients < 55 years of age yields favorable clinical outcomes and early footprint regeneration.
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http://dx.doi.org/10.1186/s12891-021-04184-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995732PMC
March 2021

COCH predicts survival and adjuvant TACE response in patients with HCC.

Oncol Lett 2021 Apr 10;21(4):275. Epub 2021 Feb 10.

Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215025, P.R. China.

The aim of the present study was to measure the expression of Cochlin (COCH) and analyze its association with survival, recurrence and the benefits from adjuvant transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) following hepatectomy. Patients with high COCH expression levels had a poorer prognosis in terms of overall and disease-free survival rate compared with those with low COCH expression levels. Further analysis revealed that patients with low COCH expression who received TACE experienced markedly lower early recurrence rates compared with those who did not receive TACE. However, patients with high COCH expression with and without adjuvant TACE after resection experienced no difference in disease recurrence rates. The expression of COCH was found to be associated with hepatitis B virus infection, portal vein tumor thrombosis and Barcelona Clinic Liver Cancer stage in HCC. Therefore, the findings of the present study indicated that clinical detection of COCH expression may help estimate the prognosis of patients with HCC, as well as determine whether to administer TACE after surgery to prevent recurrence.
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http://dx.doi.org/10.3892/ol.2021.12536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905559PMC
April 2021

MicroRNA-181a suppresses norethisterone-promoted tumorigenesis of breast epithelial MCF10A cells through the PGRMC1/EGFR-PI3K/Akt/mTOR signaling pathway.

Transl Oncol 2021 Jun 14;14(6):101068. Epub 2021 Mar 14.

Research Center of CHU Sainte-Justine, University of Montréal, 3175 Côte-Sainte-Catherine, Room 2.17.004, Montréal, Québec, Canada; Departments of Medicine, Pediatrics, Pharmacology, and Physiology, University of Montréal, Canada. Electronic address:

Background: Research suggests that hormone replacement therapy may increase the risk of breast cancer, and progestins such as norethisterone (NET) play a key role in this phenomenon. We have demonstrated that microRNA-181a (miR-181a) suppresses NET-promoted breast cancer cell survival. Nonetheless, the effects of NET and miR-181a on the tumorigenesis of human breast epithelial cells have not yet been elaborated.

Methods: Assays of cell viability, proliferation, migration, apoptosis, and colony formation were performed to investigate the pro-tumorigenesis effect of NET and the effects of miR-181a on human breast epithelial MCF10A cells. The expressions of cell-proliferation-related genes and apoptotic factors were analyzed by quantitative RT-PCR and Western blot in MCF10A cells treated with NET and miR-181a.

Results: NET significantly increased MCF10A cell viability, proliferation, migration, and colony formation, but reduced cellular apoptosis. In addition, NET increased the expression of progesterone receptor membrane component 1 (PGRMC1), EGFR, B-cell lymphoma 2, cyclin D1, and proliferating cell nuclear antigen, but decreased the expression of pro-apoptosis factors, such as Bax, caspase-7, and caspase-9. Overexpression of miR-181a strongly inhibited the effects of NET on MCF10A cells and abrogated NET-stimulated PGRMC1, EGFR, and mTOR expression.

Conclusions: Activation of the PGRMC1/EGFR-PI3K/Akt/mTOR signaling pathway is the primary mechanism underlying the pro-tumorigenesis effects of NET on human breast epithelial MCF10A cells. Additionally, miR-181a can suppress the effects of NET on these cells. These data suggest a therapeutic potential for miR-181a in reducing or preventing the risk of breast cancer in hormone replacement therapy using NET.
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http://dx.doi.org/10.1016/j.tranon.2021.101068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974027PMC
June 2021

A unique DNA-binding mode of African swine fever virus AP endonuclease.

Cell Discov 2020 Mar 17;6(1):13. Epub 2020 Mar 17.

State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Shanghai Public Health Clinical Center, School of Life Sciences, Fudan University, 200438, Shanghai, China.

African swine fever virus (ASFV) is highly contagious and can cause lethal disease in pigs. ASFV is primarily replicated in the cytoplasm of pig macrophages, which is oxidative and caused constant damage to ASFV genome. ASFV AP endonuclease (AsfvAP) catalyzes DNA cleavage reaction at the abasic site and is a key enzyme of ASFV base excision repair (BER) system. Although it plays an essential role in ASFV survival in host cells, the basis underlying substrate binding and cleavage by AsfvAP remains unclear. Here, we reported the structural and functional studies of AsfvAP, showing that AsfvAP adopts a novel DNA-binding mode distinct from other APs. AsfvAP possesses many unique structural features, including one narrower nucleotide-binding pocket at the active site, the C16-C20 disulfide bond-containing region, and histidine-rich loop. As indicated by our mutagenesis, in vitro binding and cleavage assays, these features are important for AsfvAP to suit the acidic and oxidative environment. Owing to their functional importance, these unique features could serve as targets for designing small molecule inhibitors that could disrupt the repair process of ASFV genome and help fight against this deadly virus in the future.
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http://dx.doi.org/10.1038/s41421-020-0146-2DOI Listing
March 2020

Chronic atrophic gastritis and intestinal metaplasia induced by high-salt and N-methyl-N'-nitro-N-nitrosoguanidine intake in rats.

Exp Ther Med 2021 Apr 3;21(4):315. Epub 2021 Feb 3.

Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.

The aim of the present study was to induce chronic atrophic gastritis (CAG) with intestinal metaplasia (IM) in rats by administering saturated salt and methyl-N'-nitro-N-nitrosoguanidine (MNNG) via oral gavage. Changes in gastric mucosal blood microcirculation and activation of the cyclo-oxygenase-2 (COX-2)/hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway during CAG and IM development were investigated. After administering saturated salt and MNNG for 25 weeks, mild atrophy was detected in the stomach of model rats using hematoxylin and eosin staining. CAG with IM was successfully induced in the gastric mucosa of the model rats after 35 weeks. Gastric mucosal blood flow was decreased in comparison with controls as early as 15 weeks after treatment to induce CAG and the mRNA expression levels of COX-2, HIF-1α, vascular endothelial growth factor receptor (VEGFR)1 and VEGFR2 were increased in comparison with untreated rats as early as 25 weeks after treatment. HIF-1α, COX-2 and VEGFR2 expression levels were increased as early as 25 weeks after CAG induction treatment when compared to controls and HIF-1α, COX-2, VEGFR1 and VEGFR2 expression levels were significantly increased after 35 weeks. These findings indicated that administering saturated salt and MNNG by gavage for 35 weeks successfully induced CAG and IM in rats. Furthermore, the microcirculation was disturbed before activation of the COX-2/HIF-1α/VEGF signaling pathway.
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http://dx.doi.org/10.3892/etm.2021.9746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885066PMC
April 2021

Molecular Characterization and Immunological Evaluation of Truncated Rhoptry Neck Protein 2 as a Vaccine Candidate.

Front Immunol 2021 24;12:616343. Epub 2021 Feb 24.

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China.

is a protozoan that infects red blood cells. Babesiosis is becoming a new global threat impacting human health. Rhoptry neck proteins (RONs) are proteins located at the neck of the rhoptry and studies indicate that these proteins play an important role in the process of red blood cell invasion. In the present study, we report on the bioinformatic analysis, cloning, and recombinant gene expression of two truncated rhoptry neck proteins 2 (BmRON2), as well as their potential for incorporation in a candidate vaccine for babesiosis. Western blot and immunofluorescence antibody (IFA) assays were performed to detect the presence of specific antibodies against BmRON2 in infected mice and the localization of N-BmRON2 in parasites. experiments were carried out to investigate the role of BmRON2 proteins during the invasion process and experiments to investigate immunoprotection. Homologous sequence alignment and molecular phylogenetic analysis indicated that BmRON2 showed similarities with RON2 proteins of other species. We expressed the truncated N-terminal (33-336 aa, designated rN-BmRON2) and C-terminal (915-1171 aa, designated rC-BmRON2) fragments of the BmRON2 protein, with molecular weights of 70 and 29 kDa, respectively. Western blot assays showed that the native BmRON2 protein is approximately 170 kDa, and that rN-BmRON2 was recognized by serum of mice experimentally infected with Immunofluorescence analysis indicated that the BmRON2 protein was located at the apical end of merozoites, at the opposite end of the nucleus. red blood cell invasion inhibition studies with rBmRON2 proteins showed that relative invasion rate of rN-BmRON2 and rC-BmRON2 group is 45 and 56%, respectively. Analysis of the host immune response after immunization and infection showed that both rN-BmRON2 and rC-BmRON2 enhanced the immune response, but that rN-BmRON2 conferred better protection than rC-BmRON2. In conclusion, our results indicate that truncated rhoptry neck protein 2, especially its N-terminal fragment (rN-BmRON2), plays an important role in the invasion of host red blood cells, confers immune protection, and shows good potential as a candidate vaccine against babesiosis.
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http://dx.doi.org/10.3389/fimmu.2021.616343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943735PMC
February 2021

Nrg1/ErbB2 regulates differentiation and apoptosis of neural stem cells in the cochlear nucleus through PI3K/Akt pathway.

Neurosci Lett 2021 04 8;751:135803. Epub 2021 Mar 8.

Departments of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China. Electronic address:

Sensorineural hearing loss (SNHL) is a common causes of disability. Neural stem cells (NSCs) from the cochlear nuclei have been considered to be a potential direction for the treatment of SNHL. Neuregulin 1 (NRG1)/ErbB2 signaling displays an essential role in nervous system development. In this study, we aimed to explore the roles of NRG1/ErbB2 in differentiation and apoptosis of cochlear nuclei NSCs. The data showed that the expression of NGR1 and ErbB2 in cochlear nuclei NSCs isolated from rats were increased with the age of rats. NRG1 treatment reduced the nestin-positive cells number, increased the MAP2-positive and GFAP-positive cells number, decreased the expression of cleaved-caspase-3, and increased the activation of PI3K/AKT. ErbB2 knockdown by lentiviral-mediated ErbB2 shRNA infection reversed the effect of NRG1 on cochlear nuclei NSCs. LY294002 administration further enhanced the effect of ErbB2 silencing on the expression of nestin, MAP2, GFAP and cleaved-caspase-3. Taken together, NRG1/ErbB2 regulates differentiation and apoptosis of cochlear nucleus NSCs through PI3K/Akt pathway.
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http://dx.doi.org/10.1016/j.neulet.2021.135803DOI Listing
April 2021

Analysis of the suppression of spurious frequencies by the blocking effect in an injection-locked optoelectronic oscillator.

Appl Opt 2021 Feb;60(6):1710-1718

The blocking effect causing the suppression of spurious frequencies in an injection-locked optoelectronic oscillator (IL-OEO) is studied in this paper. The blocking effect analysis in nonlinear systems is carried out using the Volterra series and is experimentally measured in a microwave amplifier. The blocking effect in the nonlinear system helps in analyzing the suppression of spurious frequencies in an IL-OEO. Under injection locking, the spurious frequencies in the IL-OEO are significantly suppressed, and the spurs are further suppressed when the power of the reference signal is increased.
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http://dx.doi.org/10.1364/AO.415600DOI Listing
February 2021

Bacterial inactivation via microfluidic electroporation device with insulating micropillars.

Electrophoresis 2021 Mar 4. Epub 2021 Mar 4.

School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore.

Electroporation is a promising method to inactivate cells and it has wide applications in medical science, biology and environmental health. Here, we investigate the bacteria inactivation performance of two different microfluidic electroporation devices with rhombus and circular micropillars used for generating locally enhanced electric field strength. Experiments are carried out to characterize the inactivation performance (i.e., the log removal efficiency) of two types of bacteria: Escherichia coli (E. coli, gram-negative) and Enterococcus faecalis (E. faecalis, gram-positive) in these two microfluidic devices. We find that under the same applied electric field, the device with rhombus micropillars performs better than the device with circular micropillars for both E. coli and E. faecalis. Numerical simulations show that due to the corner-induced singularity effect, the maximum electric field enhancement is higher in the device with rhombus micropillars than that in the device with circular micropillars. We also study the effects of DC and AC electric fields and flowrate. Our experiments demonstrate that the use of the DC field achieves higher log removal efficiencies than the use of AC field.
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http://dx.doi.org/10.1002/elps.202000326DOI Listing
March 2021

Responses of fine particulate matter and ozone to local emission reductions in the Sichuan Basin, southwestern China.

Environ Pollut 2021 May 19;277:116793. Epub 2021 Feb 19.

Department of Civil and Environmental Engineering, Louisiana State University, Baton Rouge, LA, 70803, USA; Department of Environmental Science and Engineering, Fudan University, Shanghai, 200438, China; Institute of Eco-Chongming (SIEC), Shanghai, 200062, China. Electronic address:

The Sichuan Basin (SCB) in southwestern China is largely affected by air pollution. Understanding the responses of air pollutant concentrations to emission changes is critical for designing and evaluating effective control strategies. Thus, this study used the Community Multi-scale Air Quality (CMAQ) model to simulate PM (i.e., particulate matter with an aerodynamic diameter ≤ 2.5 μm) in winter (January 2015) and ozone (O) in summer (July 2015) under nine emission reduction scenarios. For each scenario, the anthropogenic emissions of each air pollutant in each SCB grid cell were reduced by the same percentage, ranging from 10% to 90%. We found that approximately 30-70% emission reductions are required to reduce the January mean PM concentrations in all the SCB urban centers to a value that is less than the Chinese standard for daily mean PM (24-h PM: 75 μg m). However, the January mean PM concentrations under 90% emission reduction still exceeded the World Health Organization (WHO) guideline (25 μg m) in 16 SCB urban centers. Moreover, reducing both SCB and non-SCB emissions were critical for achieving the PM level recommended by WHO. An 80% emission reduction was required to prevent the occurrence of 8-h O (i.e., daily maximum 8-h mean O) non-attainment days in all SCB urban centers. Under 90% emission reduction, July mean 8-h O concentrations still exceeded the WHO guideline of 47 ppb in approximately 35% of the SCB areas. In conclusion, this study suggests that (1) compared with the governmental emission reduction targets for 2015-2020 (2-27%), more significant emission reductions are required to meet the Chinese and WHO pollution standards; and (2) both SCB and non-SCB emissions must significantly reduce to achieve the desired pollution targets.
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http://dx.doi.org/10.1016/j.envpol.2021.116793DOI Listing
May 2021

An injectable hydrogel co-loading with cyanobacteria and upconversion nanoparticles for enhanced photodynamic tumor therapy.

Colloids Surf B Biointerfaces 2021 May 18;201:111640. Epub 2021 Feb 18.

School of Life Sciences, Tianjin University, Tianjin, 300072, PR China; Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, Tianjin, 300072, PR China. Electronic address:

Photodynamic therapy (PDT) is an exceedingly promising cancer treatment. However, the hypoxic environment in tumor and the low penetration efficiency of short-wavelength light limit the effects of PDT. In this paper, an injectable red blood cell membrane doped hydrogel system (UCNPs/S7942/RB-RHY) containing upconversion nanoparticles (UCNPs), a photosensitizer (Rose Bengal) and a strain of cyanobacteria Synechococcus elongatus PCC 7942 (S. 7942) was developed to improve the PDT effects with a good biocompatibility and biosafety. In the system, S. 7942 was capable of inexhaustibly generating oxygen triggered by the 640 nm laser irradiation for alleviating hypoxic tumor microenvironment. In addition, UCNPs converted near-infrared light to visible light upon excitation by a 980 nm laser, which further activated the photosensitizer to release reactive singlet oxygen to eradicate tumors. In vivo experiments showed that the tumor volume in the UCNPs/S7942/RB-RHY combined 640 nm with 980 nm light group was 496.9 mm, in compared with 955.5 mm of the tumor volume in the group without irradiation. The results demonstrated that UCNPs/S7942/RB-RHY was able to not only dramatically alleviate tumor hypoxia but also achieve a more efficient PDT treatment. The oxygen-generating system described here provides a new idea for hypoxia-resistant cancer therapy in the future.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111640DOI Listing
May 2021

Less Social Support for Patients With COVID-19: Comparison With the Experience of Nurses.

Front Psychiatry 2021 1;12:554435. Epub 2021 Feb 1.

Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Since December 2019, more than 80,000 patients have been diagnosed with coronavirus disease 2019 (COVID-19) in China. Social support status of COVID-19 patients, especially the impact of social support on their psychological status and quality of life, needs to be addressed with increasing concern. In this study, we used social support rating scale (SSRS) to investigate the social support in COVID-19 patients and nurses. The present study included 186 COVID-19 patients at a Wuhan mobile cabin hospital and 234 nurses at a Wuhan COVID-19 control center. Responses to a mobile phone app-based questionnaire about social support, anxiety, depression, and quality of life were recorded and evaluated. COVID-19 patients scored significantly lower than nurses did on the Social Support Rating Scale (SSRS). Among these patients, 33.9% had anxiety symptoms, while 23.7% had depression symptoms. Overall SSRS, subjective social support scores and objective support scores of patients with anxiety were lower than those of patients without anxiety. This result was also found in depression. In addition, all dimensions of social support were positively correlated with quality of life. Interestingly, in all dimensions of social support, subjective support was found to be an independent predictive factor for anxiety, depression, and quality of life, whereas objective support was a predictive factor for quality of life, but not for anxiety and depression via regression analysis. Medical staffs should pay attention to the subjective feelings of patients and make COVID-19 patients feel respected, supported, and understood from the perspective of subjective support, which may greatly benefit patients, alleviate their anxiety and depression, and improve their quality of life.
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http://dx.doi.org/10.3389/fpsyt.2021.554435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901979PMC
February 2021

The Effectiveness and Safety of Intravenous Dexmedetomidine of Different Concentrations Combined with Butorphanol for Post-Caesarean Section Analgesia: A Randomized Controlled Trial.

Drug Des Devel Ther 2021 18;15:689-698. Epub 2021 Feb 18.

Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China.

Purpose: The present study aimed to determine the effectiveness of intravenous dexmedetomidine of different concentrations and to evaluate its maternal and neonatal safety when combined with butorphanol in parturients undergoing cesarean section.

Patients And Methods: A total of 114 parturients between 24 and 43 years of age, with singleton pregnancy who underwent elective cesarean section under epidural anesthesia, were randomly allocated to four groups: group C received 0.9% sodium chloride after delivery, followed by butorphanol (3 μg·kg·h); patients in groups D1, D2, and D3 received 0.5 μg·kg·h dexmedetomidine after delivery, followed by butorphanol (3 μg·kg·h) combined with dexmedetomidine 0.03, 0.05, and 0.08 μg·kg·h, respectively. The primary outcome was the visual analogue scale (VAS) score at 6 h after delivery when patients were at rest. Secondary outcome measures included VAS after delivery when patients were on movement and uterine cramping, Ramsay sedation scale (RSS), relative infant dose (RID) of dexmedetomidine, satisfaction with analgesia after surgery and symptoms of CNS depression in neonates.

Results: There were no significant differences in patient characteristics among the groups ( > 0.05). The VAS at all timepoints after delivery in groups D2 and D3 were significantly lower than in groups C and D1 ( < 0.001). RSS scores were clearly higher in group D3 than in the other three groups at 6 h and 12 h ( < 0.0001). RID in groups D1, D2, and D3 was 0.171%, 0.197%, and 0.370%, respectively. Compared with group D1, RID was higher in group D3 ( = 0.0079). Degree of satisfaction with analgesia was higher in groups D2 and D3 ( < 0.005).

Conclusion: Continuous intravenous infusion of 0.05 μg·kg·h dexmedetomidine combined with 3 μg·kg·h butorphanol could be safely applied in healthy parturients with satisfactory analgesia after cesarean section without changes in sedation.
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http://dx.doi.org/10.2147/DDDT.S287512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899314PMC
February 2021

The role of gut-brain axis in SARA-CoV-2 neuroinvasion: Culprit or innocent bystander?

Brain Behav Immun 2021 05 15;94:476-477. Epub 2021 Feb 15.

Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address:

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http://dx.doi.org/10.1016/j.bbi.2021.01.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883713PMC
May 2021

Chronic Exposure to PM Nitrate, Sulfate, and Ammonium Causes Respiratory System Impairments in Mice.

Environ Sci Technol 2021 03 10;55(5):3081-3090. Epub 2021 Feb 10.

Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.

Water-soluble inorganic (WSI) ions are major components of ambient air PM (particulate matter of diameter ≤2.5 μm); however, their potential health effects are understudied. On C57BL/6 mice, we quantified the effect of three major PM WSIs (NO, SO, and NH) on respiratory systems. Exposure scenarios include different WSI types, concentrations, animal development stages (young vs adult), and sex. The exposure effects were comprehensively assessed, with special focus on the respiratory function and tissue/cell level changes. Chronic PM NO exposure produced significant respiratory function decline, mainly presented as airflow obstruction. The decline was more profound in young mice than in adult mice. In young mice, exposure to 22 μg/m PM NO reduced FEV (forced expiratory volume in 0.05 s) by 11.3% ( = 9.6 × 10) and increased pulmonary neutrophil infiltration by 7.9% ( = 7.1 × 10). Causality tests identified that neutrophil infiltration was involved in the biological mechanism underlying PM NO toxicity. In contrast, the effects of PM SO were considerably weaker than NO. PM NO exposure was 3.4 times more potent than PM SO in causing reduction of the peak expiratory flow. PM NH exposure had no statistically significant effects on the respiratory function. In summary, this study provided strong evidence on the adverse impacts of PM WSIs, where the impacts were most profound in young mice exposed to PM NO. If confirmed in humans, toxicity of PM WSI will have broad implications in environment health and policy making.
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http://dx.doi.org/10.1021/acs.est.0c05814DOI Listing
March 2021

Scale-Invariant Multidirectional License Plate Detection with the Network Combining Indirect and Direct Branches.

Sensors (Basel) 2021 Feb 4;21(4). Epub 2021 Feb 4.

School of Computer and Communication Engineering, University of Science and Technology Beijing, Beijing 100083, China.

As the license plate is multiscale and multidirectional in the natural scene image, its detection is challenging in many applications. In this work, a novel network that combines indirect and direct branches is proposed for license plate detection in the wild. The indirect detection branch performs small-sized vehicle plate detection with high precision in a coarse-to-fine scheme using vehicle-plate relationships. The direct detection branch detects the license plate directly in the input image, reducing false negatives in the indirect detection branch due to the miss of vehicles' detection. We propose a universal multidirectional license plate refinement method by localizing the four corners of the license plate. Finally, we construct an end-to-end trainable network for license plate detection by combining these two branches via post-processing operations. The network can effectively detect the small-sized license plate and localize the multidirectional license plate in real applications. To our knowledge, the proposed method is the first one that combines indirect and direct methods into an end-to-end network for license plate detection. Extensive experiments verify that our method outperforms the indirect methods and direct methods significantly.
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http://dx.doi.org/10.3390/s21041074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915396PMC
February 2021

Effect of alcohol on the progress of hepatitis B cirrhosis.

Ann Palliat Med 2021 Jan;10(1):415-424

School of Public Health and Management, Chongqing Medical University, Chongqing, China.

Background: Hepatitis B virus (HBV) and alcohol are primary causes of cirrhosis. Alcohol can result in replication of HBV, an increase in oxidative stress, a compromised immune response to the virus and an increase in liver inflammation, all of which can result in progression of cirrhosis. The aim was to explore the interaction of alcohol with HBV and to show the effect of different levels of alcohol intake on liver fibrosis and cirrhosis.

Methods: We selected 90 patients with hepatitis B cirrhosis and divided them into three groups: non-drinking, moderate drinking and excessive drinking. Indicators of fibrosis (type III procollagen, type IV collagen, laminin, hyaluronic acid), HBV-DNA load, transaminases, quantitative detection of hepatitis B surface antigen (HBsAg), Child-Pugh scoring system rating and the number of complications were tested at three time points: 0, 3 and 6 months after quitting drinking and after medical treatment.

Results: We found that all indicators of fibrosis, HBV-DNA load, alanine (ALT) and aspartate (AST) transaminases in the excessive drinking group were highest among the three groups at any time. There were almost no differences between the moderate drinking and non-drinking groups at 0, 3 and 6 months after quitting drinking and treatment. We also found no difference among the three groups in quantitative detection of HBsAg at any time. It was observed that there are more patients with excessive drinking were in Child-Pugh C class and had more complications compared with the other two groups.

Conclusions: Patients with chronic HBV infection and an excessive drinking habit activate HBV-DNA which increases liver inflammation, thus accelerating the progress of liver cirrhosis. Moderate drinking had no significant effect on the progress of liver cirrhosis. Hepatitis B cirrhosis patients with excessive drinking had more complications and were more likely to be in Child-Pugh C class compared with the other groups.
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http://dx.doi.org/10.21037/apm-20-2353DOI Listing
January 2021

The role of microglia in chronic pain and depression: innocent bystander or culprit?

Psychopharmacology (Berl) 2021 Apr 5;238(4):949-958. Epub 2021 Feb 5.

Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Clinical evidence shows that chronic pain and depression often accompany each other, but the underlying pathogenesis of comorbid chronic pain and depression remains mostly undetermined. Biotechnology is gradually revealing the phenotype and function of microglia, with great progress regarding microglia's role in neurodegeneration, depression, chronic pain, and other conditions. This article summarizes the role of microglia in chronic pain, depression, and comorbidities, which is conducive to finding new targets to treat chronic pain and depression.
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http://dx.doi.org/10.1007/s00213-021-05780-4DOI Listing
April 2021

Loss-of-function of p53 isoform Δ113p53 accelerates brain aging in zebrafish.

Cell Death Dis 2021 Feb 4;12(2):151. Epub 2021 Feb 4.

MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University, 310058, Hangzhou, China.

Reactive oxygen species (ROS) stress has been demonstrated as potentially critical for induction and maintenance of cellular senescence, and been considered as a contributing factor in aging and in various neurological disorders including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). In response to low-level ROS stress, the expression of Δ133p53, a human p53 isoform, is upregulated to promote cell survival and protect cells from senescence by enhancing the expression of antioxidant genes. In normal conditions, the basal expression of Δ133p53 prevents human fibroblasts, T lymphocytes, and astrocytes from replicative senescence. It has been also found that brain tissues from AD and ALS patients showed decreased Δ133p53 expression. However, it is uncharacterized if Δ133p53 plays a role in brain aging. Here, we report that zebrafish Δ113p53, an ortholog of human Δ133p53, mainly expressed in some of the radial glial cells along the telencephalon ventricular zone in a full-length p53-dependent manner. EDU-labeling and cell lineage tracing showed that Δ113p53-positive cells underwent cell proliferation to contribute to the neuron renewal process. Importantly, Δ113p53 mutant telencephalon possessed less proliferation cells and more senescent cells compared to wild-type (WT) zebrafish telencephalon since 9-months old, which was associated with decreased antioxidant genes expression and increased level of ROS in the mutant telencephalon. More interestingly, unlike the mutant fish at 5-months old with cognition ability, Δ113p53 zebrafish, but not WT zebrafish, lost their learning and memory ability at 19-months old. The results demonstrate that Δ113p53 protects the brain from aging by its antioxidant function. Our finding provides evidence at the organism level to show that depletion of Δ113p53/Δ133p53 may result in long-term ROS stress, and finally lead to age-related diseases, such as AD and ALS in humans.
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http://dx.doi.org/10.1038/s41419-021-03438-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862496PMC
February 2021