Publications by authors named "Kun Sun"

297 Publications

Role of breast MRI in predicting histologic upgrade risks in high-risk breast lesions: A review.

Eur J Radiol 2021 Jul 9;142:109855. Epub 2021 Jul 9.

Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai 200025, China. Electronic address:

Purpose: This article reviews the frequency, upgrade rate and valuable imaging characteristics for predicting the histologic upgrade risks of high-risk lesions on MRI, so as to provide a reference for the management of the lesions.

Methods: A comprehensive search for relevant publications from January 2011 to January 2021 was conducted in the PubMed database. The frequency, upgrade rate and valuable imaging characteristics for predicting the upgrade risks of high-risk lesions on MRI included in the articles were reviewed, and the management of high-risk lesions was provided with a reference according to the review results.

Results And Conclusions: In terms of management options, Atypical ductal hyperplasia (ADH) and Lobular neoplasia (LN) (the top two high-risk lesions with the highest upgrade rate and frequency) were treated with surgical resection. However, the final treatment decision for other high-risk lesions should be made by a multidisciplinary committee. In terms of the value of breast MRI in predicting the upgrade risks of high-risk lesions, the lesions that were confirmed to upgrade after surgery showed some enhancement characteristics, especially for ADH and LN. At the same time, Dynamic contrast-enhanced MRI (DCE-MRI) has a high negative predictive value (NPV) in predicting the upgrade risks of the high-risk lesions, hence misdiagnosis and overtreatment can be reduced. Diffusion-weighted imaging (DWI) and relative apparent diffusion coefficient (rADC) can be used to predict the upgrade risks of the lesions, and the ADC of upgraded lesions is lower than that of non-upgraded lesions. However, these conclusions should be confirmed by further studies.
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http://dx.doi.org/10.1016/j.ejrad.2021.109855DOI Listing
July 2021

Silica nanoparticle induces pulmonary fibroblast transdifferentiation via macrophage route: Potential mechanism revealed by proteomic analysis.

Toxicol In Vitro 2021 Jul 14;76:105220. Epub 2021 Jul 14.

School of Public Health, North China University of Science of Technology, Tangshan 063210, Hebei, China. Electronic address:

Recently, more and more attention has been focused on silica nanoparticles (SiNPs) as they are increasingly used in various fields. Yet, their biological effects, especially on human beings, largely remain unknown. This study was implanted to assess the biological responses in vitro elicited by human macrophages exposed to the SiNPs and to explore its toxicity and fibrosis biomarker. We found that SiNPs suppressed the viability of THP-1 cells in a dose-dependent manner while they triggered apoptosis and promoted the secretion of inflammatory factors. Next, SiNPs-induced macrophage supernatant was used to act on fibroblast (MRC-5), indicating that the expression of hydroxyproline (Hyp), α-SMA, and collagonIin MRC-5 increased after SiNPs treatment. To further explore the biomarker of fibrosis, Liquid-mass spectrometry facilitated quantitative proteomics, identified 3247 proteins, of which 791 proteins were expressed differentially in human embryonic lung fibroblasts after treated with SiNPs. In conclusion, our observations suggest that SiNPs induced THP-1-derived macrophage damage and apoptosis. Moreover, SiNPs induced macrophages to secrete cytokines that promote fibroblasts' proliferation and differentiation and changed protein expression in MRC-5 cells, regulating biological processes such as apoptosis, protein synthesis, and cell growth. Among these results, our findings could provide a basis for determining fibrosis biomarkers of silica nanoparticle exposure.
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http://dx.doi.org/10.1016/j.tiv.2021.105220DOI Listing
July 2021

Amplitude Control Method of Magnetic Flux Vertical Modulation Structure for TMR Magnetic Sensor Based on Harmonic Component of Modulated Signal.

Micromachines (Basel) 2021 Jun 19;12(6). Epub 2021 Jun 19.

College of Intelligence Science and Technology, National University of Defense Technology, Guizhou 410073, China.

Magnetic flux vertical modulation method based on piezoelectric resonance can reduce the 1/ noise of tunnel magnetoresistance (TMR) magnetic sensor and significantly improves the low-frequency magnetic field detectivity. However, the amplitude variation of the modulation structure will lead to the instability of the sensor output. In order to improve the amplitude stability of the modulation structure, an amplitude control method based on the amplitude ratio of the first and second harmonic components of the modulated signal was proposed. Compared with the piezoelectric or capacitive feedback method, this method does not require an independent amplitude conversion circuit, and has the advantages of simple structure, high control efficiency and strong anti-interference ability. The experimental results showed that the amplitude and temperature drift of the modulated structure was significantly suppressed, which is of great significance for enhancing the adaptability of the TMR magnetic sensor to the application environments.
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http://dx.doi.org/10.3390/mi12060722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233941PMC
June 2021

Electron-Induced Perpendicular Graphene Sheets Embedded Porous Carbon Film for Flexible Touch Sensors.

Nanomicro Lett 2020 Jun 25;12(1):136. Epub 2020 Jun 25.

Key Laboratory of Education Ministry for Modern Design and Rotor-Bearing System, Xi'an Jiaotong University, Xi'an, 710049, People's Republic of China.

Graphene-based materials on wearable electronics and bendable displays have received considerable attention for the mechanical flexibility, superior electrical conductivity, and high surface area, which are proved to be one of the most promising candidates of stretching and wearable sensors. However, polarized electric charges need to overcome the barrier of graphene sheets to cross over flakes to penetrate into the electrode, as the graphene planes are usually parallel to the electrode surface. By introducing electron-induced perpendicular graphene (EIPG) electrodes incorporated with a stretchable dielectric layer, a flexible and stretchable touch sensor with "in-sheet-charges-transportation" is developed to lower the resistance of carrier movement. The electrode was fabricated with porous nanostructured architecture design to enable wider variety of dielectric constants of only 50-μm-thick Ecoflex layer, leading to fast response time of only 66 ms, as well as high sensitivities of 0.13 kPa below 0.1 kPa and 4.41 MPa above 10 kPa, respectively. Moreover, the capacitance-decrease phenomenon of capacitive sensor is explored to exhibit an object recognition function in one pixel without any other integrated sensor. This not only suggests promising applications of the EIPG electrode in flexible touch sensors but also provides a strategy for internet of things security functions.
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http://dx.doi.org/10.1007/s40820-020-00480-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770710PMC
June 2020

Transcriptional Start Site Coverage Analysis in Plasma Cell-Free DNA Reveals Disease Severity and Tissue Specificity of COVID-19 Patients.

Front Genet 2021 28;12:663098. Epub 2021 May 28.

BGI-Shenzhen, Shenzhen, China.

Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. A deep understanding of the variation of biological characteristics in severe COVID-19 patients is crucial for the detection of individuals at high risk of critical condition for the clinical management of the disease. Herein, by profiling the gene expression spectrum deduced from DNA coverage in regions surrounding transcriptional start site in plasma cell-free DNA (cfDNA) of COVID-19 patients, we deciphered the altered biological processes in the severe cases and demonstrated the feasibility of cfDNA in measuring the COVID-19 progression. The up- and downregulated genes in the plasma of severe patient were found to be closely related to the biological processes and functions affected by COVID-19 progression. More importantly, with the analysis of transcriptome data of blood cells and lung cells from control group and cases with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, we revealed that the upregulated genes were predominantly involved in the viral and antiviral activity in blood cells, reflecting the intense viral replication and the active reaction of immune system in the severe patients. Pathway analysis of downregulated genes in plasma DNA and lung cells also demonstrated the diminished adenosine triphosphate synthesis function in lung cells, which was evidenced to correlate with the severe COVID-19 symptoms, such as a cytokine storm and acute respiratory distress. Overall, this study revealed tissue involvement, provided insights into the mechanism of COVID-19 progression, and highlighted the utility of cfDNA as a noninvasive biomarker for disease severity inspections.
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http://dx.doi.org/10.3389/fgene.2021.663098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194351PMC
May 2021

Driving mechanisms of gross primary productivity geographical patterns for Qinghai-Tibet Plateau lake systems.

Sci Total Environ 2021 Jun 5;791:148286. Epub 2021 Jun 5.

Key Laboratory of Ecosystem Network Observation and Modeling, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing 100101, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China. Electronic address:

Being a fundamental property of aquatic systems, gross primary productivity (GPP) is affected by complex environmental factors, such as salinity, nutrients, pH, and sunlight. Under conditions of intensified anthropogenic activity and climate change, it is critical to understand the driving mechanisms of GPP in alpine lakes. In this study, we investigated GPP and associated environmental factors of 23 lake systems in the Qinghai-Tibet Plateau (QTP) along an altitudinal range (from 2500 m to 4500 m). Results showed an increase in chlorophyll a (Chl a) content as altitude increased and a corresponding decrease as salinity increased. Furthermore, geographical patterns of GPP were higher at the mid-gradient and lower at the extreme gradient. Higher solar radiation and water temperatures, stronger evaporation and higher salinity levels, and lower pH and higher nutrient content were all driving mechanisms of GPP in low altitudinal lake systems within high latitudinal regions. Such conditions have collectively resulted in the current GPP pattern via the promotion or inhibition of phytoplankton growth and photosynthesis. Specifically, geographical features and climate change jointly drive algal growth and GPP of alpine lake systems via internal circulation processes; however, anthropogenic activities interfere with external circulation processes for most of lower-middle altitudinal lake systems, thus playing a certain role in regulating environmental factors and GPP alongside climate change.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148286DOI Listing
June 2021

Associations between measures of pediatric human resources and the under-five mortality rate: a nationwide study in China in 2014.

World J Pediatr 2021 Jun 7;17(3):317-325. Epub 2021 Jun 7.

Department of Pediatrics, Xin Hua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: To quantify the associations between the under-five mortality rate (U5MR) and measures of pediatric human resources, including pediatricians per thousand children (PPTC) and the geographical distribution of pediatricians.

Methods: We analyzed data from a national survey in 2015-2016 in 2636 counties, accounting for 31 mainland provinces of China. We evaluated the associations between measures of pediatric human resources and the risk of a high U5MR (≥ 18 deaths per 1000 live births) using logistic regression and restricted cubic spline regression models with adjustments for potential confounders. PPTC and pediatricians per 10,000 km were categorized into quartiles. The highest quartiles were used as reference.

Results: The median values of PPTC and pediatricians per 10,000 km were 0.35 (0.20-0.70) and 150 (50-500), respectively. Compared to the counties with the highest PPTC (≥ 0.7), those with the lowest PPTC (< 0.2) had a 52% higher risk of a high U5MR, with an L-shaped relationship. An inverted J-shaped relationship was found that the risk of a high U5MR was 3.74 [95% confidence interval (CI) 2.55-5.48], 3.07 (95% CI 2.11-4.47), and 2.25 times (95% CI 1.52-3.31) higher in counties with < 50, 50-149, and 150-499 pediatricians per 10,000 km, respectively, than in counties with ≥ 500 physicians per 10,000 km. The joint association analyses show a stronger association with the risk of a high U5MR in geographical pediatrician density than PPTC.

Conclusion: Both population and geographical pediatrician density should be considered when planning child health care services, even in areas with high numbers of PPTC.
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http://dx.doi.org/10.1007/s12519-021-00433-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183000PMC
June 2021

Neutrophil elastase promotes neointimal hyperplasia by targeting toll-like receptor 4 (TLR4)-NF-κB signalling.

Br J Pharmacol 2021 Jun 2. Epub 2021 Jun 2.

Department of Cardiology and Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background And Purpose: Neointimal hyperplasia (NIH) is the fundamental cause for vascular diseases and vascular smooth muscle cell (VSMC) dysregulation has been widely implicated in NIH. Neutrophil elastase is a potential therapeutic target for multiple diseases. We investigated the role of neutrophil elastase in VSMC functions and injury-induced NIH and explored the therapeutic potential of targeting neutrophil elastase in NIH.

Experimental Approach: VSMCs were used to analyse the effects of neutrophil elastase. Proteomic analysis was used to identify potential neutrophil elastase targets. Artery injury model and neutrophil elastase inhibitor GW311616A were used to investigate the role of neutrophil elastase in NIH.

Key Results: TNF-α up-regulated neutrophil elastase in VSMCs through modulating GAPBα/Runx1/CEBPα/c-Myb signalling. Up-regulated neutrophil elastase promoted VSMC migration, proliferation and inflammation. Toll-like receptor 4 (TLR4) was identified as a target protein for neutrophil elastase in VSMCs and the TLR4/MyD88/IRAK1/TRAF6/NF-κB regulatory axis was shown to be the signalling pathway for neutrophil elastase in VSMC pathology. Importantly, TLR4 inhibition abolished neutrophil elastase-mediated VSMC dysregulation. Injury-induced NIH was significantly reduced in both neutrophil elastase-deficient mice and mice treated with GW311616A. The formation of neutrophil extracellular traps was impaired in injured arteries from neutrophil elastase-deficient mice. Finally, a similar role for neutrophil elastase in human VSMC pathology was confirmed and we observed higher expression levels of neutrophil elastase but lower expression levels of TLR4 in human atherosclerotic lesions.

Conclusion And Implications: We provide new insight into the molecular mechanisms underlying NIH and identify neutrophil elastase as a potential therapeutic target for vascular disease.
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http://dx.doi.org/10.1111/bph.15583DOI Listing
June 2021

A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes.

Nat Commun 2021 05 11;12(1):2623. Epub 2021 May 11.

Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, People's Republic of China.

COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases.
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http://dx.doi.org/10.1038/s41467-021-22926-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113581PMC
May 2021

Analysis of Endophyte Diversity of from Different Production Areas in Gansu Province of China and the Association with Secondary Metabolite.

Microorganisms 2021 Apr 30;9(5). Epub 2021 Apr 30.

College of Life Sciences, Northwest Normal University, Lanzhou 730070, China.

Investigations of the differences in the metabolites of medicinal plants have typically focused on the effects of external environmental factors. However, little is known about the relationship between endophytes diversity and host metabolites. We used high-throughput sequencing methods to compare the endophyte diversity of from eight different production areas in Gansu Province of China and to analyze the association between those areas and five secondary metabolites (aloe-emodin, rhein, emodin, chrysophanol, and physcion). The results show that the diversity and OTUs (Operational taxonomic units) abundance of endophytic fungi and bacteria of differed according to production area. Spearman analysis showed that the five secondary metabolites of were positively correlated with the diversity and abundance of endophytic fungi. Comparing both space and environmental differences to determine influences on community structure, VPA analysis revealed that geographic factors explained more difference in community composition of fungal and bacterial endophytes than climate factors. PICRUSt and FUNGuild predictive analysis indicated that metabolites were the primary components of endophytic bacteria in all samples, while the function of endophytic fungi was composed of dominant trophic modes (saprotroph and pathotroph), and relative abundances were different. Our results help elucidate the correlation of plant-microbe interactions and offer pivotal information to reveal the role of endophytes in the production of and its important secondary metabolite.
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http://dx.doi.org/10.3390/microorganisms9050978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147242PMC
April 2021

The transcription factor Sox7 modulates endocardiac cushion formation contributed to atrioventricular septal defect through Wnt4/Bmp2 signaling.

Cell Death Dis 2021 04 12;12(4):393. Epub 2021 Apr 12.

Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 200092, Shanghai, China.

Cardiac septum malformations account for the largest proportion in congenital heart defects. The transcription factor Sox7 has critical functions in the vascular development and angiogenesis. It is unclear whether Sox7 also contributes to cardiac septation development. We identified a de novo 8p23.1 deletion with Sox7 haploinsufficiency in an atrioventricular septal defect (AVSD) patient using whole exome sequencing in 100 AVSD patients. Then, multiple Sox7 conditional loss-of-function mice models were generated to explore the role of Sox7 in atrioventricular cushion development. Sox7 deficiency mice embryos exhibited partial AVSD and impaired endothelial to mesenchymal transition (EndMT). Transcriptome analysis revealed BMP signaling pathway was significantly downregulated in Sox7 deficiency atrioventricular cushions. Mechanistically, Sox7 deficiency reduced the expressions of Bmp2 in atrioventricular canal myocardium and Wnt4 in endocardium, and Sox7 binds to Wnt4 and Bmp2 directly. Furthermore, WNT4 or BMP2 protein could partially rescue the impaired EndMT process caused by Sox7 deficiency, and inhibition of BMP2 by Noggin could attenuate the effect of WNT4 protein. In summary, our findings identify Sox7 as a novel AVSD pathogenic candidate gene, and it can regulate the EndMT involved in atrioventricular cushion morphogenesis through Wnt4-Bmp2 signaling. This study contributes new strategies to the diagnosis and treatment of congenital heart defects.
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http://dx.doi.org/10.1038/s41419-021-03658-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041771PMC
April 2021

MiR-1297 attenuates high glucose-induced injury in HK-2 cells via targeting COL1A2.

Nephrology (Carlton) 2021 Jul 14;26(7):623-631. Epub 2021 Apr 14.

Department of Endocrinology, Zibo Central Hospital, Zibo, China.

Background: In this study, we aimed to explore whether COL1A2 and miR-1297 participated in the progression of diabetic nephropathy (DN) in vitro and classified the underlying mechanisms.

Methods: d-Glucose (30 mM; high glucose, HG)-stimulated HK-2 cells were used to mimic DN condition. RNA and non-coding RNA profiles were from Gene Expression Omnibus (GEO) database. The interaction between miR-1297 and COL1A2 was measured by dual-luciferase reporter assay. Gene Set Enrichment Analysis (GSEA) method was conducted to analyse COL1A2-associated signalling pathways. The role of miR-1297/COL1A2 in biological behaviours of HG-induced HK-2 cells were analysed by cell counting kit-8 and apoptosis assays.

Results: Bioinformatics analysis revealed that COL1A2 was up-regulated in DN tissues. We predicted and verified miR-1297 as the regulatory miRNA of COL1A2, and the expression of miR-1297 was decreased in DN tissues and HG-stimulated HK-2 cells. Overexpression of miR-1297 could promote cell proliferation and inhibit apoptosis to protect HK-2 cells from HG-induced damage. And knockdown of COL1A2 enhanced the protective effects of miR-1297 on HG-stimulated HK-2 cells. GSEA results revealed that several inflammatory pathways were enriched in COL1A2 high-expression group. Meanwhile, transfection of miR-1297 reduced the phosphorylation of NFκB and expression of three important pro-inflammatory genes including cytokine CCL5, adhesion molecules ICAM1 and VCAM1 via targeting COL1A2. These results suggested that miR-1297 protected HG-treated HK-2 cells probably through suppressing inflammation via targeting COL1A2.

Conclusion: This study sheds a light on the role miR-1297/COL1A2 in DN progression and provides a novel promising therapy strategy for suppressing DN progression.
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http://dx.doi.org/10.1111/nep.13881DOI Listing
July 2021

Development of a polycaprolactone/poly(-dioxanone) bioresorbable stent with mechanically self-reinforced structure for congenital heart disease treatment.

Bioact Mater 2021 Sep 1;6(9):2969-2982. Epub 2021 Mar 1.

College of Textiles, Donghua University, Shanghai, 201620, China.

Recent progress in bioresorbable stents (BRSs) has provided a promising alternative for treating coronary artery disease. However, there is still lack of BRSs with satisfied compression and degradation performance for pediatric patients with congenital heart disease, leading to suboptimal therapy effects. Here, we developed a mechanically self-reinforced composite bioresorbable stent (cBRS) for congenital heart disease application. The cBRS consisted of poly(-dioxanone) monofilaments and polycaprolactone/poly(-dioxanone) core-shell composite yarns. Interlacing points in cBRS structure were partially bonded, offering the cBRS with significantly higher compression force compared to typical braids and remained good compliance. The suitable degradation profile of the cBRS can possibly preserve vascular remodeling and healing process. In addition, the controllable structural organization provides a method to customize the performance of the cBRS by altering the proportion of different components in the braids. The in vivo results suggested the cBRS supported the vessel wall similar to that of metallic stent. In both abdominal aorta and iliac artery of porcine, cBRS was entirely endothelialized within 1 month and maintained target vessels with good patency in the 12-month follow-up. The in vivo degradation profile of the cBRS is consistent with static degradation results in vitro. It is also demonstrated that there is minimal impact of pulsatile pressure of blood flow and variation of radial force on the degradation rate of the cBRS. Moreover, the lumen of cBRS implanted vessels were enlarged after 6 months, and significantly larger than the vessels implanted with metallic stent in 12 months.
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http://dx.doi.org/10.1016/j.bioactmat.2021.02.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930591PMC
September 2021

Silica dust exposure induces pulmonary fibrosis through autophagy signaling.

Environ Toxicol 2021 Jul 15;36(7):1269-1277. Epub 2021 Mar 15.

School of Public Health, North China University of Science of Technology, Tangshan, China.

Silicosis is a well-acknowledged occupational lung disease caused by inhalation of a large amount of free silica dust during the production period and eventually a considerable negative impact on the patients' quality of life. Autophagy exerts a critical influence on immune and inflammatory responses during the pathogenesis of pulmonary fibrosis. In this study, we sought to determine whether autophagy is involved in silicosis's pathogenesis and how it may affect pulmonary cellular physiology. In the animal experiments, we found persistent activation of autophagy in the development of pulmonary fibrosis, which was also accompanied by tumor necrosis factor and transforming growth factor expression increased. Therefore, the autophagy signaling pathway may regulate the inflammatory response and affect the progression of fibrosis. Further, in vitro experiments, we used LY294002, RAPA, and N-acetylcysteine (NAC) intervened autophagy. Our results showed that PI3K/Akt/mTOR signaling pathway is involved in the autophagy changed mediated by SiO exposed, and autophagy might play a protective role in the progression of pulmonary fibrosis. Additionally, NAC's effect is not apparent on SiO -mediated autophagy through the PI3K/Akt/mTOR signaling pathway, but it can reduce the inflammatory response on NR8383 cells mediated by SiO2-exposed. Nevertheless, it's interesting that NAC can reduce the inflammatory response on NR8383 cells mediated by SiO -exposed. Taken together, our data demonstrated that SiO -exposed can induce pulmonary fibrosis along with autophagy both in vivo and in vitro, NAC could alleviate the inflammatory response NR8383 cells by SiO -exposed through non PI3K/Akt/mTOR signaling pathway, and the specific mechanism of its action needs further studying.
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http://dx.doi.org/10.1002/tox.23124DOI Listing
July 2021

SOX7 suppresses endothelial-to-mesenchymal transitions by enhancing VE-cadherin expression during outflow tract development.

Clin Sci (Lond) 2021 Mar;135(6):829-846

Department of Pediatric Cardiology, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.

The endothelial-to-mesenchymal transition (EndMT) is a critical process that occurs during the development of the outflow tract (OFT). Malformations of the OFT can lead to the occurrence of conotruncal defect (CTD). SOX7 duplication has been reported in patients with congenital CTD, but its specific role in OFT development remains poorly understood. To decipher this, histological analysis showed that SRY-related HMG-box 7 (SOX7) was regionally expressed in the endocardial endothelial cells and in the mesenchymal cells of the OFT, where EndMT occurs. Experiments, using in vitro collagen gel culture system, revealed that SOX7 was a negative regulator of EndMT that inhibited endocardial cell (EC) migration and resulted in decreased number of mesenchymal cells. Forced expression of SOX7 in endothelial cells blocked further migration and improved the expression of the adhesion protein vascular endothelial (VE)-cadherin (VE-cadherin). Moreover, a VE-cadherin knockdown could partly reverse the SOX7-mediated repression of cell migration. Luciferase and electrophoretic mobility shift assay (EMSA) demonstrated that SOX7 up-regulated VE-cadherin by directly binding to the gene's promoter in endothelial cells. The coding exons and splicing regions of the SOX7 gene were also scanned in the 536 sporadic CTD patients and in 300 unaffected controls, which revealed four heterozygous SOX7 mutations. Luciferase assays revealed that two SOX7 variants weakened the transactivation of the VE-cadherin promoter. In conclusion, SOX7 inhibited EndMT during OFT development by directly up-regulating the endothelial-specific adhesion molecule VE-cadherin. SOX7 mutations can lead to impaired EndMT by regulating VE-cadherin, which may give rise to the molecular mechanisms associated with SOX7 in CTD pathogenesis.
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http://dx.doi.org/10.1042/CS20201496DOI Listing
March 2021

LARP7 Protects Against Heart Failure by Enhancing Mitochondrial Biogenesis.

Circulation 2021 May 5;143(20):2007-2022. Epub 2021 Mar 5.

Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Department of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Xin Hua Hospital, Shanghai Jiao Tong University, China (H.J.Y., F.Z., P.Y.Y., S.S.Z., Y.M.L., Z.L.G., Z.X.L., Y.J.X., Y.N.L., K.S., B.Z.).

Background: Heart failure (HF) is among the leading causes of morbidity and mortality, and its prevalence continues to rise. LARP7 (La ribonucleoprotein domain family member 7) is a master regulator that governs the DNA damage response and RNAPII (RNA polymerase II) pausing pathway, but its role in HF pathogenesis is incompletely understood.

Methods: We assessed LARP7 expression in human HF and in nonhuman primate and mouse HF models. To study the function of LARP7 in heart, we generated global and cardiac-specific knockout mice. We acutely abolished LARP7 in mature cardiomyocytes by Cas9-mediated somatic knockout. We overexpressed LARP7 in cardiomyocytes using adeno-associated virus serotype 9 and ATM (ataxia telangiectasia mutated protein) inhibitor. The therapeutic potential of LARP7-regulated pathways in HF was tested in a mouse myocardial infarction model.

Results: LARP7 was profoundly downregulated in failing human hearts and in nonhuman primate and murine hearts after myocardial infarction. Low LARP7 levels in failing hearts were linked to elevated reactive oxygen species, which activated the ATM-mediated DNA damage response pathway and promoted LARP7 ubiquitination and degradation. Constitutive knockout in mouse resulted in impaired mitochondrial biogenesis, myocardial hypoplasia, and midgestational lethality. Cardiac-specific inactivation resulted in defective mitochondrial biogenesis, impaired oxidative phosphorylation, elevated oxidative stress, and HF by 4 months of age. These abnormalities were accompanied by reduced SIRT1 (silent mating type information regulation 2 homolog 1) stability and deacetylase activity that impaired SIRT1-mediated transcription of genes for oxidative phosphorylation and energy metabolism and dampened cardiac function. Restoring LARP7 expression after myocardial infarction by either adeno-associated virus-mediated LARP7 expression or small molecule ATM inhibitor substantially improved the function of injured heart.

Conclusions: LARP7 is essential for mitochondrial biogenesis, energy production, and cardiac function by modulating SIRT1 homeostasis and activity. Reduction of LARP7 in diseased hearts owing to activation of the ATM pathway contributes to HF pathogenesis and restoring LARP7 in the injured heart confers myocardial protection. These results identify the ATM-LARP7-SIRT1 pathway as a target for therapeutic intervention in HF.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050812DOI Listing
May 2021

Effects of forest gap disturbance on forest ecosystem.

Ying Yong Sheng Tai Xue Bao 2021 Feb;32(2):701-710

Institute of Subtropical Forestry, Chinese Academy of Forestry, Hangzhou 311400, Zhejiang, China.

Forest gap disturbance has important consequences on plant species assemblage, stand structure and ecosystem functions of forests via changing micro-scale heterogeneity and community succession. Here, we reviwed research progress in the effects of forest gap disturbance on forest ecosystem. The effects of forest gap disturbance on plant species assemblage was analyzed based on the intrinsic biological characteristics and external environmental factors. The effects of forest gap disturbance on stand structure was discussed from the perspectives of texture and architecture of plant community. Forest gap disturbance effect on forest ecosystem functions was reviewed. After analyzing the theoretical shortcomings and the key bottleneck of forest ecosystem management practices, the following research directions were proposed, including the methods of determining threshold of forest gap, the mechanism of canopy closure, the effect of forest gap disturbance on forest ecosystem processes, and the relationship between forest gap disturbance and forest productivity. The advantage of forest gap disturbance in accelerating plant species regeneration and structure complexities could provide scientific evidence for enhancing the quality of low yield and low function plantations in China.
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http://dx.doi.org/10.13287/j.1001-9332.202102.029DOI Listing
February 2021

Sediment carbon short-term response to water carbon content change in a large floodplain-lake system.

Environ Sci Pollut Res Int 2021 Jun 19;28(24):31497-31510. Epub 2021 Feb 19.

Key Laboratory of Ecosystem Network Observation and Modeling, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, 100101, China.

After carbon (C) enters a lake through surface runoff and atmospheric deposition, most of it, being influenced by the environmental conditions of the basin, is deposited into lake sediment, thus, becoming one of the most important C pools in the world. Therefore, it is critical to understand sediment response characteristics under the context of increasing C concentrations in lake water. Based on the changes of sediment C concentration at different depths in Poyang Lake, belonging to China's large floodplain-lake system, we revealed the sediment C short-term response characteristics to changes in lake water C concentrations as well as their associated impacting factors. We found that dissolved total carbon (DTC) concentrations increased by 25.78% in winter compared to spring, while total carbon (TC) sediment concentrations increased by only 4.37% during the corresponding period. Specifically, we found that there was a hysteresis effect in the response of sediment C to the increase of water C concentration in the short term. When DTC concentrations in water were below a threshold value (12.50 mg/L), sediment TC concentrations were generally maintained at approximately 5.79 mg/kg. We also believed that biological and environmental factors and sediment stratification characteristics collectively resulted in this sediment C hysteresis effect. Among these factors and characteristics, phytoplankton can affect sediment C response by changing C absorption and utilization in water or cause a synergistic effect along with environmental factors, which is the key link that causes this C sediment hysteresis effect to occur. Furthermore, we found that the combined effect of sediment C from different depths also resulted in a hysteresis effect in C deposition.
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http://dx.doi.org/10.1007/s11356-021-13016-3DOI Listing
June 2021

Isorhamnetin Enhances the Radiosensitivity of A549 Cells Through Interleukin-13 and the NF-κB Signaling Pathway.

Front Pharmacol 2020 25;11:610772. Epub 2021 Jan 25.

College of Life Science, Northwest Normal University, Lanzhou, China.

Isorhamnetin (ISO), a naturally occurring plant flavonoid, is widely used as a phytomedicine. The major treatment modality for non-small-cell lung carcinoma (NSCLC) is radiotherapy. However, radiotherapy can induce radioresistance in cancer cells, thereby resulting in a poor response rate. Our results demonstrated that pretreatment with ISO induced radiosensitizing effect in A549 cells using colony formation, micronucleus, and γH2AX foci assays. In addition, ISO pretreatment significantly enhanced the radiation-induced incidence of apoptosis, the collapse of mitochondrial membrane potential, and the expressions of proteins associated with cellular apoptosis and suppressed the upregulation of NF-κBp65 induced by irradiation in A549 cells. Interestingly, the expression of interleukin-13 (IL-13), an anti-inflammatory cytokine, was positively correlated with the ISO-mediated radiosensitization of A549 cells. The knockdown of IL-13 expression by RNA interference decreased the IL-13 level and thus reduced ISO-mediated radiosensitivity in cells. We also found that the IR-induced NF-κB signaling activation was inhibited by ISO pretreatment, and it was abrogated in IL-13 silenced cells. We speculated that ISO may confer radiosensitivity on A549 cells via increasing the expression of IL-13 and inhibiting the activation of NF-κB. To our knowledge, this is the first report demonstrating the effects of ISO treatment on the responsiveness of lung cancer cells to irradiation through IL-13 and the NF-κB signaling pathway. In summary, ISO is a naturally occurring radiosensitizer with a potential application in adjuvant radiotherapy.
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http://dx.doi.org/10.3389/fphar.2020.610772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868540PMC
January 2021

Podocyte RNF166 deficiency alleviates diabetic nephropathy by mitigating mitochondria impairment and apoptosis via regulation of CYLD signal.

Biochem Biophys Res Commun 2021 03 2;545:46-53. Epub 2021 Feb 2.

Department of Nephrology, Shandong Province Zibo Central Hospital, 54 West Communist Youth League Road, Zhangdian District, Zibo, Shandong, 255000, China.

Diabetic nephropathy (DN) is a major cause of renal failure in diabetic patients. RING-finger protein 166 (RNF166), composed of an N-terminal RING domain and C-terminal ubiquitin interaction motif, plays a critical role in mediating various cellular processes. However, its potential in DN has not been investigated. In the present study, we found that DN patients exhibited significantly increased expression of RNF166 in renal tissues compared with the normal individuals, and abundant RNF166 was detected in podocytes. We then showed that podocyte-conditional RNF166 knockout (RNF166) markedly reduced blood glucose levels and ameliorated renal dysfunction in streptozotocin (STZ)-induced diabetic mice. Additionally, abnormal histological changes and podocyte injury were observed in STZ-induced diabetic mice, while being markedly ameliorated by RNF166. Furthermore, podocyte-specific RNF166 deficiency considerably mitigated apoptosis and mitochondrial impairments in glomeruli podocytes of STZ-challenged mice through suppressing Caspase-3 cleavage and improving mitochondrial fission-associated molecules. In vitro studies further confirmed that high glucose (HG) induced mitochondrial dysfunction, along with enhanced releases of Cyto-c from mitochondria and elevated expression of cleaved Caspase-9, contributing to intrinsic apoptosis in podocytes. Intriguingly, these effects triggered by HG were dramatically ameliorated by RNF166 knockout. Mechanistically, we demonstrated that RNF166 directly interacted with cylindromatosis (CYLD), and negatively regulated CYLD expression. Notably, RNF166 knockout-attenuated mitochondrial damage and apoptosis were mainly through CYLD in podocytes upon HG stimulation. Together, all these findings provided new insights into the novel effects of RNF166 on maintaining mitochondrial function and apoptosis in podocytes during DN progression both in vivo and in vitro through interacting with CYLD, indicating that RNF166/CYLD may be an innovative therapeutic target for developing effective strategy against DN development.
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http://dx.doi.org/10.1016/j.bbrc.2020.12.014DOI Listing
March 2021

GAA deficiency promotes angiogenesis through upregulation of Rac1 induced by autophagy disorder.

Biochim Biophys Acta Mol Cell Res 2021 Apr 26;1868(5):118969. Epub 2021 Jan 26.

Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address:

Angiogenesis, the formation of new blood vessels from pre-existing ones, is vital for vertebrate development and adult homeostasis. Acid α-glucosidase (GAA) is a glycoside hydrolase involved in the lysosomal breakdown of glycogen. Our previous study showed that GAA was highly expressed in mouse pulmonary veins. While whether GAA was involved in angiogenesis remained largely unknown, thus, we performed knockdown experiments both in vivo and in vitro and endothelial cell function experiments to clarify this concern point. We identified that GAA expressed widely at different levels during zebrafish embryonic development and GAA morphants showed excessive angiogenesis of ISV at later stage. In GAA knockdown HUVECs, the migration and tube formation capacity were increased, resulted from the formation of large lamellipodia-like protrusions at the edge of cells. By analyzing autophagic flux, we found that autophagy disorder was the mechanism of GAA knockdown-induced excessive angiogenesis. The block of autophagic flux caused upregulation of Rac1, a small GTPase, and the latter promoted excessive sprouts in zebrafish and enhanced angiogenic behavior in HUVECs. In addition, overexpression of transcription factor E3, a master regulator of autophagy, rescued upregulation of RAC1 and enhanced angiogenic function in GAA-knockdown HUVECs. Also, inhibition of Rac1 partly restored enhanced angiogenic function in GAA-knockdown HUVECs. Taken together, our study firstly reported a novel function of GAA in angiogenesis which is mediated by upregulation of Rac1 induced by autophagy disorder.
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http://dx.doi.org/10.1016/j.bbamcr.2021.118969DOI Listing
April 2021

Gibberellins are required for dimorphic flower development in Viola philippica.

Plant Sci 2021 Feb 24;303:110749. Epub 2020 Nov 24.

State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, Chinese Academy of Sciences, Nanxincun 20, Xiangshan, 100093 Beijing, China; University of Chinese Academy of Sciences, Yuquan Road 19A, 100049 Beijing, China. Electronic address:

Photoperiod is a major determinant of chasmogamous (CH)-cleistogamous (CL) dimorphic flower development in Viola philippica, and only long-day (LD) conditions induce CL flowers. In this study, it was found that the active gibberellin (GA) content in CL floral buds was higher than in CH floral buds formed under short-day (SD) conditions, suggesting that the biosynthesis of active GAs is enhanced by a longer photoperiod and may be associated with dimorphic flower development. Thus, the next step was to molecularly characterize the key V. philippica GA synthesis genes GA 20-oxidase (VpGA20ox) and GA 3-oxidase (VpGA3ox). In terms of the expression of VpGA20ox and VpGA3ox, it was found that the active GAs could be upregulated in developing pistils under both LD and SD conditions to develop functional pistils, and GAs could also accumulate in the stamens under SD conditions. The anthers and the adjacent petals were well developed under SD conditions. In contrast, the above-mentioned floral organs displayed low GA contents under LD conditions and were poorly developed. Although the application of paclobutrazol, an inhibitor of GA synthesis, did not reverse CL development under LD conditions, exogenous GAs could partially trigger the transition from CH to CL flowers under relative SD conditions (≤12 h daylight). This was coupled with the downregulation of B-class MADS-box genes, thereby restraining stamen and petal development. Both VpGA20ox and VpGA3ox exhibited similar expression profiles with B-class MADS-box genes in the development of the stamens and petals. Therefore, in response to photoperiod, GA signaling could affect the expression of B-class homeotic genes and regulate dimorphic flower development in Viola. As a compensation for poorly-developed nectaries, anthers, and petals, filament elongation, style shortness, and inward bending could ensure self-pollination in CL flowers. This work provides new insights into the regulation of CH-CL floral development and the evolutionary significance of the formation of dimorphic flowers.
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http://dx.doi.org/10.1016/j.plantsci.2020.110749DOI Listing
February 2021

Atlas of ACE2 gene expression reveals novel insights into transmission of SARS-CoV-2.

Heliyon 2021 Jan 26;7(1):e05850. Epub 2020 Dec 26.

Beijing Huayuan Academy of Biotechnology, Beijing, 100192, China.

The recent pandemic, COVID-19, is caused by a novel coronavirus, SARS-CoV-2, with elusive origin. SARS-CoV-2 infects mammalian cells via ACE2, a transmembrane protein. Therefore, the conservation and expression patterns of ACE2 may provide valuable insights into tracing the carriers of SARS-CoV-2. In this work, we analyzed the conservation of ACE2 and its expression pattern among various mammalian species that are close to human beings. We show that mammalian ACE2 gene is deeply conserved at both DNA and peptide levels, suggesting that a broad range of mammals can potentially host SARS-CoV-2. We further report that ACE2 expression in certain human tissues are consistent with clinical symptoms of COVID-19 patients. Furthermore, we have built the first atlas of ACE2 expression in various common mammals, which shows that ACE2 expresses in mammalian tissues in a species-specific manner. Most notably, we observe exceptionally high expression of ACE2 in external body parts of cats and dogs, suggesting that these household pet animals could be vulnerable to viral infections and/or may serve as intermediate hosts, thus yielding novel insights into the transmission of SARS-CoV-2.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762714PMC
January 2021

Genome-wide data mining to construct a competing endogenous RNA network and reveal the pivotal therapeutic targets of Parkinson's disease.

J Cell Mol Med 2020 Dec 15. Epub 2020 Dec 15.

School of Public Health, North China University of Science and Technology, Tangshan, China.

Parkinson's disease (PD) is one of the most common neurodegenerative movement disorders, for which there has been no effective treatments. To clarify the pathogenesis of PD, we constructed a competing endogenous RNA (ceRNA) network based on the genome-wide RNA sequencing data. It was found that 92 RNAs were differentially expressed, including 50 mRNAs, 25 miRNAs and 17 lncRNAs, based on which a ceRNA network was constructed and evaluated from 4 aspects of number of nodes, topological coefficients, closeness centrality and betweenness centrality. The functional annotation and enrichment analysis suggested that 6 functional modules, particularly the peripheral nervous system development and toxin metabolic process, dominated the development of PD. To validate the assumption, the gene set enrichment analysis (GSEA) was conducted basing on the genome-wide RNAs regardless whether they were differentially expressed or not. Consistently, the results revealed that dysregulation of MAG, HOXB3, MYRF and PLP1 led to metabolic disorders of sphingolipid and glutathione, which contributed to the pathogenesis of PD. Also, in-depth mining of previous literature confirmed a pivotal role of these dysregulated RNAs, which had been indicated to be potential diagnostic and therapeutic biomarkers of PD. Overall, we constructed a ceRNA network based on the dysregulated mRNAs, lncRNAs and miRNAs in PD, and the aberrant expression of MAG, HOXB3, MYRF and PLP1 caused metabolism disorder of sphingolipid and glutathione, and these genes are of great significance for the diagnosis and treatment of PD.
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http://dx.doi.org/10.1111/jcmm.16190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256352PMC
December 2020

Msuite: A High-Performance and Versatile DNA Methylation Data-Analysis Toolkit.

Patterns (N Y) 2020 Nov 15;1(8):100127. Epub 2020 Oct 15.

Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR 999077, China.

DNA methylation is a pervasive and important epigenetic regulator in mammalian genome. For DNA methylome profiling, emerging bisulfite-free methods have demonstrated desirable superiority over the conventional bisulfite-treatment-based approaches, although current analysis software could not make full use of their advantages. In this work, we present Msuite, an easy-to-use, all-in-one data-analysis toolkit. Msuite implements a unique 4-letter analysis mode specifically optimized for emerging protocols; it also integrates quality controls, methylation call, and data visualizations. Msuite demonstrates substantial performance improvements over current state-of-the-art tools as well as fruitful functionalities, thus holding the potential to serve as an optimal toolkit to facilitate DNA methylome studies. Source codes and testing datasets for Msuite are freely available at https://github.com/hellosunking/Msuite/.
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http://dx.doi.org/10.1016/j.patter.2020.100127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691389PMC
November 2020

Elabela: A Novel Biomarker for Right Ventricular Pressure Overload in Children With Pulmonary Stenosis or Pulmonary Atresia With Intact Ventricular Septum.

Front Cardiovasc Med 2020 12;7:581848. Epub 2020 Nov 12.

Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Assessing right ventricular overload in children is challenging. We conducted this study involving children with pulmonary valvular stenosis (PS) or pulmonary atresia with intact ventricular septum (PA/IVS) to evaluate the potential of a new endogenous ligand of apelin receptor, Elabela (ELA), as a potential biomarker for right heart overload. In this prospective cohort study, a total of 118 congenital heart diseases patients with right ventricle outflow tract obstruction were recruited from 2018 to 2019. Among them, 44 isolated PS and 7 PA/IVS patients were selected. Their venous blood was collected, and all patients underwent an echocardiographic examination. Among them, post-operative blood was collected from 24 patients with PS after percutaneous balloon pulmonary valvuloplasty. The plasma ELA concentration was measured using enzyme-linked immunosorbent assay. The ELA was significantly associated with the peak transvalvular pulmonary gradient ( = -0.62; = 0.02), thus reflecting the severity of PS or PA/IVS. The ELA significantly increased at 3 days after intervention, when mechanical obstruction of the right outflow tract was relieved. Based on the receiver-operator characteristic curve results, ELA could be a risk factor for duct dependence in patients with critical PS or PA/IVS who are younger than 6 months (AUC: 0.82). ELA concentration and severity of PS or PA/IVS had a significant negative correlation, indicating that ELA might be a novel biomarker for right ventricular afterload and reflect the immediate pressure changes in the right heart. Furthermore, ELA could predict duct-dependency in PS and PA/IVS patients, as valuable as classical echocardiographic indexes.
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http://dx.doi.org/10.3389/fcvm.2020.581848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688667PMC
November 2020

A loss-of-function mutation p.T256M in NDRG4 is implicated in the pathogenesis of pulmonary atresia with ventricular septal defect (PA/VSD) and tetralogy of Fallot (TOF).

FEBS Open Bio 2021 02 9;11(2):375-385. Epub 2021 Jan 9.

Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Pulmonary atresia with ventricular septal defect (PA/VSD) is a rare congenital heart disease (CHD) characterized by a lack of luminal continuity and blood flow from either the right ventricle or the pulmonary artery, together with VSDs. The prevalence of PA/VSD is about 0.2% of live births and approximately 2% of CHDs. PA/VSD is similar to tetralogy of Fallot (TOF) in terms of structural and pathological characteristics. The pathogenesis of these two CHDs remains incompletely understood. It was previously reported that N-myc downstream-regulated gene (NDRG)4 is required for myocyte proliferation during early cardiac development. In the present study, we enrolled 80 unrelated patients with PA/VSD or TOF and identified a probably damaging variant p.T256M of NDRG4. The p.T256M variant impaired the proliferation ability of human cardiac myocytes (hCM). Furthermore, the p.T256M variant resulted in G1 and G2 arrest of hCM, followed by an increase in p27 and caspase-9 expression. Our results provide evidence that the p.T256M variant in NDRG4 is a pathogenic variant associated with impaired hCM proliferation and cell-cycle arrest and likely contributes towards the pathogenesis of PA/VSD and TOF.
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http://dx.doi.org/10.1002/2211-5463.13044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876499PMC
February 2021

Size-Dependent Mechanical Properties of Amorphous SiO Nanowires: A Molecular Dynamics Study.

Materials (Basel) 2020 Nov 12;13(22). Epub 2020 Nov 12.

State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.

Uniaxial tension tests were performed for amorphous SiO nanowires using molecular dynamics simulation to probe the size effect on the mechanical properties and plastic deformation by varying the length of nanowires. The simulation results showed that the Young's modulus of SiO nanowires increased with the decrease of nanowires length due to its higher surface stress. The corresponding deformation of SiO nanowires during tension exhibited two periods: atomic arrangement at small strain and plastic deformation at large strain. During the atomic arrangement period, the percentage variations of atom number of 2-coordinated silicon and 3-coordinated silicon (PCN2 and PCN3) decreased, while the percentage variations of atom number of 4-coordinated silicon, 5-coordinated silicon (PCN4 and PCN5) and the Si-O bond number (PCB) rose slightly with increasing strain, as the strain was less than 22%. The situation reversed at the plastic deformation period, owing to the numerous breakage of Si-O bonds as the strain grew beyond 22%. The size effect of nanowires radius was considered, finding that the Young's modulus and fracture stress were higher for the larger nanowire because of fewer dangling bonds and coordinate defeats in the surface area. The elastic deformation occurred at a small strain for the larger nanowire, followed by the massive plastic deformation during tension. A brittle mechanism covers the fracture characteristics, irrespective of the nanowire size.
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http://dx.doi.org/10.3390/ma13225110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696835PMC
November 2020

NAMS webserver: coding potential assessment and functional annotation of plant transcripts.

Brief Bioinform 2021 May;22(3)

Recent advances in transcriptomics have uncovered lots of novel transcripts in plants. To annotate such transcripts, dissecting their coding potential is a critical step. Computational approaches have been proven fruitful in this task; however, most current tools are designed/optimized for mammals and only a few of them have been tested on a limited number of plant species. In this work, we present NAMS webserver, which contains a novel coding potential classifier, NAMS, specifically optimized for plants. We have evaluated the performance of NAMS using a comprehensive dataset containing more than 3 million transcripts from various plant species, where NAMS demonstrates high accuracy and remarkable performance improvements over state-of-the-art software. Moreover, our webserver also furnishes functional annotations, aiming to provide users informative clues to the functions of their transcripts. Considering that most plant species are poorly characterized, our NAMS webserver could serve as a valuable resource to facilitate the transcriptomic studies. The webserver with testing dataset is freely available at http://sunlab.cpy.cuhk.edu.hk/NAMS/.
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http://dx.doi.org/10.1093/bib/bbaa200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138890PMC
May 2021

Dynamic transcriptome profiling toward understanding the development of the human embryonic heart during different Carnegie stages.

FEBS Lett 2020 12 12;594(24):4307-4319. Epub 2020 Oct 12.

Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, China.

Transcriptional regulation participates in heart development. However, the transcriptomes of human embryonic hearts during Carnegie stage (CS)10-CS16 have not been elucidated. Here, we found marked changes in the morphology and transcriptome of the human embryonic heart from CS10 to CS11. At CS12-CS14, the embryonic heart undergoes hypoxia-to-aerobic transformation. At CS14-CS16, transcriptome functions were related to energy metabolism, regulation of cholesterol, and processes related to inorganic substances. Moreover, the transcriptomes of cardiac progenitor cells derived from human embryonic stem cells (hESCs) most overlapped with those of human embryonic hearts at CS10. Cardiomyocytes derived from hESCs considerably overlapped with embryonic hearts at CS14-CS16. Overall, these results provide a new perspective into the characteristics of human embryonic heart development.
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http://dx.doi.org/10.1002/1873-3468.13930DOI Listing
December 2020
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