Publications by authors named "Xiyu Zhu"

41 Publications

Synthesis and physical properties of perovskite Sm1-xSrxNiO3 (x = 0, 0.2) and infinite-layer Sm0.8Sr0.2NiO2 nickelates.

J Phys Condens Matter 2021 Apr 26. Epub 2021 Apr 26.

Nanjing University, Center for Superconducting Physics and Materials, National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China, Nanjing, 210093, CHINA.

Recently, superconductivity at about 9-15 K was discovered in Nd1-xSrxNiO2 (Nd-112, x ≈ 0.125-0.25) infinite-layer thin films, which has stimulated enormous interests in related rare-earth nickelates. Usually, the first step to synthesize this 112 phase is to fabricate the RNiO3 (R-113, R: rare-earth element) phase, however, it was reported that the 113 phase is very difficult to be synthesized successfully due to the formation of unusual Ni3+oxidation state. And the difficulty of preparation is enhanced as the ionic radius of rare-earth element decreases. In this work, we report the synthesis and investigation on multiple physical properties of polycrystalline perovskites Sm1-xSrxNiO3 (x = 0, 0.2) in which the ionic radius of Sm3+ is smaller than that of Pr3+ and Nd3+ in related superconducting thin films. The structural and compositional analyses conducted by X-ray diffraction and energy dispersive X-ray spectrum reveal that the samples mainly contain the perovskite phase of Sm1-xSrxNiO3 with small amount of NiO impurities. Magnetization and resistivity measurements indicate that the parent phase SmNiO3 undergoes a paramagnetic-antiferromagnetic transition at about 224 K on a global insulating background. In contrast, the Sr-doped sample Sm0.8Sr0.2NiO3 shows a metallic behavior from 300 K down to about 12 K, while below 12 K the resistivity exhibits a slight logarithmic increase. Meanwhile, from the magnetization curves, we can see that a possible spin-glass state occurs below 12 K in Sm0.8Sr0.2NiO3. Using a soft chemical reduction method, we also obtain the infinite-layer phase Sm0.8Sr0.2NiO2 with square NiO2 planes. The compound shows an insulating behavior which can be described by the three-dimensional variable-range-hopping model. And superconductivity is still absent in the polycrystalline Sm0.8Sr0.2NiO2.
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http://dx.doi.org/10.1088/1361-648X/abfb90DOI Listing
April 2021

Prompt surgery is effective for acute type A aortic dissection with cerebral ischemia.

J Thorac Dis 2021 Mar;13(3):1403-1412

Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.

Background: Acute type A aortic dissection (aTAAD) with preoperative cerebral ischemia (CI) is common and lethal, but the timing and treatment method remain uncertain. We retrospectively reviewed our aTAAD patients with CI and analyzed the outcomes and related risk factors.

Methods: From January 2011 to December 2019, 1,173 patients diagnosed with aTAAD from Nanjing Drum Tower Hospital were enrolled. Among them, 131 patients had CI preoperatively (CI group), and 1,042 patients were in the non-CI group. One hundred eight in the CI group and 984 in the non-CI group received central repair surgery. Fifteen patients had postoperative cerebral complications (CC) and 93 had non-CCs. ROC curves were used to identify the safe duration of preoperative CI.

Results: The CI group was older (56.3 . 53.2 years, P=0.013) and had lower rates of pain, chest pain and back pain (77.9% . 94.4%, 75.4% . 87.5% and 30.8% . 42.3%, respectively) than the non-CI group. The CI group had a higher rate of preoperative hypotension and tamponade (13.7% . 6.0%, 26.9% . 10.4%, respectively; P=0.000). More patients in the CI group did not receive central repair surgery, and the CI had higher mortality (28.2% . 15.9%). CI without central repair surgery was a strong risk factor for mortality. CI patients with CC after central repair had a higher mortality, and preoperative coma was the strongest risk factor for postoperative CC.A duration between CI symptoms and central repair surgery of less than 12.75 hours is recommended.

Conclusions: Prompt surgery is effective for aTAAD with CI, and preoperative coma and a safe duration longer than 12.75 hours would predict worse outcomes.
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http://dx.doi.org/10.21037/jtd-20-2349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024860PMC
March 2021

Prepubertal Environmental Enrichment Prevents Dopamine Dysregulation and Hippocampal Hyperactivity in MAM Schizophrenia Model Rats.

Biol Psychiatry 2021 02 5;89(3):298-307. Epub 2020 Oct 5.

Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania.

Background: Schizophrenia (SCZ) is a neurodevelopmental disorder with a progressive, prolonged course. Early prevention for SCZ is promising but overall lacks support from preclinical evidence. Previous studies have tested environmental enrichment (EE) in certain models of SCZ and discovered a broadly beneficial effect in preventing behavioral abnormalities relevant, yet not specific, to the disorder. Nonetheless, whether EE can prevent dopamine (DA) dysregulation, a hallmark of psychosis and SCZ, had not been tested.

Methods: Using the MAM (methylazoxymethanol acetate) rat model of schizophrenia and saline-treated control animals, we investigated the long-term electrophysiological effects of prepubertal (postnatal day 21-40) EE on DA neurons, pyramidal neurons in the ventral hippocampus, and projection neurons in the basolateral amygdala. Anxiety-related behaviors in the elevated plus maze and locomotor responses to amphetamine were also analyzed.

Results: Prepubertal EE prevented the increased population activity of DA neurons and the associated increase in locomotor response to amphetamine. Prepubertal EE also prevented hyperactivity in the ventral hippocampus but did not prevent hyperactivity in the basolateral amygdala. Anxiety-like behaviors in MAM rats were not ameliorated by prepubertal exposure to EE.

Conclusions: Twenty-day prepubertal EE is sufficient to prevent DA hyperresponsivity in the MAM model, measured by electrophysiological recordings and locomotor response to amphetamine. This effect is potentially mediated by normalizing excessive firing in the ventral hippocampus without affecting anxiety-like behaviors and basolateral amygdala firing. This study identified EE as a useful preventative approach that may protect against the pathophysiological development of SCZ.
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http://dx.doi.org/10.1016/j.biopsych.2020.09.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927755PMC
February 2021

Expression Profiles of Circular RNA in Human Atrial Fibrillation With Valvular Heart Diseases.

Front Cardiovasc Med 2020 20;7:597932. Epub 2020 Nov 20.

Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Circular RNAs (circRNA) are involved in a variety of human heart diseases, however, circRNA expression profiles and circRNA-miRNA-mRNA regulatory network in human atrial fibrillation (AF) especially with valvular heart diseases (VHD) remain poorly understood. A high-throughput RNA sequencing was used to investigate the differentially expressed circRNAs in left atrial appendage from VHD patients with or without persistent AF. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the potential functions of the host genes of differentially expressed circRNA and their downstream targets. CircRNA-miRNA-mRNA regulatory network was constructed to identify mechanisms underlying circRNAs. qRT-PCR and sanger sequencing were further performed to validate the results. Compared with sinus rhythm (SR) patients, there were 3094 upregulated and 4472 downregulated circRNAs in AF patients respectively. The expression of 10 most differentially expressed circRNAs (circ 255-ITGA7, circ 418-KCNN2, circ 13913-MIB1, circ 44670-BARD1, circ 44782-LAMA2, circ 81906-RYR2, circ 35880-ANO5, circ 22249-TNNI3K, circ 3136-TNNI3K, circ 56186-TNNI3K) between SR and persistent AF patients were verified by qRT-PCR. In addition, specific back-splicing sites of these circRNAs was confirmed by sanger sequencing. GO and KEGG pathway analysis indicated that cAMP signal pathway and Wnt signal pathway might play important role in the development of AF in VHD patients, which might be affected by circRNAs. This study provided a preliminary landscape of circRNAs expression profiles which are involved in persistent AF due to VHD, and established the possibility for future related researches in this field.
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http://dx.doi.org/10.3389/fcvm.2020.597932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714832PMC
November 2020

Single particle tunneling spectrum of superconducting NdSrNiO thin films.

Nat Commun 2020 Nov 27;11(1):6027. Epub 2020 Nov 27.

National Laboratory of Solid State Microstructures and Department of Physics, Center for Superconducting Physics and Materials, Collaborative Innovation Center for Advanced Microstructures, Nanjing University, Nanjing, China.

The pairing mechanism in cuprates remains as one of the most challenging issues in condensed matter physics. Recently, superconductivity was discovered in thin films of the infinite-layer nickelate NdSrNiO (x = 0.12-0.25) which is believed to have the similar 3d orbital electrons as that in cuprates. Here we report single-particle tunneling measurements on the superconducting nickelate thin films. We find predominantly two types of tunneling spectra, one shows a V-shape feature which can be fitted well by a d-wave gap function with gap maximum of about 3.9 meV, another one exhibits a full gap of about 2.35 meV. Some spectra demonstrate mixed contributions of these two components. Combining with theoretical calculations, we attribute the d-wave gap to the pairing potential of the [Formula: see text] orbital. Several possible reasons are given for explaining the full gap feature. Our results indicate both similarities and distinctions between the newly found Ni-based superconductors and cuprates.
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http://dx.doi.org/10.1038/s41467-020-19908-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695741PMC
November 2020

Valproate reverses mania-like behaviors in mice via preferential targeting of HDAC2.

Mol Psychiatry 2020 Nov 24. Epub 2020 Nov 24.

Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15219, USA.

Valproate (VPA) has been used in the treatment of bipolar disorder since the 1990s. However, the therapeutic targets of VPA have remained elusive. Here we employ a preclinical model to identify the therapeutic targets of VPA. We find compounds that inhibit histone deacetylase proteins (HDACs) are effective in normalizing manic-like behavior, and that class I HDACs (e.g., HDAC1 and HDAC2) are most important in this response. Using an RNAi approach, we find that HDAC2, but not HDAC1, inhibition in the ventral tegmental area (VTA) is sufficient to normalize behavior. Furthermore, HDAC2 overexpression in the VTA prevents the actions of VPA. We used RNA sequencing in both mice and human induced pluripotent stem cells (iPSCs) derived from bipolar patients to further identify important molecular targets. Together, these studies identify HDAC2 and downstream targets for the development of novel therapeutics for bipolar mania.
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http://dx.doi.org/10.1038/s41380-020-00958-2DOI Listing
November 2020

Exaggerated Autophagy in Stanford Type A Aortic Dissection: A Transcriptome Pilot Analysis of Human Ascending Aortic Tissues.

Genes (Basel) 2020 Oct 13;11(10). Epub 2020 Oct 13.

Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Institute of Cardiothoracic Vascular Disease, Nanjing University, Nanjing 210008, China.

Stanford type A aortic dissection (TAAD) is one of the most dangerous diseases of acute aortic syndrome. Molecular pathological studies on TAAD can aid in understanding the disease comprehensively and can provide insights into new diagnostic markers and potential therapeutic targets. In this study, we defined the molecular pathology of TAAD by performing transcriptome sequencing of human ascending aortic tissues. Pathway analysis revealed that activated inflammation, cell death and smooth muscle cell degeneration are the main pathological changes in aortic dissection. However, autophagy is considered to be one of the most important biological processes, regulating inflammatory reactions and degenerative changes. Therefore, we focused on the pathological role of autophagy in aortic dissection and identified 10 autophagy-regulated hub genes, which are all upregulated in TAAD. These results indicate that exaggerated autophagy participates in the pathological process of aortic dissection and may provide new insight for further basic research on TAAD.
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http://dx.doi.org/10.3390/genes11101187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650806PMC
October 2020

Quantitative proteomic analysis to identify differentially expressed proteins in the persistent atrial fibrillation using TMT coupled with nano-LC-MS/MS.

Am J Transl Res 2020 15;12(9):5032-5047. Epub 2020 Sep 15.

Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008, China.

Persistent atrial fibrillation (PeAF) is a progressive cardiovascular disease with a high risk for most patients after diagnosis. Poor molecular description of PeAF has led to unsatisfactory interpretation of the pathogenesis of it, resulting in the lack of effective treatments. The aim of the present study was to find several new potential biomarkers for early prevention, diagnosis and treatment of this disease and explore the underlying molecular mechanisms. An absolute quantitation Tandem Mass Tag (TMT)-liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was applied to identify differentially expressed proteins (DEPs) in left atrial appendage. Totally, 4682 proteins were identified and 4159 proteins were quantified. Compared with control subjects, 118 DEPs (85 upregulated proteins and 33 downregulated proteins) were identified in the atrial tissues of PeAF patients. Using String software, a regulatory network containing 87 nodes and 244 edges was built, and the functional enrichment showed that DEPs were predominantly involved in protein digestion and absorption, regulation of metabolism and focal adhesion. Four proteins, collagen 1 (COL-I), collagen 2 (COL-II), ras-related protein 1 (RAP1) and leucine-rich alpha-2-glycoprotein 1 (LRG1) were selected for validation using Western blot analysis to distinguish PeAF patients and control subjects. The present results provide a comprehensive understanding of the pathophysiological mechanisms of PeAF and the validated biomarkers for the diagnosis of PeAF, which facilitate the development of therapeutic targets.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540158PMC
September 2020

Generation of induced pluripotent stem cells (NJDTHi001-A) from a Danon disease child with mutation of c.467 T > G in LAMP2 gene.

Stem Cell Res 2020 12 23;49:101994. Epub 2020 Sep 23.

Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China. Electronic address:

The induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) isolated from a male child with Danon disease. Next-generation sequencing (NGS) revealed a stop gained mutation c.467 T > G in LAMP2 gene. PBMCs were reprogrammed by using non-integrating Sendai reprogramming kits. It is a possible cell model to screen alternative medicine treatment of the Danon disease.
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http://dx.doi.org/10.1016/j.scr.2020.101994DOI Listing
December 2020

Preoperative monocyte-to-HDL-cholesterol ratio predicts early recurrence after radiofrequency maze procedure of valvular atrial fibrillation.

J Clin Lab Anal 2021 Feb 25;35(2):e23595. Epub 2020 Sep 25.

Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospita,the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Background: Monocyte-to-high-density lipoprotein (M/H) ratio has emerged as a novel cardiovascular prognostic biomarker. We aimed to evaluate the prognostic values of M/H with early recurrence in persistent valvular atrial fibrillation (AF) patients after radiofrequency (RF) maze procedure.

Methods: We retrospectively analyzed 131 consecutive persistent AF patients with valvular heart diseases who were followed up 3 months after RF maze procedure. Their clinical data were recorded. Logistic regression analyses were performed for significant predictors. Receiver operating characteristic analysis was used for validation with corresponding area under the curve.

Results: 70 (53.4%) patients experienced early recurrence after procedure. Patients with early recurrence were older, have longer AF duration history, larger left atria diameter (LAD), higher plasma C-reactive protein (CRP), lower triglycerides (TG), lower cholesterol (TC), increased monocyte counts, lower HDL cholesterol, and increased M/H ratio. In multivariate analysis, age (OR 1.1 95% CI 1.0-1.1 P = .003), LAD (OR 2.1, 95%CI 1.2-3.5, P = .006), TG (OR 0.35, 95% CI 0.15-0.84, P = .019), M/H (OR 6.1, 95% CI 2.9-13.0, P < .001) were significantly independent predictors of AF early recurrence. M/H ratio demonstrated a significant predictive value (AUC = 0.77, sensitivity 89.0%, specificity 54%). Further, there was a positive correlation of M/H ratio with CRP and white blood cell.

Conclusion: Preoperative M/H ratio was an independent risk factor of AF early recurrence following RF maze operation. M/H ratio should be considered in prediction of early recurrence for valvular AF patients.
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http://dx.doi.org/10.1002/jcla.23595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891499PMC
February 2021

Magnetic Stress Sensing System for Nondestructive Stress Testing of Structural Steel and Steel Truss Components Based on Existing Magnetism.

Sensors (Basel) 2020 Jul 21;20(14). Epub 2020 Jul 21.

Mechanical Engineering College, Xi'an Shiyou University, Xi'an 710065, China.

To detect the stress of steel structures and members using the existing magnetism, a magnetic stress sensing system integrating a magnetic flux induction coil, a magnetic flux measurement device, a loaded device, and data acquisition software was developed. The magnetic coupling test research was carried out for different grades of structural building and bridge steel specimens to establish the magnetic stress flux mathematical model, and the fitting equation of the magnetic flux changes with the positions of different sections of specimens was analyzed. Furthermore, a practical formula for stress detection was obtained through the experiments. Meanwhile, on these bases, the typical steel truss structure model of a Bailey beam was designed and manufactured under different working conditions, nondestructive online stress testing was carried out, and the stress of the model structure and its members was measured by strain and magnetic flux tests to obtain the curves of the test results for the stress-strain and magnetic stress flux, respectively. The results of these two methods are in good agreement with each other. The stress of the steel truss model structure was analyzed and calculated using the finite element method. The results agreed well with the experimental results from the magnetic stress sensing system-the maximum error was about 5%, which meets the requirements of engineering applications.
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http://dx.doi.org/10.3390/s20144043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412352PMC
July 2020

Synthesis, characterization and in vitro antibacterial mechanism study of two Keggin-type polyoxometalates.

J Inorg Biochem 2020 09 10;210:111131. Epub 2020 Jun 10.

Henan Key Laboratory of Polyoxometalate Chemistry, Institute of Molecular and Crystal Engineering, School of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004, China. Electronic address:

In this article, two Keggin-type polyoxometalates [Co(L)][PMoO] (1) and [Co(L)][PWO] (2) (HL = 2-acetylpyrazine thiosemicarbazone) were prepared and fully characterized. The compounds are stable in aqueous solution with different pH values and show superior antibacterial activity against Escherichia coli (E. coli: minimal inhibitory concentration (MIC) = 0.00375, 0.12 μg/mL), Agrobacterium tumefaciens (A. tumefaciens: MIC = 0.06, 0.12 μg/mL), Bacillus subtilis (B. subtilis: MIC = 0.015, 0.06 μg/mL) and especially for Staphylococcus aureus (S. aureus: MIC = 0.00048, 0.015 μg/mL) for 1 and 2, respectively. The time kill studies showed the entire killing of specific bacteria during 4 to 8 h. In addition, the possible antibacterial mechanism of compound 1 was explored systematically. The experimental results proved that cell wall/membrane damage, leakage of protein, inhibition of respiratory chain dehydrogenases activity, enhancement of intracellular reactive oxygen species (ROS) and depletion of glutathione (GSH) were the potential causes of bacteria death.
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http://dx.doi.org/10.1016/j.jinorgbio.2020.111131DOI Listing
September 2020

Decoupling of itinerant and localized d-orbital electrons in the compound ScZrCo.

J Phys Condens Matter 2020 Jun 11;32(40):40LT01. Epub 2020 Jun 11.

National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, People's Republic of China.

By using the arc-melting method, we successfully synthesize the compound ScZrCo with the space group of Pm-3m. Both the resistivity and magnetic susceptibility measurements reveal a phase transition at about 86 K. This transition might be attributed to the establishment of an antiferromagnetic order. The magnetization hysteresis loop measurements in wide temperature region show a weak ferromagnetic feature, which suggests a possible canted arrangement of the magnetic moments. Bounded by the phase transition temperature, the resistivity at ambient pressure shows a change from Fermi liquid behavior to a super-linear behavior as temperature increases. By applying pressure up to 32.1 GPa, the transition temperature does not show a clear change and no superconductivity is observed above 2 K. The density functional theory calculations simulate the antiferromagnetic order and reveal a gap between the spin-up and spin-down d-orbital electrons. This kind of behavior may suggest that the antiferromagnetic order in this compound originates from the localized d-electrons which do not contribute to the electric conduction. Thus the itinerant and localized d-orbital electrons in the compound are decoupled.
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http://dx.doi.org/10.1088/1361-648X/ab9bceDOI Listing
June 2020

Predictors of Failure Cardioversion for Recurrent Atrial Fibrillation Following Mitral Valve Surgery With Ablation.

Heart Surg Forum 2020 May 13;23(3):E300-E304. Epub 2020 May 13.

Department of Thoracic and Cardiovascular Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Background: Electrical cardioversion (ECV) often is required for terminating recurrent atrial fibrillation (AF) after surgical radiofrequency ablation in patients undergoing mitral valve surgery. However, ECV is unsuccessful in some cases. In this study, we aimed to identify possible predictors of failed ECV for recurrent atrial fibrillation following mitral valve surgery with concomitant radiofrequency ablation.

Methods: We enrolled 1,136 persistent AF patients with history of mitral valve surgery and concomitant radiofrequency ablation. Three-hundred-nineteen patients experienced recurrence of persistent AF and received ECV therapy. Comparison was made between patients with failed ECV (Failure group, N = 68) and successful ECV (Success group, N = 251).

Results: In multivariate regression analysis, age, pre-ECV loading-dose amiodarone, left atrial diameter, atrial flutter and time from surgery to ECV were independent predictors for outcomes of ECV. According to receiver operating characteristic curve analysis, the best threshold values of age, left atrial diameter and time from surgery to ECV for predicting failed ECV were 55.5 years, 64.5 mm, and 90.5 days, respectively.

Conclusion: Older age, larger left atrium and longer time from surgery to ECV are independent predictors for failed ECV in this group. Compared with AF, atrial flutter is easier to be successfully terminated by ECV. Pre-ECV loading-dose amiodarone is helpful for successful ECV. These findings have important implications for identifying the kinds of patients to receive effective ECV.
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http://dx.doi.org/10.1532/hsf.2997DOI Listing
May 2020

"Double Jacket Wrapping" Root Reconstruction for Acute Type A Aortic Dissection.

Ann Thorac Surg 2020 09 30;110(3):1060-1062. Epub 2020 Apr 30.

Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China. Electronic address:

This report describes a simple and effective method of aortic root repair and reconstruction in acute type A aortic dissection to reduce the risks of hemorrhage and late aortic root new intimal tear and dilation. "Double jacket wrapping" (DJW) has 2 steps: the first jacket is used for aortic root "sandwich" repair, with a patch between the outer and inner layers; and the second jacket is wrapped outside the reconstructed root at the level of the supracoronary ostium. Compared with aortic root replacement, the DJW method may avoid prosthetic valve-related complications and decrease the complexity of valve-sparing root replacement; thus, DJW is a method worthy of wide use.
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http://dx.doi.org/10.1016/j.athoracsur.2020.03.081DOI Listing
September 2020

The PGC-1α/NRF1/miR-378a axis protects vascular smooth muscle cells from FFA-induced proliferation, migration and inflammation in atherosclerosis.

Atherosclerosis 2020 03 8;297:136-145. Epub 2020 Feb 8.

State Key Laboratory of Pharmaceutical Biotechnology, Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, China; State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, China; Institute of Cardiothoracic Vascular Disease, Nanjing University, China. Electronic address:

Background And Aims: Atherosclerosis (AS) is the leading cause of cardiovascular diseases. PGC-1α is a key regulator of cellular energy homeostasis, but its role in AS remains debatable.

Methods And Results: In our study, PGC-1α was shown to be significantly decreased in the media of human atherosclerotic vessels. To explore whether miRNAs might be regulated by PGC-1α in vascular smooth muscle cells (VSMCs), microarray analysis was performed. Microarray and Pearson's correlation analysis showed that PGC-1α and miR-378a were positively correlated in vivo and in vitro. As an upstream co-activator, PGC-1α was found to regulate miR-378a through binding to the transcriptional factor NRF1 in VSMCs. Therefore, the decreased expression of PGC-1α might account for suppression of miR-378a in VSMCs in AS. Furthermore, IGF1 and TLR8, two genes known to be aberrantly up-regulated in atherogenic vessels, were identified as direct targets of miR-378a. In vitro up-regulation of miR-378a markedly inhibited free fatty acid (FFA)-induced VSMC proliferation, migration and inflammation through targeting IGF1 and TLR8.

Conclusions: These findings highlight the protective role of the PGC-1α/NRF1/miR-378a regulatory axis in AS progression and suggest miR-378a as potential therapeutic target for AS treatment.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.02.001DOI Listing
March 2020

Root reconstruction for proximal repair in acute type A aortic dissection.

J Thorac Dis 2019 Nov;11(11):4708-4716

Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China.

Background: Retrospective compared the results of root reconstruction and root replacement for acute type A aortic dissection (ATAAD) patients and observed the rate of aortic insufficiency (AI) and aortic root dilation in the midterm follow-up period.

Methods: From 2008-2016, 427 ATAAD patients received surgical therapy in our center. There were 328 male and 99 female patients, aging from 22 to 83 years with a mean age of (51.1±12.5) years. These patients were divided into two major groups: 298 cases with root reinforcement reconstruction (Root Reconstruction), 129 cases with Bentall procedure (Root Replacement).

Results: The 30-day mortality was 7.7% (33/427), while no difference between the 2 procedures (8.1% and 7.0%, P=0.844). Cross-clamp, cardiopulmonary bypass, and circulatory arrest times of all the patients were 252.5±78.1, 173.6±68.9, 30.7±9.5 minutes, respectively. In the average follow-up time of (34.5±26.1) months, midterm survival rates were similar between the 2 procedures (86.2% and 86.0%, P=0.957). Only one patient received redo Bentall procedure because of severe aortic regurgitation and dilated aortic root (50 mm) in the Root Reconstruction Group.

Conclusions: The indication of root management of ATAAD is based on the diameter of aortic root, structure of aortic root, and the dissection involvement. For most ATAAD patients, aortic root reinforcement reconstruction is a feasible and safe method.
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http://dx.doi.org/10.21037/jtd.2019.10.62DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940217PMC
November 2019

Correction: The pathophysiological impact of stress on the dopamine system is dependent on the state of the critical period of vulnerability.

Mol Psychiatry 2020 Dec;25(12):3449

Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA.

A correction to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41380-019-0527-9DOI Listing
December 2020

Aortic dissection patients mimic acute coronary syndrome with preoperative antiplatelet therapy.

J Thorac Dis 2019 Aug;11(8):3385-3390

Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China.

Background: Acute Stanford type A aortic dissection (ATAAD) is often misdiagnosed as an acute coronary syndrome (ACS), and antiplatelet therapy (APT) for ACS will influence the timing and outcome of ATAAD. We reviewed the surgical outcome of these misdiagnosed ATAAD patients.

Methods: From January 2011 to December 2015, 309 ATAAD patients received surgical therapy in our department, among whom 15 patients were misdiagnosed as ACS and took oral APT. We retrospectively reviewed the data of the perioperative and follow-up period.

Results: The average age of these 15 patients was 60.6±8.7 years old (9 males, 6 females). Five patients took aspirin orally, and 10 took aspirin and clopidogrel. Operations were performed 7, 3, and 1 day after stopping the agents in 2, 3, and 1 patient, respectively; the other 5 patients received emergency operation without stopping the agents. The cardiopulmonary bypass (CPB) time was 259.7±64.8 minutes, aortic cross-clamp time was 181.0±51.7 minutes, and selective cerebral perfusion and lower body arrest time were 34.9±8.1 minutes. There were two in-hospital deaths due to circulation failure (mortality 13.3%). The average drainage volume in the first 24 h after operation was 800.7±598.8 mL. During a mean follow-up period of 20.6±17.4 months, one patient had a sudden death.

Conclusions: ATAAD misdiagnosed as ACS is not rare, and APT will increase the risk of bleeding in ATAAD patients. The decision of operation time relies on considering the balance between the rupture risk of aortic dissection and the hemorrhage risk of APT. The emergency operation for these patients will increase bleeding and transfusion.
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http://dx.doi.org/10.21037/jtd.2019.08.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753422PMC
August 2019

Multitag-Regulated Cascade Reaction: A Generalizable Ultrasensitive MicroRNA Biosensing Approach for Cancer Prognosis.

ACS Appl Mater Interfaces 2019 Oct 26;11(40):36444-36448. Epub 2019 Sep 26.

State Key Joint Laboratory of ESPC, Center for Sensor Technology of Environment and Health School of Environment , Tsinghua University , Beijing 100084 , China.

Ultrasensitive PCR-free microRNA (miR) analysis based on biosensors with enzyme-free nucleic acid amplification and reusable surface has great clinical significance in cancer prognosis. However, building such a biosensing strategy has long been challenging due to uncontrollable miR-triggered cascade amplifiers and insufficient sensing surface regeneration capability. To meet the challenge, for the first time, a general approach, named enzyme-free multitag-regulated cascade reaction (MCR), is developed to fabricate reliable trace miR biosensors. As a proof of concept, miR is detected on an evanescent wave fluorescent optical-fiber biosensing platform. The size and morphology of well-formed MCR assemblies (∼1 μm in length) are characterized by atomic force microscopy. This MCR method achieves a 30 000-fold improved sensitivity (detection limit 0.8 fM) compared to the MCR-free system and can detect abnormal urinary miR levels in lung cancer patients. Moreover, the biosensor is robust enough to be reused for over 100 cycles, which greatly reduces the cost of single detection. In sum, MCR is developed as a generalizable ultrasensitive miR biosensing approach for cancer prognosis, which opens a broad field for facile enzyme-free biosensing applications by nucleic acid assembling regulation.
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http://dx.doi.org/10.1021/acsami.9b14452DOI Listing
October 2019

The pathophysiological impact of stress on the dopamine system is dependent on the state of the critical period of vulnerability.

Mol Psychiatry 2020 12 5;25(12):3278-3291. Epub 2019 Sep 5.

Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA.

Unregulated stress during critical periods of development is proposed to drive deficits consistent with schizophrenia in adults. If accurate, reopening the critical period could make the adult susceptible to pathology. We evaluated the impact of early adolescent and adult stress exposure (combination of daily footshock for 10 days and 3 restraint sessions) on (1) midbrain dopamine (DA) neuron activity, (2) ventral hippocampal (vHipp) pyramidal neuron activity, and (3) the number of parvalbumin (PV) interneurons in the vHipp and their associated perineuronal nets (PNNs). Ventral tegmental area (VTA) DA neuron population activity and vHipp activity was increased 1-2 and 5-6 weeks post-adolescent stress, along with a decrease in the number of PV+, PNN+, PV + /PNN + cells in the vHipp, which are consistent with the MAM model of schizophrenia. In contrast, adult stress decreased VTA DA neuron population activity only at 1-2 weeks post stress, which is consistent with what has been observed in animal models of depression, without impacting vHipp activity and PV/PNN expression. Administration of valproate (VPA), which can re-instate the critical period of plasticity via histone deacetylase (HDAC) inhibition, caused adult stress to produce changes similar to those induced by adolescent stress, presumably by increasing stress vulnerability to early adolescent levels. Our findings indicate that timing of stress is a critical determinant of the pathology produced in the adult: adolescent stress led to circuit deficits that recapitulates schizophrenia, whereas adult stress induced a depression-like hypodopaminergic state. Reopening the critical period in the adult restores vulnerability to stress-induced pathology resembling schizophrenia.
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http://dx.doi.org/10.1038/s41380-019-0514-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056584PMC
December 2020

A photoregulated split aptaswitch for small molecules with improved sensitivity.

Chem Commun (Camb) 2019 Aug;55(64):9555-9558

State Key Joint Laboratory of ESPC, Center for Sensor Technology of Environment and Health School of Environment, Tsinghua University, Beijing 100084, China.

Here we show the design of a photoregulated split aptaswitch (PSA) for the challenging small-molecule biorecognition and its sensing application. The PSA specifically binds with the target in a binary reaction, and can easily rule out false positive signals by azobenzene photoisomerization, exhibiting an approximately 50-fold improved sensitivity over a control assay.
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http://dx.doi.org/10.1039/c9cc04083hDOI Listing
August 2019

Expression profiles of circRNAs and the potential diagnostic value of serum circMARK3 in human acute Stanford type A aortic dissection.

PLoS One 2019 28;14(6):e0219013. Epub 2019 Jun 28.

Department of Cardiothoracic Surgery, Nanjing University Medical School Affiliated Drum Tower Hospital, Nanjing, China.

CircRNAs are involved in a variety of human diseases, however, the expression profiles and the potential diagnostic value of circRNAs in human acute Stanford type A aortic dissection (AAAD) remains largely unknown. In this study, high-throughput RNA sequencing (RNA-Seq) was used to investigate the differentially expressed circRNAs, microRNAs (miRs) and mRNAs in human AAAD tissues (n = 10) compared with normal aortic tissues (n = 10). The results of RNA-Seq revealed that 506 circRNAs were significantly dysregulated (P<0.05, false discovery rate, FDR<0.05, fold change>2). The subsequent weighted gene correlation network analysis and the following co-expression network analysis revealed that tyrosine-protein kinase Fgr might play important roles in the occurrence and development of AAAD. According to the circRNA-miRNA-mRNA network, we found that the upstream regulatory molecule of Fgr is circMARK3. Finally, a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of the serum circMARK3 as biomarkers for AAAD (cutoff value = 1.497, area under the curve = 0.9344, P < 0.0001, sensitivity = 90.0%, specificity = 86.7%). These results provided a preliminary landscape of circRNAs expression profiles and indicated that circMARK3 was a potential biomarker for AAAD diagnosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219013PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599129PMC
February 2020

Stress during critical periods of development and risk for schizophrenia.

Schizophr Res 2019 11 30;213:107-113. Epub 2019 Jan 30.

Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, PA, USA. Electronic address:

Schizophrenia is a neurodevelopmental disorder with genetic predisposition, and stress has long been linked to its etiology. While stress affects all stages of the illness, increasing evidence suggests that stress during critical periods of development may be particularly detrimental, increasing individual's vulnerability to psychosis. To thoroughly understand the potential causative role of stress, our group has been focusing on the prenatal methylazoxymethanol acetate (MAM) rodent model, and discovered that MAM offspring display abnormal stress reactivity and heightened anxiety prepubertally, prior to the manifestation of a hyperdopaminergic state. Furthermore, pharmacologically treating anxiety during prepuberty prevented the emergence of the dopamine dysfunction in adulthood. Interestingly, sufficiently strong stressors applied to normal rats selectively during early development can recapitulate multiple schizophrenia-related phenotypes of MAM rats, whereas the same stress paradigm during adulthood only produced short-term depression-related deficits. Altogether, the evidence is thus converging: developmental disruption (genetic or environmental) might render animals more susceptible to the deleterious effects of stress during critical time windows, during which unregulated stress can lead to the emergence of psychosis later in life. As an important region regulating the midbrain dopamine system, the ventral hippocampus is particularly vulnerable to stress, and the distinct maturational profile of its fast-spiking parvalbumin interneurons may largely underlie such vulnerability. In this review, by discussing emerging evidence spanning clinical and basic science studies, we propose developmental stress vulnerability as a novel link between early predispositions and environmental triggering events in the pathophysiology of schizophrenia. This promising line of research can potentially provide not only insights into the etiology, but also a "roadmap" for disease prevention.
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http://dx.doi.org/10.1016/j.schres.2019.01.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667322PMC
November 2019

Unprecedented high irreversibility line in the nontoxic cuprate superconductor (Cu,C)BaCaCuO.

Sci Adv 2018 09 28;4(9):eaau0192. Epub 2018 Sep 28.

Center for Superconducting Physics and Materials National Laboratory of Solid State Microstructures and Department of Physics, Nanjing University, Nanjing 210093, China.

One of the key factors that limit the high-power applications for a type II superconductor is the irreversibility line (), which reflects the very boundary of resistive dissipation in the phase diagram of magnetic field versus temperature. In cuprate family, the Y-, Bi-, Hg-, and Tl-based systems have superconducting transition temperatures exceeding the liquid nitrogen boiling temperature (~77 K). However, the toxic elements Hg and Tl in the latter two systems strongly constrain the applications. The best perspective so far is relying on the YBaCuO ( ≈ 90 K) system, which is nontoxic and has a relatively high irreversibility magnetic field. We report the study of a nontoxic superconductor (Cu,C)BaCaCuO with = 116 K. We found that the irreversibility magnetic field is extremely high, and it thus provides great potential for applications above the liquid nitrogen temperature.
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http://dx.doi.org/10.1126/sciadv.aau0192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162075PMC
September 2018

NAD+ cellular redox and SIRT1 regulate the diurnal rhythms of tyrosine hydroxylase and conditioned cocaine reward.

Mol Psychiatry 2019 11 4;24(11):1668-1684. Epub 2018 May 4.

Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh Medical School, Pittsburgh, PA, 15219, USA.

The diurnal regulation of dopamine is important for normal physiology and diseases such as addiction. Here we find a novel role for the CLOCK protein to antagonize CREB-mediated transcriptional activity at the tyrosine hydroxylase (TH) promoter, which is mediated by the interaction with the metabolic sensing protein, Sirtuin 1 (SIRT1). Additionally, we demonstrate that the transcriptional activity of TH is modulated by the cellular redox state, and daily rhythms of redox balance in the ventral tegmental area (VTA), along with TH transcription, are highly disrupted following chronic cocaine administration. Furthermore, CLOCK and SIRT1 are important for regulating cocaine reward and dopaminergic (DAergic) activity, with interesting differences depending on whether DAergic activity is in a heightened state and if there is a functional CLOCK protein. Taken together, we find that rhythms in cellular metabolism and circadian proteins work together to regulate dopamine synthesis and the reward value for drugs of abuse.
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http://dx.doi.org/10.1038/s41380-018-0061-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215755PMC
November 2019

Discrete energy levels of Caroli-de Gennes-Matricon states in quantum limit in FeTeSe.

Nat Commun 2018 03 6;9(1):970. Epub 2018 Mar 6.

Center for Superconducting Physics and Materials, National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center for Advanced Microstructures, Nanjing University, 210093, Nanjing, China.

Caroli-de Gennes-Matricon (CdGM) states were predicted in 1964 as low-energy excitations within vortex cores of type-II superconductors. In the quantum limit, the energy levels of these states were predicted to be discrete with the basic levels at ±μΔ/E (μ = 1/2, 3/2, 5/2, …) with Δ the superconducting energy gap and E the Fermi energy. However, due to the small ratio of Δ/E in most type-II superconductors, it is very difficult to observe the discrete CdGM states, but rather a symmetric peak which appears at zero bias at the vortex center. Here we report the clear observation of these discrete energy levels of CdGM states in FeTeSe. The rather stable energies of these bound state peaks vs. space clearly validate our conclusion. Analysis based on the energies of these CdGM states indicates that the Fermi energy in the present system is very small.
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http://dx.doi.org/10.1038/s41467-018-03404-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840178PMC
March 2018

Screening Criteria for Qualified Antibiotic Targets in Unmodified Gold Nanoparticles-Based Aptasensing.

ACS Appl Mater Interfaces 2017 Oct 2;9(40):35492-35497. Epub 2017 Oct 2.

State Key Joint Laboratory of ESPC, Center for Sensor Technology of Environment and Health, School of Environment, Tsinghua University , Beijing 100084, China.

In designing unmodified gold nanoparticles-based aptasensing (uGA) assays for antibiotics, we find that some antibiotics can adsorb directly on gold nanoparticles (GNP) regardless of the presence of aptamers, which have been long overlooked in the past. Some adsorptions, however, would strongly disturb the charge distribution on the GNP surface, break up the static colloidal profile, and thus generate false positive colorimetric signals. To identify antibiotics qualified for uGA assays, we established two rational screening criteria for antibiotic targets relying on their oil-water partition coefficients (log P values) and net physiological charges: log P > 0 and charge ≤0. A good agreement of the GNP color change was obtained between the two criteria-based predictions and the actual tests using six representative antibiotics. The proposed criteria help to shed light on GNP-target interactions, which is significant for developing novel GNP-based colorimetric assays with high reliability.
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http://dx.doi.org/10.1021/acsami.7b12796DOI Listing
October 2017

The methylazoxymethanol acetate rat model: molecular and epigenetic effect in the developing prefrontal cortex: An Editorial Highlight for 'Epigenetic mechanisms underlying NMDA receptor hypofunction in the prefrontal cortex of juvenile animals in the MAM model for schizophrenia' on page 320.

J Neurochem 2017 11 5;143(3):264-267. Epub 2017 Sep 5.

Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA.

This Editorial highlights an article by Gulchina and colleagues in the current issue of the Journal of Neurochemistry, in which the authors describe molecular and epigenetic changes in the developing prefrontal cortex of the rats exposed to methylazoxymethanol acetate (MAM). They found an NMDAR hypofunction present in the prefrontal cortex of juvenile MAM rats which was associated with abnormal epigenetic regulation of the Grin2b gene. These changes may be related to early cognitive impairments observed in MAM rats and schizophrenia patients.
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http://dx.doi.org/10.1111/jnc.14133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679231PMC
November 2017

Isoelectric Bovine Serum Albumin: Robust Blocking Agent for Enhanced Performance in Optical-Fiber Based DNA Sensing.

ACS Sens 2017 Feb 6;2(2):257-262. Epub 2017 Feb 6.

State Key Joint Laboratory of ESPC; Research Centre of Environmental and Health Sensing Technology, School of Environment, Tsinghua University , Beijing 100084, China.

Surface blocking is a well-known process for reducing unwanted nonspecific adsorption in sensor fabrication, especially important in the emerging field where DNA/RNA applied. Bovine serum albumin (BSA) is one of the most popular blocking agents with an isoelectric point at pH 4.6. Although it is widely recognized that the adsorption of a blocking agent is strongly affected by its net charge and the maximum adsorption is often observed under its isoelectric form, BSA has long been perfunctorily used for blocking merely in neutral solution, showing poor blocking performances in the optical-fiber evanescent wave (OFEW) based sensing toward DNA target. To meet this challenge, we first put forward the view that isoelectric BSA (iep-BSA) has the best blocking performance and use an OFEW sensor platform to demonstrate this concept. An optical-fiber was covalently modified with amino-DNA, and further coupled with the optical system to detect fluorophore labeled complementary DNA within the evanescent field. A dramatic improvement in the reusability of this DNA modified sensing surface was achieved with 120 stable detection cycles, which ensured accurate quantitative bioassay. As expected, the iep-BSA blocked OFEW system showed enhanced sensing performance toward target DNA with a detection limit of 125 pM. To the best of our knowledge, this is the highest number of regeneration cycles ever reported for a DNA immobilized optical-fiber surface. This study can also serve as a good reference and provide important implications for developing similar DNA-directed surface biosensors.
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http://dx.doi.org/10.1021/acssensors.6b00746DOI Listing
February 2017