Wang Xi - Academia.edu (original) (raw)

Papers by Wang Xi

Research paper thumbnail of Low-Temperature Gas Plasma Combined with Antibiotics for the Reduction of Methicillin-Resistant Staphylococcus aureus Biofilm Both In Vitro and In Vivo

Life, 2021

Biofilm infections in wounds seriously delay the healing process, and methicillin-resistant Staph... more Biofilm infections in wounds seriously delay the healing process, and methicillin-resistant Staphylococcus aureus is a major cause of wound infections. In addition to inactivating micro-organisms, low-temperature gas plasma can restore the sensitivity of pathogenic microbes to antibiotics. However, the combined treatment has not been applied to infectious diseases. In this study, low-temperature gas plasma treatment promoted the effects of different antibiotics on the reduction of S. aureus biofilms in vitro. Low-temperature gas plasma combined with rifampicin also effectively reduced the S. aureus cells in biofilms in the murine wound infection model. The blood and histochemical analysis demonstrated the biosafety of the combined treatment. Our findings demonstrated that low-temperature gas plasma combined with antibiotics is a promising therapeutic strategy for wound infections.

Research paper thumbnail of Mixed Lineage Leukemia 1 Promoted Neuron Apoptosis in Ischemic Penumbra via Regulating ASK-1/TNF-α Complex

Frontiers in Neuroanatomy, 2020

Neuron apoptosis in ischemic penumbra was proved to be involved in ischemic stroke (IS) developme... more Neuron apoptosis in ischemic penumbra was proved to be involved in ischemic stroke (IS) development and contributed to the poor prognosis of IS. Recent studies showed that aberrant trimethylation of histone H3 lysine 4 (H3K4me3) level was associated with cell apoptosis. This study aimed to explore the underlying mechanism of neuron apoptosis in ischemic penumbra via histone methyltransferase (HMT) mixed lineage leukemia 1 (MLL1) mediated epigenetic pathway. Mouse IS model was established by middle cerebral artery occlusion (MCAO). Mouse primary cortical mixed cells were cultured and treated with oxygen-glucose deprivation (OGD) to simulate IS process. The expressions of apoptosis signal regulating kinase-1 (ASK-1), pASK-1, cleaved caspase-3, ASK-1/serine-threonine kinase receptor-associated protein (STRAP)/14-3-3 complex, ASK-1/tumor necrosis factor-α (TNF-α) complex, and MLL1 in mouse brain tissue and mouse primary cortical mixed cells were analyzed. The function of MLL1 was investigated using small interfering RNA (siRNA) targeting MLL1 and vector overexpressing MLL1. In vivo inhibition of MLL1 was conducted to explore its value as a therapeutic target. The prognostic value of MLL1 was investigated in IS patients. Results showed that the expressions of ASK-1, pASK-1, cleaved caspase-3, ASK-1/TNF-α complex, and MLL1 increased significantly in ischemic penumbra compared to brain tissue from the control group (P < 0.05). MCAO and OGD significantly upregulated the H3K4me3 level in ASK-1 promoter region and promoted the recruitment of MLL1 to this region (P < 0.05). siMLL1 significantly reversed the proapoptosis effects of OGD in primary cortical mixed cells, while MLL1 overexpression induced apoptosis of cells (P < 0.05). In vivo inhibition of MLL1 significantly reduced the infarct volume and the neurological score of MCAO mice (P < 0.05). Serum MLL1 level had a positive association with that in ischemic core and penumbra in mouse model and was positively correlated with the infarct volume and neurological score (P < 0.05). Besides, serum MLL1 level was also significantly correlated with the severity of IS (P < 0.05), and high

Research paper thumbnail of C. China

Yearbook of International Environmental Law, 2020

Research paper thumbnail of B. China

Yearbook of International Environmental Law, 2016

Research paper thumbnail of Local epigenomic state cannot discriminate interacting and non-interacting enhancer–promoter pairs with high accuracy

PLOS Computational Biology, 2018

We report an experimental design issue in recent machine learning formulations of the enhancer-pr... more We report an experimental design issue in recent machine learning formulations of the enhancer-promoter interaction problem arising from the fact that many enhancer-promoter pairs share features. Cross-fold validation schemes which do not correctly separate these feature sharing enhancer-promoter pairs into one test set report high accuracy, which is actually arising from high training set accuracy and a failure to properly evaluate generalization performance. Cross-fold validation schemes which properly segregate pairs with shared features show markedly reduced ability to predict enhancer-promoter interactions from epigenomic state. Parameter scans with multiple models indicate that local epigenomic features of individual pairs of enhancers and promoters cannot distinguish those pairs that interact from those which do with high accuracy, suggesting that additional information is required to predict enhancer-promoter interactions.

Research paper thumbnail of Phosphodiesterase expression in the normal and failing heart

Archives of Biochemistry and Biophysics, 2018

The number of patients with heart failure with reduced ejection fraction (HFrEF) and preserved ej... more The number of patients with heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) is increasing, and for HFpEF, no therapies have clinical benefit. It has been hypothesized that PKG attenuates pathological remodelling, and increasing cGMP would be beneficial for patients with HF. However, neither the RELAX nor NEAT-HFpEF trial showed benefit. But there is still enthusiasm for increasing cGMP in patients with HF, which highlight the need to determine the expression of PDEs in cardiac muscle. This study used immunoblotting to examine the expression of the PDEs that have been suggested to be targets for therapy of HF in both canines (normal and HFpEF) and humans (normal and HFrEF). Our results demonstrate PDE1C and PDE3A are expressed in cardiac muscle, but we could not detect the expression of PDE2A, PDE5A, PDE7A and PDE9A in cardiac tissue lysates from either normal or failing hearts. Thus, one should not expect a clinical benefit for a therapy targeting these PDEs in heart failure, which highlights the importance of rigorous demonstration of the target of therapy prior to undertaking a clinical trial. 2. Material and methods 2.1. Human samples Human studies were approved by the ethical review boards of the

Research paper thumbnail of Material approaches to active tissue mechanics

Nature Reviews Materials, 2018

Epithelial tissue is one of the four basic types of animal tissue and contains more than 60% of t... more Epithelial tissue is one of the four basic types of animal tissue and contains more than 60% of the cells in a vertebrate's body 1. Together with connective, muscle and nervous tissue, epithelial tissue forms the human body and plays crucial roles in many biological processes, including wound healing 2 , embryonic development 3 , morphogenesis 4 , homeostasis 4 and cancer metastasis 5. Epithelia have dynamic physical properties and can behave like a fluid 6,7 or like a solid 6. They exhibit various complicated behaviours, such as collective migration 8 , oscillation 9,10 , turbulent motion 11 , active cell rearrangement 12 , cell division and extrusion 13,14 , guided by biochemical and biophysical cues in the microenvironment, which can be sensed by epithelial cells. Apart from genes and biochemical signalling cascades, the mechanical properties of both the tissue and its microenvironment substantially impact epithelial behaviours 8. Epithelial cells sense the mechanical environment by exerting forces to the substrate mainly through actomyosin-dependent contraction, provided by the active walking of myosin motor proteins along actin filaments. These forces can also propagate through the tissue through cell-cell junctions, in particular E-cadherin-mediated adherens junctions, which form dynamic cellular contacts 15. Cell-substrate and cell-cell junctions are under constant mechanical stress 16 , which causes remodelling of the junctions 17 and triggers cell signalling events within the tissue 8. Therefore, the rheological behaviour of biological materials, from cytoskeleton networks to large cell assemblies, is a complicated compromise between competing forces, cellular events and exogenous stimuli. For example, motor protein activity changes the viscoelasticity of the cytoskeleton, causing the network to be substantially stiffened in a stress-dependent manner 18 and allowing cells to respond to substrate stiffness changes through remodelling and rheological adaptation 19. At the tissue level, epithelia sense their mechanical environment through cell-substrate adhesion complexes, and they exhibit durotaxis in response to changes in rigidity; for example, during neural crest migration in Xenopus laevis in vivo 20 and on surfaces with stiffness gradients in vitro 21. To relieve high intercellular mechanical stress, cells can be delaminated from the tissue at sites of highest crowding to mitigate epithelial hyperplasia, for example, during homeostasis in the Drosophila germ band 14 , zebrafish fins 13 and colon epithelia 13. Epithelia and their microenvironment show reciprocal mechanical effects. During Drosophila oogenesis, disorganized extracellular matrix (ECM) can be remodelled into a global polarized, restrictive ECM, which aligns with the actin bundles in the follicular epithelium

Research paper thumbnail of Analysis of Passivation Techniques in InP HEMTs and Implementation of an Analytical Model of fT Based on the Small Signal Equivalent Circuit

Journal of Nanoscience and Nanotechnology, 2019

This paper analyses, the influence of Si 3 N 4-PECVD and Al 2 O 3-ALD surface passivation on the ... more This paper analyses, the influence of Si 3 N 4-PECVD and Al 2 O 3-ALD surface passivation on the DC and RF characteristics of InP HEMTs with different gate lengths 0.08 m, 0.1 m, 0.12 m, and 0.15 m. A significant improvement in maximum drain current I DS MAX , transconductance g m MAX and oscillation frequency f max MAX is obtained by scaling the thickness of the passivation layers An increase in g m MAX and f max MAX , f T MAX is observed by reducing parasitic capacitance w.r.t. the decrease in gate length. In addition, an analytical model of f T based on a small-signal equivalent circuit is developed, which consist of extrinsic parameters R s , R d , C gs_ext and C gd_ext and intrinsic parameters C gsi , C gdi , g mi and g oi. The carrier transport is improved by increasing g mi , thus the transit time t , the parasitic charging delay ext and the par are reduced by lowering the extrinsic capacitances. An excellent fitting between measured and simulated f T is achieved, which inturn leads a realistic way for further improvement in f T .

Research paper thumbnail of Short-term outcomes from drug-coated balloon for coronary de novo lesions in large vessels

Journal of cardiology, Jan 23, 2018

A drug-coated balloon (DCB) has been designed as a new device for the treatment of coronary arter... more A drug-coated balloon (DCB) has been designed as a new device for the treatment of coronary artery disease. The data regarding DCB-treated lesions in large coronary artery are limited. The purpose of our study was to explore the effectiveness and safety of DCB in large coronary artery. We prospectively analyzed all patients treated with DCB in de novo lesions consistent with inclusion criteria between May 2015 and April 2017. The observed outcomes included target lesion revascularization (TLR), myocardial infarction, cardiac death and non-cardiac death, and major adverse cardiac events (MACE). There were 92 patients including 94 coronary de novo lesions treated in all. The most often utilized DCB diameters were 3.0 mm (41.5%) and 3.5 mm (39.4%). Two acute closures occurred in hospital. Six bailout drug-eluting stents were used in the percutaneous coronary interventions (6.4%). Quantitative coronary angiography measurement at follow-up showed late lumen loss was -0.02 ± 0.49 mm. The ...

Research paper thumbnail of Biological Tissues as Active Nematic Liquid Crystals

Advanced materials (Deerfield Beach, Fla.), Jan 29, 2018

Live tissues can self-organize and be described as active materials composed of cells that genera... more Live tissues can self-organize and be described as active materials composed of cells that generate active stresses through continuous injection of energy. In vitro reconstituted molecular networks, as well as single-cell cytoskeletons show that their filamentous structures can portray nematic liquid crystalline properties and can promote nonequilibrium processes induced by active processes at the microscale. The appearance of collective patterns, the formation of topological singularities, and spontaneous phase transition within the cell cytoskeleton are emergent properties that drive cellular functions. More integrated systems such as tissues have cells that can be seen as coarse-grained active nematic particles and their interaction can dictate many important tissue processes such as epithelial cell extrusion and migration as observed in vitro and in vivo. Here, a brief introduction to the concept of active nematics is provided, and the main focus is on the use of this framework ...

Research paper thumbnail of Human Epicardial Adipose Tissue Activin A Expression Predicts Occurrence of Postoperative Atrial Fibrillation in Patients Receiving Cardiac Surgery

Heart, lung & circulation, Jan 7, 2018

Activin A secreted by epicardial adipose tissue (EAT) plays a major role in the progress of atria... more Activin A secreted by epicardial adipose tissue (EAT) plays a major role in the progress of atrial fibrosis. However, the potential of Activin A in predicting the occurrence of postoperative AF (POAF) has yet to be elucidated. We aimed to investigate the predicable value of Activin A expression in EAT on POAF. A total of 89 patients receiving cardiac surgery without atrial fibrillation (AF) history were enrolled in this study, including 49 patients with valvular heart disease (VHD) and 40 patients with non-valvular heart disease (NVHD). Activin A expression in EAT was determined by quantitative polymerase chain reaction (qPCR), while the thickness of EAT (EATT) was estimated by echocardiography. New onset POAF before discharge was documented. Eventually 32 patients (36.0%) developed POAF, including 20 patients with VHD (40.8%) and 12 patients with NVHD (30.0%). Activin A expression was higher in POAF than sinus rhythm (SR) patients, whether for VHD or NVHD group (All p<0.001). In...

Research paper thumbnail of Optogenetic Stimulation of GABAergic Neurons in the Globus Pallidus Produces Hyperkinesia

Frontiers in behavioral neuroscience, 2018

The globus pallidus (GP) is emerging as a critical locus of basal ganglia control of motor activi... more The globus pallidus (GP) is emerging as a critical locus of basal ganglia control of motor activity, but the exact role of GABAergic GP neurons remain to be defined. By targeted expression of channelrhodopsin 2 (ChR2) in GABAergic neurons using the VGAT-ChR2-EYFP transgenic mice, we showed that optogenetic stimulation of GABAergic neurons in the right GP produced hyperkinesia. Optogenetic stimulation of GABAergic GP neurons increased c-Fos-positive cells in GP, M1 cortex, and caudate-putamen (CPu), and decreased c-Fos-positive cells in entopeduncular nucleus (EPN), compared to the contralateral hemisphere. In agreement with the canonical basal ganglia model. Furthermore, we delivered AAV-CaMKIIα-ChR2-mCherry virus to the excitatory neurons of the subthalamic nucleus (STN) and selectively stimulated glutamatergic afferent fibers from the STN onto the GP. This optogenetic stimulation produced abnormal movements, similar to the behaviors that observed in the VGAT-ChR2-EYFP transgenic m...

Research paper thumbnail of Aggregation-Induced Emission Luminogen with Near-Infrared-II Excitation and Near-Infrared-I Emission for Ultradeep Intravital Two-Photon Microscopy

ACS nano, 2018

Currently, a serious problem obstructing the large-scale clinical applications of fluorescence te... more Currently, a serious problem obstructing the large-scale clinical applications of fluorescence technique is the shallow penetration depth. Two-photon fluorescence microscopic imaging with excitation in the longer-wavelength near-infrared (NIR) region (>1100 nm) and emission in the NIR-I region (650-950 nm) is a good choice to realize deep-tissue and high-resolution imaging. Here, we report ultradeep two-photon fluorescence bioimaging with 1300 nm NIR-II excitation and NIR-I emission (peak ∼810 nm) based on a NIR aggregation-induced emission luminogen (AIEgen). The crab-shaped AIEgen possesses a planar core structure and several twisting phenyl/naphthyl rotators, affording both high fluorescence quantum yield and efficient two-photon activity. The organic AIE dots show high stability, good biocompatibility, and a large two-photon absorption cross section of 1.22 × 10 GM. Under 1300 nm NIR-II excitation, in vivo two-photon fluorescence microscopic imaging helps to reconstruct the 3...

Research paper thumbnail of YKL-40 is highly expressed in the epicardial adipose tissue of patients with atrial fibrillation and associated with atrial fibrosis

Journal of translational medicine, Jan 15, 2018

YKL-40 (CHI3L1) is a novel biomarker for inflammation, tissue remodeling, and fibrosis, as well a... more YKL-40 (CHI3L1) is a novel biomarker for inflammation, tissue remodeling, and fibrosis, as well as cardiovascular diseases. We investigated the association between YKL-40 expression in epicardial adipose tissue (EAT) and atrial fibrosis in patients with atrial fibrillation (AF). Blood samples, subcutaneous adipose tissue (SAT), paracardial adipose tissue (PAT), EAT, and adjacent atrial myocardium were acquired from patients receiving coronary artery bypass grafts. The patients were divided into the AF group (n = 28) and the sinus rhythm (SR) group (n = 36). We did not detect a significant difference in the serum YKL-40 levels in the SR and AF groups (P = 0.145). Quantitative real-time PCR showed that YKL-40 (CHI3L1) mRNA levels in the EAT were significantly higher than in the SAT or PAT of AF patients, or the EAT of SR patients (All P < 0.001). We found similar results for YKL-40 protein levels by immunohistochemistry. Masson staining showed significantly more fibrosis in AF pati...

Research paper thumbnail of Mechanical Valve Replacement for Congenital Heart Disease Complicated by Native Pulmonary Valve Endocarditis: A Case Report and Literature Review

The heart surgery forum, Mar 7, 2018

Congenital heart disease (CHD) is one of the most common risk factors for infective endocarditis.... more Congenital heart disease (CHD) is one of the most common risk factors for infective endocarditis. However, it is rare to find a CHD patient complicated by isolated pulmonary valve endocarditis. Here, we report an adult patient with congenital heart disease complicated by native pulmonary valve endocarditis who underwent a mechanical valve replacement. We also review previous literature to examine key points in the treatment of such patients.

Research paper thumbnail of Incorporation of CD40 ligand enhances the immunogenicity of tumor‑associated calcium signal transducer 2 virus‑like particles against lung cancer

International journal of molecular medicine, Jan 15, 2018

The cell surface glycoprotein Trop‑2 is overexpressed in various types of cancer, including in lu... more The cell surface glycoprotein Trop‑2 is overexpressed in various types of cancer, including in lung cancer, and has recently been used as an effective immunotherapeutic target. CD40 ligand (CD40L), a tumor necrosis factor superfamily member, is a promising immune adjuvant. Human immunodeficiency virus (HIV) gag‑based virus‑like particles (VLPs) are highly immunogenic, and foreign antigens can be incorporated onto their membrane envelope for cancer vaccine development. In the present study, a HIV gag‑based VLP strategy and Bac‑to‑Bac system were utilized to construct Trop‑2, CD40L and gag recombinant baculoviruses, which were then used to infect TN5 cells in order to form Trop‑2 VLPs or Trop‑2‑CD40L VLPs. These VLPs were characterized using transmission electron microscopy and western blot analysis methods. VLPs incorporating murine Trop‑2 only or incorporating Trop‑2 and CD40L were used to immunize C57BL/6 mice. Immunized mice demonstrated high humoral and cellular immunity response...

Research paper thumbnail of Human Epicardial Adipose Tissue cTGF Expression is an Independent Risk Factor for Atrial Fibrillation and Highly Associated with Atrial Fibrosis

Scientific reports, Jan 26, 2018

Epicardial adipose tissue (EAT) is associated with the incidence, perpetuation, and recurrence of... more Epicardial adipose tissue (EAT) is associated with the incidence, perpetuation, and recurrence of atrial fibrillation (AF), with elusive underlying mechanisms. We analyzed adipokine expression in samples from 20 patients with sinus rhythm (SR) and 16 with AF. Quantitative real-time PCR showed that connective tissue growth factor (cTGF) expression was significantly higher in EAT than in subcutaneous adipose tissue (SAT) or paracardial adipose tissue (PAT) from patients with AF, and in EAT from patients with SR (P < 0.001). Galectin-3 expression was significantly higher in EAT than in SAT or PAT (P < 0.001), with no significant differences between patients with AF and SR (P > 0.05). Leptin and vaspin expression were lower in EAT than in PAT (P < 0.001). Trichrome staining showed that the fibrosis was much more severe in patients with AF than SR (P < 0.001). We found a linear relationship between cTGF mRNA expression level and collagen volume fraction (y = 1.471x + 27.33...

Research paper thumbnail of Emergent patterns of collective cell migration under tubular confinement

Nature communications, Nov 15, 2017

Collective epithelial behaviors are essential for the development of lumens in organs. However, c... more Collective epithelial behaviors are essential for the development of lumens in organs. However, conventional assays of planar systems fail to replicate cell cohorts of tubular structures that advance in concerted ways on out-of-plane curved and confined surfaces, such as ductal elongation in vivo. Here, we mimic such coordinated tissue migration by forming lumens of epithelial cell sheets inside microtubes of 1-10 cell lengths in diameter. We show that these cell tubes reproduce the physiological apical-basal polarity, and have actin alignment, cell orientation, tissue organization, and migration modes that depend on the extent of tubular confinement and/or curvature. In contrast to flat constraint, the cell sheets in a highly constricted smaller microtube demonstrate slow motion with periodic relaxation, but fast overall movement in large microtubes. Altogether, our findings provide insights into the emerging migratory modes for epithelial migration and growth under tubular confine...

Research paper thumbnail of Real-Time and High-Resolution Bioimaging with Bright Aggregation-Induced Emission Dots in Short-Wave Infrared Region

Advanced materials (Deerfield Beach, Fla.), Jan 17, 2018

Fluorescence imaging in the spectral region beyond the conventional near-infrared biological wind... more Fluorescence imaging in the spectral region beyond the conventional near-infrared biological window (700-900 nm) can theoretically afford high resolution and deep tissue penetration. Although some efforts have been devoted to developing a short-wave infrared (SWIR; 900-1700 nm) imaging modality in the past decade, long-wavelength biomedical imaging is still suboptimal owing to the unsatisfactory materials properties of SWIR fluorophores. Taking advantage of organic dots based on an aggregation-induced emission luminogen (AIEgen), herein microscopic vasculature imaging of brain and tumor is reported in living mice in the SWIR spectral region. The long-wavelength emission of AIE dots with certain brightness facilitates resolving brain capillaries with high spatial resolution (≈3 µm) and deep penetration (800 µm). Owning to the deep penetration depth and real-time imaging capability, in vivo SWIR microscopic angiography exhibits superior resolution in monitoring blood-brain barrier dam...

Research paper thumbnail of Short-term outcomes of minimally invasive mitral valve repair: a propensity-matched comparison

Interactive cardiovascular and thoracic surgery, Jan 3, 2018

We aimed to investigate the effect of minimally invasive mitral valve repair on early pulmonary f... more We aimed to investigate the effect of minimally invasive mitral valve repair on early pulmonary function and haemodynamics, as well as its short-term efficacy. From March 2012 to July 2015, 78 cases of minimally invasive mitral valve repair and 89 cases of conventional mitral valve repair were included in this study, with 67 well-matched pairs of patients identified by a propensity score matching, who were divided into the conventional sternotomy group and the right minithoracotomy group (the RT group). The in-hospital mortality was similar between the 2 groups (3.0% vs 1.5%, P = 1.000). Both cross-clamp time and bypass time were higher in the RT group (P < 0.001), whereas drainage amount, blood transfusion and length of intensive care unit stay were higher in the conventional sternotomy group (P < 0.001). There was not much discrepancy in pulmonary function between the 2 groups, except that partial pressure of O2 in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) in ...

Research paper thumbnail of Low-Temperature Gas Plasma Combined with Antibiotics for the Reduction of Methicillin-Resistant Staphylococcus aureus Biofilm Both In Vitro and In Vivo

Life, 2021

Biofilm infections in wounds seriously delay the healing process, and methicillin-resistant Staph... more Biofilm infections in wounds seriously delay the healing process, and methicillin-resistant Staphylococcus aureus is a major cause of wound infections. In addition to inactivating micro-organisms, low-temperature gas plasma can restore the sensitivity of pathogenic microbes to antibiotics. However, the combined treatment has not been applied to infectious diseases. In this study, low-temperature gas plasma treatment promoted the effects of different antibiotics on the reduction of S. aureus biofilms in vitro. Low-temperature gas plasma combined with rifampicin also effectively reduced the S. aureus cells in biofilms in the murine wound infection model. The blood and histochemical analysis demonstrated the biosafety of the combined treatment. Our findings demonstrated that low-temperature gas plasma combined with antibiotics is a promising therapeutic strategy for wound infections.

Research paper thumbnail of Mixed Lineage Leukemia 1 Promoted Neuron Apoptosis in Ischemic Penumbra via Regulating ASK-1/TNF-α Complex

Frontiers in Neuroanatomy, 2020

Neuron apoptosis in ischemic penumbra was proved to be involved in ischemic stroke (IS) developme... more Neuron apoptosis in ischemic penumbra was proved to be involved in ischemic stroke (IS) development and contributed to the poor prognosis of IS. Recent studies showed that aberrant trimethylation of histone H3 lysine 4 (H3K4me3) level was associated with cell apoptosis. This study aimed to explore the underlying mechanism of neuron apoptosis in ischemic penumbra via histone methyltransferase (HMT) mixed lineage leukemia 1 (MLL1) mediated epigenetic pathway. Mouse IS model was established by middle cerebral artery occlusion (MCAO). Mouse primary cortical mixed cells were cultured and treated with oxygen-glucose deprivation (OGD) to simulate IS process. The expressions of apoptosis signal regulating kinase-1 (ASK-1), pASK-1, cleaved caspase-3, ASK-1/serine-threonine kinase receptor-associated protein (STRAP)/14-3-3 complex, ASK-1/tumor necrosis factor-α (TNF-α) complex, and MLL1 in mouse brain tissue and mouse primary cortical mixed cells were analyzed. The function of MLL1 was investigated using small interfering RNA (siRNA) targeting MLL1 and vector overexpressing MLL1. In vivo inhibition of MLL1 was conducted to explore its value as a therapeutic target. The prognostic value of MLL1 was investigated in IS patients. Results showed that the expressions of ASK-1, pASK-1, cleaved caspase-3, ASK-1/TNF-α complex, and MLL1 increased significantly in ischemic penumbra compared to brain tissue from the control group (P < 0.05). MCAO and OGD significantly upregulated the H3K4me3 level in ASK-1 promoter region and promoted the recruitment of MLL1 to this region (P < 0.05). siMLL1 significantly reversed the proapoptosis effects of OGD in primary cortical mixed cells, while MLL1 overexpression induced apoptosis of cells (P < 0.05). In vivo inhibition of MLL1 significantly reduced the infarct volume and the neurological score of MCAO mice (P < 0.05). Serum MLL1 level had a positive association with that in ischemic core and penumbra in mouse model and was positively correlated with the infarct volume and neurological score (P < 0.05). Besides, serum MLL1 level was also significantly correlated with the severity of IS (P < 0.05), and high

Research paper thumbnail of C. China

Yearbook of International Environmental Law, 2020

Research paper thumbnail of B. China

Yearbook of International Environmental Law, 2016

Research paper thumbnail of Local epigenomic state cannot discriminate interacting and non-interacting enhancer–promoter pairs with high accuracy

PLOS Computational Biology, 2018

We report an experimental design issue in recent machine learning formulations of the enhancer-pr... more We report an experimental design issue in recent machine learning formulations of the enhancer-promoter interaction problem arising from the fact that many enhancer-promoter pairs share features. Cross-fold validation schemes which do not correctly separate these feature sharing enhancer-promoter pairs into one test set report high accuracy, which is actually arising from high training set accuracy and a failure to properly evaluate generalization performance. Cross-fold validation schemes which properly segregate pairs with shared features show markedly reduced ability to predict enhancer-promoter interactions from epigenomic state. Parameter scans with multiple models indicate that local epigenomic features of individual pairs of enhancers and promoters cannot distinguish those pairs that interact from those which do with high accuracy, suggesting that additional information is required to predict enhancer-promoter interactions.

Research paper thumbnail of Phosphodiesterase expression in the normal and failing heart

Archives of Biochemistry and Biophysics, 2018

The number of patients with heart failure with reduced ejection fraction (HFrEF) and preserved ej... more The number of patients with heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) is increasing, and for HFpEF, no therapies have clinical benefit. It has been hypothesized that PKG attenuates pathological remodelling, and increasing cGMP would be beneficial for patients with HF. However, neither the RELAX nor NEAT-HFpEF trial showed benefit. But there is still enthusiasm for increasing cGMP in patients with HF, which highlight the need to determine the expression of PDEs in cardiac muscle. This study used immunoblotting to examine the expression of the PDEs that have been suggested to be targets for therapy of HF in both canines (normal and HFpEF) and humans (normal and HFrEF). Our results demonstrate PDE1C and PDE3A are expressed in cardiac muscle, but we could not detect the expression of PDE2A, PDE5A, PDE7A and PDE9A in cardiac tissue lysates from either normal or failing hearts. Thus, one should not expect a clinical benefit for a therapy targeting these PDEs in heart failure, which highlights the importance of rigorous demonstration of the target of therapy prior to undertaking a clinical trial. 2. Material and methods 2.1. Human samples Human studies were approved by the ethical review boards of the

Research paper thumbnail of Material approaches to active tissue mechanics

Nature Reviews Materials, 2018

Epithelial tissue is one of the four basic types of animal tissue and contains more than 60% of t... more Epithelial tissue is one of the four basic types of animal tissue and contains more than 60% of the cells in a vertebrate's body 1. Together with connective, muscle and nervous tissue, epithelial tissue forms the human body and plays crucial roles in many biological processes, including wound healing 2 , embryonic development 3 , morphogenesis 4 , homeostasis 4 and cancer metastasis 5. Epithelia have dynamic physical properties and can behave like a fluid 6,7 or like a solid 6. They exhibit various complicated behaviours, such as collective migration 8 , oscillation 9,10 , turbulent motion 11 , active cell rearrangement 12 , cell division and extrusion 13,14 , guided by biochemical and biophysical cues in the microenvironment, which can be sensed by epithelial cells. Apart from genes and biochemical signalling cascades, the mechanical properties of both the tissue and its microenvironment substantially impact epithelial behaviours 8. Epithelial cells sense the mechanical environment by exerting forces to the substrate mainly through actomyosin-dependent contraction, provided by the active walking of myosin motor proteins along actin filaments. These forces can also propagate through the tissue through cell-cell junctions, in particular E-cadherin-mediated adherens junctions, which form dynamic cellular contacts 15. Cell-substrate and cell-cell junctions are under constant mechanical stress 16 , which causes remodelling of the junctions 17 and triggers cell signalling events within the tissue 8. Therefore, the rheological behaviour of biological materials, from cytoskeleton networks to large cell assemblies, is a complicated compromise between competing forces, cellular events and exogenous stimuli. For example, motor protein activity changes the viscoelasticity of the cytoskeleton, causing the network to be substantially stiffened in a stress-dependent manner 18 and allowing cells to respond to substrate stiffness changes through remodelling and rheological adaptation 19. At the tissue level, epithelia sense their mechanical environment through cell-substrate adhesion complexes, and they exhibit durotaxis in response to changes in rigidity; for example, during neural crest migration in Xenopus laevis in vivo 20 and on surfaces with stiffness gradients in vitro 21. To relieve high intercellular mechanical stress, cells can be delaminated from the tissue at sites of highest crowding to mitigate epithelial hyperplasia, for example, during homeostasis in the Drosophila germ band 14 , zebrafish fins 13 and colon epithelia 13. Epithelia and their microenvironment show reciprocal mechanical effects. During Drosophila oogenesis, disorganized extracellular matrix (ECM) can be remodelled into a global polarized, restrictive ECM, which aligns with the actin bundles in the follicular epithelium

Research paper thumbnail of Analysis of Passivation Techniques in InP HEMTs and Implementation of an Analytical Model of fT Based on the Small Signal Equivalent Circuit

Journal of Nanoscience and Nanotechnology, 2019

This paper analyses, the influence of Si 3 N 4-PECVD and Al 2 O 3-ALD surface passivation on the ... more This paper analyses, the influence of Si 3 N 4-PECVD and Al 2 O 3-ALD surface passivation on the DC and RF characteristics of InP HEMTs with different gate lengths 0.08 m, 0.1 m, 0.12 m, and 0.15 m. A significant improvement in maximum drain current I DS MAX , transconductance g m MAX and oscillation frequency f max MAX is obtained by scaling the thickness of the passivation layers An increase in g m MAX and f max MAX , f T MAX is observed by reducing parasitic capacitance w.r.t. the decrease in gate length. In addition, an analytical model of f T based on a small-signal equivalent circuit is developed, which consist of extrinsic parameters R s , R d , C gs_ext and C gd_ext and intrinsic parameters C gsi , C gdi , g mi and g oi. The carrier transport is improved by increasing g mi , thus the transit time t , the parasitic charging delay ext and the par are reduced by lowering the extrinsic capacitances. An excellent fitting between measured and simulated f T is achieved, which inturn leads a realistic way for further improvement in f T .

Research paper thumbnail of Short-term outcomes from drug-coated balloon for coronary de novo lesions in large vessels

Journal of cardiology, Jan 23, 2018

A drug-coated balloon (DCB) has been designed as a new device for the treatment of coronary arter... more A drug-coated balloon (DCB) has been designed as a new device for the treatment of coronary artery disease. The data regarding DCB-treated lesions in large coronary artery are limited. The purpose of our study was to explore the effectiveness and safety of DCB in large coronary artery. We prospectively analyzed all patients treated with DCB in de novo lesions consistent with inclusion criteria between May 2015 and April 2017. The observed outcomes included target lesion revascularization (TLR), myocardial infarction, cardiac death and non-cardiac death, and major adverse cardiac events (MACE). There were 92 patients including 94 coronary de novo lesions treated in all. The most often utilized DCB diameters were 3.0 mm (41.5%) and 3.5 mm (39.4%). Two acute closures occurred in hospital. Six bailout drug-eluting stents were used in the percutaneous coronary interventions (6.4%). Quantitative coronary angiography measurement at follow-up showed late lumen loss was -0.02 ± 0.49 mm. The ...

Research paper thumbnail of Biological Tissues as Active Nematic Liquid Crystals

Advanced materials (Deerfield Beach, Fla.), Jan 29, 2018

Live tissues can self-organize and be described as active materials composed of cells that genera... more Live tissues can self-organize and be described as active materials composed of cells that generate active stresses through continuous injection of energy. In vitro reconstituted molecular networks, as well as single-cell cytoskeletons show that their filamentous structures can portray nematic liquid crystalline properties and can promote nonequilibrium processes induced by active processes at the microscale. The appearance of collective patterns, the formation of topological singularities, and spontaneous phase transition within the cell cytoskeleton are emergent properties that drive cellular functions. More integrated systems such as tissues have cells that can be seen as coarse-grained active nematic particles and their interaction can dictate many important tissue processes such as epithelial cell extrusion and migration as observed in vitro and in vivo. Here, a brief introduction to the concept of active nematics is provided, and the main focus is on the use of this framework ...

Research paper thumbnail of Human Epicardial Adipose Tissue Activin A Expression Predicts Occurrence of Postoperative Atrial Fibrillation in Patients Receiving Cardiac Surgery

Heart, lung & circulation, Jan 7, 2018

Activin A secreted by epicardial adipose tissue (EAT) plays a major role in the progress of atria... more Activin A secreted by epicardial adipose tissue (EAT) plays a major role in the progress of atrial fibrosis. However, the potential of Activin A in predicting the occurrence of postoperative AF (POAF) has yet to be elucidated. We aimed to investigate the predicable value of Activin A expression in EAT on POAF. A total of 89 patients receiving cardiac surgery without atrial fibrillation (AF) history were enrolled in this study, including 49 patients with valvular heart disease (VHD) and 40 patients with non-valvular heart disease (NVHD). Activin A expression in EAT was determined by quantitative polymerase chain reaction (qPCR), while the thickness of EAT (EATT) was estimated by echocardiography. New onset POAF before discharge was documented. Eventually 32 patients (36.0%) developed POAF, including 20 patients with VHD (40.8%) and 12 patients with NVHD (30.0%). Activin A expression was higher in POAF than sinus rhythm (SR) patients, whether for VHD or NVHD group (All p<0.001). In...

Research paper thumbnail of Optogenetic Stimulation of GABAergic Neurons in the Globus Pallidus Produces Hyperkinesia

Frontiers in behavioral neuroscience, 2018

The globus pallidus (GP) is emerging as a critical locus of basal ganglia control of motor activi... more The globus pallidus (GP) is emerging as a critical locus of basal ganglia control of motor activity, but the exact role of GABAergic GP neurons remain to be defined. By targeted expression of channelrhodopsin 2 (ChR2) in GABAergic neurons using the VGAT-ChR2-EYFP transgenic mice, we showed that optogenetic stimulation of GABAergic neurons in the right GP produced hyperkinesia. Optogenetic stimulation of GABAergic GP neurons increased c-Fos-positive cells in GP, M1 cortex, and caudate-putamen (CPu), and decreased c-Fos-positive cells in entopeduncular nucleus (EPN), compared to the contralateral hemisphere. In agreement with the canonical basal ganglia model. Furthermore, we delivered AAV-CaMKIIα-ChR2-mCherry virus to the excitatory neurons of the subthalamic nucleus (STN) and selectively stimulated glutamatergic afferent fibers from the STN onto the GP. This optogenetic stimulation produced abnormal movements, similar to the behaviors that observed in the VGAT-ChR2-EYFP transgenic m...

Research paper thumbnail of Aggregation-Induced Emission Luminogen with Near-Infrared-II Excitation and Near-Infrared-I Emission for Ultradeep Intravital Two-Photon Microscopy

ACS nano, 2018

Currently, a serious problem obstructing the large-scale clinical applications of fluorescence te... more Currently, a serious problem obstructing the large-scale clinical applications of fluorescence technique is the shallow penetration depth. Two-photon fluorescence microscopic imaging with excitation in the longer-wavelength near-infrared (NIR) region (>1100 nm) and emission in the NIR-I region (650-950 nm) is a good choice to realize deep-tissue and high-resolution imaging. Here, we report ultradeep two-photon fluorescence bioimaging with 1300 nm NIR-II excitation and NIR-I emission (peak ∼810 nm) based on a NIR aggregation-induced emission luminogen (AIEgen). The crab-shaped AIEgen possesses a planar core structure and several twisting phenyl/naphthyl rotators, affording both high fluorescence quantum yield and efficient two-photon activity. The organic AIE dots show high stability, good biocompatibility, and a large two-photon absorption cross section of 1.22 × 10 GM. Under 1300 nm NIR-II excitation, in vivo two-photon fluorescence microscopic imaging helps to reconstruct the 3...

Research paper thumbnail of YKL-40 is highly expressed in the epicardial adipose tissue of patients with atrial fibrillation and associated with atrial fibrosis

Journal of translational medicine, Jan 15, 2018

YKL-40 (CHI3L1) is a novel biomarker for inflammation, tissue remodeling, and fibrosis, as well a... more YKL-40 (CHI3L1) is a novel biomarker for inflammation, tissue remodeling, and fibrosis, as well as cardiovascular diseases. We investigated the association between YKL-40 expression in epicardial adipose tissue (EAT) and atrial fibrosis in patients with atrial fibrillation (AF). Blood samples, subcutaneous adipose tissue (SAT), paracardial adipose tissue (PAT), EAT, and adjacent atrial myocardium were acquired from patients receiving coronary artery bypass grafts. The patients were divided into the AF group (n = 28) and the sinus rhythm (SR) group (n = 36). We did not detect a significant difference in the serum YKL-40 levels in the SR and AF groups (P = 0.145). Quantitative real-time PCR showed that YKL-40 (CHI3L1) mRNA levels in the EAT were significantly higher than in the SAT or PAT of AF patients, or the EAT of SR patients (All P < 0.001). We found similar results for YKL-40 protein levels by immunohistochemistry. Masson staining showed significantly more fibrosis in AF pati...

Research paper thumbnail of Mechanical Valve Replacement for Congenital Heart Disease Complicated by Native Pulmonary Valve Endocarditis: A Case Report and Literature Review

The heart surgery forum, Mar 7, 2018

Congenital heart disease (CHD) is one of the most common risk factors for infective endocarditis.... more Congenital heart disease (CHD) is one of the most common risk factors for infective endocarditis. However, it is rare to find a CHD patient complicated by isolated pulmonary valve endocarditis. Here, we report an adult patient with congenital heart disease complicated by native pulmonary valve endocarditis who underwent a mechanical valve replacement. We also review previous literature to examine key points in the treatment of such patients.

Research paper thumbnail of Incorporation of CD40 ligand enhances the immunogenicity of tumor‑associated calcium signal transducer 2 virus‑like particles against lung cancer

International journal of molecular medicine, Jan 15, 2018

The cell surface glycoprotein Trop‑2 is overexpressed in various types of cancer, including in lu... more The cell surface glycoprotein Trop‑2 is overexpressed in various types of cancer, including in lung cancer, and has recently been used as an effective immunotherapeutic target. CD40 ligand (CD40L), a tumor necrosis factor superfamily member, is a promising immune adjuvant. Human immunodeficiency virus (HIV) gag‑based virus‑like particles (VLPs) are highly immunogenic, and foreign antigens can be incorporated onto their membrane envelope for cancer vaccine development. In the present study, a HIV gag‑based VLP strategy and Bac‑to‑Bac system were utilized to construct Trop‑2, CD40L and gag recombinant baculoviruses, which were then used to infect TN5 cells in order to form Trop‑2 VLPs or Trop‑2‑CD40L VLPs. These VLPs were characterized using transmission electron microscopy and western blot analysis methods. VLPs incorporating murine Trop‑2 only or incorporating Trop‑2 and CD40L were used to immunize C57BL/6 mice. Immunized mice demonstrated high humoral and cellular immunity response...

Research paper thumbnail of Human Epicardial Adipose Tissue cTGF Expression is an Independent Risk Factor for Atrial Fibrillation and Highly Associated with Atrial Fibrosis

Scientific reports, Jan 26, 2018

Epicardial adipose tissue (EAT) is associated with the incidence, perpetuation, and recurrence of... more Epicardial adipose tissue (EAT) is associated with the incidence, perpetuation, and recurrence of atrial fibrillation (AF), with elusive underlying mechanisms. We analyzed adipokine expression in samples from 20 patients with sinus rhythm (SR) and 16 with AF. Quantitative real-time PCR showed that connective tissue growth factor (cTGF) expression was significantly higher in EAT than in subcutaneous adipose tissue (SAT) or paracardial adipose tissue (PAT) from patients with AF, and in EAT from patients with SR (P < 0.001). Galectin-3 expression was significantly higher in EAT than in SAT or PAT (P < 0.001), with no significant differences between patients with AF and SR (P > 0.05). Leptin and vaspin expression were lower in EAT than in PAT (P < 0.001). Trichrome staining showed that the fibrosis was much more severe in patients with AF than SR (P < 0.001). We found a linear relationship between cTGF mRNA expression level and collagen volume fraction (y = 1.471x + 27.33...

Research paper thumbnail of Emergent patterns of collective cell migration under tubular confinement

Nature communications, Nov 15, 2017

Collective epithelial behaviors are essential for the development of lumens in organs. However, c... more Collective epithelial behaviors are essential for the development of lumens in organs. However, conventional assays of planar systems fail to replicate cell cohorts of tubular structures that advance in concerted ways on out-of-plane curved and confined surfaces, such as ductal elongation in vivo. Here, we mimic such coordinated tissue migration by forming lumens of epithelial cell sheets inside microtubes of 1-10 cell lengths in diameter. We show that these cell tubes reproduce the physiological apical-basal polarity, and have actin alignment, cell orientation, tissue organization, and migration modes that depend on the extent of tubular confinement and/or curvature. In contrast to flat constraint, the cell sheets in a highly constricted smaller microtube demonstrate slow motion with periodic relaxation, but fast overall movement in large microtubes. Altogether, our findings provide insights into the emerging migratory modes for epithelial migration and growth under tubular confine...

Research paper thumbnail of Real-Time and High-Resolution Bioimaging with Bright Aggregation-Induced Emission Dots in Short-Wave Infrared Region

Advanced materials (Deerfield Beach, Fla.), Jan 17, 2018

Fluorescence imaging in the spectral region beyond the conventional near-infrared biological wind... more Fluorescence imaging in the spectral region beyond the conventional near-infrared biological window (700-900 nm) can theoretically afford high resolution and deep tissue penetration. Although some efforts have been devoted to developing a short-wave infrared (SWIR; 900-1700 nm) imaging modality in the past decade, long-wavelength biomedical imaging is still suboptimal owing to the unsatisfactory materials properties of SWIR fluorophores. Taking advantage of organic dots based on an aggregation-induced emission luminogen (AIEgen), herein microscopic vasculature imaging of brain and tumor is reported in living mice in the SWIR spectral region. The long-wavelength emission of AIE dots with certain brightness facilitates resolving brain capillaries with high spatial resolution (≈3 µm) and deep penetration (800 µm). Owning to the deep penetration depth and real-time imaging capability, in vivo SWIR microscopic angiography exhibits superior resolution in monitoring blood-brain barrier dam...

Research paper thumbnail of Short-term outcomes of minimally invasive mitral valve repair: a propensity-matched comparison

Interactive cardiovascular and thoracic surgery, Jan 3, 2018

We aimed to investigate the effect of minimally invasive mitral valve repair on early pulmonary f... more We aimed to investigate the effect of minimally invasive mitral valve repair on early pulmonary function and haemodynamics, as well as its short-term efficacy. From March 2012 to July 2015, 78 cases of minimally invasive mitral valve repair and 89 cases of conventional mitral valve repair were included in this study, with 67 well-matched pairs of patients identified by a propensity score matching, who were divided into the conventional sternotomy group and the right minithoracotomy group (the RT group). The in-hospital mortality was similar between the 2 groups (3.0% vs 1.5%, P = 1.000). Both cross-clamp time and bypass time were higher in the RT group (P < 0.001), whereas drainage amount, blood transfusion and length of intensive care unit stay were higher in the conventional sternotomy group (P < 0.001). There was not much discrepancy in pulmonary function between the 2 groups, except that partial pressure of O2 in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) in ...