Publications by authors named "Yijun Yang"

103 Publications

Cortical Bone Stem Cells Modify Cardiac Inflammation After Myocardial Infarction By Inducing a Novel Macrophage Phenotype.

Am J Physiol Heart Circ Physiol 2021 08 20. Epub 2021 Aug 20.

Department of Physiology, Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States.

Acute damage to the heart, as in the case of myocardial infarction (MI), triggers a robust inflammatory response to the sterile injury that is part of a complex and highly organized wound healing process. Cortical bone stem cell (CBSC) therapy after MI has been shown to reduce adverse structural and functional remodeling of the heart after MI in both mouse and swine models. The basis for these CBSC treatment effects on wound healing are unknown. The present experiments show that CBSCs secrete paracrine factors known to have immunomodulatory properties, most notably Macrophage Colony Stimulating Factor (M-CSF) and Transforming Growth Factor-b, but not IL-4. CBSC therapy increased the number of Galectin-3+ macrophages, CD4+ T-cells, and fibroblasts in the heart while decreasing apoptosis in an in vivo swine model of MI. Macrophages treated with CBSC medium in vitro polarized to a pro-reparative phenotype characterized by increased CD206 expression, increased efferocytic ability, increased IL-10, TGF-b, and IL-1RA secretion, and increased mitochondrial respiration. Next generation sequencing revealed a transcriptome significantly different from M2a or M2c macrophage phenotypes. Paracrine factors from CBSC-treated macrophages increased proliferation, decreased a-Smooth Muscle Actin expression, and decreased contraction by fibroblasts in vitro. These data support the idea that CBSCs are modulating the immune response to MI to favor cardiac repair through a unique macrophage polarization that ultimately reduces cell death and alters fibroblast populations that may result in smaller scar size and preserved cardiac geometry and function.
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http://dx.doi.org/10.1152/ajpheart.00304.2021DOI Listing
August 2021

Chinese expert recommendations on management of hepatocellular carcinoma during COVID-19 pandemic: a nationwide multicenter survey.

HPB (Oxford) 2021 Jul 26. Epub 2021 Jul 26.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic.

Methods: A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic.

Results: 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the "face-to-face" visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC.

Discussion: During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery.
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http://dx.doi.org/10.1016/j.hpb.2021.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312214PMC
July 2021

Response to Letter Regarding Article, "Cardiac Remodeling During Pregnancy With Metabolic Syndrome: Prologue of Pathological Remodeling".

Circulation 2021 Jul 26;144(4):e69. Epub 2021 Jul 26.

Independence Blue Cross Cardiovascular Research Center and Department of Physiology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.055583DOI Listing
July 2021

Tunable microstructures of ultralong organic phosphorescence materials.

Chem Commun (Camb) 2021 Jul 1;57(59):7276-7279. Epub 2021 Jul 1.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, China.

Three kinds of microstructures were prepared for one organic phosphor based on a solution-concentration-controlled self-assembly strategy. These microstructures show different phosphorescence efficiencies, which holds considerable promise for the miniaturized optical device applications of ultralong organic phosphorescence materials.
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http://dx.doi.org/10.1039/d1cc01563jDOI Listing
July 2021

Nestin Is Required for Spindle Assembly and Cell-Cycle Progression in Glioblastoma Cells.

Mol Cancer Res 2021 Jun 22. Epub 2021 Jun 22.

Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania.

Nestin, a class IV intermediate filament protein, is generally considered as a putative marker of neural stem and progenitor cells in the central nervous system. Glioma is a common type of adult brain tumors, and glioblastoma (GBM) represents the most aggressive form of glioma. Here, we report that Nestin expression is significantly upregulated in human GBM, compared with other types of glioma. Nestin knockdown or deletion in U251 cells and tumor cells from GBM patients derived xenografts resulted in G-M arrest, finally leading to apoptosis in tumor cells. Using proximity-dependent biotin identification method, we identified βII-tubulin as an interacting protein of Nestin in U251 cells. Nestin stabilized βII-tubulin in U251 cells through physical interaction. Knockdown of Nestin or βII-tubulin disrupted spindle morphology in tumor cells. Our studies further revealed that Nestin deficiency in U251 cells and GBM PDX cells repressed tumor growth upon transplantation. Finally, we found that Nestin deficiency sensitized GBM cells to microtubule-destabilizing drugs such as vinblastine and vincristine. Our studies demonstrate the essential functions and underlying mechanisms of Nestin in the growth and drug response of GBM cells. IMPLICATIONS: Through interaction with βII-tubulin, Nestin facilitates cell-cycle progression and spindle assembly of tumor cells in glioblastoma.
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http://dx.doi.org/10.1158/1541-7786.MCR-20-0994DOI Listing
June 2021

Purification of differentiated tumor cells from medulloblastoma for transplantation into mouse cerebellum.

STAR Protoc 2021 Jun 26;2(2):100409. Epub 2021 Mar 26.

Cancer biology program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA, USA.

This protocol provides the procedures for isolating differentiated tumor cells from medulloblastoma (MB) in mice. Procedures for transplantation into cerebella are also included to examine the tumorigenesis of differentiated MB cells. This protocol outlines the detailed steps required for (1) isolation of tumor cells from mouse MB, (2) purification of differentiated tumor cells by fluorescence-activated cell sorting, and (3) transplantation of tumor cells into cerebella. This protocol is useful to purify differentiated tumor cells for investigating mechanisms underlying MB progression. For complete details on the use and execution of this protocol, please refer to Cheng et. al. (2020).
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http://dx.doi.org/10.1016/j.xpro.2021.100409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039855PMC
June 2021

PTIP Inhibits Cell Invasion in Esophageal Squamous Cell Carcinoma Modulation of EphA2 Expression.

Front Oncol 2021 23;11:629916. Epub 2021 Mar 23.

Department of Neurosurgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy and treatment failure is largely due to metastasis and invasion. Aberrant tumor cell adhesion is often associated with tumor progression and metastasis. However, the exact details of cell adhesion in ESCC progression have yet to be determined. In our study, the clinical relevance of Pax2 transactivation domain-interacting protein (PTIP/PAXIP1) was analyzed by immunohistochemistry of ESCC tissues. We found that low expression of PTIP was associated with lymph node metastasis in ESCC, and loss-of-function approaches showed that depletion of PTIP promoted ESCC cell migration and invasion both and . Analysis integrating RNA-seq and ChIP-seq data revealed that PTIP directly regulated ephrin type-A receptor 2 (EphA2) expression in ESCC cells. Moreover, PTIP inhibited EphA2 expression by competing with Fosl2, which attenuated the invasion ability of ESCC cells. These results collectively suggest that PTIP regulates ESCC invasion through modulation of EphA2 expression and hence presents a potential therapeutic target for its treatment.
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http://dx.doi.org/10.3389/fonc.2021.629916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021923PMC
March 2021

Cardiac Remodeling During Pregnancy With Metabolic Syndrome: Prologue of Pathological Remodeling.

Circulation 2021 Feb 15;143(7):699-712. Epub 2021 Feb 15.

Independence Blue Cross Cardiovascular Research Center and Department of Physiology (Y.Y., G.S., J.J., H.K., D.M.E., S.R.H.).

Background: The heart undergoes physiological hypertrophy during pregnancy in healthy individuals. Metabolic syndrome (MetS) is now prevalent in women of child-bearing age and might add risks of adverse cardiovascular events during pregnancy. The present study asks if cardiac remodeling during pregnancy in obese individuals with MetS is abnormal and whether this predisposes them to a higher risk for cardiovascular disorders.

Methods: The idea that MetS induces pathological cardiac remodeling during pregnancy was studied in a long-term (15 weeks) Western diet-feeding animal model that recapitulated features of human MetS. Pregnant female mice with Western diet (45% kcal fat)-induced MetS were compared with pregnant and nonpregnant females fed a control diet (10% kcal fat).

Results: Pregnant mice fed a Western diet had increased heart mass and exhibited key features of pathological hypertrophy, including fibrosis and upregulation of fetal genes associated with pathological hypertrophy. Hearts from pregnant animals with WD-induced MetS had a distinct gene expression profile that could underlie their pathological remodeling. Concurrently, pregnant female mice with MetS showed more severe cardiac hypertrophy and exacerbated cardiac dysfunction when challenged with angiotensin II/phenylephrine infusion after delivery.

Conclusions: These results suggest that preexisting MetS could disrupt physiological hypertrophy during pregnancy to produce pathological cardiac remodeling that could predispose the heart to chronic disorders.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.051264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888689PMC
February 2021

Simultaneous acquisition of current and lateral force signals during AFM for characterising the piezoelectric and triboelectric effects of ZnO nanorods.

Sci Rep 2021 Feb 3;11(1):2904. Epub 2021 Feb 3.

Department of Manufacturing Systems and Design Engineering (MSDE), Seoul National University of Science and Technology (SeoulTech), Seoul, 01811, Republic of Korea.

Atomic force microscopy (AFM) is central to investigating the piezoelectric potentials of one-dimensional nanomaterials. The AFM probe is used to deflect individual piezoelectric nanorods and to measure the resultant current. However, the torsion data of AFM probes have not been exploited to elucidate the relationship between the applied mechanical force and resultant current. In this study, the effect of the size of ZnO nanorods on the efficiency of conversion of the applied mechanical force into current was investigated by simultaneously acquiring the conductive AFM and lateral force microscopy signals. The conversion efficiency was calculated based on linear regression analysis of the scatter plot of the data. This method is suitable for determining the conversion efficiencies of all types of freestanding piezoelectric nanomaterials grown under different conditions. A pixel-wise comparison of the current and lateral force images elucidated the mechanism of current generation from dense arrays of ZnO nanorods. The current signals generated from the ZnO nanorods by the AFM probe originated from the piezoelectric and triboelectric effects. The current signals contributed by the triboelectric effect were alleviated by using an AFM probe with a smaller spring constant and reducing the normal force.
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http://dx.doi.org/10.1038/s41598-021-82506-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859228PMC
February 2021

Activation of MC1R with BMS-470539 attenuates neuroinflammation via cAMP/PKA/Nurr1 pathway after neonatal hypoxic-ischemic brain injury in rats.

J Neuroinflammation 2021 Jan 19;18(1):26. Epub 2021 Jan 19.

Department of Physiology and Pharmacology, Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, 92354, USA.

Background: Microglia-mediated neuroinflammation plays a crucial role in the pathogenesis of hypoxic-ischemic (HI)-induced brain injury. Activation of melanocortin-1 receptor (MC1R) has been shown to exert anti-inflammatory and neuroprotective effects in several neurological diseases. In the present study, we have explored the role of MC1R activation on neuroinflammation and the potential underlying mechanisms after neonatal hypoxic-ischemic brain injury in rats.

Methods: A total of 169 post-natal day 10 unsexed rat pups were used. HI was induced by right common carotid artery ligation followed by 2.5 h of hypoxia. BMS-470539, a specific selective MC1R agonist, was administered intranasally at 1 h after HI induction. To elucidate the potential underlying mechanism, MC1R CRISPR KO plasmid or Nurr1 CRISPR KO plasmid was administered via intracerebroventricular injection at 48 h before HI induction. Percent brain infarct area, short- and long-term neurobehavioral tests, Nissl staining, immunofluorescence staining, and Western blot were conducted.

Results: The expression levels of MC1R and Nurr1 increased over time post-HI. MC1R and Nurr1 were expressed on microglia at 48 h post-HI. Activation of MC1R with BMS-470539 significantly reduced the percent infarct area, brain atrophy, and inflammation, and improved short- and long-term neurological deficits at 48 h and 28 days post-HI. MC1R activation increased the expression of CD206 (a microglial M2 marker) and reduced the expression of MPO. Moreover, activation of MC1R with BMS-470539 significantly increased the expression levels of MC1R, cAMP, p-PKA, and Nurr1, while downregulating the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-1β) at 48 h post-HI. However, knockout of MC1R or Nurr1 by specific CRISPR reversed the neuroprotective effects of MC1R activation post-HI.

Conclusions: Our study demonstrated that activation of MC1R with BMS-470539 attenuated neuroinflammation, and improved neurological deficits after neonatal hypoxic-ischemic brain injury in rats. Such anti-inflammatory and neuroprotective effects were mediated, at least in part, via the cAMP/PKA/Nurr1 signaling pathway. Therefore, MC1R activation might be a promising therapeutic target for infants with hypoxic-ischemic encephalopathy (HIE).
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http://dx.doi.org/10.1186/s12974-021-02078-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814630PMC
January 2021

Netherton syndrome caused by compound heterozygous mutation, c.80A>G mutation in SPINK5 and large-sized genomic deletion mutation, and successful treatment of intravenous immunoglobulin.

Mol Genet Genomic Med 2021 03 16;9(3):e1600. Epub 2021 Jan 16.

Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Netherton syndrome (NS) is an autosomal recessive disorder due to mutations in the SPINK5 gene. Here, we report the first case of NS caused by a large genomic deletion.

Methods: We present the clinical data of a 3-year-old Chinese boy who was initially misdiagnosed with severe atopic dermatitis. Subsequently, the patient presented with typical ichthyosis linearis circumflexa and had representative hair shaft of trichorrhexis invaginate, which alerted the physician of the high possibility of NS. A genomic DNA sample was extracted from peripheral blood and whole-exome sequencing (WES) was performed. Sanger sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to verify the mutation and genomic deletion, respectively, in the pedigree.

Results: WES revealed compound heterozygous mutations in SPINK5, including a c.80A>G mutation and a ~275 Kb-sized genomic deletion (chr5:147443576-147719312). The c.80A>G mutation was verified by Sanger sequencing in the pedigree. The father had the same heterozygous mutation; however, the mutation was absent in the proband's mother. The qRT-PCR results identified a large deletion (chr5:147444834-147445034) in SPINK5 in the proband and his mother. The eruptions improved remarkably after intravenous immunoglobulin (IVIG) therapy.

Conclusions: This is the first observation of NS caused by a large deletion. Our findings have important implications for mutation screening and genetic counseling in NS. Our report also verifies and supports the safety and efficacy of IVIG therapy in patients with NS.
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http://dx.doi.org/10.1002/mgg3.1600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104177PMC
March 2021

Postsurgery echocardiography can predict the amount of ischemia-reperfusion injury and the resultant scar size.

Am J Physiol Heart Circ Physiol 2021 02 24;320(2):H690-H698. Epub 2020 Dec 24.

Independence Blue Cross Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.

Despite advances in the diagnosis and treatment of ischemic heart disease (IHD), it remains the leading cause of death globally. Thus, there is a need to investigate the underlying pathophysiology and develop new therapies for the prevention and treatment of IHD. Murine models are widely used in IHD research because they are readily available, relatively inexpensive, and can be genetically modified to explore mechanistic questions. Ischemia-reperfusion (I/R)-induced myocardial infarction in mice is produced by the blockage followed by reperfusion of the left anterior descending branch (LAD) to imitate human IHD disease and its treatment. This I/R model can be widely used to investigate the potential reparative effect of putative treatments in the setting of reperfusion. However, the surgical technique is demanding and can produce an inconsistent amount of damage, which can make identification of treatment effects challenging. Therefore, determining which hearts have been significantly damaged by I/R is an important consideration in studies designed to either explore the mechanisms of disrupted function or test possible therapies. Noninvasive echocardiography (ECHO) is often used to determine structural and functional changes in the mouse heart following injury. In the present study, we determined that ECHO performed 3 days post I/R surgery could predict the permanent injury produced by the ischemic insult. We believe our work is noteworthy due to its creation of standards for early evaluation of the level of myocardial injury in mouse models of ischemia-reperfusion. This improvement to study design could reduce the sample sizes used in evaluating therapeutics and lead to increased confidence in conclusions drawn regarding the therapeutic efficacy of treatments tested in these translational mouse models.
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http://dx.doi.org/10.1152/ajpheart.00672.2020DOI Listing
February 2021

Exosomes from microRNA-126 overexpressing mesenchymal stem cells promote angiogenesis by targeting the PIK3R2-mediated PI3K/Akt signalling pathway.

J Cell Mol Med 2021 02 21;25(4):2148-2162. Epub 2020 Dec 21.

Department of Orthopaedic Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

microRNA-126 (miR-126), an endothelial-specific miRNA, is associated with vascular homeostasis and angiogenesis. However, the efficiency of miR-126-based treatment is partially compromised due to the low efficiency of miRNA delivery in vivo. Lately, exosomes have emerged as a natural tool for therapeutic molecule delivery. Herein, we investigated whether exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) can be utilized to deliver miR-126 to promote angiogenesis. Exosomes were isolated from BMMSCs overexpressed with miR-126 (Exo-miR-126) by ultracentrifugation. In vitro study, Exo-miR-126 treatment promoted the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs). Furthermore, the gene/protein expression of angiogenesis-related vascular endothelial growth factor (VEGF) and angiotensin-1 (Ang-1) were up-regulated after incubation with Exo-miR-126. Additionally, the expression level of phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) showed an inverse correlation with miR-126 in HUVECs. Particularly, the Exo-miR-126 treatment contributed to enhanced angiogenesis of HUVECs by targeting PIK3R2 to activate the PI3K/Akt signalling pathway. Similarly, Exo-miR-126 administration profoundly increased the number of newly formed capillaries in wound sites and accelerated the wound healing in vivo. The results demonstrate that exosomes derived from BMMSCs combined with miR-126 may be a promising strategy to promote angiogenesis.
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http://dx.doi.org/10.1111/jcmm.16192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882955PMC
February 2021

Medulloblastoma cells resemble neuronal progenitors in their differentiation.

Mol Cell Oncol 2020 Sep 5;7(6):1810514. Epub 2020 Sep 5.

Cancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA, USA.

Medulloblastoma (MB) often originate from cerebellar granule neuron precursors (GNPs). We recently found that medulloblastoma cells undergo differentiation as GNPs. Differentiated MB cells have permanently lost their proliferative capacity and tumorigenicity. The differentiation of MB cells is driven by the transcription factor NeuroD1 (Neurogenic differentiation 1), and NeuroD1 expression in MB cells is repressed by EZH2-mediated H3K27me3.
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http://dx.doi.org/10.1080/23723556.2020.1810514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671073PMC
September 2020

Interaction of the Joining Region in Junctophilin-2 With the L-Type Ca Channel Is Pivotal for Cardiac Dyad Assembly and Intracellular Ca Dynamics.

Circ Res 2021 01 23;128(1):92-114. Epub 2020 Oct 23.

Department of Physiology, Cardiovascular Research Center (P.G., J.J., C.M.R., D.M.E., Y.Y., M.W., E.A.F., H.K., R.M.B., V.R., A.S., X.C., S.R.H.), Lewis Katz Temple University School of Medicine, Philadelphia, PA.

Rationale: Ca-induced Ca release (CICR) in normal hearts requires close approximation of L-type calcium channels (LTCCs) within the transverse tubules (T-tubules) and RyR (ryanodine receptors) within the junctional sarcoplasmic reticulum. CICR is disrupted in cardiac hypertrophy and heart failure, which is associated with loss of T-tubules and disruption of cardiac dyads. In these conditions, LTCCs are redistributed from the T-tubules to disrupt CICR. The molecular mechanism responsible for LTCCs recruitment to and from the T-tubules is not well known. JPH (junctophilin) 2 enables close association between T-tubules and the junctional sarcoplasmic reticulum to ensure efficient CICR. JPH2 has a so-called joining region that is located near domains that interact with T-tubular plasma membrane, where LTCCs are housed. The idea that this joining region directly interacts with LTCCs and contributes to LTCC recruitment to T-tubules is unknown.

Objective: To determine if the joining region in JPH2 recruits LTCCs to T-tubules through direct molecular interaction in cardiomyocytes to enable efficient CICR.

Methods And Results: Modified abundance of JPH2 and redistribution of LTCC were studied in left ventricular hypertrophy in vivo and in cultured adult feline and rat ventricular myocytes. Protein-protein interaction studies showed that the joining region in JPH2 interacts with LTCC-α1C subunit and causes LTCCs distribution to the dyads, where they colocalize with RyRs. A JPH2 with induced mutations in the joining region (mutJPH2) caused T-tubule remodeling and dyad loss, showing that an interaction between LTCC and JPH2 is crucial for T-tubule stabilization. mutJPH2 caused asynchronous Ca-release with impaired excitation-contraction coupling after β-adrenergic stimulation. The disturbed Ca regulation in mutJPH2 overexpressing myocytes caused calcium/calmodulin-dependent kinase II activation and altered myocyte bioenergetics.

Conclusions: The interaction between LTCC and the joining region in JPH2 facilitates dyad assembly and maintains normal CICR in cardiomyocytes.
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http://dx.doi.org/10.1161/CIRCRESAHA.119.315715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790862PMC
January 2021

Differential promoter methylation and G-712A polymorphism of brain-derived neurotrophic factor in post-traumatic stress disorder patients of Li and Han populations in Hainan province.

Gene 2021 Feb 30;769:145192. Epub 2020 Sep 30.

Psychological Research Center, Hainan General Hospital, Haikou 570311, Hainan, PR China.

This study aimed to explore the correlations of promoter methylation and single-nucleotide polymorphism (SNP) of brain-derived neurotrophic factor (BDNF) with post-traumatic stress disorder (PTSD) in Li and Han nationalities in Hainan province. Depression- and anxiety-related questionnaires were performed for PTSD-related information collection and analysis, with 164 PTSD patients and 141 healthy controls included. Serum BDNF level was measured and the methylation of BDNF promoter was evaluated. The BDNF SNP genotyping was performed, after which the risk genotypes for PTSD were detected and analyzed using logistic regression analysis. Our study found that the PTSD incidence was different in Li and Han nationalities. Serum BDNF level in PTSD patients in Li nationality was obviously lower than that in patients in Han nationality, while the methylation of BDNF promoter was higher in patients in Li nationality. The G-712A rather than rs6265 genotypes presented significant difference between PTSD patients and healthy controls. Meanwhile, the patients in Li nationality with AG genotype at G-712A inclined to depression, and patients with GG genotype had a greater degree of PTSD. G-712A and promoter methylation of BDNF were independent risk factors for PTSD. Our study demonstrated that the differences of PTSD patients between Li and Han nationalities were attributed by SNP G-712A genotypes and promoter methylation of BDNF.
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http://dx.doi.org/10.1016/j.gene.2020.145192DOI Listing
February 2021

Production and Characterization of an Integrated Multi-Layer 3D Printed PLGA/GelMA Scaffold Aimed for Bile Duct Restoration and Detection.

Front Bioeng Biotechnol 2020 26;8:971. Epub 2020 Aug 26.

Department of Hepatobiliary Surgery, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, China.

We successfully fabricated artificial bile duct via 3D printing technique which was composed of poly (lactic-co-glycolic acid) (PLGA) and gelatin methacrylate (GelMA). The PLGA-inner layer provided sufficient strength to support the bile duct contraction, the GelMA-outer layer possessed good biocompatibility to provide a good living environment for the cells. Moreover, IKVAV laminin peptide (Ile-Lys-Val-Ala-Val) and ultrasmall superparamagnetic iron oxide (USPIO) were used to regulate scaffold cell adhesion and magnetic resonance imaging (MRI) detection, respectively. After BMSCs co-culture with IKVAV at a certain concentration, the survival rate and adhesion of BMSCs was increased obviously. Meanwhile, the fabricated scaffold exhibited the tensile modulus in the range of 17.19 - 29.05 MPa and the compressive modulus in the range of 0.042 - 0.066 MPa, which could meet the needs of human implantation. In an animal experiment pig bile duct regeneration, PLGA/GelMA/IKVAV/USPIO duct conduits could promote bile duct regeneration and enhance cytokeratin 19 (CK19) expression. In summary, the composite bile duct scaffold with excellent MRI imaging function and biocompatibility could be used to develop bioactive artificial bile ducts.
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http://dx.doi.org/10.3389/fbioe.2020.00971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479063PMC
August 2020

sp/sp Hybridized Carbon as an Anode with Extra Li-Ion Storage Capacity: Construction and Origin.

ACS Cent Sci 2020 Aug 21;6(8):1451-1459. Epub 2020 Jul 21.

Key Laboratory of Photochemistry, Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.

Doping in carbon anodes can introduce active sites, usually leading to extra capacity in Li-ion batteries (LIBs), but the underlying reasons have not been uncovered deeply. Herein, the dodecahedral carbon framework (N-DF) with a low nitrogen content (3.06 wt %) is fabricated as the anode material for LIBs, which shows an extra value of 298 mA h g during 250 cycles at 0.1 A g. Various characterizations and theoretical calculations demonstrate that the essence of the extra capacity mainly stems from non-coplanar sp/sp hybridized orbital controlling non-Euclidean geometrical structure, which acts as new Li-ion active sites toward the excess Li adsorption. The electrochemical kinetics and transmission electron microscope further reveal that the positive and negative curvature architectures not only provide supernumerary Li storage sites on the surface but also hold an enhanced (002) spacing for fast Li transport. The sp/sp hybridized orbital design concept will help to develop advanced electrode materials.
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http://dx.doi.org/10.1021/acscentsci.0c00593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453565PMC
August 2020

Iron isotope evidence for arsenic mobilization in shallow multi-level alluvial aquifers of Jianghan Plain, central China.

Ecotoxicol Environ Saf 2020 Dec 27;206:111120. Epub 2020 Aug 27.

School of Environmental Studies, China University of Geosciences, Wuhan, 430074, PR China.

Intake of groundwater with arsenic (As) concentrations exceeding the World Health Organization standard of 10 μg L adversely impacts over 100 million people worldwide. Geogenic As contaminated groundwater within central Yangtze River Basin has recently been reported, but the variations within different depths of aquifers are not commonly observed and the processes controlling As variations have yet to be resolved. Here we report the significant As variations within two different depths (10 m and 25 m) of shallow multi-level alluvial aquifers at Jianghan Plain, a floodplain in the central Yangtze River Basin, which is also a recently discovered geogenic As affected area with cases of waterborne arsenicosis. The multi-year monitoring of aquifer chemistry results show that the As concentrations increase with the Fe(II) concentrations when As contents are relatively lower (<200 μg L) in upper phreatic aquitard (at 10 m depth), while decrease with Fe(II) concentrations when As contents are much greater in lower confined aquifer (at 25 m depth), and the highest is up to 1070 μg L. Iron isotope analysis were conducive to characterize Fe cycling in the aquifers and thus illustrate geochemical processes controlling As mobilization of shallow groundwaters. Results showed that groundwater is generally enriched in isotopically light Fe with δFe values between - 1.60‰ and + 0.06‰ (median - 0.55‰). In the upper phreatic aquitard, microbial reductive dissolution of As-associated Fe(III) oxides, hydroxides and oxyhydroxides is the major process controlling As concentrations lower than 200 μg L. The reduction process could lead to the increasing As concentrations with the gradually increasing δFe values, and a positive correlation between Fe and δFe, and between dissolved As and δFe values is observed, respectively. In strongly reducing conditions as the lower confined aquifer, jointly microbial reduction of sulfate promotes the As mobilization through HS abiotic reduction of Fe(III) minerals, resulting in As concentrations greater than 200 μg L. These findings could provide new insights for differentiating the major factors controlling As mobilization at different depths of aquifers, and provide better water managements for similar geogenic As-affected shallow alluvial aquifers.
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http://dx.doi.org/10.1016/j.ecoenv.2020.111120DOI Listing
December 2020

Cortical Bone Derived Stem Cells Modulate Cardiac Fibroblast Response via miR-18a in the Heart After Injury.

Front Cell Dev Biol 2020 23;8:494. Epub 2020 Jun 23.

Independence Blue Cross Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States.

The adult heart following injury such as a myocardial infarction forms a fibrotic scar associated with transformation of resident cardiac fibroblasts into myofibroblast, accelerating cardiac remodeling and dysfunction. Cell therapies provide a novel direction for the enhancement of cardiac structure and function but remain poorly described in terms of the effect on resident cardiac fibroblasts. We have shown cortical bone derived stem cells (CBSCs) exhibit an ability to repair the heart after myocardial injury together with reduced scar formation. Nevertheless, whether CBSCs possess ability to modulate resident fibroblast response after myocardial injury remains untested.

Objective: To determine the effect of secreted factors from CSBCs to attenuate myofibroblast formation in the heart after injury.

Methods And Results: CBSCs were injected in mice after myocardial infarction which demonstrated reduced fibrosis as determined by Masson's trichrome and Picro-Sirius red staining. In parallel, decreased expression of myofibroblast markers such as Acta2 was observed compared to PBS injected mice. To determine the effect of CBSCs on cardiac fibrosis, adult mouse cardiac fibroblasts were isolated from C57BL/6 mice, primed with CBSC pre-conditioned media for 12 h, and treated with 10ng TGF-β for 48 h to mimic cardiac injury. Decreased expression of Acta2, periostin and CTGF was observed in adult cardiac fibroblasts cultured in CBSC medium compared to control cells. Additionally, analysis of myofibroblast markers such as vimentin and pSMAD/SMAD was also decreased compared to control cells. To determine the mechanism, we looked for enriched miRNA in CBSCs that can mediate anti fibrotic response after injury. Results showed significantly increased expression of miR-18a in CBSCs. The upregulation of miR-18a was also validated in adult fibroblasts treated with CBSCs compared to control cells. Adult fibroblasts treated with mimic for miR-18a followed by TGF-β showed significant decrease in myofibroblast formation while miR-18a inhibitor completely inhibited the effect of CBSC medium.

Conclusion: CBSCs reduce fibroblast to myofibroblast transition and differentiation in adult cardiac fibroblasts via miR-18a-5p. This finding reveals a new avenue for cell therapies to target myocardial scar modulation and provides a resolution for the cardiac repair response after injury in the adult myocardium.
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http://dx.doi.org/10.3389/fcell.2020.00494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324629PMC
June 2020

Identification of metastasis and prognosis-associated genes for serous ovarian cancer.

Biosci Rep 2020 06;40(6)

Department of Obstetrics and Gynecology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.

Serous ovarian cancer is one of the most fatal gynecological tumors with an extremely low 5-year survival rate. Most patients are diagnosed at an advanced stage with wide metastasis. The dysregulation of genes serves an important role in the metastasis progression of ovarian cancer. Differentially expressed genes (DEGs) between primary tumors and metastases of serous ovarian cancer were screened out in the gene expression profile of GSE73168 from Gene Expression Omnibus (GEO). Cytoscape plugin cytoHubba and weighted gene co-expression network analysis (WGCNA) were utilized to select hub genes. Univariate and multivariate Cox regression analyses were used to screen out prognosis-associated genes. Furthermore, the Oncomine validation, prognostic analysis, methylation mechanism, gene set enrichment analysis (GSEA), TIMER database analysis and administration of candidate molecular drugs were conducted for hub genes. Nine hundred and fifty-seven DEGs were identified in the gene expression profile of GSE73168. After using Cytoscape plugin cytoHubba, 83 genes were verified. In co-expression network, the blue module was most closely related to tumor metastasis. Furthermore, the genes in Cytoscape were analyzed, showing that the blue module and screened 17 genes were closely associated with tumor metastasis. Univariate and multivariate Cox regression revealed that the age, stage and STMN2 were independent prognostic factors. The Cancer Genome Atlas (TCGA) suggested that the up-regulated expression of STMN2 was related to poor prognosis of ovarian cancer. Thus, STMN2 was considered as a new key gene after expression validation, survival analysis and TIMER database validation. GSEA confirmed that STMN2 was probably involved in ECM receptor interaction, focal adhesion, TGF beta signaling pathway and MAPK signaling pathway. Furthermore, three candidate small molecule drugs for tumor metastasis (diprophylline, valinomycin and anisomycin) were screened out. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot showed that STMN2 was highly expressed in ovarian cancer tissue and ovarian cancer cell lines. Further studies are needed to investigate these prognosis-associated genes for new therapy target.
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http://dx.doi.org/10.1042/BSR20194324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317593PMC
June 2020

Efficient Tetra-Functional Electrocatalyst with Synergetic Effect of Different Active Sites for Multi-Model Energy Conversion and Storage.

ACS Appl Mater Interfaces 2020 May 9;12(20):23017-23027. Epub 2020 May 9.

CAS Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, P.R. China.

Energy crisis and global warming due to excessive CO emissions are the two major challenges of the world. Conversion of CO into useful fuels along with rechargeable metal air batteries and water splitting is one way to combat the energy crisis, which is bottlenecked due to the lack of multifunctional electrocatalyst. Herein simple but multifunctional electrocatalyst, which combined CoNi nanoalloy, N-doped carbon nanotubes, and single atomic Ni sites together is reported. The prepared electrocatalyst has shown remarkable performance for CORR, ORR, OER, and HER. The practical utilization of the catalyst is mansifested by a dual model metal CO/air battery and water electrolyzer. An excellent CORR with FE of 99% is achieved in 0.5 M KHCO medium. The catalyst exhibits more positive onset (0.98 V) and half wave potential (0.86 V) than Pt/C for ORR, extremely low overpotential (η) of 250 mV for OER, and thus the lowest ORR/OER potential gap of 0.62 V. In alkaline medium, the catalyst also shows excellent HER performance with η of 49 mV, resulting in the smallest cell bias of 1.57 V for overall water splitting to date. This work provides a new pathway to design more stellar multifunctional electrocatalyst for sustainable and clean renewable energy technology.
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http://dx.doi.org/10.1021/acsami.0c05481DOI Listing
May 2020

Assessment of the impact of geogenic and climatic factors on global risk of urinary stone disease.

Sci Total Environ 2020 Jun 6;721:137769. Epub 2020 Mar 6.

Institute of Applied Geosciences, Division of Hydrogeology, Karlsruhe Institute of Technology, Karlsruhe 76131, Germany.

Urinary Stone Disease (USD) or urolithiasis has plagued humans for centuries, and its prevalence has increased over the past few decades. Although USD pathology could vary significantly among individuals, previous qualitative assessments using limited survey data demonstrated that the prevalence of USD might exhibit a distinctive geographical distribution (the so-called "stone belt"), without any knowledge about the characteristics and contribution factors of the belt. Here, we argue that the spatial distribution of USD can at least partly be explained by geogenic and climatic factors, as it correlates with the ambient geo-environmental conditions modulated by lithology/mineralogy, water quality and climate. Using a Bayesian risk model, we assessed the global risk of USD based on updated big data of four key geogenic factors: phosphorite mines (inventory >1600 points), carbonate rocks (at the scale of 1:40 million), Ca/Mg molar ratio of river water (1.27 million samples distributed over 17,000 sampling locations), and mean air temperature (0.5 × 0.5° resolution) representing the climate. We quantitatively identified possible contributions of the factors to USD and delineated the regions with the high USD risk which stretched from southern North America, via the Mediterranean region, northeastern Africa, southern China to Australia, and roughly coincide with the world's major areas of carbonate outcropping. Under current climate conditions, the areas with the probabilities for the USD prevalence of ≥50% and ≥30% covered 3.7% and 20% of the Earth's land surface, respectively. By the end of the 21st century, such total areas could rise to 4.4% and 25% as a result of global warming. Since the USD data used in this study were quite heterogeneous, the prediction results needed further calibration with additional high-quality prevalence data in the future.
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http://dx.doi.org/10.1016/j.scitotenv.2020.137769DOI Listing
June 2020

Foes or Friends? Bacteria Enriched in the Tumor Microenvironment of Colorectal Cancer.

Cancers (Basel) 2020 Feb 6;12(2). Epub 2020 Feb 6.

State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, Hubei, China.

Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the third cause of cancer death in the world, while intestinal microbiota is a community of microbes living in human intestine that can potentially impact human health in many ways. Accumulating evidence suggests that intestinal microbiota, especially that from the intestinal bacteria, play a key role in the CRC development; therefore, identification of bacteria involved in CRC development can provide new targets for the CRC diagnosis, prevention, and treatment. Over the past decade, there have been considerable advances in applying 16S rDNA sequencing data to verify associated intestinal bacteria in CRC patients; however, due to variations of individual and environment factors, these results seem to be inconsistent. In this review, we scrutinized the previous 16S rDNA sequencing data of intestinal bacteria from CRC patients, and identified twelve genera that are specifically enriched in the tumor microenvironment. We have focused on their relationship with the CRC development, and shown that some bacteria could promote CRC development, acting as foes, while others could inhibit CRC development, serving as friends, for human health. Finally, we highlighted their potential applications for the CRC diagnosis, prevention, and treatment.
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http://dx.doi.org/10.3390/cancers12020372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072156PMC
February 2020

MiR-200a-3p promoted the malignant behaviors of ovarian cancer cells through regulating PCDH9.

Onco Targets Ther 2019 8;12:8329-8338. Epub 2019 Oct 8.

Department of Obstetrics and Gynecology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, People's Republic of China.

Background: Increasing evidence has revealed that the aberrant expression of microRNAs (miRNAs) plays vital roles in the development and progression of ovarian cancer. MiR-200a-3p was found to act as an oncogene in a variety of cancers, however, the expression and function of miR-200a-3p in ovarian cancer has not been characterized.

Materials And Methods: The expression of miR-200a-3p in ovarian cancer tissues and cell lines was detected by the RT-qPCR. The influence of miR-200a-3p on the growth of ovarian cancer cells was determined with the Cell Counting Kit-8 assay, colony formation and cell invasion assay. The binding of miR-200a-3p with the 3'-untranslated region (UTR) of PDCH9 was detected by luciferase reporter assay. The expression of PCDH9 was investigated by RT-qPCR and Western blot analysis.

Results: miR-200a-3p was up-regulated in ovarian cancer tissues and cell lines. Highly expressed miR-200a-3p was significantly associated with the tumor size, tumor metastasis and TNM stage. Overexpression of miR-200a-3p markedly promoted the proliferation, colony formation and invasion of ovarian cancer cells. Functional study uncovered that miR-200a-3p bound the 3'-untranslated region (UTR) of PCDH9 and decreased the expression of PCDH9 in ovarian cancer cells. The expression of miR-200a-3p in ovarian cancer tissues was significantly negatively correlated with that of PCDH9. Restored PCDH9 inhibited the promoting effect of miR-200a-3p on the proliferation of ovarian cancer cells.

Conclusion: Our results suggested the potential oncogenic function of miR-200a-3p via modulating PCDH9 in ovarian cancer.
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http://dx.doi.org/10.2147/OTT.S220339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790212PMC
October 2019

In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles.

Nat Biotechnol 2019 11 30;37(11):1322-1331. Epub 2019 Sep 30.

Department of Chemistry and Bio-X, Stanford University, Stanford, CA, USA.

The near-infrared-IIb (NIR-IIb) (1,500-1,700 nm) window is ideal for deep-tissue optical imaging in mammals, but lacks bright and biocompatible probes. Here, we developed biocompatible cubic-phase (α-phase) erbium-based rare-earth nanoparticles (ErNPs) exhibiting bright downconversion luminescence at ~1,600 nm for dynamic imaging of cancer immunotherapy in mice. We used ErNPs functionalized with cross-linked hydrophilic polymer layers attached to anti-PD-L1 (programmed cell death-1 ligand-1) antibody for molecular imaging of PD-L1 in a mouse model of colon cancer and achieved tumor-to-normal tissue signal ratios of ~40. The long luminescence lifetime of ErNPs (~4.6 ms) enabled simultaneous imaging of ErNPs and lead sulfide quantum dots emitting in the same ~1,600 nm window. In vivo NIR-IIb molecular imaging of PD-L1 and CD8 revealed cytotoxic T lymphocytes in the tumor microenvironment in response to immunotherapy, and altered CD8 signals in tumor and spleen due to immune activation. The cross-linked functionalization layer facilitated 90% ErNP excretion within 2 weeks without detectable toxicity in mice.
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http://dx.doi.org/10.1038/s41587-019-0262-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858548PMC
November 2019

Comparison of efficacy of robotic surgery, laparoscopy, and laparotomy in the treatment of ovarian cancer: a meta-analysis.

World J Surg Oncol 2019 Sep 13;17(1):162. Epub 2019 Sep 13.

Department of Obstetrics and Gynecology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, No. 1 Huanghe West Road, Huaiyin District, Huai'an, 223300, Jiangsu, China.

Background: We intended to compare the clinical effect of robotic surgery with laparoscopy and laparotomy in ovarian cancer treatment.

Methods: The included studies were retrieved from PubMed, Embase, and the Cochrane Library databases. The Methodological Index for Nonrandomized Studies (MINORS) was used to evaluate the study quality. Effect measures were presented with weighted mean difference (WMD)/odds ratio (OR) and 95% confidence interval (CI), and heterogeneity test was assessed using Q test and I statistics to determine the use of the random effects model or fixed effects model. Egger's test was used to assess the publication bias.

Results: A total of eight studies was included in this meta-analysis with a MINORS score of 16-18. In the random effects model, estimated blood loss (EBL) of robotic surgery was significantly less compared with laparotomy (WMD = - 521.7027, 95% CI - 809.7816; - 233.6238). In the fixed effects model, length of hospital stay (LHS) (WMD = - 5.2225, 95% CI - 6.1485; - 4.2965) and postoperative complication (PC) (OR = 0.4710, 95% CI 0.2537; 0.8747) of robotic surgery were significantly less, and overall survival (OS) rate (OR = 6.4355, 95% CI 1.6722; 24.7678, P = 0.0070) of robotic surgery was significantly higher compared with laparotomy. There was no difference in the effect size of all variables between robotic surgery and laparoscopy. Meanwhile, a publication bias (t = 6.8290, P = 0.002405) was only identified for PC in robotic surgery and laparotomy groups; no publication bias was identified for the other variables.

Conclusions: Despite the above results, it failed to show oncological safety and recurrence by pathological stages or histologic types in this meta-analysis, and those confounding factors might affect the clinical outcome. Future meta-analyses with a larger number of eligible randomized controlled trial studies were needed to determine the most suitable treatment method for patients with different stages and types of ovarian cancer.
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http://dx.doi.org/10.1186/s12957-019-1702-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743103PMC
September 2019

Using Mechanical Stress to Investigate the Rashba Effect in Organic-Inorganic Hybrid Perovskites.

J Phys Chem Lett 2019 Sep 3;10(18):5446-5450. Epub 2019 Sep 3.

Key Laboratory of Luminescence and Optical Information, Ministry of Education, School of Science , Beijing Jiaotong University , Beijing 100044 , People's Republic of China.

Organic-inorganic hybrid perovskites simultaneously possess strong spin-orbit coupling (SOC) and structure inversion asymmetry, establishing a Rashba effect to influence light emission and photovoltaics. Here, we use mechanical bending as a convenient approach to investigate the Rashba effect through SOC in perovskite (MAPbICl) films by elastically deforming grains. It is observed that applying a concave bending can broaden the line shape of the magnetophotocurrent, increasing the internal magnetic parameter from 121 to 205 mT, which indicates an enhancement on SOC. Interestingly, the PL lifetime is found to be enlarged from 9.9 to 14.8 ns under this bending, which suggests that introducing compressive strain can essentially increase the Rashba effect through SOC, leading to an increase upon indirect band transition. Furthermore, the PL peak associated with the Rashba effect is shifted from 776 to 780 nm under this mechanical bending. Therefore, mechanical bending provides a convenient experimental method to approach the Rashba effect in hybrid perovskites.
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http://dx.doi.org/10.1021/acs.jpclett.9b01985DOI Listing
September 2019

Multiscale Buffering Engineering in Silicon-Carbon Anode for Ultrastable Li-Ion Storage.

ACS Nano 2019 Sep 22;13(9):10179-10190. Epub 2019 Aug 22.

State Key Laboratory of Multi-Phase Complex Systems, Institute of Process Engineering , Chinese Academy of Sciences (CAS) , Zhongguancun Beiertiao 1 Hao , Beijing 100190 , People's Republic of China.

Silicon-carbon (Si-C) hybrids have been proven to be the most promising anodes for the next-generation lithium-ion batteries (LIBs) due to their superior theoretical capacity (∼4200 mAh g). However, it is still a critical challenge to apply this material for commercial LIB anodes because of the large volume expansion of Si, unstable solid-state interphase (SEI) layers, and huge internal stresses upon lithiation/delithiation. Here, we propose an engineering concept of multiscale buffering, taking advantage of a nanosized Si-C nanowire architecture through fabricating specific microsized wool-ball frameworks to solve all the above-mentioned problems. These wool-ball-like frameworks, prepared at high yields, nearly matching industrial scales (they can be routinely produced at a rate of ∼300 g/h), are composed of Si/C nanowire building blocks. As anodes, the Si-C wool-ball frameworks show ultrastable Li storage (2000 mAh g for 1000 cycles), high initial Coulombic efficiency of ∼90%, and volumetric capacity of 1338 mAh cm. TEM proves that the multiscale buffering design enables a small volume variation, only ∼19.5%, reduces the inner stresses, and creates a very thin SEI. The perfect multiscale elastic buffering makes this material more stable compared to common Si nanoparticle-assembled counterpart electrodes.
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http://dx.doi.org/10.1021/acsnano.9b03355DOI Listing
September 2019

Identification of significant gene and pathways involved in HBV-related hepatocellular carcinoma by bioinformatics analysis.

PeerJ 2019 30;7:e7408. Epub 2019 Jul 30.

Department of Hepatobiliary Surgery, Haikou People's Hospital/Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, Hainan, China.

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor affecting the digestive system and causes serious financial burden worldwide. Hepatitis B virus (HBV) is the main causative agent of HCC in China. The present study aimed to investigate the potential mechanisms underlying HBV-related HCC and to identify core biomarkers by integrated bioinformatics analyses.

Methods: In the present study, HBV-related HCC GSE19665, GSE55092, GSE94660 and GSE121248 expression profiles were downloaded from the Gene Expression Omnibus database. These databases contain data for 299 samples, including 145 HBV-related HCC tissues and 154 non-cancerous tissues (from patients with chronic hepatitis B). The differentially expressed genes (DEGs) from each dataset were integrated and analyzed using the RobustRankAggreg (RRA) method and R software, and the integrated DEGs were identified. Subsequently, the gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the DAVID online tool, and the protein-protein interaction (PPI) network was constructed using STRING and visualized using Cytoscape software. Finally, hub genes were identified, and the cBioPortal online platform was used to analyze the association between the expression of hub genes and prognosis in HCC.

Results: First, 341 DEGs (117 upregulated and 224 downregulated) were identified from the four datasets. Next, GO analysis showed that the upregulated genes were mainly involved in cell cycle, mitotic spindle, and adenosine triphosphate binding. The majority of the downregulated genes were involved in oxidation reduction, extracellular region, and electron carrier activity. Signaling pathway analysis showed that the integrated DEGs shared common pathways in retinol metabolism, drug metabolism, tryptophan metabolism, caffeine metabolism, and metabolism of xenobiotics by cytochrome P450. The integrated DEG PPI network complex comprised 288 nodes, and two important modules with high degree were detected using the MCODE plug-in. The top ten hub genes identified from the PPI network were SHCBP1, FOXM1, KIF4A, ANLN, KIF15, KIF18A, FANCI, NEK2, ECT2, and RAD51AP1. Finally, survival analysis revealed that patients with HCC showing altered ANLN and KIF18A expression profiles showed worse disease-free survival. Nonetheless, patients with FOXM1, NEK2, RAD51AP1, ANLN, and KIF18A alterations showed worse overall survival.

Conclusions: The present study identified key genes and pathways involved in HBV-related HCC, which improved our understanding of the mechanisms underlying the development and recurrence of HCC and identified candidate targets for the diagnosis and treatment of HBV-related HCC.
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http://dx.doi.org/10.7717/peerj.7408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677124PMC
July 2019
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