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87 result(s) for "Zhao, Shuchun"
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Point-of-Care and Dual-Response Detection of Hydrazine/Hypochlorite-Based on a Smart Hydrogel Sensor and Applications in Information Security and Bioimaging
A novel dual-response fluorescence probe (XBT-CN) was developed by using a fluorescence priming strategy for quantitative monitoring and visualization of hydrazine (N2H4) and hypochlorite (ClO−). With the addition of N2H4/ClO−, the cleavage reaction of C=C bond initiated by N2H4/ClO− was transformed into corresponding hydrazone and aldehyde derivatives, inducing the probe XBT-CN appeared a fluorescence “off-on” response, which was verified by DFT calculation. HRMS spectra were also conducted to confirm the sensitive mechanism of XBT-CN to N2H4 and ClO−. The probe XBT-CN had an obvious fluorescence response to N2H4 and ClO−, which caused a significant color change in unprotected eyes. In addition, the detection limits of XBT-CN for N2H4 and ClO− were 27 nM and 34 nM, respectively. Interference tests showed that other competitive analytes could hardly interfere with the detection of N2H4 and ClO− in a complex environment. In order to realize the point-of-care detection of N2H4 and ClO−, an XBT-CN@hydrogel test kit combined with a portable smartphone was developed. Furthermore, the portable test kit has been applied to the detection of N2H4 and ClO− in a real-world environment and food samples, and a series of good results have been achieved. Attractively, we demonstrated that XBT-CN@hydrogel was successfully applied as an encryption ink in the field of information security. Finally, the probe can also be used to monitor and distinguish N2H4 and ClO− in living cells, exhibiting excellent biocompatibility and low cytotoxicity.
Integrated systems analysis reveals a molecular network underlying autism spectrum disorders
Autism is a complex disease whose etiology remains elusive. We integrated previously and newly generated data and developed a systems framework involving the interactome, gene expression and genome sequencing to identify a protein interaction module with members strongly enriched for autism candidate genes. Sequencing of 25 patients confirmed the involvement of this module in autism, which was subsequently validated using an independent cohort of over 500 patients. Expression of this module was dichotomized with a ubiquitously expressed subcomponent and another subcomponent preferentially expressed in the corpus callosum, which was significantly affected by our identified mutations in the network center. RNA‐sequencing of the corpus callosum from patients with autism exhibited extensive gene mis‐expression in this module, and our immunochemical analysis showed that the human corpus callosum is predominantly populated by oligodendrocyte cells. Analysis of functional genomic data further revealed a significant involvement of this module in the development of oligodendrocyte cells in mouse brain. Our analysis delineates a natural network involved in autism, helps uncover novel candidate genes for this disease and improves our understanding of its molecular pathology. Synopsis An integrative analysis of the interactome, gene expression and genome sequencing data identifies protein interaction modules implicated in autism spectrum disorders and reveals the corpus callosum as a potential tissue of origin in ASD. Topological clustering of the human protein‐protein interaction network reveals two modules implicated in ASD, module #2 for chromatin remodeling proteins and transcription factors and #13 for proteins involved in brain function. Module #13 has dichotomized expression with one sub‐component ubiquitously expressed in the brain, and the other enriched in the corpus callosum. Module #13 is involved in oligodendrocyte development and axon myelination in the corpus callosum. This study suggests interhemispheric disconnectivity in the brain as a potential cause underlying autism. Graphical Abstract An integrative analysis of the interactome, gene expression and genome sequencing data identifies protein interaction modules implicated in autism spectrum disorders and reveals the corpus callosum as a potential tissue of origin in ASD.
Development and validation of real time load estimator on Goldwind 6 MW wind turbine
Modern wind turbines have access to highly reliable measurements of important control input signals, such as generator speed and nacelle acceleration. They also have high fidelity numerical models such as in Bladed, which can be used to estimate structural loads under simulated normal and extreme operating conditions. However, if we want to know the structural loads that occurred in a time period on the real turbine, presently this requires instrumentation with strain gauges. These sensors can be unreliable and expensive to install, calibrate and maintain. The price of reliable sensors is unlikely to drop to an affordable level for onshore wind in the near future. This paper describes a method of fusing the control input signals with the turbine numerical model to estimate structural loads online in real time. The estimator is validated in Bladed simulations of a Goldwind 6 MW turbine.
Spatial phenotyping of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma with sparse tumor B-cells and a favorable prognosis. Variant growth patterns of NLPHL, however, often show advanced stage, progression to T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) and a worse prognosis. We studied the tumor microenvironment (TME) of NLPHL and THRLBCL using highplex imaging and spatial profiling at the single cell level. Our findings show distinct differences in TME composition and spatial configuration that differ among typical and variant NLPHL and THRLBCL. Typical NLPHL show abundant helper T-cell subsets, while THRLBCL show abundant cytotoxic T-cells and macrophages. Tumor B-cell size and content is lowest in typical NLPHL, followed by variant NLPHL, and highest in THRLBCL, whereas an opposite trend characterized TME B-cells. CD4/CD8 double-positive T-cells are seen in all NLPHL but not in the majority of THRLBCL and are spatially distant from LP-cells and TFH-rosettes. The differences in macrophage/monocyte content in distinguishing NLPHL pattern E from THRLBCL is further corroborated in independent cohorts of cases. Our results validate the current approach to classification and in addition provide novel insights that could be leveraged to refine clinical management for patients with this spectrum of lymphomas.
Magnetoviscous Property and Hyperthermia Effect of Amorphous Nanoparticle Aqueous Ferrofluids
Magnetic Fe-B, Fe-Ni-B, and Co-B nanoparticles were successfully synthesized and introduced to water to prepare aqueous ferrofluids. The Fe-B, Fe-Ni-B, and Co-B particles are homogeneous amorphous nanoparticles with an average particle size 15 nm. The shape of the amorphous nanoparticles is regular. The Fe-B, Fe-Ni-B, and Co-B amorphous nanoparticles are superparamagnetic. Moreover, the saturation magnetizations of Fe-B and Fe-Ni-B amorphous nanoparticles are 75 emu/g and 51 emu/g. These are approximately 2.8 and 1.9-fold larger than Co-B nanoparticles, respectively. The viscosity of the amorphous ferrofluids has a strong response to external magnetic field. The yield stress increases with increasing magnetic field. The hyperthermia research of amorphous ferrofluids was firstly investigated. The experimental results indicate that the heating temperature of Fe-B ferrofluid and Fe-Ni-B ferrofluid could increase to 42 °C in 750 s and 960 s, respectively, when the output current is 300 A. The temperature could reach 61.6 °C for a Fe-B ferrofluid. The heating efficiencies of the amorphous ferrofluids demonstrate that the Fe-B ferrofluid and Fe-Ni-B ferrofluid may have great potential for biomedical applications.
Distinct cell state ecosystems for nodular lymphocyte-predominant Hodgkin lymphoma
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and few studies have comprehensively investigated the immune microenvironment and rare lymphocyte-predominant (LP) cells. Here we develop a NLPHL specific lymphocyte-predominant ecotype (LPE) model to identify 34 distinct cell states across 14 cell types that co-occur within 3 LPEs for 171 cases. LPE1 and LPE2 were characterized by immunosuppressive microenvironments with high expression of B2M on LP cells, CD8 T-cell exhaustion, immune checkpoint genes expressed by follicular T-cells, and an improved freedom from progression compared to LPE3 in training ( n  = 109, with 65% LPE1/2) and validation cohorts ( n  = 62, with 61% LPE1/2). We validate the co-occurrence and co-localization of cell states using spatial transcriptomics. Protein expression of HLA-I and HLA-II on LP cells and SSTR2 on dendritic cells was predictive of LPE1 (C-statistic=0.69), LPE2 (C-statistic=0.79), and LPE3 (C-statistic=0.60). This study establishes a clinically relevant biologic categorization for NLPHL. Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer. Here, the authors develop a NLPHL specific model to identify 34 distinct cell states across 14 cell types that co-occur within 3 lymphocyte predominant ecotypes (LPEs) for 171 cases.
Interactions between Dislocations and Penta-Twins in Metallic Nanocrystals
Dislocation interactions with twin boundary (TB) have been well-established in nanotwinned metals. Penta-twins, as an extreme of crystal twinning, are tacitly assumed to be more effective at blocking dislocation motions than conventional single or coplanar nanotwins. However, the mechanism underlying the interactions between dislocations and penta-twins remains largely unclear. Here, by combining in situ transmission electron microscope (TEM) nanomechanical testing and atomistic simulations, we rationalize the fundamental interactions between dislocations and penta-twins in Au nanocrystals. Our results reveal that the interactions between dislocations and penta-twins show some similar behaviors to the ones in the cases of coplanar nanotwins, including dislocation impedance at TBs, cross-slip into the twinning plane and transmission across the TB. In addition, penta-twins also exhibit some unique behaviors during dislocation interactions, including multiple cross-slip, dislocation-induced core dissociation and climb-induced annihilation/absorption at the penta-twin core. These findings enhance our mechanistic understanding of dislocation behaviors in penta-twins, shedding light on the accessible design of high-performance nanomaterials with multi-twinned nanostructures.
Transient expression of Bcl6 is sufficient for oncogenic function and induction of mature B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma and can be separated into two subtypes based upon molecular features with similarities to germinal centre B-cells (GCB-like) or activated B-cells (ABC-like). Here we identify gain of 3q27.2 as being significantly associated with adverse outcome in DLBCL and linked with the ABC-like subtype. This lesion includes the BCL6 oncogene, but does not alter BCL6 transcript levels or target-gene repression. Separately, we identify expression of BCL6 in a subset of human haematopoietic stem/progenitor cells (HSPCs). We therefore hypothesize that BCL6 may act by ‘hit-and-run’ oncogenesis. We model this hit-and-run mechanism by transiently expressing Bcl6 within murine HSPCs, and find that it causes mature B-cell lymphomas that lack Bcl6 expression and target-gene repression, are transcriptionally similar to post-GCB cells, and show epigenetic changes that are conserved from HSPCs to mature B-cells. Together, these results suggest that BCL6 may function in a ‘hit-and-run’ role in lymphomagenesis. Diffuse large B-cell lymphoma is an aggressive heterogeneous tumour type with poorly understood aetiology. Here, Green et al. show that transient expression of Bcl6 in haematopoietic stem cells is sufficient to induce mature B-cell lymphoma, indicating that it acts as a ‘hit-and-run’ oncogene.
OSdlbcl: An online consensus survival analysis web server based on gene expression profiles of diffuse large B‐cell lymphoma
Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of non‐Hodgkin lymphoma (NHL) and is a clinical, pathological, and molecular heterogeneous disease with highly variable clinical outcomes. Currently, valid prognostic biomarkers in DLBCL are still lacking. To optimize targeted therapy and improve the prognosis of DLBCL, the performance of proposed biomarkers needs to be evaluated in multiple cohorts, and new biomarkers need to be investigated in large datasets. Here, we developed a consensus Online Survival analysis web server for Diffuse Large B‐Cell Lymphoma, abbreviated OSdlbcl, to assess the prognostic value of individual gene. To build OSdlbcl, we collected 1100 samples with gene expression profiles and clinical follow‐up information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. In addition, DNA mutation data were also collected from the TCGA database. Overall survival (OS), progression‐free survival (PFS), disease‐specific survival (DSS), disease‐free interval (DFI), and progression‐free interval (PFI) are important endpoints to reflect the survival rate in OSdlbcl. Moreover, clinical features were integrated into OSdlbcl to allow data stratifications according to the user's special needs. By inputting an official gene symbol and selecting desired criteria, the survival analysis results can be graphically presented by the Kaplan‐Meier (KM) plot with hazard ratio (HR) and log‐rank p value. As a proof‐of‐concept demonstration, the prognostic value of 23 previously reported survival associated biomarkers, such as transcription factors FOXP1 and BCL2, was evaluated in OSdlbcl and found to be significantly associated with survival as reported (HR = 1.73, P < .01; HR = 1.47, P = .03, respectively). In conclusion, OSdlbcl is a new web server that integrates public gene expression, gene mutation data, and clinical follow‐up information to provide prognosis evaluations for biomarker development for DLBCL. The OSdlbcl web server is available at https://bioinfo.henu.edu.cn/DLBCL/DLBCLList.jsp. To assess and identify appropriate prognostic biomarkers for diffuse large B‐cell lymphoma, we integrated public gene expression data and clinical follow‐up information and developed the consensus online survival analysis web server OSdlbcl for researchers and clinicians.
Prognostic significance of VEGF, VEGF receptors, and microvessel density in diffuse large B cell lymphoma treated with anthracycline-based chemotherapy
Vascular endothelial growth factor-mediated signaling has at least two potential roles in diffuse large B cell lymphoma: potentiation of angiogenesis, and potentiation of lymphoma cell proliferation and/or survival induced by autocrine vascular endothelial growth factor receptor-mediated signaling. We have recently shown that diffuse large B cell lymphomas expressing high levels of vascular endothelial growth factor protein also express high levels of vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2. We have now assessed a larger multi-institutional cohort of patients with de novo diffuse large B cell lymphoma treated with anthracycline-based therapy to address whether tumor vascularity, or expression of vascular endothelial growth factor protein and its receptors, contribute to patient outcomes. Our results show that increased tumor vascularity is associated with poor overall survival (P=0.047), and is independent of the international prognostic index. High expression of vascular endothelial growth factor receptor-1 by lymphoma cells by contrast is associated with improved overall survival (P=0.044). The combination of high vascular endothelial growth factor and vascular endothelial growth factor receptor-1 protein expression by lymphoma cells identifies a subgroup of patients with improved overall (P=0.003) and progression-free (P=0.026) survival; these findings are also independent of the international prognostic index. The prognostic significance of overexpression of this ligand-receptor pair suggests that autocrine signaling via vascular endothelial growth factor receptor-1 may represent a survival or proliferation pathway in diffuse large B cell lymphoma. Dependence on autocrine vascular endothelial growth factor receptor-1-mediated signaling may render a subset of diffuse large B-cell lymphomas susceptible to anthracycline-based therapy.