Publications by authors named "Zhao Wang"

1,231 Publications

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[Exhaustion of CD8T Lymphocytes Plays a Critical Role in the Pathogenesis of Secondary Hemophagocytic Lymphohistiocytosis].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):963-968

Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China,E-mail:

Objective: To investigate the changes in function of CD8 T cell subsets, and explore its significance in pathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH).

Methods: Flow cytometry was used to detect the expressions of PD-1, TIM-3, and LAG-3, which were the markers of exhausted CD8 T cell, as well as the secretion levels of interferon γ (IFN-γ) and expression of ΔCD107a after the stimulation; the numbers of effector-memory CD8 T cells, regulatory T cells and double negative T cells were also detected.

Results: The expressions of inhibitory receptors (PD-1, TIM3 and LAG-3) on CD8 T cells of sHLH patients were 40.73±22.64, 15.97±14.45 and 0.73 (0-37.41), respectively, which were significantly higher than those of the control group (P<0.001). In contrast, the expression of ΔCD107a (4.49±2.71 vs 6.07±2.14, P=0.035) and secretion level of IFN-γ (37.30±24.46 vs 55.17±22.23, P=0.034) were significantly lower. The number of effector-memory CD8 T cells in sHLH patients was also lower as compared with that in control group (14.35±10.37 vs 22.92±11.12, P=0.016). But there was no significant difference in the number of regulatory T cell and double negative T cell. In addition, the expressions of PD-1, TIM3 and LAG-3 in active stage of sHLH were 38.09±21.87, 14.35±13.70 and 0.82 (0-13.22), respectively, which were significant higher than those in remission stage [24.27±17.23 (P=0.03), 8.64±5.60 (P=0.014) and 0.13 (0-3.69)].

Conclusion: The exhausted CD8 T lymphocytes may play a critical role in the development of sHLH.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.049DOI Listing
June 2021

PKM1 Exerts Critical Roles in Cardiac Remodeling Under Pressure Overload in the Heart.

Circulation 2021 Jun 9. Epub 2021 Jun 9.

Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.

Metabolic remodeling precedes most alterations during cardiac hypertrophic growth under hemodynamic stress. The elevation of glucose utilization has been recognized as a hallmark of metabolic remodeling. However, its role in cardiac hypertrophic growth and heart failure in response to pressure overload remains to be fully illustrated. Here, we aimed to dissect the role of cardiac PKM1 (pyruvate kinase muscle isozyme 1) in glucose metabolic regulation and cardiac response under pressure overload. Cardiac specific deletion of PKM1 was achieved by crossing the floxed PKM1 mouse model with the cardiomyocyte-specific Cre transgenic mouse. PKM1 transgenic mice were generated under the control of tetracycline response elements, and cardiac specific overexpression of PKM1 was induced by doxycycline administration in adult mice. Pressure overload was triggered by transverse aortic constriction (TAC). Primary neonatal rat ventricular myocytes were used to dissect molecular mechanisms. Moreover, metabolomics and NMR spectroscopy analyses were conducted to determine cardiac metabolic flux in response to pressure overload. We found that PKM1 expression is reduced in failing human and mouse hearts. Importantly, cardiomyocyte-specific deletion of PKM1 exacerbates cardiac dysfunction and fibrosis in response to pressure overload. Inducible overexpression of PKM1 in cardiomyocytes protects the heart against TAC-induced cardiomyopathy and heart failure. At the mechanistic level, PKM1 is required for the augmentation of glycolytic flux, mitochondrial respiration, and ATP production under pressure overload. Furthermore, deficiency of PKM1 causes a defect in cardiomyocyte growth and a decrease in pyruvate dehydrogenase complex activity at both and levels. These findings suggest that PKM1 plays an essential role in maintaining a homeostatic response in the heart under hemodynamic stress.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.121.054885DOI Listing
June 2021

Stimuli-responsive polydopamine-based smart materials.

Chem Soc Rev 2021 Jun 8. Epub 2021 Jun 8.

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China.

Stimuli responsiveness has long been a fascinating feature of smart material design. Polydopamine (PDA), a nature inspired polymeric pigment, exhibits excellent photo-responsive properties and has active surface functionality for loading various responsive motifs, making it a promising candidate for the construction of stimuli-responsive smart functional materials. PDA has long been considered as a robust coating material, but its responsive feature has rarely been emphasized in the past reviews. Herein, we present the first effort to summarize recent advances in the design strategies, responsive mechanisms, and diverse applications of stimuli-responsive PDA-based smart materials; the stimuli include light, pH, chemicals, temperature, humidity, electric fields, mechanical force, magnetic fields, and ultrasound. Moreover, the current trends, challenges, and future directions of stimuli-responsive PDA-based materials are also elaborated.
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http://dx.doi.org/10.1039/d1cs00374gDOI Listing
June 2021

Polymorphism of IL-1β rs16944(T/C) Associated with Serum Levels of IL-1β and Subsequent Stimulation of Extracellular Matrix Degradation Affects Intervertebral Disk Degeneration Susceptibility.

Ther Clin Risk Manag 2021 24;17:453-461. Epub 2021 May 24.

Department of Critical Care Medicine, The Second Poverty Relief Hospital of Xinjiang Uygur Autonomous Region (The Fifth People's Hospital of Xinjiang Uygur Autonomous Region), Urumqi, Xinjiang, People's Republic of China.

Purpose: To investigate the association of polymorphism of IL-1β rs16944(T/C) with intervertebral disk degeneration (IDD), explore the possible mechanism and evaluate the predictive value of IL-1β for IDD.

Patients And Methods: A total of 196 consecutive patients with IDD were recruited, and 196 healthy controls were matched to these patients based on sex and age (±3 years). The polymorphisms of IL-1β rs16944(T/C), rs1143623(G/C), rs10490571(T/C) and rs2853550(A/G) were determined, and serum IL-1β, MMP-1, MMP-3, MMP-9 and a disintegrin-like and metalloproteinase with thrombospondin motif-4 (ADAMTS-4) levels were measured. Univariate analysis was performed with Student -test or one-way ANOVA followed by post hoc and Chi-square test. Variables with two-sided <0.10 were included in multivariate analysis, which employed a backward stepwise logistic regression model. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value.

Results: Multivariate analysis showed that the polymorphism of IL-1β rs16944(T/C) was independently associated with IDD. The risk for IDD was significantly increased in TT and TC genotype compared with CC genotype, and the OR of TT genotype was higher than that of TC genotype. ANOVA analysis showed that serum concentration of IL-1β was highest in IL-1β rs16944 TT genotype, intermediate in TC genotype, and lowest in CC genotype. Similarly, serum concentrations of MMP-3 and ADAMTS-4 demonstrated the same tendency of TT > TC > CC genotype. Serum concentrations of MMP-1 and MMP-9 were higher in TT genotype than in TC and CC genotype. The area under curve (AUC) of IL-1β levels in predicting IDD was 0.788 (SE: 0.023, =0.001, 95% CI: 0.742-0.834), and the predictive value was modest with a sensitivity of 77.0% and a specificity of 75%.

Conclusion: Polymorphism of IL-1β rs16944(T/C) affected IDD susceptibility through upregulation of serum levels of IL-1β and subsequent stimulation of ECM degradation. IL-1β levels could be applied in predicting IDD.
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http://dx.doi.org/10.2147/TCRM.S308653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163728PMC
May 2021

Steroid receptor-coregulator transcriptional complexes: new insights from CryoEM.

Essays Biochem 2021 Jun 1. Epub 2021 Jun 1.

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, U.S.A.

Steroid receptors activate gene transcription through recruitment of a number of coregulators to facilitate histone modification, chromatin remodeling, and general transcription machinery stabilization. Understanding the structures of full-length steroid receptor and coregulatory complexes has been difficult due to their large molecular sizes and dynamic structural conformations. Recent developments in cryo-electron microscopy (cryoEM) technology and proteomics have advanced the structural studies of steroid receptor complexes. Here, we will review the insights we learned from cryoEM studies of the estrogen and androgen receptor transcriptional complexes. Despite similar domain organizations, the two receptors have different coregulator interaction modes. The cryoEM structures now have revealed the fundamental differences between the two receptors and their functional mechanisms.
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http://dx.doi.org/10.1042/EBC20210019DOI Listing
June 2021

Infrared photoconductor based on surface-state absorption in silicon.

Opt Lett 2021 Jun;46(11):2577-2580

We report on a normal-incidence infrared photoconductor based on surface-state absorption in silicon, featuring broad-spectrum photoresponse, sensitivity of ${-}46\;{\rm dBm} $ enabled by lock-in readouts, CMOS-compatible fabrication process, and near transparency to incident light. Its applications in infrared imaging and measuring the beam profiles are demonstrated and presented. Future extension from this single-pixel element to a many-pixel camera is discussed.
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http://dx.doi.org/10.1364/OL.426316DOI Listing
June 2021

Successful resolution of hemophagocytic lymphohistiocytosis during the chemotherapy course of acute myelocytic leukemia with ruxolitinib.

Chin Med J (Engl) 2021 May 28. Epub 2021 May 28.

Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.

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http://dx.doi.org/10.1097/CM9.0000000000001559DOI Listing
May 2021

Functional study of a role of N-terminal HA stem region of swine influenza A virus in virus replication.

Vet Microbiol 2021 Jul 25;258:109132. Epub 2021 May 25.

M. H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA. Electronic address:

Swine influenza A virus (SIV) is both a pathogen of economic significance to the swine industry and a potential zoonotic organism that may be transmitted to humans. We described here the detailed characterization of a role of N-terminal B-loop and CD helix of HA2 in swine influenza A virus replication. Results of our experiments demonstrated that Hemagglutinin (HA) protein of swine influenza virus could tolerate some mutations in functionally conserved B-loop and CD helix. These mutations, however, have substantially attenuated influenza virus replication in both cell lines and porcine primary tracheal epithelial cells. Significantly, we found that some B-loop or CD helix mutations generated virus mutants that replicated in MDCK and ST cell lines but failed to replicate in primary tracheal epithelial cells, thereby suggesting that swine HA protein may function as a viral virulence and pathogenesis factor. The described mutations may be further explored as attenuated vaccine candidates that can effectively prevent or eliminate the spread of influenza virus within and between swine herds.
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http://dx.doi.org/10.1016/j.vetmic.2021.109132DOI Listing
July 2021

Denitrification potential of sodium alginate gel beads immobilized iron-carbon, Zoogloea sp. L2, and riboflavin: Performance optimization and mechanism.

Bioresour Technol 2021 May 25;336:125326. Epub 2021 May 25.

School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China; Shaanxi Key Laboratory of Environmental Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China.

A kind of gel beads loaded with iron-carbon powder (Fe-C), Zoogloea sp. L2, and riboflavin (VB2) were prepared through cross-linking of sodium alginate (SA) to establish an immobilized bioreactor. The optimal ratio of SA beads was adjusted by orthogonal experiment. The change of oxidation-reduction potential (ORP) and the concentration of Fe and Fe showed that the addition of VB2 as a redox mediator can promote denitrification. Under the optimal conditions (carbon to nitrogen (C/N) ratio = 2.0, pH = 7.0, and hydraulic retention time (HRT) = 8 h), the nitrate removal efficiency (NRE) of bioreactor reached 98.48% (1.99 mg Lh). Furthermore, Fourier transform infrared spectrometer (FTIR), Fluorescence excitation-emission matrix (EEM), X-ray diffraction (XRD), and gas chromatography (GC) analysis revealed that the immobilization and denitrification of the immobilized bioreactor were excellent. High throughput sequencing also showed that Zoogloea played a vital role in nitrate removal.
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http://dx.doi.org/10.1016/j.biortech.2021.125326DOI Listing
May 2021

PHLDA3 promotes lung adenocarcinoma cell proliferation and invasion via activation of the Wnt signaling pathway.

Lab Invest 2021 May 18. Epub 2021 May 18.

Department of Pathology, The First Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.

The PHLDA3 gene encodes a small 127 amino acid protein with a pleckstrin homology (PH)-only domain. The expression and significance of PHLDA3 in lung cancer remain unclear. Here, we investigated the role of PHLDA3 in tumor proliferation and invasion in lung adenocarcinoma. Immunohistochemistry and immunoblotting analyses were used to assess PHLDA3 expression in lung cancer tissues, and its correlation with clinicopathological factors in lung cancer. Plasmids encoding PHLDA3 and small interfering RNA against PHLDA3 were used to regulate the expression of PHLDA3 in lung cancer cells. Furthermore, the effects of PHLDA3 on lung cancer cell proliferation and invasion were investigated using the MTS, colony formation, Matrigel invasion, and wound healing assays. Co-immunoprecipitation analysis and inhibitors of both the Wnt signaling pathway and GSK3β were used to explore the regulatory mechanisms underlying the role of PHLDA3 in lung cancer cells. PHLDA3 was found to be overexpressed in lung cancer tissues, and its expression was correlated with poor outcomes in lung adenocarcinoma patients. PHLDA3 expression promoted the proliferation, invasion, and migration of lung cancer cells. Overexpression of PHLDA3 activated the Wnt signaling pathway and facilitated epithelial-mesenchymal transition. Inhibition of Wnt signaling pathway activity, using XAV-939, reversed the effects of PHLDA3 overexpression in lung cancer cells; moreover, PHLDA3 could bind to GSK3β. Inhibition of GSK3β activity, using CHIR-99021, restored the proliferative and invasive abilities of PHLDA3 knockdown cells. Our findings demonstrate that PHLDA3 is highly expressed in lung adenocarcinomas and is correlated with poor outcomes. Furthermore, it promotes the proliferation and invasion of lung cancer cells by activating the Wnt signaling pathway.
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http://dx.doi.org/10.1038/s41374-021-00608-3DOI Listing
May 2021

Doxycycline Induces Apoptosis of S2 Strain-Infected HMC3 Microglial Cells by Activating Calreticulin-Dependent JNK/p53 Signaling Pathway.

Front Cell Infect Microbiol 2021 28;11:640847. Epub 2021 Apr 28.

Neurology Center, The General Hospital of Ningxia Medical University, Yinchuan, China.

Neurobrucellosis is a chronic complication of human brucellosis that is caused by the presence of spp in the central nervous system (CNS) and the inflammation play a key role on the pathogenesis. Doxycycline (Dox) is a widely used antibiotic that induces apoptosis of bacteria-infected cells. However, the mechanisms of inhibition of microglial apoptosis and Dox induction of apoptosis are still poorly understood. In this study, we found that S2 strain ( S2) increased calreticulin (CALR) protein levels and inhbited HMC3 cell apoptosis. Hence, we constructed two HMC3 cell line variants, one with stable overexpression (HMC3-CALR) and one with low expression of CALR (HMC3-sh-CALR). CALR was found to decrease levels of p-JNK and p-p53 proteins, as well as suppress apoptosis in HMC3 cells. These findings suggest that CALR suppresses apoptosis by inhibiting the JNK/p53 signaling pathway. Next, we treated HMC3, HMC3-CALR and HMC3-sh-CALR cell lines with S2 or Dox. Our results demonstrate that S2 restrains the JNK/p53 signaling pathway to inhibit HMC3 cell apoptosis increasing CALR protein expression, while Dox plays the opposite role. Finally, we treated S2-infected HMC3 cells with Dox. Our results confirm that Dox induces JNK/p53-dependent apoptosis in S2-infected HMC3 cells through inhibition of CALR protein expression. Taken together, these results reveal that CALR and the JNK/p53 signaling pathway may serve as novel therapeutic targets for treatment of neurobrucellosis.
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http://dx.doi.org/10.3389/fcimb.2021.640847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113685PMC
April 2021

Neuroprotective effects of aucubin on hydrogen peroxide-induced toxicity in human neuroblastoma SH-SY5Y cells via the Nrf2/HO-1 pathway.

Phytomedicine 2021 Apr 18:153577. Epub 2021 Apr 18.

Biomedicine Key Laboratory of Shaanxi Province, School of Pharmacy, Northwest University, Xi'an, P.R. China; Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, P.R. China. Electronic address:

Background: When redox balance is lost in the brain, oxidative stress can cause serious damage that leads to neuronal loss, in congruence with neurodegenerative diseases. Aucubin (AU) is an iridoid glycoside and that is one of the active constituents of Eucommia ulmoides, has many pharmacological effects such as anti-inflammation, anti-liver fibrosis, and anti-atherosclerosis.

Purpose: The present study aimed to evaluate the inhibitory effects of AU on cell oxidative stress against hydrogen peroxide (HO)-induced injury in SH-SY5Y cells in vitro.

Methods: SH-SY5Y cells were simultaneously treated with AU and HO for 24 h. Cell viability was measured by CCK-8. Additionally, mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, and cell apoptosis were measured by flow cytometry.

Results: The results showed that AU can significantly increase the HO-induced cell viability and the mitochondrial membrane potential, decrease the ROS generation, malondialdehyde (MDA), and increase glutathione (GSH) contents and the superoxide dismutase (SOD) activity. We also found that HO stimulated the production of nitric oxide (NO), which could be reduced by treatment with AU through inhibiting the inducible nitric oxide synthase (iNOS) protein expression. In HO-induced SH-SY5Y cells, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) content and cell apoptosis were significantly reduced by AU treatment through nuclear factor E2-related factor 2/hemo oxygenase-1 (Nrf2/HO-1) activation, inhibiting the expression of p-NF-κB/NF-κB and down-regulating MAPK and Bcl-2/Bax pathways.

Conclusion: These results indicate that AU can reduce inflammation and oxidative stress through the NF-κB, Nrf2/HO-1, and MAPK pathways.
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http://dx.doi.org/10.1016/j.phymed.2021.153577DOI Listing
April 2021

Batch fluidized bed reactor based modified biosynthetic crystals: Optimization of adsorptive properties and application in fluoride removal from groundwater.

Chemosphere 2021 May 10;281:130841. Epub 2021 May 10.

School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, China; Shaanxi Key Laboratory of Environmental Engineering, Xi'an University of Architecture and Technology, Xi'an, 710055, China.

A batch fluidized bed reactor (BFBR) with modified biosynthetic crystals (MBC), derived from Pseudomonas sp. HXF1, was investigated for the treatment of the groundwater containing fluoride (F). Impacts of different hydraulic retention time (HRT), pH, and initial F concentration on F removal were examined and the maximum defluorination efficiency was recorded as 95.20%. Moreover, recycling experiments were performed to evaluate the stability of repeated use. BFBR/MBC system showed a long-term effective treatment outcome with low fluctuation in the concentrations of residual Ca and F. The formed precipitates were characterized by SEM, XPS, XRD, and FTIR. The defluorination mechanisms of BFBR/MBC system were defined as the chemisorption and induced crystallization of Ca(PO)F on the MBC surface. As a feasible, economical, and environment-friendly technique, the method has a long-term value, which suggests promising applications in F removal and resourceful treatment.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130841DOI Listing
May 2021

The E3 ligase TRAF4 Promotes IGF Signaling by Mediating Atypical Ubiquitination of IRS-1.

J Biol Chem 2021 May 12:100739. Epub 2021 May 12.

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:

Insulin-like growth factor (IGF) is a potent mitogen that activates the IGF receptor (IGFR)/insulin receptor substrate (IRS) axis, thus stimulating growth in normal cells and uncontrolled cell proliferation in cancer. Post-translational modifications of IRS such as ubiquitination tightly control IGF signaling, and we previously identified IRS-1 as a potential substrate for the E3 ubiquitin ligase TRAF4 using an unbiased screen. Here we provide evidence that TRAF4-mediated ubiquitination of IRS-1 is physiologically relevant and crucial for IGF signal transduction. Through site-directed mutagenesis we found that TRAF4 promotes an atypical K29-linked ubiquitination at the C-terminal end of IRS-1. Its depletion abolishes AKT and ERK phosphorylation downstream of IGF-1, and inhibits breast cancer cell proliferation. Overexpression of TRAF4 enhances IGF1-induced IGFR-IRS-1 interaction, IRS-1 tyrosine phosphorylation, and downstream effector protein activation while mutation of IRS-1 ubiquitination sites completely abolishes these effects. Altogether, our studies demonstrate that non-proteolytic ubiquitination of IRS-1 is a key step in conveying IGF-1 stimulation from IGFR to IRS-1.
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http://dx.doi.org/10.1016/j.jbc.2021.100739DOI Listing
May 2021

KIF15 is involved in development and progression of Burkitt lymphoma.

Cancer Cell Int 2021 May 13;21(1):261. Epub 2021 May 13.

Department of Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine, 651 Dong feng East Road, Guangzhou, 510060, Guangdong, China.

Background: Burkitt lymphoma (BL) is a highly aggressive, fast-growing B-cell non-Hodgkin's lymphoma, manifested in several subtypes, including sporadic, endemic, and immunodeficiency-related forms, the mechanism of which is still not clear. Abundant evidence reported that KIF15 was involved in the progression of human cancer. The emphasis of this study is to explore the functions of KIF15 in the development of BL.

Methods: Firstly, tumor and normal tissues were collected for detecting expression of KIF15 in BL. Lentivirus-mediated shRNA knockdown of KIF15 was used to construct BL cell model, which was verified by qRT-PCR and Western Blot. The cell proliferation was detected by CCK8 assay, cell apoptosis and cell cycle were measured through flow cytometry. Transwell assay was conducted to detect the migration.

Results: We first found that KIF15 is highly expressed in BL. Knockdown of KIF15 can inhibit proliferation and migration, promote apoptosis and arrest the cell cycle. Moreover, KIF15 is involved in BL cell activity through regulating expression of apoptosis-related proteins (Caspase3, Caspase8, HTRA, IGFBP-6, p53, SMAC, sTNF-R1, TNF-β and Bcl-2) and downstream pathways, such as p-Akt, CCND1, CDK6 and PIK3CA.

Conclusions: These findings justify the search for small molecule inhibitors targeting KIF15 as a novel therapeutic strategy in BL.
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http://dx.doi.org/10.1186/s12935-021-01967-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117549PMC
May 2021

Photometric constraint for absolute phase unwrapping from single-frequency fringe patterns.

Opt Express 2021 Apr;29(8):12663-12680

As a fundamental step in fringe projection profilometry, absolute phase unwrapping via single-frequency fringe patterns is still a challenging ill-posed problem, which attracts lots of interest in the research area. To solve the problem above, additional constraints were constructed, such as spatial smoothness constraint (SSC) in spatial phase unwrapping algorithm and viewpoint consistency constraint (VCC) in multi-view systems (e.g., stereo and light-field cameras). However, there still exists phase ambiguity in the unwrapping result based on SSC. Moreover, VCC-based methods rely on additional cameras or light-field cameras, which makes the system complicated and expensive. In this paper, we propose to construct a novel constraint directly from photometric information in captured image intensity, which has never been fully exploited in phase unwrapping. The proposed constraint, named photometric constraint (PC), provides a prospective constraint for absolute phase unwrapping from single-frequency fringe patterns without any additional cameras. Extensive experiments have been conducted for the validation of the proposed method, which achieved comparable performance with the state-of-the-art method, given a traditional camera-projector setup and single high-frequency fringe patterns.
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http://dx.doi.org/10.1364/OE.420127DOI Listing
April 2021

Multi-level height maps-based registration method for sparse LiDAR point clouds in an urban scene.

Appl Opt 2021 May;60(14):4154-4164

The LiDAR sensor has been widely used for reconstruction in urban scenes. However, the current registration method makes it difficult to find stable 3D point correspondences from sparse and low overlapping LiDAR point clouds. In the urban situation, most of the LiDAR point clouds have a common flat ground. Therefore, we propose a novel, to the best of our knowledge, multi-level height (MH) maps-based coarse registration method. It requires that source and target point clouds have a common flat ground, which is easily satisfied for LiDAR point clouds in urban scenes. With MH maps, 3D registration is simplified as 2D registration, increasing the speed of registration. Robust correspondences are extracted in MH maps with different height intervals and statistic height information, improving the registration accuracy. The solid-state LiDAR Livox Mid-100 and mechanical LiDAR Velodyne HDL-64E are used in real-data and dataset experiments, respectively. Verification results demonstrate that our method is stable and outperforms state-of-the-art coarse registration methods for the sparse case. Runtime analysis shows that our method is faster than these methods, for it is non-iterative. Furthermore, our method can be extended for the unordered multi-view point clouds.
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http://dx.doi.org/10.1364/AO.419746DOI Listing
May 2021

Design, synthesis and anti-HIV evaluation of novel 5-substituted diarylpyrimidine derivatives as potent HIV-1 NNRTIs.

Bioorg Med Chem 2021 Jun 5;40:116195. Epub 2021 May 5.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Ji'nan 250012, China; China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province, 44 West Culture Road, 250012 Jinan, Shandong, PR China. Electronic address:

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are widely used in combination therapies against HIV-1. As a continuation of our efforts to discover and develop "me-better" drugs of DAPYs, novel diarylpyrimidine derivatives were designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells. All the compounds demonstrated strong inhibition activity against wide-type HIV-1 strain (III) with EC values in the range of 2.5 nM ~ 0.93 μM. Among them, compounds IVB-5-4 and IVB-5-8 were the most potent ones which showed anti-HIV-1 activity much superior than that of Nevirapine, comparable to Efavirenz and Etravirine. What's more, some compounds also showed low nanomole activity against some mutant strains such as K103N and E138K. The selected compound IVB-5-4 was also evaluated for the activity against reverse transcriptase (RT), and exhibited submicromolar IC values indicating that this series compounds are specific RT inhibitors. Preliminary structure-activity relationships and modeling studies of these new analogues provide valuable avenues for future molecular optimization.
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http://dx.doi.org/10.1016/j.bmc.2021.116195DOI Listing
June 2021

Dissecting Cellular Function and Distribution of β-Glucosidases in Trichoderma reesei.

mBio 2021 May 11;12(3). Epub 2021 May 11.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China

has 11 putative β-glucosidases in its genome, playing key parts in the induction and production of cellulase. Nevertheless, the reason why the genome encodes so many β-glucosidases and the distinct role each β-glucosidase plays in cellulase production remain unknown. In the present study, the cellular function and distribution of 10 known β-glucosidases (CEL3B, CEL3E, CEL3F, CEL3H, CEL3J, CEL1A, CEL3C, CEL1B, CEL3G, and CEL3D) were explored in , leaving out BGL1 (CEL3A), which has been well investigated. We found that the overexpression of or significantly enhanced extracellular β-glucosidase production, whereas the overexpression of severely inhibited cellulase production by cellulose, resulting in nearly no growth of Four types of cellular distribution patterns were observed for β-glucosidases in : (i) CEL3B, CEL3E, CEL3F, and CEL3G forming clearly separated protein secretion vesicles in the cytoplasm; (ii) CEL3H and CEL3J diffusing the whole endomembrane as well as the cell membrane with protein aggregation, like a reticular network; (iii) CEL1A and CEL3D in vacuoles; (iv) and CEL3C in the nucleus. β-glucosidases CEL1A, CEL3B, CEL3E, CEL3F, CEL3G, CEL3H, and CEL3J were identified as extracellular, CEL3C and CEL3D as intracellular, and CEL1B as unknown. The extracellular β-glucosidases CEL3B, CEL3E, CEL3F, CEL3H, and CEL3G were secreted through a tip-directed conventional secretion pathway, and CEL1A, via a vacuole-mediated pathway that was achieved without any signal peptide, while CEL3J was secreted via an unconventional protein pathway bypassing the endoplasmic reticulum (ER) and Golgi. Although β-glucosidases play an important role in fungal cellulase induction and production, our current understanding does not provide a global perspective on β-glucosidase function. This work comprehensively studies all the β-glucosidases regarding their effect on cellulase production and their cellular distribution and secretion. Overexpression of or significantly enhanced β-glucosidase production, whereas overexpression of severely inhibited cellulase production on cellulose. In addition, overexpression of , , , , , , or delayed endoglucanase (EG) production. We first identified four cellular distribution patterns of β-glucosidases in Specially, CEL3C was located in the nucleus. CEL3J was secreted through the nonclassical protein secretion pathway bypassing endoplasmic reticulum (ER) and Golgi. CEL1A was secreted via a vacuole-mediated conventional secretion route without a signal peptide. These findings advance our understanding of β-glucosidase properties and secretory pathways in filamentous fungi, holding key clues for future study.
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http://dx.doi.org/10.1128/mBio.03671-20DOI Listing
May 2021

LncRNA CCAT1 downregulation increases the radiosensitivity of non-small cell lung cancer cells.

Authors:
Zhao Wang

Kaohsiung J Med Sci 2021 May 6. Epub 2021 May 6.

Department of Oncology Radiotherapy 2, Yantai Yantaishan Hospital, Yantai, Shandong, China.

This study aims to investigate if the radiosensitivity of non-small cell lung cancer (NSCLC) cells can be regulated by long noncoding RNA (lncRNA) colon cancer associated transcript1 (CCAT1). CCAT1 was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in NSCLC cells (A549, H1299, SK-MES1, H460, and H647) and human bronchial epithelial cells (16HBE). H460 and A549 cells were then selected for the determination of CCAT1 expression after exposure to radiation (0, 2, 4, 6 Gy) at different time points (0, 6, 12, 24 h). Colony forming assay was performed to evaluate the effects of CCAT1 siRNA or pcDNA3.1-CCAT1 vector on the radiosensitivity of H460 and A549 cells. Then, flow cytometry, western blotting and qRT-PCR were also conducted. CCAT1 was increased in NSCLC cells when compared with 16HBE cells, which was declined in a time- and dosage-dependent manner after exposure to radiation. The H460 and A549 cell colonies were decreased and the γ-H2AX expression was elevated with the increase of radiation dosage, which was more obvious in those transfected with CCAT1 siRNA. CCAT1 downregulation arrested NSCLC cells at G2/M phase. Moreover, the enhanced apoptosis of radiotherapy-treated NSCLC cells with reductions of p-p38/p38, p-ERK/ERK, and p-JNK/JNK was promoted by siCCAT1, but it was reversed by pcDNA3.1-CCAT1 vector. Inhibiting CCAT1 regulated cell cycle, DNA damage and apoptosis of NSCLC cells, and affected MAPK pathway, eventually improving the radiosensitivity of NSCLC.
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http://dx.doi.org/10.1002/kjm2.12387DOI Listing
May 2021

Impact of Paroxetine, a Strong CYP2D6 Inhibitor, on SPN-812 (Viloxazine Extended-Release) Pharmacokinetics in Healthy Adults.

Clin Pharmacol Drug Dev 2021 May 4. Epub 2021 May 4.

Supernus Pharmaceuticals, Inc., Rockville, Maryland, USA.

SPN-812 (viloxazine extended-release) is a novel nonstimulant recently approved as a treatment for attention-deficit/hyperactivity disorder in children and adolescents. Given that SPN-812 is metabolized by CYP2D6 and may be coadministered with CYP2D6 inhibitors, this trial investigated the pharmacokinetics and safety of SPN-812 coadministered with the potent CYP2D6 inhibitor paroxetine. In this single-sequence, 3-treatment period study in healthy volunteers, subjects received a single oral dose of 700 mg SPN-812 alone (period 1), 20 mg daily paroxetine (10 days, period 2), followed by concurrent administration of SPN-812 and paroxetine (period 3). Blood samples were collected for 72 hours post-SPN-812 dosing and analyzed for viloxazine and its primary metabolite, 5-HVLX-gluc. Twenty-two healthy adults were enrolled; all completed the trial. The potential for drug interaction between SPN-812 and paroxetine was assessed using analysis of variance on the log-transformed pharmacokinetic parameters C , AUC , and AUC . The least-squares geometric mean ratios for viloxazine were (reported as the ratio of combination/SPN-812 alone) C , 116.04%; 90%CI, 109.49%-122.99%; AUC , 134.65%; 90%CI, 127.65-142.03; and AUC , 134.80%; 90%CI, 127.94%-142.03%. CYP2D6 inhibition resulted in a modest change (<35%) on viloxazine AUCs with no change in C . All adverse events were mild in severity.
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http://dx.doi.org/10.1002/cpdd.948DOI Listing
May 2021

Successful treatment of cytomegalovirus-induced hemophagocytic lymphohistiocytosis with ruxolitinib as a first-line treatment.

Infect Dis Now 2021 May 30;51(3):311-313. Epub 2020 Dec 30.

Department of hematology, Beijing Friendship Hospital, Capital Medical University, 100050 Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.idnow.2020.10.010DOI Listing
May 2021

Epstein-Barr virus infection is an important cause of hemophagocytic lymphohistiocytosis during chemotherapy for lymphoma.

Infect Dis Now 2021 May 30;51(3):310-311. Epub 2020 Dec 30.

Department of Hematology, Beijing Friendship Hospital, Capital Medical University, 95 Yong An Road, Xicheng District, 100050 Beijing, China. Electronic address:

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http://dx.doi.org/10.1016/j.idnow.2020.10.002DOI Listing
May 2021

Metal Oxide Based Heterojunctions for Gas Sensors: A Review.

Nanomaterials (Basel) 2021 Apr 17;11(4). Epub 2021 Apr 17.

Hubei Key Laboratory for Processing and Application of Catalytic Materials, School of Physics and Electronic Information, Huanggang Normal University, Huanggang 438000, China.

The construction of heterojunctions has been widely applied to improve the gas sensing performance of composites composed of nanostructured metal oxides. This review summarises the recent progress on assembly methods and gas sensing behaviours of sensors based on nanostructured metal oxide heterojunctions. Various methods, including the hydrothermal method, electrospinning and chemical vapour deposition, have been successfully employed to establish metal oxide heterojunctions in the sensing materials. The sensors composed with the built nanostructured heterojunctions were found to show enhanced gas sensing performance with higher sensor responses and shorter response times to the targeted reducing or oxidising gases compare with those of the pure metal oxides. Moreover, the enhanced gas sensing mechanisms of the metal oxide-based heterojunctions to the reducing or oxidising gases are also discussed, with the main emphasis on the important role of the potential barrier on the accumulation layer.
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http://dx.doi.org/10.3390/nano11041026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073732PMC
April 2021

Facile Synthesis of CO -Responsive Nano-Objects: Batch versus Semi-Batch RAFT Copolymerization.

Macromol Rapid Commun 2021 May 26;42(10):e2000765. Epub 2021 Apr 26.

School of Chemistry, Monash University, Clayton Campus, Clayton, VIC, 3800, Australia.

Precise polymer architecture and self-assembled morphological control are attractive due to their promising applications, such as drug delivery, biosensors, tissue engineering and "smart" optical systems. Herein, starting from the same hydrophilic units poly(ethylene glycol) (PEG), using CO -sensitive monomer N, N-diethylaminoethyl methacrylate (DEAEMA) and hydrophobic monomer benzyl methacrylate (BzMA), a series of well-defined statistical, block, and gradient copolymers is designed and synthesized with similar degree of polymerization but different monomer sequences by batch and semi-batch RAFT polymerization process and their CO -responsive behaviors of these nano-objects is systematically studied. The gradient copolymers are generated by using semi-batch methods with programmed monomer feed rate controlled by syringe pumps, achieving precise control over desired gradient copolymer composition distribution. In aqueous solution, the copolymers could self-assemble into various aggregates before CO stimulus. Upon bubbling CO , the gradient copolymers preferred to form nanosheet-like structures, while the block and statistical copolymers with similar molar mass could only form larger vesicles with thinner membrane thickness or disassemble. The semi-batch strategy to precisely control over the desired composition distribution of the gradient segment presents an emerging trend for the fabrication and application of stimuli-responsive polymers.
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http://dx.doi.org/10.1002/marc.202000765DOI Listing
May 2021

Icariin reduces Glu-induced excitatory neurotoxicity via antioxidative and antiapoptotic pathways in SH-SY5Y cells.

Phytother Res 2021 Apr 23. Epub 2021 Apr 23.

Biomedicine Key Laboratory of Shaanxi Province, School of Pharmacy, Northwest University, Xi'an, PR China.

Excessive glutamate (Glu) can lead to significant effects on neural cells through the generation of neurotoxic or excitotoxic cascades. Icariin (ICA) is a main active ingredient of Chinese Medicine Berberidaceae epimedium L., and has many biological activities, such as antiinflammation, antioxidative stress, and anti-depression. This study aims to evaluate the effect of ICA on Glu-induced excitatory neurotoxicity of SH-SY5Y cells. The cell viability assay was evaluated by the CCK-8 assay. The apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential were assessed by flow cytometry. Intracellular Ca concentration was determined by using the fluorescent probe Fluo-3. Protein expression was detected by western blotting analysis. ICA can significantly enhance the SH-SY5Y cell viability reduced by Glu. At the same time, ICA can significantly reduce apoptosis, ROS, nitric oxide (NO) levels, and intracellular Ca concentration, and significantly inhibit the increase of mitochondrial membrane potential. In addition, ICA significantly increased the expression of P47phox and iNOS, decreased p-JNK/JNK, p-P38/P38, Bax/Bcl-2, active caspase-3, and active caspase-9. These results indicate that ICA may reduce the excitatory neurotoxicity of Glu-induced SH-SY5Y cells through suppression of oxidative stress and apoptotic pathways, suggesting that ICA could be a potential therapeutic candidate for neurological disorders propagated by Glu toxicity.
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http://dx.doi.org/10.1002/ptr.7057DOI Listing
April 2021

Co S @CN Composites Obtained from Thiacalix[4]arene-Based Coordination Polymers for Supercapacitor Applications.

Chem Asian J 2021 Jun 29;16(11):1486-1492. Epub 2021 Apr 29.

College of Chemistry, Chemical Engineering and Environmental Engineering, Liaoning Shihua University, Fushun, Liaoning, 113001, P. R. China.

Metal sulfides have been recognized as promising electrodes for electrochemical energy storage owing to their remarkable electrochemical properties. Here, we demonstrate the preparation of Co S nanoparticles anchored on a carbon matrix (denoted as Co S [email protected] (X=1, 2)) from precursor sources, two 1D infinite coordination polymers 1 and 2. The two polymers were assembled by linking Co -TC4A secondary building blocks (SBUs) with ligands L and L , respectively (H TC4A=p-tert-butylthiacalix[4]arene, L =1,4-bis(2H-tetrazol-5-yl)benzene, L =1,3-bis(2H-tetrazol-5-yl)benzene). The composites obtained from 1D polymers showed different morphologies, that is, the Co S nanoparticles of Co S [email protected] are octahedral with a size of ca. 140 nm, while the lamellar Co S nanoparticles in Co S [email protected] possess different sizes (50-150 nm). The Co S [email protected] immobilized on nickel foam (Co S [email protected]/NF) show better supercapacitive performance than that of Co S [email protected] Co S [email protected] showed exceptionally high activities, combining higher specific capacitances (445.2 F g at 2 A g and 393.9 F g and 5 A g ), rate capacity (94.5% retention at 2 A g ), and long-term stability (79.2% retention at 5 A g over 1000 cycles). The smaller size and larger BET surface area of Co S [email protected] nanoparticles can improve the electrical conductivity and provide facile pathways for charge transport, thus leading to conspicuous electrochemical performance of Co S [email protected] compared with its Co S [email protected] counterpart.
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http://dx.doi.org/10.1002/asia.202100228DOI Listing
June 2021

DEK is highly expressed in breast cancer and is associated with malignant phenotype and progression.

Oncol Lett 2021 Jun 1;21(6):440. Epub 2021 Apr 1.

Department of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning 110001, P.R. China.

DEK proto-oncogene (DEK) has been demonstrated as an oncogene and is associated with the development of many types of tumor; however, the expression and role of DEK in breast cancer remain unknown. The present study aimed to determine the role of DEK in the progression of breast cancer. The expression of DEK in 110 breast cancer tissues and 50 adjacent normal breast tissues was examined using immunohistochemistry. Furthermore, DEK expression was upregulated by DEK transfection or downregulated by DEK shRNA interference in MCF7 cells. Proliferative and invasive abilities were examined in MCF7 cells using MTT assay, colony-formation assay and transwell invasion assays. The results demonstrated that DEK expression level was significantly increased in breast cancer tissues compared with normal breast tissues. Furthermore, high DEK expression was associated with high histological grade, lymph node metastasis, advanced Tumor-Node-Metastasis stage and high Ki-67 index; however, DEK expression was not associated with the expression level of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. High DEK expression indicated poor prognosis in patients with breast cancer. DEK overexpression upregulated the protein expression of β-catenin and Wnt and increased the proliferative and invasive abilities of breast cancer cells. DEK downregulation had the opposite effect. Taken together, the results from the present study demonstrated that high expression of DEK was common in patients with breast cancer and was associated with progression of the disease and poor prognosis, and that DEK overexpression promoted the proliferative and invasive abilities of breast cancer cells.
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http://dx.doi.org/10.3892/ol.2021.12701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045159PMC
June 2021

Corrigendum to Sub-toxic levels of cobalt ions impair mechanostranduction via HDAC6-depedent primary cilia shortening.

Biochem Biophys Res Commun 2021 May 16;555:213. Epub 2021 Apr 16.

Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, UK.

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http://dx.doi.org/10.1016/j.bbrc.2021.03.157DOI Listing
May 2021

Computer-aided Intraoperative Toric Intraocular Lens Positioning and Alignment During Cataract Surgery.

IEEE J Biomed Health Inform 2021 Apr 9;PP. Epub 2021 Apr 9.

Cataract causes more than half of all blindness worldwide. The most effective treatment is surgery, where cataract is often replaced by intraocular lens (IOL). Beyond saving vision, toric IOL implantation is becoming increasingly popular to correct corneal astigmatism. It is important to precisely position and align the axis of IOL during surgery to achieve optimal post-operative astigmatism correction. Comparing with conventional manual marking, automated markerless IOL alignment can be faster, more accurate and non-invasive. Here we propose a framework for computer-assisted intraoperative IOL positioning and alignment based on detection and tracking. Firstly, the iris boundary was segmented and the eye center was determined. A statistical sampling method was developed to segment iris and generate training labels, and both conventional algorithms and deep convolutional neural network (CNN) methods were evaluated. Then, regions of interests (ROIs) containing high density of scleral capillaries were used for tracking eye rotations. Both correlation filter and CNN methods were evaluated for tracking. Cumulative errors during long-term tracking were corrected using a reference image. Validation studies against manual labeling using 7 clinical cataract surgical videos demonstrated that the proposed algorithm achieved an average position error around 0.2 mm, an axis alignment error of < 1 degree, and a frame rate of > 25 FPS, and can be potentially used intraoperatively for markerless IOL positioning and alignment during cataract surgery.
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http://dx.doi.org/10.1109/JBHI.2021.3072246DOI Listing
April 2021