Publications by authors named "Yun Zhang"

2,893 Publications

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A novel -dimethylaminophenylether-based fluorescent probe for the detection of native ONOO in cells and zebrafish.

Analyst 2021 Aug 2. Epub 2021 Aug 2.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China.

Peroxynitrite (ONOO-) is a highly reactive substance, and plays an essential part in maintaining cellular homeostasis. It is crucial to monitor the ONOO- level in cells in normal and abnormal states. We introduced a p-dimethylaminophenylether-based fluorescent probe PDPE-PN, which could be synthesized readily. The new probe had prominent sensitivity and specificity, and a fast response towards ONOO-. The spectral performance of probe PDPE-PN was outstanding and the limit of detection was 69 nM. Probe PDPE-PN with low toxicity was applied to detect endogenous/exogenous ONOO- in RAW 264.7 macrophages and zebrafish. Importantly, successful application of the new receptor opens up new ideas for the design of ONOO- probes.
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http://dx.doi.org/10.1039/d1an00608hDOI Listing
August 2021

Spurious lymphocytopenia due to lymphoagglutination in a child with pneumonia.

Int J Lab Hematol 2021 Jul 29. Epub 2021 Jul 29.

Department of Clinical Laboratory, The District People's Hospital of Zhangqiu, Jinan, China.

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http://dx.doi.org/10.1111/ijlh.13673DOI Listing
July 2021

Heterochronous Metastases of Lung Adenocarcinoma to Pancreas and Liver: A Case Report from Pathological Perspectives.

Onco Targets Ther 2021 22;14:4269-4273. Epub 2021 Jul 22.

Department of Surgery, Shengzhou People's Hospital, Shaoxing, 312400, People's Republic of China.

Immunohistochemistry (IHC) is a vital tool to distinguish tumor metastases from primary lesions in addition to morphologic analysis. In this study, a 64-year-old female with a past surgical history of lung adenocarcinoma 11 years ago was presented with recurrence of liver nodular lesions after multiple surgical procedures, including the Whipple procedure for pancreatic head adenocarcinoma and cytoreductive surgery for liver metastasis. Liver biopsy and review of the previous specimens, based on IHC analyses, suggested heterochronous metastases of lung adenocarcinoma to the digestive systems in a long-time span, instead of primary pancreatic adenocarcinoma. This case demonstrates the potential for misdiagnoses from morphologic analysis alone and suggests the necessity of IHC analyses to avoid misjudgment on tumor phenotypes, when a previous oncologic history is presented.
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http://dx.doi.org/10.2147/OTT.S314385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314683PMC
July 2021

Efficacy and safety of seltorexant as adjunctive therapy in major depressive disorder: A phase 2b, randomized, placebo-controlled, adaptive dose-finding study.

Int J Neuropsychopharmacol 2021 Jul 29. Epub 2021 Jul 29.

Janssen Research & Development LLC, San Diego, CA.

Background: Seltorexant, a selective antagonist of human orexin-2 receptors, demonstrated antidepressant effects in a previous exploratory study in patients with major depressive disorder (MDD).

Methods: To replicate and extend this observation, a double-blind, adaptive dose-finding study was performed in patients with MDD who had an inadequate response to 1-3 selective serotonin/serotonin-norepinephrine reuptake inhibitors in the current episode. Patients were randomized (2:1:1) to placebo or seltorexant (20 mg or 40 mg) once-daily, administered adjunctively to the antidepressant which the patient had been receiving at screening. After an interim analysis (6 weeks post-randomization of 160 th patient), newly recruited patients randomly received (3:3:1) placebo or seltorexant 10 mg or 20 mg; the 40 mg dose was no longer assigned. Patients were stratified by baseline Insomnia Severity Index scores (ISI ≥15 vs ISI <15). Primary endpoint was change from baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 6.

Results: Mixed-Model for Repeated Measures (MMRM) analysis showed a greater improvement in MADRS total score in the seltorexant 20 mg group vs placebo at weeks 3 and 6; least-square means (LSM) difference (90% CI): -4.5 (-6.96;-2.07), p=0.003 and -3.1 (-6.13; -0.16), p=0.083, respectively. The improvement in MADRS score at week 6 for seltorexant 20 mg was greater in patients with baseline ISI ≥15 vs those with ISI <15; LSM difference (90% CI) vs placebo: -4.9 (-8.98;-0.80) and -0.7 (-5.16;3.76), respectively. The most common (≥5%) adverse events with seltorexant were somnolence, headache, and nausea.

Conclusions: A clinically meaningful reduction of depressive symptoms was observed for seltorexant 20 mg. In the subset of patients with sleep disturbance (ISI ≥15), a larger treatment difference between seltorexant 20 mg and placebo was observed, warranting further investigation. No new safety signal was identified.
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http://dx.doi.org/10.1093/ijnp/pyab050DOI Listing
July 2021

The application of computer vision to visual prosthesis.

Artif Organs 2021 Jul 27. Epub 2021 Jul 27.

School of Information, Shanghai Ocean University, Shanghai, China.

A visual prosthesis is an auxiliary device for patients with blinding diseases that cannot be treated with conventional surgery or drugs. It converts captured images into corresponding electrical stimulation patterns, according to which phosphenes are generated through the action of internal electrodes on the visual pathway to form visual perception. However, due to some restrictions such as the few implantable electrodes that the biological tissue can accommodate, the induced perception is far from ideal. Therefore, an important issue in visual prosthesis research is how to detect and present useful information in low-resolution prosthetic vision to improve the visual function of the wearer. In recent years, with the development and broad application of computer vision methods, researchers have investigated the possibility of their utilization in visual prostheses by simulating prosthetic visual percepts. Through the optimization of visual perception by image processing, the efficiency of visual prosthesis devices can be further improved to better meet the needs of prosthesis wearers. In this article, recent works on prosthetic vision centering on implementing computer vision methods are reviewed. Differences, strengths, and weaknesses of the mentioned methods are discussed. The development directions of optimizing prosthetic vision and improving methods of visual perception are analyzed.
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http://dx.doi.org/10.1111/aor.14022DOI Listing
July 2021

Single-Cell Transcriptomics Identifies a Unique Entity and Signature Markers of Transit-Amplifying Cells in Human Corneal Limbus.

Invest Ophthalmol Vis Sci 2021 Jul;62(9):36

Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States.

Purpose: Differentiated from adult stem cells (ASCs), transit-amplifying cells (TACs) play an important role in tissue homeostasis, development, and regeneration. This study aimed to characterize the gene expression profile of a candidate TAC population in limbal basal epithelial cells using single-cell RNA sequencing (scRNA-seq).

Methods: Single cells isolated from the basal corneal limbus were subjected to scRNA-seq using the 10x Genomics platform. Cell types were clustered by graph-based visualization methods and unbiased computational analysis. BrdU proliferation assays, immunofluorescent staining, and real-time reverse transcription quantitative polymerase chain reaction were performed using multiple culture models of primary human limbal epithelial cells to characterize the TAC pool.

Results: Single-cell transcriptomics of 16,360 limbal basal cells revealed 12 cell clusters. A unique cluster (3.21% of total cells) was identified as a TAC entity, based on its less differentiated progenitor status and enriched exclusive proliferation marker genes, with 98.1% cells in S and G2/M phases. The cell cycle-dependent genes were revealed to be largely enriched by the TAC population. The top genes were characterized morphologically and functionally at protein and mRNA levels. The specific expression patterns of RRM2, TK1, CENPF, NUSAP1, UBE2C, and CDC20 were well correlated in a time- and cycle-dependent manner with proliferation stages in the cell growth and regeneration models.

Conclusions: For the first time, to the best of our knowledge, we have identified a unique TAC entity and uncovered a group of cell cycle-dependent genes that serve as TAC signature markers. The findings provide insight into ASCs and TACs and lay the foundation for understanding corneal homeostasis and diseases.
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http://dx.doi.org/10.1167/iovs.62.9.36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300054PMC
July 2021

Smart Manganese Dioxide-Based Lanthanide Nanoprobes for Triple-Negative Breast Cancer Precise Gene Synergistic Chemodynamic Therapy.

ACS Appl Mater Interfaces 2021 Jul 22. Epub 2021 Jul 22.

State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, P. R. China.

Small interfering RNA (siRNA)-based gene therapy has been widely studied as a promising treatment for malignant triple-negative breast cancer (TNBC), but efficient delivery of siRNA still remains a challenge. In this study, a smart manganese dioxide (MnO)-based lanthanide nanoprobe therapeutic nanoplatform ([email protected]) was developed for tumor imaging and precise stimuli-responsive S100A4 siRNA (siS100A4)-mediated gene therapy in synergism with chemodynamic therapy (CDT) of TNBC. [email protected] has a tumor microenvironment-responsive capability attributed to the presence of MnO, which can be degraded by glutathione (GSH) in the tumor region while releasing siRNA and generating Mn to achieve precise gene therapy and a Fenton-like reaction-mediated CDT effect on TNBC. Subsequently, the lanthanide nanoprobes (ErNPs) are exposed to the second near-infrared region (NIR-II) fluorescence emission to realize the precise tumor location. Both the and results demonstrated that the smart nanoplatform possessed high siRNA delivery efficiency and GSH-responsive precise siRNA releasing ability, and compared with individual gene therapy, the GSH-depletion-enhanced CDT effect further reinforced TNBC inhibition, demonstrating excellent GSH-responsive-enhanced NIR-II precise tumor imaging therapy. These results indicate that the nanoplatform provides a crucial foundation for further research on theranostic systems of TNBC.
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http://dx.doi.org/10.1021/acsami.1c08927DOI Listing
July 2021

An Aerolysin-like Pore-Forming Protein Complex Targets Viral Envelope to Inactivate Herpes Simplex Virus Type 1.

J Immunol 2021 08 21;207(3):888-901. Epub 2021 Jul 21.

Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Science/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China;

Because most of animal viruses are enveloped, cytoplasmic entry of these viruses via fusion with cellular membrane initiates their invasion. However, the strategies in which host cells counteract cytoplasmic entry of such viruses are incompletely understood. Pore-forming toxin aerolysin-like proteins (ALPs) exist throughout the animal kingdom, but their functions are mostly unknown. In this study, we report that βγ-crystallin fused aerolysin-like protein and trefoil factor complex (βγ-CAT), an ALP and trefoil factor complex from the frog , directly blocks enveloped virus invasion by interfering with cytoplasmic entry. βγ-CAT targeted acidic glycosphingolipids on the HSV type 1 (HSV-1) envelope to induce pore formation, as indicated by the oligomer formation of protein and potassium and calcium ion efflux. Meanwhile, βγ-CAT formed ring-like oligomers of ∼10 nm in diameter on the liposomes and induced dye release from liposomes that mimic viral envelope. Unexpectedly, transmission electron microscopy analysis showed that the βγ-CAT-treated HSV-1 was visibly as intact as the vehicle-treated HSV-1, indicating that βγ-CAT did not lyse the viral envelope. However, the cytoplasmic entry of the βγ-CAT-treated HSV-1 into HeLa cells was totally hindered. In vivo, topical application of βγ-CAT attenuated the HSV-1 corneal infection in mice. Collectively, these results uncovered that βγ-CAT possesses the capacity to counteract enveloped virus invasion with its featured antiviral-acting manner. Our findings will also largely help to illustrate the putative antiviral activity of animal ALPs.
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http://dx.doi.org/10.4049/jimmunol.2001056DOI Listing
August 2021

Erythropoietin promotes abdominal aortic aneurysms in mice through angiogenesis and inflammatory infiltration.

Sci Transl Med 2021 07;13(603)

Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China.

Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disease, but the underlying mechanisms remain unknown. Here, we tested the hypothesis that erythropoietin (EPO) may promote the formation of AAA. We found that EPO dose-dependently promoted the formation of AAA in both (66.7%) and wild-type (WT) (60%) mice receiving a high dose of EPO. EPO monoclonal antibodies given to mice receiving angiotensin II (AngII) stimulation resulted in a markedly lower incidence of AAA (from 86.7 to 20%, < 0.001), and EPO receptor (EPOR) knockdown in mice substantially reduced the incidence of AAA compared to mice after AngII stimulation (from 86.7 to 45.5%, < 0.05), further supporting the finding that EPO is a contributor to AAA formation. EPO-induced AAA resulted in increased microvessels, phagocyte infiltration, and matrix metalloproteinase secretion, as well as reduced collagen and smooth muscle cells (SMCs). Experiments in vitro and ex vivo demonstrated that EPO induced proliferation, migration, and tube formation of endothelial cells via the JAK2/STAT5 signaling pathway. In humans, serum EPO concentrations were higher in patients with AAA than in healthy individuals and correlated with the size of the AAA, suggesting a potential link between EPO and the severity of AAA in humans. In conclusion, we found that EPO promotes the formation of AAA in both and WT mice by enhancing angiogenesis, inflammation, collagen degradation, and apoptosis of SMCs and that EPO/EPOR signaling is essential for AngII-induced AAA. The association between EPO and AAA in humans warrants further study.
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http://dx.doi.org/10.1126/scitranslmed.aaz4959DOI Listing
July 2021

Bisindole compound 4ae ameliorated cognitive impairment in rats with vascular dementia by anti-inflammation effect via microglia cells.

Eur J Pharmacol 2021 Jul 17;908:174357. Epub 2021 Jul 17.

School of Pharmacy, Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng, 475004, PR China. Electronic address:

Neuroinflammation is considered as an important mechanism of vascular dementia (VaD). Our primary study showed that the bisindole analogue (2-(2-(bis(5-chloro-1H-indol-3-yl)methyl)phenoxy)aniline, compound 4ae) had great anti-inflammation in zebrafish. Rat model of permanent occlusion of the bilateral common carotid arteries (2-vessel occlusion, 2VO) was utilized to evaluate the neuroprotective effect of 4ae. Our results showed that 4ae treatment effectively reduced Iba-1 positive microglia cells in cerebral cortex and hippocampus after cerebral ischemia. Compared with the model group, neuroinflammation characterized by Interleukin (IL)-6 and tumor necrosis factor (TNF)-α, oxidative stress characterized by reactive oxygen species (ROS) and superoxide dismutase (SOD) were both improved significantly after treatment with 4ae. Moreover, 4ae treatment significantly reversed ischemia-induced ACE enhancement, while notably increased the level of ACE2. To further elucidate the role of 4ae on neuroinflammation, we investigated the effects of 4ae on lipopolysaccharide (LPS)-induced inflammation in BV2 microglia cells, a kind of innate immune cells in central nervous system. The results demonstrated that the expressions of CD11b, TNFα and IL-6 and the level of ROS were up-regulated after treatment with LPS. More importantly, 4ae was able to block the activation of BV2 by reducing ROS production and the expression of inflammatory cytokines. In addition, our results suggested that 4ae inhibited the inflammatory response mediated by microglia cells by inhibiting NF-κB. This anti-inflammatory effect on microglia may be a potential mechanism for the neuroprotective effect of 4ae in VaD.
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http://dx.doi.org/10.1016/j.ejphar.2021.174357DOI Listing
July 2021

Wide-Range, Rapid, and Specific Identification of Pathogenic Bacteria by Surface-Enhanced Raman Spectroscopy.

ACS Sens 2021 Jul 20. Epub 2021 Jul 20.

State Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.

Sensitive, selective, rapid, and label-free detection of pathogenic bacteria with high generality is of great importance for clinical diagnosis, biosecurity, and public health. However, most traditional approaches, such as microbial cultures, are time-consuming and laborious. To circumvent these problems, surface-enhanced Raman spectroscopy (SERS) appears to be a powerful technique to characterize bacteria at the single-cell level. Here, by SERS, we report a strategy for the rapid and specific detection of 22 strains of common pathogenic bacteria. A novel and high-quality silver nanorod SERS substrate, prepared by the facile interface self-assembly method, was utilized to acquire the chemical fingerprint information of pathogens with improved sensitivity. We also applied the mathematical analysis methods, such as the -test and receiver operating characteristic method, to determine the Raman features of these 22 strains and demonstrate the clear identification of most bacteria (20 strains) from the rest and also the reliability of this SERS sensor. This rapid and specific strategy for wide-range bacterial detection offers significant advantages over existing approaches and sets the base for automated and onsite detection of pathogenic bacteria in a complex real-life situation.
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http://dx.doi.org/10.1021/acssensors.1c00641DOI Listing
July 2021

The prognostic value of USP14 and PSMD14 expression in non-small cell lung cancer.

Ann Transl Med 2021 Jun;9(12):1019

Department of Pathology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Background: Ubiquitin specific peptidase 14 (USP14) and proteasome 26S subunit, non-ATPase 14 (PSMD14) are two deubiquitinases that are closely related to the human 19S proteasome. These are highly expressed in various types of cancers and are associated with prognosis. However, the expression, clinicopathological features, and prognostic relevance of these two deubiquitinases remain unclear in patients with non-small cell lung cancer (NSCLC). Moreover, the correlation between the expression of these two deubiquitinases in NSCLC has not been reported.

Methods: In this study, the expression of USP14 and PSMD14 in NSCLC tissues and adjacent non-tumor tissues were examined by immunohistochemical staining. The association of these two deubiquitinases with the clinicopathological features and overall survival (OS) of patients with NSCLC was evaluated meanwhile.

Results: The expression of USP14 and PSMD14 was upregulated in NSCLC tissues compared with adjacent non-tumor tissues. High expression of both these deubiquitinases was positively correlated with the TNM stage of NSCLC. In addition, PSMD14 was positively correlated with lymph node metastasis in NSCLC. The survival analysis showed that elevated levels of USP14 or PSMD14 were associated with poorer survival of NSCLC patients compared with low expression of USP14 or PSMD14. Cox regression analysis indicated that TNM stage, USP14, and PSMD14 were independent prognostic factors for OS in NSCLC.

Conclusions: This study demonstrated that USP14 and PSMD14 may play important roles in the progression of NSCLC, especially when they are expressed simultaneously at elevated levels. Thus, USP14 and PSMD14 may be potential novel biomarkers and therapeutic targets for the prognosis and treatment of patients with NSCLC.
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http://dx.doi.org/10.21037/atm-21-2748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267284PMC
June 2021

2D Echocardiographic Right Ventricular Size and Systolic Function Measurements Stratified by Sex, Age and Ethnicity: Results of the World Alliance of Societies of Echocardiography Study.

J Am Soc Echocardiogr 2021 Jul 15. Epub 2021 Jul 15.

University of Chicago, Chicago IL.

Background: Echocardiographic assessment of right ventricular (RV) systolic function is an important component of clinical decision-making. While societal guidelines have worked to define normal ranges of RV size and function, they have not included the impact of age, sex and ethnicity on these parameters, as they have for the left ventricle. The World Alliance of Societies of Echocardiography (WASE) study was designed to investigate the effect of age, sex and ethnicity on all cardiac chambers. In this study, we sought to explore whether these differences exist for RV systolic parameters.

Methods: Adequate 2D RV focused-views for measurement of systolic parameters, including fractional area change (FAC), global and free-wall longitudinal strain (GLS, FWS) were available in 1913 subjects (47±17 years; 51% male). Basal and mid-RV dimensions, length, tricuspid annular peak systolic excursion (TAPSE), tissue Doppler S' velocity and myocardial performance index (MPI) were also measured. Subjects were grouped by age (<40, 41-65, >65 years), with results also stratified by sex and ethnicity (Asian, Black or White) and analyzed using vendor-independent software. Differences between groups were evaluated using ANOVA.

Results: Women had smaller absolute and indexed RV areas, absolute RV dimensions and higher magnitude FAC, FWS and GLS, compared to men. With respect to age, most of the statistically significant differences were noted between the <40 and >65 age groups, with RV areas and length smaller in older age groups and RV functional parameters (S', FAC, TAPSE, GLS, FWS and MPI) showing minimal decrease or no change with age. While there were no meaningful differences in functional parameters between ethnic groups, RV size was smallest in Asians.

Conclusions: Our findings suggest that while 2D RV parameters are age- and sex-dependent, association with race is less apparent, excepting that the Asian population appears to have smaller chamber sizes when compared with whites and blacks.
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http://dx.doi.org/10.1016/j.echo.2021.06.013DOI Listing
July 2021

Structure-based molecular networking for the target discovery of novel germicidin derivatives from the sponge-associated streptomyces sp. 18A01.

J Antibiot (Tokyo) 2021 Jul 16. Epub 2021 Jul 16.

Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, People's Republic of China.

Four new α-pyrone derivatives, named germicidins P-S (1-4) along with nine known analogues (5-13) were discovered from the sponge-associated Streptomyces sp. 18A01 guided by Global Natural Products Social (GNPS) molecular networking, the LC-DAD-MS profile, and hexokinase II (HK2) inhibitory activity. The structures of 1-13 were elucidated by analysis of their HRMS, optical rotation, and NMR spectroscopic data. The absolute configurations of germicidin P (1) and germicidin Q (2) were determined on the basis of comparisons of experimental and theoretically calculated ECD spectra. Bioactivities of the isolated compounds were assayed against human HK2. The bioassay results showed that compounds 1-4 and 11-13 exhibited significant inhibitory activities against HK2, with IC values ranging from 5.1 to 11.0 μM. A molecular docking simulation demonstrated that these germicidins were docked in the inner active site tunnel of HK2. Interestingly, the amino residue Arg91 has a better binding affinity and efficacy than the amino residue Asn89 in the process of HK2 binding to the ligands, resulting in better hexokinase inhibitory activity. This result provided a valuable perspective for better understanding their HK2 inhibition activity.
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http://dx.doi.org/10.1038/s41429-021-00447-wDOI Listing
July 2021

Identification and Fine-mapping of a New Bacterial Blight Resistance Gene, Xa47(t), in G252, an Introgression Line of Yuanjiang Common Wild Rice (Oryza rufipogon).

Plant Dis 2021 Jul 14. Epub 2021 Jul 14.

Yunnan Agricultural University, 12616, Rice Research Institute, Kunming, Yunnan, China;

Bacterial blight (BB) disease caused by Xanthomonas oryzae pv. oryzae (Xoo) is a common, widespread, and highly devastating disease that affects rice yield. Breeding resistant cultivars is considered the most effective measure for controlling this disease. The introgression line G252 derived from Yuanjiang common wild rice (Oryza rufipogon) was highly resistant to all tested Xoo strains, including C5, C9, PXO99, PB, T7147Y8, Hzhj19, YM1, YM187, YJdp-2, and YJws-2. To identify the BB resistance gene(s) of G252, we developed an F2 population from the cross between G252 and 02428. A linkage analysis was carried out between the phenotype and genotype in the population. A segregation ratio of 3:1 was observed between the resistant and susceptible individuals in F2 progeny, indicating a dominant resistance gene, Xa47(t), in G252. The resistance gene was mapped within an approximately 26.24 kb physical region on chromosome 11 between two InDel markers, R13I14 and 13rbq-71; and moreover, one InDel marker, Hxjy-1, co-segregated with Xa47(t). Three genes were predicted within the target region, including a promising candidate gene encoding a nucleotide-binding domain and leucine-rich repeat (NLR) protein (LOC_Os11g46200) by combining the structure and expression analysis. Physical mapping data suggested that Xa47(t) was a new broad-spectrum BB resistance gene.
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http://dx.doi.org/10.1094/PDIS-05-21-0939-REDOI Listing
July 2021

Developmental toxicity caused by sanguinarine in zebrafish embryos via regulating oxidative stress, apoptosis and wnt pathways.

Toxicol Lett 2021 Jul 9;350:71-80. Epub 2021 Jul 9.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Shandong Provincial Engineering Laboratory for Biological Testing Technology, 28789 Jingshidong Road, Licheng District, Jinan, 250103, Shandong Province, PR China. Electronic address:

Sanguinarine, derived from the root of Sanguinaria canadensis, have multiple biological activities, such as antimicrobial, insecticidal, antitumor, anti-inflammatory and anti-angiogenesis effect, but little is known about its toxicity on normal embryonic development. Here, we study the developmental toxicity using zebrafish model. Notably, sanguinarine caused a significant increase of the malformation rate and decrease of hatching rates and body length of zebrafish embryos. Sanguinarine also impaired the normal development of heart, liver and nerve system of zebrafish embryos. Further, the ROS level and MDA concentrations were remarkably increased, while the activity of T-SOD was decreased. In addition, obvious increase of apoptosis were observed by AO staining or TUNEL assay. Further studies showed that the oxidative stress-, apoptosis-related genes were changed, while genes of nrf2 and wnt pathways were inhibited by sangunarine. To sum up, our study will be helpful to understand the adverse effect of sanguinarine on embryonic development and the underlying molecular mechanism.
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http://dx.doi.org/10.1016/j.toxlet.2021.07.001DOI Listing
July 2021

Traditional Chinese Medication Tongxinluo Attenuates Lipidosis in Ox-LDL-Stimulated Macrophages by Enhancing Beclin-1-Induced Autophagy.

Front Pharmacol 2021 25;12:673366. Epub 2021 Jun 25.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China.

Tongxinluo (TXL), a traditional Chinese medication, plays a key role in the formation and progression of plaques in atherosclerosis. The formation of foam cells by macrophages accelerates the destabilisation of plaques. In previous research, we had found that TXL significantly inhibits ox-LDL-induced apoptosis in macrophages by improving the dissociation of the Beclin-1-Bcl-2 complex. Therefore, here, we explored the effect of TXL on lipid metabolism in macrophages and the mechanism involved. To evaluate the role of TXL in atherosclerotic plaques, we construct the atherosclerotic animal model with lentiviral injection and performed immunofluorescence staining analysis . Western blot, immunofluorescence staining and microscopy were performed to elucidate the mechanism underlying TXL-mediated regulation of autophagy in THP-1 macrophages . Immunofluorescence assay revealed that TXL treatment inhibited lipid deposition in advanced atherosclerotic plaques. TXL treatment inhibited lipid deposition in THP-1 macrophages by enhancing autophagy via Beclin-1. TXL reversed the high expression of class I histone deacetylases (HDACs) induced by ox-LDL ( < 0.05). Compared with the TXL + ox-LDL group, TXL failed to promote intracellular lipid droplet decomposition after the addition of the histone deacetylase agonist. We found that TXL attenuates the accumulation of lipids in macrophage by enhancing Beclin-1-induced autophagy, and additionally, it inhibits the inhibitory effect of class I HDAC on the expression of Beclin-1.
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http://dx.doi.org/10.3389/fphar.2021.673366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267176PMC
June 2021

A positive-negative switching LC-MS/MS method for quantification of fenoldopam and its phase II metabolites: Applications to a pharmacokinetic study in rats.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Jul 5;1179:122854. Epub 2021 Jul 5.

Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne Street, Houston, TX 77004, USA. Electronic address:

Fenoldopam is an approved drug used to treat hypotension. The purpose of this study is to develop and validate an LC-MS method to quantify fenoldopam and its major metabolites fenoldopam-glucuronide and fenoldopam-sulfate in plasma and apply the method to a pharmacokinetic study in rats. A Waters C column was used with 0.1% formic acid in acetonitrile and 0.1% formic acid in water as the mobile phases to elute the analytes. A positive-negative switching method was performed in a triple quadrupole mass spectrometer using Multiple Reaction Monitoring (MRM) mode. A one-step protein precipitation using methanol and ethyl acetate was successfully applied for plasma sample preparation. The method was validated following the FDA guidance. The results show that the LLOQ of fenoldopam, fenoldopam-glucuronide and fenoldopam-sulfate is 0.98, 9.75 and 0.98 nM, respectively. The intraday and interday variance is less than 8.4% and the accuracy is between 82.5 and 116.0 %. The extraction recovery for these three analytes ranged from 81.3 ± 4.1% to 113.9 ± 13.2%. There was no significant matrix effect and no significant degradation under the experimental conditions. PK studies showed that fenoldopam was rapidly eliminated (t = 0.63 ± 0.24 h) from the plasma and glucuronide is the major metabolite. This method was suitably selective and sensitive for pharmacokinetic and phase II metabolism studies.
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http://dx.doi.org/10.1016/j.jchromb.2021.122854DOI Listing
July 2021

Black soldier fly (Hermetia illucens L.) larval diet improves CD8 lymphocytes proliferation to eliminate chicken coronavirus at an early infection stage.

Vet Microbiol 2021 Jul 2;260:109151. Epub 2021 Jul 2.

State Key Laboratory of Biocontrol, School of Life Science, Sun Yat-sen University, Guangzhou, 510006, China. Electronic address:

Avian infectious bronchitis virus (IBV), belonging to Gammacoronavirus, is an economically important respiratory virus affecting poultry industry worldwide. The virus can infect chickens at all ages, whereas young chickens (less than 15 day old) are more susceptible to it. The present study was conducted to investigate effects of dietary supplementation of black soldier fly (Hermetia illucens L.) larvae (BSFL) on immune responses in IBV infected 10-day-old chickens. BSFL were ground to powder and mixed with commercial fodder (1%, 5%, and 10 % [mass] BSFL powder) to feed 1-day-old yellow broilers for ten days and then challenged with IBV. Our results indicated that commercial fodder supplemented with 10 % BSFL [mass] reduced mortalities (20 %) and morbidities (80 %), as well as IBV viral loads in tracheas (65.8 %) and kidneys (20.4 %) from 3-day post challenge (dpc), comparing to that of IBV-infected chickens fed with non-additive commercial fodder. Furthermore, at 3-day post challenge (dpc), 10 % BSFL [mass] supplemented chickens presented more CD8 T lymphocytes in peripheral blood and a rise in interferon-g (IFN-γ) at both mRNA and protein levels in spleens, comparing with chickens fed with commercial fodder. Furthermore, the mRNA abundance of MHC-I, Fas, LITAF, and IL-2 in the spleens of 10 % BSFL [mass] supplemented chickens increased at different time points after challenge. The present results suggest that supplemental BSFL could improve CD8 T lymphocytes proliferation, thus benefit young chickens to defend against IBV infection.
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http://dx.doi.org/10.1016/j.vetmic.2021.109151DOI Listing
July 2021

Quantitative proteomic and phosphoproteomic analysis of chicken skeletal muscle during embryonic development.

Anim Biotechnol 2021 Jul 8:1-12. Epub 2021 Jul 8.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P. R. China.

Skeletal muscle also plays a vital role in regulating the movement energy storage and health of metabolism. In order to investigate the expression profile of protein and phosphor-proteins in chicken skeletal muscle during embryonic development, we performed phosphor-proteomics analysis by label-free and TiO enrichment strategy in chicken leg muscle tissues of at embryonic age embryo day 7(E7), E12, E17 and 3-day post-hatch (D3). The study led to the identification of 4332 proteins in the proteome and 1043 phosphorylation modification sites in the phosphorylated proteome, corresponding to 718 proteins (FC ≥ 2 or FC ≤ 0.5 and  < 0.05). The DEP-associated biological processes were involved in Focal adhesion, Glycolysis/gluconeogenesis, Arginine and proline metabolism by KEGG analysis. PPI analyses revealed that these DEPs TNNC1, TNNC2, TNNT2, TNNT3 and phosphorylated DEPs MYLPF interacted with involved pathways. Integrative analysis of proteome and phosphoproteome data found 324 common proteins, corresponding to 521 modification sites and Focal adhesion was the only pathway significantly enriched. These results provide a basis for further understanding the proteome and phosphoproteome and their regulatory biochemical pathways during the development of embryonic chicken skeletal muscle.
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http://dx.doi.org/10.1080/10495398.2021.1941071DOI Listing
July 2021

Impact of SARS-CoV-2 variants on the total CD4 and CD8 T cell reactivity in infected or vaccinated individuals.

Cell Rep Med 2021 Jul 2;2(7):100355. Epub 2021 Jul 2.

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.

The emergence of SARS-CoV-2 variants with evidence of antibody escape highlight the importance of addressing whether the total CD4 and CD8 T cell recognition is also affected. Here, we compare SARS-CoV-2-specific CD4 and CD8 T cells against the B.1.1.7, B.1.351, P.1, and CAL.20C lineages in COVID-19 convalescents and in recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. The total reactivity against SARS-CoV-2 variants is similar in terms of magnitude and frequency of response, with decreases in the 10%-22% range observed in some assay/VOC combinations. A total of 7% and 3% of previously identified CD4 and CD8 T cell epitopes, respectively, are affected by mutations in the various VOCs. Thus, the SARS-CoV-2 variants analyzed here do not significantly disrupt the total SARS-CoV-2 T cell reactivity; however, the decreases observed highlight the importance for active monitoring of T cell reactivity in the context of SARS-CoV-2 evolution.
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http://dx.doi.org/10.1016/j.xcrm.2021.100355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249675PMC
July 2021

Genetic Variants in Genes Are Associated With the Susceptibility to HCV Infection in a High-Risk Chinese Population.

Front Immunol 2021 18;12:632353. Epub 2021 Jun 18.

Department of Infectious Diseases, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: KIR/HLA-C signaling pathway influences the innate immune response which is the first defense to hepatitis C virus (HCV) infection. The aim of this study was to determine the association between the genetic polymorphisms of genes and the outcomes of HCV infection in a high-risk Chinese population.

Methods: In this case-control study, four single nucleotide polymorphisms (SNPs) of genes (// rs35440472, rs2308557, rs1130838, and rs2524094) were genotyped by TaqMan assay among drug users and hemodialysis (HD) patients including 1,378 uninfected control cases, 307 subjects with spontaneous viral clearance, and 217 patients with persistent HCV infection. Bioinformatics analysis was used to functionally annotate the SNPs.

Results: After logistic regression analysis, the rs35440472-A and rs1130838-A alleles were found to be associated with a significantly elevated risk of HCV infection (OR = 1.562, 95% CI: 1.229-1.987, < 0.001; OR = 2.134, 95% CI: 1.180-3.858, = 0.012, respectively), which remained significant after Bonferroni correction (0.05/4). The combined effect of their risk alleles and risk genotypes (rs35440472-AA and rs1130838-AA) were linked to the increased risk of HCV infection in a locus-dosage manner (all < 0.001). Based on the SNPinfo web server, rs35440472 was predicted to be a transcription factor binding site (TFBS) while rs1130838 was predicted to have a splicing (ESE or ESS) function.

Conclusion: // rs35440472-A and rs1130838-A variants are associated with increased susceptibility to HCV infection in a high-risk Chinese population.
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http://dx.doi.org/10.3389/fimmu.2021.632353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253047PMC
June 2021

Histone methyltransferase SETD1A participates in lung cancer progression.

Thorac Cancer 2021 Jul 4. Epub 2021 Jul 4.

Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Lung cancer is the leading cause of cancer-related death worldwide, with an estimated 1.2 million deaths each year. Despite advances in lung cancer treatment, 5-year survival rates are lower than ~15%, which is attributes to diagnosis limitations and current clinical drug resistance. Recently, more evidence has suggested that epigenome dysregulation is associated with the initiation and progress of cancer, and targeting epigenome-related molecules improves cancer symptoms. Interestingly, some groups reported that the level of methylation of histone 3 lysine 4 (H3K4me3) was increased in lung tumors and participated in abnormal transcriptional regulation. However, a mechanistic analysis is not available. In this report, we found that the SET domain containing 1A (SETD1A), the enzyme for H3K4me3, was elevated in lung cancer tissue compared to normal lung tissue. Knockdown of SETD1A in A549 and H1299 cells led to defects in cell proliferation and epithelial-mesenchymal transition (EMT), as evidenced by inhibited WNT and transforming growth factor β (TGFβ) pathways, compared with the control group. Xenograft assays also revealed a decreased tumor growth and EMT in the SETD1A silenced group compared with the control group. Mechanistic analysis suggested that SETD1A might regulate tumor progression via several critical oncogenes, which exhibited enhanced H3K4me3 levels around transcriptional start sites in lung cancer. This study illustrates the important role of SETD1A in lung cancer and provides a potential drug target for treatment.
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http://dx.doi.org/10.1111/1759-7714.14065DOI Listing
July 2021

Intra-articular Injection of Kartogenin-Enhanced Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Knee Osteoarthritis in a Rat Model.

Am J Sports Med 2021 Aug 2;49(10):2795-2809. Epub 2021 Jul 2.

Orthopedic Research Institution, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China.

Background: In this study, we investigated the in vitro and in vivo chondrogenic capacity of kartogenin (KGN)-enhanced bone marrow-derived mesenchymal stem cells (BMSCs) for cartilage regeneration.

Purpose: To determine (1) whether functionalized nanographene oxide (NGO) can effectively deliver KGN into BMSCs and (2) whether KGN would enhance BMSCs during chondrogenesis in vitro and in vivo in an animal model.

Study Design: Controlled laboratory study.

Methods: Functionalized NGO with line chain amine-terminated polyethylene glycol (PEG) and branched polyethylenimine (BPEI) were used to synthesize biocompatible NGO-PEG-BPEI (PPG) and for loading hydrophobic KGN molecules noncovalently via π-π stacking and hydrophobic interactions (PPG-KGN). Then, PPG-KGN was used for the intracellular delivery of hydrophobic KGN by simple mixing and co-incubation with BMSCs to acquire KGN-enhanced BMSCs. The chondrogenic efficacy of KGN-enhanced BMSCs was evaluated in vitro. In vivo, osteoarthritis (OA) was induced by anterior cruciate ligament transection in rats. A total of 5 groups were established: normal (OA treated with nothing), phosphate-buffered saline (PBS; intra-articular injection of PBS), PPG-KGN (intra-articular injection of PPG-KGN), BMSCs (intra-articular injection of BMSCs), and BMSCs + PPG-KGN (intra-articular injection of PPG-KGN-preconditioned BMSCs). At 6 and 9 weeks after the surgical induction of OA, the rats received intra-articular injections of PPG-KGN, BMSCs, or KGN-enhanced BMSCs. At 14 weeks after the surgical induction of OA, radiographic and behavioral evaluations as well as histological analysis of the knee joints were performed.

Results: The in vitro study showed that PPG could be rapidly uptaken in the first 4 hours after incubation, reaching saturation at 12 hours and accumulating in the lysosome and cytoplasm of BMSCs. Thus, PPG-KGN could enhance the efficiency of the intracellular delivery of KGN, which showed a remarkably high chondrogenic differentiation capacity of BMSCs. When applied to an OA model of cartilage injuries in rats, PPG-KGN-preconditioned BMSCs contributed to protection from joint space narrowing, pathological mineralization, OA development, and OA-induced pain, as well as improved tissue regeneration, as evidenced by radiographic, weightbearing, and histological findings.

Conclusion: Our results demonstrate that KGN-enhanced BMSCs showed markedly improved capacities for chondrogenesis and articular cartilage repair. We believe that this work demonstrates that a multifunctional nanoparticle-based drug delivery system could be beneficial for stem cell therapy. Our results present an opportunity to reverse the symptoms and pathophysiology of OA.

Clinical Relevance: The intracellular delivery of KGN to produce BMSCs with enhanced chondrogenic potential may offer a new approach for the treatment of OA.
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http://dx.doi.org/10.1177/03635465211023183DOI Listing
August 2021

Emodin from Inhibits via Toll-Like Receptor 3 Activation.

Viruses 2021 Jun 26;13(7). Epub 2021 Jun 26.

State Key Laboratory of Biocontrol, School of Life Science, Sun Yat-sen University, Guangzhou 510006, China.

(PRRSV) causes severe reproductive failure in sows and respiratory diseases in growing and finishing pigs and results in great economic losses to the swine industry. Although vaccines are available, PRRSV remains a major threat to the pig farms. Thus, there is an urgent need to develop antiviral drugs to compensate for vaccines. In this study, we report that extract (Ae) can strongly inhibit PRRSV in Marc-145 cells and porcine alveolar macrophages lines (iPAMs) in vitro. Furthermore, we identified a novel anti-PRRSV molecule, Emodin, from Ae by high-performance liquid chromatography (HPLC). Emodin exerted its inhibitory effect through targeting the whole stages of PRRSV infectious cycle. Moreover, we also found that Emodin can inactivate PRRSV particles directly. Notably, we confirmed that Emodin was able to significantly induce Toll-like receptor 3 (TLR3) ( < 0.01), IFN-α ( < 0.05) and IFN-β expression in iPAMs, indicating that induction of antiviral agents via TLR3 activation by Emodin might contribute to its anti-PRRSV effect. These findings imply that the Emodin from could hamper the proliferation of PRRSV in vitro and might constitute a new approach for treating PRRSV infection.
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http://dx.doi.org/10.3390/v13071243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310261PMC
June 2021

High PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor in urothelial carcinoma.

Future Oncol 2021 Aug 30;17(22):2893-2905. Epub 2021 Jun 30.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China.

To explore the prognostic value of high PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (TIIC) in urothelial carcinoma (UC). 162 UC specimens were evaluated for PD-L1 expression on TIIC and TC with the SP263 assay. High PD-L1 expression was defined as ≥25% staining. High PD-L1 expression on TC in UC patients with stage T1-4 disease was associated with poor overall survival. However, high PD-L1 expression on TIIC in UC patients with stage T1-4 disease revealed favorable disease-free and overall survival; more significant differences were observed in patients with stages T2-4. Multivariate analysis revealed that high PD-L1 expression on TIIC was an independent prognostic predictor for better disease-free and overall survival. High PD-L1 expression on TIIC, but not on TC, is a favorable prognostic factor in UC.
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http://dx.doi.org/10.2217/fon-2021-0092DOI Listing
August 2021

Novel Broad-Spectrum Antimicrobial Peptide Derived from Anoplin and Its Activity on Bacterial Pneumonia in Mice.

J Med Chem 2021 Jun 28. Epub 2021 Jun 28.

Institute of Pharmaceutics, School of Pharmacy, Lanzhou University, Lanzhou 730000, China.

The emergence of multidrug-resistant bacteria has major issues for treating bacterial pneumonia. Currently, anoplin (GLLKRIKTLL-NH) is a natural antimicrobial candidate derived from wasp venom. In this study, a series of new antimicrobial peptide (AMP) anoplin analogues were designed and synthesized. The relationship between their biological activities and their positive charge, hydrophobicity, amphipathicity, and secondary structure are described. The characteristic shared by these peptides is that positively charged amino acids and hydrophobic amino acids are severally arranged on the hydrophilic and hydrophobic surface of the α-helix to form a completely amphiphilic structure. To achieve ideal AMPs, below the range of the threshold of the cytotoxicity and hemolytic activity, their charges and hydrophobicity were increased as much. Among the new analogues, A-21 (KWWKKWKKWW-NH) exhibited the greatest antimicrobial activity (geometric mean of minimum inhibitory concentrations = 4.76 μM) against all the tested bacterial strains, high bacterial cell selectivity , high effectiveness against bacterial pneumonia in mice infected with , and low toxicity in mice (LD = 82.01 mg/kg). A-21 exhibited a potent bacterial membrane-damaging mechanism and lipopolysaccharide-binding ability. These data provide evidence that A-21 is a promising antimicrobial candidate for the treatment of bacterial pneumonia.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00614DOI Listing
June 2021

[A Gaussian mixture-hidden Markov model of human visual behavior].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2021 Jun;38(3):512-519

School of Electrical Engineering, Sichuan University, Chengdu 610065, P.R.China.

Vision is an important way for human beings to interact with the outside world and obtain information. In order to research human visual behavior under different conditions, this paper uses a Gaussian mixture-hidden Markov model (GMM-HMM) to model the scanpath, and proposes a new model optimization method, time-shifting segmentation (TSS). The TSS method can highlight the characteristics of the time dimension in the scanpath, improve the pattern recognition results, and enhance the stability of the model. In this paper, a linear discriminant analysis (LDA) method is used for multi-dimensional feature pattern recognition to evaluates the rationality and the accuracy of the proposed model. Four sets of comparative trials were carried out for the model evaluation. The first group applied the GMM-HMM to model the scanpath, and the average accuracy of the classification could reach 0.507, which is greater than the opportunity probability of three classification (0.333). The second set of trial applied TSS method, and the mean accuracy of classification was raised to 0.610. The third group combined GMM-HMM with TSS method, and the mean accuracy of classification reached 0.602, which was more stable than the second model. Finally, comparing the model analysis results with the saccade amplitude (SA) characteristics analysis results, the modeling analysis method is much better than the basic information analysis method. Via analyzing the characteristics of three types of tasks, the results show that the free viewing task have higher specificity value and a higher sensitivity to the cued object search task. In summary, the application of GMM-HMM model has a good performance in scanpath pattern recognition, and the introduction of TSS method can enhance the difference of scanpath characteristics. Especially for the recognition of the scanpath of search-type tasks, the model has better advantages. And it also provides a new solution for a single state eye movement sequence.
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http://dx.doi.org/10.7507/1001-5515.202008022DOI Listing
June 2021

Circ_0084043 Facilitates High Glucose-Induced Retinal Pigment Epithelial Cell Injury by Activating miR-128-3p/TXNIP-Mediated Wnt/β-Catenin Signaling Pathway.

J Cardiovasc Pharmacol 2021 07;78(1):e112-e121

Department of Ophthalmology, Affiliated Hospital of Jiangnan University (Wuxi Third People' Hospital), Wuxi, Jiangsu, China.

Abstract: Diabetic retinopathy is a frequent complication of diabetes mellitus and one of the common causes of blindness. Circular RNAs (circRNAs) can modulate various biological behaviors of human diseases. Circ_0084043 is a novel circRNA, and its function in diabetic retinopathy progression is unclear. Adult retinal pigment epithelial cells (ARPE-19) were treated with high glucose (HG). RNA levels of circ_0084043, microRNA-128-3p (miR-128-3p), and thioredoxin-interacting protein (TXNIP) were detected by quantitative real-time polymerase chain reaction. 3-(4, 5-dimethylthiazole-2-y1)-2, 5-diphenyl tetrazolium bromide and flow cytometry were, respectively, used to examine cell viability and apoptosis. Apoptotic and TNXIP relative protein levels were measured by Western blot. The combination between targets was analyzed through dual-luciferase reporter assay or RNA immunoprecipitation assay. Results showed that HG induced the upregulation of circ_0084043 and the downregulation of miR-128-3p in ARPE-19 cells. Circ_0084043 knockdown or miR-128-3p overexpression mitigated the HG-mediated cell viability inhibition, apoptosis promotion, and inflammatory response. Circ_0084043 targeted miR-128-3p and miR-128-3p inhibitor returned the regulation of si-circ_0084043 in HG-treated cells. TXNIP was the target gene of miR-128-3p and TXNIP overexpression abolished the miR-128-3p-mediated effects after HG treatment. Circ_0084043 regulated the TXNIP expression to activate Wnt/β-catenin signal pathway by targeting miR-128-3p. Our findings unraveled that circ_0084043 promoted the HG-induced retinal pigment epithelial cell injury through activating the Wnt/β-catenin signal pathway by the miR-128-3p/TXNIP axis. Circ_0084043 might be an available biomarker in diabetic retinopathy diagnosis and therapy.
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http://dx.doi.org/10.1097/FJC.0000000000001039DOI Listing
July 2021

High SVR12 With 8-Week Course of Direct-Acting Antivirals in Adolescents and Children With Chronic Hepatitis C: A Comprehensive Analysis.

Front Med (Lausanne) 2021 8;8:608760. Epub 2021 Jun 8.

Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Direct-acting antiviral (DAA) treatment for 8 weeks has a sustained virological response rate in adults with chronic hepatitis C. We have conducted a systematic review and meta-analysis to compare the efficacy and safety of the 8-week vs. 12/24-week DAA treatment in adolescents and children with CHC. The PubMed, Web of Science, and Cochrane databases were searched for the relevant articles from January 1, 2017 to August 28, 2020 and further screened for literature reviews on April 1, 2021. Pool proportions with 95% CIs for SVR12 were summarized with fixed/random effects models using Freeman-Tukey double arcsine transformation. Subgroup analysis was used to explore the source of heterogeneity. Thirty-six relevant publications were identified. For adolescents aged 12-17 years old, the pooled SVR12 and AE rate were 99.4% (95% CI: 98.7-99.9) and 34.7% (95% CI: 31.9-37.6). No one discontinued treatment due to drug intolerance. In addition, the SVR12 adolescents treated for 12 and 8/24 weeks were 99.3% (95% CI: 98.4-99.9) and 100%, respectively. The pooled SVR12 rate, AEs, and SAEs for children younger than 12 years were 98.9% (95% CI: 97.3-99.8), 51.6% (95% CI: 47.0-56.2), and 1.1% (95% CI: 0.4-2.5), respectively. The most common AE was fatigue (28.4%). The SVR12 was 98.8% (95% CI: 97.1-99.8) and 100% for the pediatric patients treated for 12 weeks and 8/24 weeks, respectively. Taken together, DAAs are generally effective against CHC and well-tolerated by the adolescents and children. A treatment duration of 8 weeks is equally effective and safe as 12/24 weeks in this demographic group.
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http://dx.doi.org/10.3389/fmed.2021.608760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217461PMC
June 2021
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