Publications by authors named "Ying Tang"

758 Publications

Pathogenesis of acephalic spermatozoa syndrome caused by SUN5 Variant.

Mol Hum Reprod 2021 Apr 12. Epub 2021 Apr 12.

Laboratory of Basic Medicine, Dongfang Hospital (900th Hospital of the Joint Logistics Team), Xiamen University, Fuzhou, 350025, China.

Acephalic spermatozoa syndrome (ASS) is a rare teratozoospermia that leads to male infertility. Previous work suggested a genetic origin. Variants of Sad1 and UNC84 domain containing 5 (SUN5) are the main genetic cause of ASS, however its pathogenesis remains unclear. Here, we performed whole-exome sequencing in ten unrelated ASS and identified two homozygous variants, c.381delA[p.V128Sfs7*] and c.675C>A[p.Y225X], and one compound variant, c.88 C > T[p.R30X] and c.381 delA [p.V128Sfs7*], in SUN5 in four patients. The c.381delA variant had been identified as pathogenic in previous reports, while c.675C>A and c.88 C > T were two novel variants which could lead to a premature termination codon (PTC) and resulted in loss of SUN5, and may also be pathogenic. SUN5 mRNA and protein were present at very low levels in ASS patients with SUN5 nonsense mutation. Furthermore, the distribution of outer dense fiber protein 1 (ODF1) and Nesprin3 was altered in sperm of ASS patients with SUN5 variants. The co-immunoprecipitation analysis indicated that SUN5 and ODF1, SUN5 and Nesprin3, and ODF1 and Nesprin3 interacted with each other in transfected HEK293T cells. Thus, we propose that SUN5, Nesprin3, and ODF1 may form a "triplet" structure through interactions at neck of sperm. When gene variants resulted in a loss of SUN5, the "triplet" structure disappears and then the head-tail junction becomes fragile, leading to the occurrence of ASS.
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http://dx.doi.org/10.1093/molehr/gaab028DOI Listing
April 2021

Enhanced Removal of Sulfonated Lignite from Oil Wastewater with Multidimensional MgAl-LDH Nanoparticles.

Nanomaterials (Basel) 2021 Mar 28;11(4). Epub 2021 Mar 28.

Shaanxi Province Key Laboratory of Environmental Pollution Control and Reservoir Protection Technology of Oilfields, College of Chemistry and Chemical Engineering, Xi'an Shiyou University, Xi'an 710065, China.

In this study, hierarchical MgAl-LDH (layered double hydroxide) nanoparticles with a flower-like morphology were prepared under a hydrothermal condition by employing worm-like micelles formed by cetyltrimethylammonium bromide (CTAB) and salicylic acid (SA) as templates. The morphology and structure of the materials were characterized by Brunauer-Emmett-Teller (BET), SEM, and XRD analyses. The performance for the adsorption of sulfonated lignite (SL) was also investigated in detail. FTIR was used to detect the presence of active functional groups and determine whether they play important roles in adsorption. The results showed that the hierarchical MgAl-LDH nanoparticles with a specific surface area of 126.31 m/g possessed a flower-like morphology and meso-macroporous structures. The adsorption capacity was high-its value was 1014.20 mg/g at a temperature of 298 K and an initial pH = 7, which was higher than traditional MgAl-LDH (86 mg/g). The adsorption process of sulfonated lignite followed the pseudo-second-order kinetics model and conformed to Freundlich isotherm model with a spontaneous exothermic nature. In addition, the hierarchical MgAl-LDH could be regenerated and used, and the adsorption was high after three adsorption cycles. The main adsorption mechanisms were electrostatic attraction and ion exchange between the hierarchical MgAl-LDH and sulfonated lignite.
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http://dx.doi.org/10.3390/nano11040861DOI Listing
March 2021

High Prevalence of Genogroup I and Genogroup II Picobirnaviruses in Dromedary Camels.

Viruses 2021 Mar 8;13(3). Epub 2021 Mar 8.

Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Picobirnaviruses (PBVs) are small non-enveloped bisegmented double-stranded RNA viruses found in humans, mammals, and birds. Increasing molecular epidemiology studies suggest a high sequence diversity of PBVs in numerous hosts and the environment. In this study, using 229 fecal samples from dromedary camels in Dubai, 52.8% were positive for PBVs, of which 77.7% and 41.3% were positive for genogroup I and II, respectively, and 19.0% were positive for both genotypes. Phylogenetic analysis showed high diversity among the sequences of genogroup I and II dromedary PBVs. Marked nucleotide polymorphisms were observed in 75.5% and 46.0% of genogroup I and II RNA-dependent RNA polymerase (RdRp) sequences, respectively, suggesting the co-existence of multiple strains in the same specimen. Both high genetic diversity and prevalence of genogroup I and II PBV in dromedaries were observed. In fact, the prevalence of genogroup II PBV in dromedaries is the highest among all animals to date. The complete/near-complete core genomes of five genogroup I and one genogroup II dromedary PBVs and partial segment 1 and 2 of both genotypes were also sequenced. The dromedary PBV genome organizations were similar to those of other animals. Genetic reassortment and mutation are both important in the ecology and evolution of PBVs.
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http://dx.doi.org/10.3390/v13030430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999184PMC
March 2021

Swertiamarin supplementation prevents obesity-related chronic inflammation and insulin resistance in mice fed a high-fat diet.

Adipocyte 2021 Dec;10(1):160-173

School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou Zhejiang, China.

Obesity is characterized by low-grade chronic inflammation, which underlies insulin resistance and non-alcoholic fatty liver disease (NAFLD). Swertiamarin is a secoiridoid glycoside that has been reported to ameliorate diabetes and NAFLD in animal models. However, the effects of swertiamarin on obesity-related inflammation and insulin resistance have not been fully elucidated. Thus, this study investigated the effects of swertiamarin on inflammation and insulin resistance in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed a HFD or HFD containing swertiamarin for 8 weeks. Obesity-induced insulin resistance and inflammation were assessed in the epididymal white adipose tissue (eWAT) and livers of the mice. Swertiamarin attenuated HFD-induced weight gain, glucose intolerance, oxidative stress, and insulin resistance, and enhanced insulin signalling in mice. Compared to HFD-fed mice, the swertiamarin-treated mice exhibited increased lipolysis and reduced adipocyte hypertrophy and macrophage infiltration in eWAT. Moreover, swertiamarin alleviated HFD-mediated hepatic steatosis and inflammation by suppressing activation of the p38 MAPK and NF-κB pathways within the eWAT and liver of obese mice. In conclusion, supplementation with swertiamarin attenuated weight gain and hepatic steatosis, and alleviated obesity-associated inflammation and insulin resistance, in obese mice.
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http://dx.doi.org/10.1080/21623945.2021.1906510DOI Listing
December 2021

Involvement of HECTD1 in LPS-induced astrocyte activation via σ-1R-JNK/p38-FOXJ2 axis.

Cell Biosci 2021 Mar 30;11(1):62. Epub 2021 Mar 30.

Department of Pharmacology, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.

Background: Astrocytes participate in innate inflammatory responses within the mammalian central nervous system (CNS). HECT domain E3 ubiquitin protein ligase 1 (HECTD1) functions during microglial activation, suggesting a connection with neuroinflammation. However, the potential role of HECTD1 in astrocytes remains largely unknown.

Results: Here, we demonstrated that HECTD1 was upregulated in primary mouse astrocytes after 100 ng/ml lipopolysaccharide (LPS) treatment. Genetic knockdown of HECTD1 in vitro or astrocyte-specific knockdown of HECTD1 in vivo suppressed LPS-induced astrocyte activation, whereas overexpression of HECTD1 in vitro facilitated LPS-induced astrocyte activation. Mechanistically, we established that LPS activated σ-1R-JNK/p38 pathway, and σ-1R antagonist BD1047, JNK inhibitor SP600125, or p38 inhibitor SB203580 reversed LPS-induced expression of HECTD1, thus restored LPS-induced astrocyte activation. In addition, FOXJ2 functioned as a transcription factor of HECTD1, and pretreatment of primary mouse astrocytes with BD1047, SB203580, and SP600125 significantly inhibited LPS-mediated translocation of FOXJ2 into the nucleus.

Conclusions: Overall, our present findings suggest that HECTD1 participates in LPS-induced astrocyte activation by activation of σ-1R-JNK/p38-FOXJ2 pathway and provide a potential therapeutic strategy for neuroinflammation induced by LPS or any other neuroinflammatory disorders.
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http://dx.doi.org/10.1186/s13578-021-00572-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008527PMC
March 2021

Potent allelopathy and non-PSTs, non-spirolides toxicity of the dinoflagellate Alexandrium leei to phytoplankton, finfish and zooplankton observed from laboratory bioassays.

Sci Total Environ 2021 Mar 17;780:146484. Epub 2021 Mar 17.

CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, China. Electronic address:

The dinoflagellate genus Alexandrium has been well known for causing paralytic shellfish poisoning (PSP) worldwide. Several non-PSP toxin-producing species, however, have shown to exhibit fish-killing toxicity. Here, we report the allelopathic activity of Alexandrium leei from Malaysia to other algal species, and its toxicity to finfish and zooplankton, via laboratory bioassays. Thirteen microalgal species that co-cultured with Al. leei revealed large variability in the allelopathic effects of Al. leei on the test algae, with the growth inhibition rates ranging from 0 to 100%. The negative allelopathic effects of Al. leei on microalgae included loss of flagella and thus the motility, damages of chain structure, deformation in cell morphology, and eventually cell lysis. The finfish experienced 100% mortality within 24 h exposed to the live culture (2000-6710 cells·mL), while the rotifer and brine shrimp exhibited 96-100% and 90-100% mortalities within 48 h when exposed to 500-6000 cells·mL of Al. leei. The mortality of the test animals depended on the Al. leei cell density exposed, leading to a linear relationship between mortality and cell density for the finfish, and a logarithmic relationship for the two zooplankters. When exposed to the treatments using Al. leei whole live culture, cell-free culture medium, extract of algal cells in the f/2-Si medium, extract of methanol, and the re-suspended freeze-and-thaw algal cells, the test organisms (Ak. sanguinea and rotifers) all died at the cell density of 8100 cells·mL within 24 h. Toxin analyses by HILIC-ESI-TOF/MS and LC-ESI-MS/MS demonstrated that Al. leei did not produce PSP-toxins and 13-desmethyl spirolide C. Overall, our findings demonstrated potent allelopathy and toxicity of Al. leei, which do not only pose threats to the aquaculture industry, fisheries, and marine ecosystems but may also play a part role in the population dynamics and bloom formation of this species.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146484DOI Listing
March 2021

Impaired airway epithelial barrier integrity was mediated by PI3Kδ in a mouse model of lipopolysaccharide-induced acute lung injury.

Int Immunopharmacol 2021 Mar 24;95:107570. Epub 2021 Mar 24.

Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Cell-cell junctions are critical for the maintenance of cellular as well as tissue polarity and integrity. Dysfunction of airway epithelial barrier has been shown to be involved in the pathogenesis of acute lung injury (ALI). Yet the role of phosphatidylinositol 3-kinase delta (PI3Kδ) in dysregulation of airway epithelial barrier integrity in ALI has not been addressed. Mice were subjected to intratracheal instillation of lipopolysaccharide (LPS) to generate a ALI model. Two pharmacological inhibitors of PI3Kδ, IC87114 and AMG319, were respectively given to the mice. Expression of p110δ and its downstream substrate phospho-AKT (Ser473) was increased in LPS-exposed lungs. These increases were inhibited by IC87114 or AMG319. LPS led to pronounced lung injury that was accompanied by significant airway neutrophil recruitment and bronchial epithelial morphological alterations 72 h after exposure. We also found compromised expression of adherens junction protein E-cadherin and tight junction protein claudin-2 in the airway epithelial cells. Treatment with either IC87114 or AMG319 not only attenuated LPS-induced edema, lung injury and neutrophilc inflammation, reduced total protein concentration and IL-6, TNF-α secretion in BALF, but also restored epithelial E-cadherin and claudin-2 expression. In summary, our results showed that LPS can induce a delayed effect on airway epithelial barrier integrity that is mediated by PI3Kδ in a mouse model of ALI.
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http://dx.doi.org/10.1016/j.intimp.2021.107570DOI Listing
March 2021

Robert's uterus with delayed diagnosis and potential consequences: a case report.

J Int Med Res 2021 Mar;49(3):300060521999531

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

A 24-year-old woman who wished to become pregnant presented to our hospital with an enlarged ovarian endometrioma and developmental abnormality of the uterus. Robert's uterus complicated by hematosalpinx, ovarian endometrioma, and endometriosis were finally identified 1 year after previously being diagnosed with a cyst and uterine abnormality at a local hospital. The function of the salpinx and the pelvic environment were damaged because of the delayed diagnosis and operation. Gynecologists and sonologists should be aware of and alert to this rare entity while evaluating and managing cases of uterine abnormalities and endometriosis. Prompt early diagnosis and proper management of Robert's uterus are important for avoiding future morbidity because these are major factors in protecting fertility.
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http://dx.doi.org/10.1177/0300060521999531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995457PMC
March 2021

Recent Progress of Near-Infrared Persistent Phosphors in Bio-related and Emerging Applications.

Chem Asian J 2021 Mar 18. Epub 2021 Mar 18.

State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, 100029, P. R. China.

Near-infrared persistent phosphors (NIR-PPs) are an emerging category of luminescent materials that can continuously emit NIR luminescence with super-long decay time of minutes, hours, or even days after the excitation ceases. Their unique excitation-free long-lasting afterglow, together with the NIR emission, has not only attracted wide research interests in the areas of photochemistry, photophysics, spectroscopy, and materials science, but also stimulated advanced applications in biosensing, bioimaging, biomedicine, and therapy in the past decade. Beyond these bio-related applications, the active research field triggers a number of novel applications recently. In this review, a brief outline of NIR-PPs including the luminescence mechanism, main material systems, and how they were applied into various fields was depicted. Particular emphasis was put on the emerging applications outside the field of biology. Future perspectives in this exploration research area were also presented. We hope this review can help researchers grab the latest information in the fast-growing field of NIR-PPs.
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http://dx.doi.org/10.1002/asia.202100108DOI Listing
March 2021

Deep Learning for Automatic Differential Diagnosis of Primary Central Nervous System Lymphoma and Glioblastoma: Multi-Parametric Magnetic Resonance Imaging Based Convolutional Neural Network Model.

J Magn Reson Imaging 2021 Mar 11. Epub 2021 Mar 11.

Academy for Engineering and Technology, Fudan University, Shanghai, China.

Background: Differential diagnosis of primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is useful to guide treatment strategies.

Purpose: To investigate the use of a convolutional neural network (CNN) model for differentiation of PCNSL and GBM without tumor delineation.

Study Type: Retrospective.

Population: A total of 289 patients with PCNSL (136) or GBM (153) were included, the average age of the cohort was 54 years, and there were 173 men and 116 women.

Field Strength/sequence: 3.0 T Axial contrast-enhanced T -weighted spin-echo inversion recovery sequence (CE-T WI), T -weighted fluid-attenuation inversion recovery sequence (FLAIR), and diffusion weighted imaging (DWI, b = 0 second/mm , 1000 seconds/mm ).

Assessment: A single-parametric CNN model was built using CE-T WI, FLAIR, and the apparent diffusion coefficient (ADC) map derived from DWI, respectively. A decision-level fusion based multi-parametric CNN model (DF-CNN) was built by combining the predictions of single-parametric CNN models through logistic regression. An image-level fusion based multi-parametric CNN model (IF-CNN) was built using the integrated multi-parametric MR images. The radiomics models were developed. The diagnoses by three radiologists with 6 years (junior radiologist Y.Y.), 11 years (intermediate-level radiologist Y.T.), and 21 years (senior radiologist Y.L.) of experience were obtained.

Statistical Analysis: The 5-fold cross validation was used for model evaluation. The Pearson's chi-squared test was used to compare the accuracies. U-test and Fisher's exact test were used to compare clinical characteristics.

Results: The CE-T WI, FLAIR, and ADC based single-parametric CNN model had accuracy of 0.884, 0.782, and 0.700, respectively. The DF-CNN model had an accuracy of 0.899 which was higher than the IF-CNN model (0.830, P = 0.021), but had no significant difference in accuracy compared to the radiomics model (0.865, P = 0.255), and the senior radiologist (0.906, P = 0.886).

Data Conclusion: A CNN model can differentiate PCNSL from GBM without tumor delineation, and comparable to the radiomics models and radiologists.

Level Of Evidence: 4 TECHNICAL EFFICACY: Stage 2.
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http://dx.doi.org/10.1002/jmri.27592DOI Listing
March 2021

Resilience patterns and transitions in the Be Resilient To Breast Cancer trial: an exploratory latent profile transition analysis.

Psychooncology 2021 Mar 10. Epub 2021 Mar 10.

South China University of Technology, Guangzhou, Guangdong Province, China.

Objective: Be Resilient to Breast Cancer (BRBC), a theoretically-derived, resilience-based, culturally-tailored, supportive-expressive group therapy (SEGT), has been developed to help promote patients' resilience in breast cancer. Data from patients receiving BRBC intervention was utilized to explore and define characteristics of resilience patterns and their transitions over time.

Methods: Resilience was used as a primary outcome and 391 patients completed Resilience Scale Specific to Cancer at enrollment (T0), 2 months (T1), 6 months(T2), and 12 months (T3) after intervention. latent profile transition analysis was performed to model the change in resilience and predict positive transitioning probabilities between resilience patterns (from one pattern to another pattern with a higher level) over time.

Results: One hundred and forty four resilience patterns were identified after BRBC intervention. 33.1%, 50.3%, and 40.5% of patients experienced positive resilience transitions from T0 to T1, T1 to T2, and T2 to T3, respectively. Patients with middle age, unmarried status, higher education level, and less advanced tumor stage were more likely to experience positive resilience transitions.

Conclusion: Different transitions of resilience patterns are observed after BRBC intervention. Age, marital status, education, and tumor stage may be four factors affecting the efficacy of SEGT intervention in breast cancer.
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http://dx.doi.org/10.1002/pon.5668DOI Listing
March 2021

Correction to: ISSLS prize in basic science 2021: a novel inducible system to regulate transgene expression of TIMP1.

Eur Spine J 2021 Mar 7. Epub 2021 Mar 7.

Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

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http://dx.doi.org/10.1007/s00586-021-06783-7DOI Listing
March 2021

Quantifying information accumulation encoded in the dynamics of biochemical signaling.

Nat Commun 2021 02 24;12(1):1272. Epub 2021 Feb 24.

Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, CA, USA.

Cellular responses to environmental changes are encoded in the complex temporal patterns of signaling proteins. However, quantifying the accumulation of information over time to direct cellular decision-making remains an unsolved challenge. This is, in part, due to the combinatorial explosion of possible configurations that need to be evaluated for information in time-course measurements. Here, we develop a quantitative framework, based on inferred trajectory probabilities, to calculate the mutual information encoded in signaling dynamics while accounting for cell-cell variability. We use it to understand NFκB transcriptional dynamics in response to different immune threats, and reveal that some threats are distinguished faster than others. Our analyses also suggest specific temporal phases during which information distinguishing threats becomes available to immune response genes; one specific phase could be mapped to the functionality of the IκBα negative feedback circuit. The framework is generally applicable to single-cell time series measurements, and enables understanding how temporal regulatory codes transmit information over time.
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http://dx.doi.org/10.1038/s41467-021-21562-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904837PMC
February 2021

Cytotoxicity and polyol pathway inhibitory activities of chemical constituents isolated from the pericarp of .

Nat Prod Res 2021 Feb 24:1-6. Epub 2021 Feb 24.

School of Pharmacy, Weifang Medical University, Weifang, P. R. China.

is a medicinal and edible plant that belongs to the genus of family Meliaceae. Phytochemical investigations carried out on this plant, seven apotirucallane-type triterpenoids (), two cycloartane-type triterpenoids (), four sterols (), two sesquiterpenes (), four phenols (), and one lignin () were isolated from the pericarp of by silica gel column and preparative middle pressure liquid chromatography. Their structures were identified by interpretation of NMR and comparison with those reported in the literature. Compounds , , and were isolated from the family Meliaceae, compounds were obtained from the genus , and compound was obtained from for the first time. Additionally, the cytotoxicity and polyol pathway (PP) inhibitory activities of active constituents were evaluated in rat glomerular mesangial cells cultured under high glucose conditions, suggesting their potential application for a PP inhibitor.
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http://dx.doi.org/10.1080/14786419.2021.1886102DOI Listing
February 2021

Impaired local intrinsic immunity to SARS-CoV-2 infection in severe COVID-19.

bioRxiv 2021 Feb 20. Epub 2021 Feb 20.

Infection with SARS-CoV-2, the virus that causes COVID-19, can lead to severe lower respiratory illness including pneumonia and acute respiratory distress syndrome, which can result in profound morbidity and mortality. However, many infected individuals are either asymptomatic or have isolated upper respiratory symptoms, which suggests that the upper airways represent the initial site of viral infection, and that some individuals are able to largely constrain viral pathology to the nasal and oropharyngeal tissues. Which cell types in the human nasopharynx are the primary targets of SARS-CoV-2 infection, and how infection influences the cellular organization of the respiratory epithelium remains incompletely understood. Here, we present nasopharyngeal samples from a cohort of 35 individuals with COVID-19, representing a wide spectrum of disease states from ambulatory to critically ill, as well as 23 healthy and intubated patients without COVID-19. Using standard nasopharyngeal swabs, we collected viable cells and performed single-cell RNA-sequencing (scRNA-seq), simultaneously profiling both host and viral RNA. We find that following infection with SARS-CoV-2, the upper respiratory epithelium undergoes massive reorganization: secretory cells diversify and expand, and mature epithelial cells are preferentially lost. Further, we observe evidence for deuterosomal cell and immature ciliated cell expansion, potentially representing active repopulation of lost ciliated cells through coupled secretory cell differentiation. Epithelial cells from participants with mild/moderate COVID-19 show extensive induction of genes associated with anti-viral and type I interferon responses. In contrast, cells from participants with severe lower respiratory symptoms appear globally muted in their anti-viral capacity, despite substantially higher local inflammatory myeloid populations and equivalent nasal viral loads. This suggests an essential role for intrinsic, local epithelial immunity in curbing and constraining viral-induced pathology. Using a custom computational pipeline, we characterized cell-associated SARS-CoV-2 RNA and identified rare cells with RNA intermediates strongly suggestive of active replication. Both within and across individuals, we find remarkable diversity and heterogeneity among SARS-CoV-2 RNA+ host cells, including developing/immature and interferon-responsive ciliated cells, "hillock"-like cells, and unique subsets of secretory, goblet, and squamous cells. Finally, SARS-CoV-2 RNA+ cells, as compared to uninfected bystanders, are enriched for genes involved in susceptibility (e.g., , ) or response (e.g., , , ) to infection. Together, this work defines both protective and detrimental host responses to SARS-CoV-2, determines the direct viral targets of infection, and suggests that failed anti-viral epithelial immunity in the nasal mucosa may underlie the progression to severe COVID-19.
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http://dx.doi.org/10.1101/2021.02.20.431155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899452PMC
February 2021

The Roles of circRNAs in Liver Cancer Immunity.

Front Oncol 2020 4;10:598464. Epub 2021 Feb 4.

Department of Oncology, Guangzhou University of Chinese Medicine, Guangzhou, China.

Circular RNAs (circRNAs) are stable covalently closed non-coding RNAs (ncRNAs). Many studies indicate that circRNAs are involved in the pathological and physiological processes of liver cancer. However, the functions of circRNAs in liver cancer immunity are less known. In this review, we summarized the functions of circRNAs in liver cancer, including proliferative, metastasis and apoptosis, liver cancer stemness, cell cycle, immune evasion, glycolysis, angiogenesis, drug resistance/sensitizer, and senescence. Immune escape is considered to be one of the hallmarks of cancer development, and circRNA participates in the immune escape of liver cancer cells by regulating natural killer (NK) cell function. CircRNAs may provide new ideas for immunotherapy in liver cancer.
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http://dx.doi.org/10.3389/fonc.2020.598464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890029PMC
February 2021

Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China.

Transl Neurodegener 2021 Feb 16;10(1). Epub 2021 Feb 16.

Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.

Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.
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http://dx.doi.org/10.1186/s40035-021-00231-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885391PMC
February 2021

Antinociceptive C-diterpenoid alkaloids isolated from .

J Asian Nat Prod Res 2021 Feb 15:1-6. Epub 2021 Feb 15.

Department of Quality Management, General Hospital of Northern Theater Command,, Shenyang, 110015, China.

Phytochemical investigation on the roots of resulted in the isolation of three new aconitine-type C-diterpenoid alkaloids, pseudostapines A-C (). Their structures were determined by spectral methods such as 1D and 2D (HH COSY, HMQC, NOESY and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated alkaloids were tested for their antinociceptive potential. As a result, pseudostapine C () showed 2-fold more potent antinociceptive effect (ID = 60.3 μmol/kg) than the positive control drugs aspirin and acetaminophen.
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http://dx.doi.org/10.1080/10286020.2021.1886091DOI Listing
February 2021

Cytokine profile and glial activation following brachial plexus roots avulsion injury in mice.

J Neuroimmunol 2021 Apr 4;353:577517. Epub 2021 Feb 4.

Department of Anatomy, School of Medicine (Shenzhen), Sun Yat-sen University, Guangzhou, Guangdong 510089, China. Electronic address:

Inflammation and tissue infiltration by various immune cells play a significant role in the pathogenesis of neurons suffering the central nervous systems diseases. Although brachial plexus root avulsion (BPRA) leads to dramatic motoneurons (MNs) death and permanent loss of function, however, the knowledge gap on cytokines and glial reaction in the spinal cord injury is still existing. The current study is sought to investigate the alteration of specific cytokine expression patterns of the BPRA injured spinal cord during an acute and subacute period. The cytokine assay, transmission electron microscopy, and histological staining were utilized to assess cytokine network alteration, ultrastructure morphology, and glial activation and MNs loss within two weeks post-injury on a mouse unilateral BPRA model. The BPRA injury caused a progressively spinal MNs loss, reduced the alpha-(α) MNs synaptic inputs, whereas enhanced glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule-1 (IBA-1), F4/80 expression in ipsilateral but not the contralateral spinal segments. Additionally, cytokine assays revealed BPRA significantly altered the level of CXCL1, ICAM1, IP10, MCP-5, MIP1-α, and CD93. Notably, the elevated MIP1-α was mainly expressed in the injured spinal MNs. While the re-distribution of CD93 expression, from the cytoplasm to the nucleus, occasionally occurred at neurons of the ipsilateral spinal segment after injury. Overall, these findings suggest that the inflammatory cytokines associated with glial cell activation might contribute to the pathophysiology of the MNs death caused by nerve roots injury.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577517DOI Listing
April 2021

Diatomite encapsulated AgNPs as novel hair dye cosmetics: Preparation, performance, and toxicity.

Colloids Surf B Biointerfaces 2021 Apr 2;200:111599. Epub 2021 Feb 2.

Beijing Key Laboratory of Plant Resources Research and Development, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, 100048, China; Department of Cosmetics, College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing, 100048, China. Electronic address:

Naturally-occurring diatomite has been successfully utilised as a unique encapsulating material to obtain a highly dispersed suspension of uniformly-sized silver nanoparticles (AgNPs). Plant derived gallic acid was used as the reducing and capping agent. High-resolution scanning and transmission electron microscopy results confirmed the attachment of AgNPs on the surface of diatom frustule and maintained an excellent dispersion stability against particle aggregation. The AgNPs obtained were employed for the colouration of bleached human hair owing to the local surface plasmonic absorption (LSPR) of the AgNPs. The effects of Ag/diatomite concentration, dyeing pH, temperature and time on the produced colour were investigated. Hair fibres treated under optimised conditions display good colour fastness toward solar radiation. The morphology and chemical composition of AgNP-dyed hair were determined by energy-dispersive spectroscopy, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy analyses. The biocompatibility of the Ag/diatomite composite, AgNPs, and the dyebaths were confirmed by in vitro acute dermal and ocular toxicity tests. The diatomite supporting AgNPs therefore hold good promise and enormous potential to be exploited for sustainable dyeing of human hair.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111599DOI Listing
April 2021

Matrix Stiffening Induces a Pathogenic QKI-miR-7-SRSF1 Signaling Axis in Pulmonary Arterial Endothelial Cells.

Am J Physiol Lung Cell Mol Physiol 2021 Feb 10. Epub 2021 Feb 10.

Medicine, University of Pittsburgh School of Medicine, United States.

Pulmonary arterial hypertension (PAH) refers to a set of heterogeneous vascular diseases defined by elevation of pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), leading to right ventricular (RV) remodeling and often death. Early increases in pulmonary artery stiffness in PAH drive pathogenic alterations of pulmonary arterial endothelial cells (PAECs), leading to vascular remodeling. Dysregulation of microRNAs can drive PAEC dysfunction. However, the role of vascular stiffness in regulating pathogenic microRNAs in PAH is incompletely understood. Here, we demonstrated that extracellular matrix (ECM) stiffening downregulated miR-7 levels in PAECs. The RNA binding protein Quaking (QKI) has been implicated in the biogenesis of miR-7. Correspondingly, we found that ECM stiffness up-regulated QKI, and QKI knockdown led to increased miR-7. Downstream of the QKI-miR-7 axis, the serine and arginine rich splicing factor 1 (SRSF1) was identified as a direct target of miR-7. Correspondingly, SRSF1 was reciprocally up-regulated in PAECs exposed to stiff ECM and was negatively correlated with miR-7. Decreased miR-7 and increased QKI and SRSF1 were observed in lungs from PAH patients and PAH rats exposed to SU5416/hypoxia. Lastly, miR-7 upregulation inhibited human PAEC migration, while forced SRSF1 expression reversed this phenotype, proving that miR-7 depended upon SRSF1 to control migration. In aggregate, these results define the QKI-miR-7-SRSF1 axis as a mechanosensitive mechanism linking pulmonary arterial vascular stiffness to pathogenic endothelial function. These findings emphasize implications relevant to PAH and suggest the potential benefit of developing therapies that target this miRNA-dependent axis in PAH.
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http://dx.doi.org/10.1152/ajplung.00407.2020DOI Listing
February 2021

Wideband Anti-Jamming Based on Free Space Optical Communication and Photonic Signal Processing.

Sensors (Basel) 2021 Feb 6;21(4). Epub 2021 Feb 6.

Department of Electrical and Computer Engineering, Rowan University, 201 Mullica Hill Rd., Glassboro, NJ 08028, USA.

We propose and demonstrate an anti-jamming system to defend against wideband jamming attack. Free space optical communication is deployed to provide a reference for jamming cancellation. The mixed signal is processed and separated with photonic signal processing method to achieve large bandwidth. As an analog signal processing method, the cancellation system introduces zero latency. The radio frequency signals are modulated on optical carriers to achieve wideband and unanimous frequency response. With wideband and zero latency, the system meets the key requirements of high speed and real-time communications in transportation systems.
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http://dx.doi.org/10.3390/s21041136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914862PMC
February 2021

Prognostic Value of lncRNA NEAT1 as a New Biomarker in Digestive System Tumors: a Systematic Study and Meta-analysis.

Expert Rev Mol Diagn 2021 Jan 8;21(1):91-99. Epub 2021 Feb 8.

Department of Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin, China.

Objective: Nuclear paraspeckle assembly transcript 1 (NEAT1), a newly found lncRNA, is found abnormally expressed in digestive system tumors. This meta-analysis aims to evaluate the effect of NEAT1 on digestive system tumors.

Methods: An analysis was conducted to investigate NEAT1 expression in digestive system tumors from the PubMed, Embase, and Web of Science databases. The relationship between NEAT1 expression and patient overall survival (OS) and clinicopathology was evaluated by correlation analysis with the pooled hazard ratio (HR), 95% confidence interval (CI), and odds ratio (OR).

Results: A total of 12 published studies were enrolled in this meta-analysis. The NEAT1 overexpression was significantly associated with poor OS (HR = 1.64, 95% CI:1.41-1.91, < 0.05), lymphatic metastasis (OR = 2.70, 95% CI: 2.02-3.61, < 0.05), distal metastasis (OR = 3.01, 95% CI: 1.97-4.59, < 0.05) and advanced tumor stage (OR = 3.04, 95% CI: 2.32-3.99, < 0.05). However, digestive system tumor patients with high NEAT1 expression was not related to the patients' age (OR = 0.91, 95% CI: 0.65-1.26, = 0.561), gender (OR = 1.04, 95% CI: 0.81-1.33, = 0.761), tumor size (OR = 1.84, 95% CI: 0.88-3.88, = 0.106), and tumor differentiation (OR = 0.86, 95% CI: 0.51-1.44, = 0.570).

Conclusion: Collectively, NEAT1 can be used as a potential biomarker to predict the prognosis of patients with digestive system tumors, which is worth verifying in clinical practice.
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http://dx.doi.org/10.1080/14737159.2021.1874921DOI Listing
January 2021

Systematic review and subgroup analysis of the incidence of acute kidney injury (AKI) in patients with COVID-19.

BMC Nephrol 2021 02 5;22(1):52. Epub 2021 Feb 5.

Department of Nephrology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China.

Background: Acute kidney injury (AKI) occurs among patients with coronavirus disease-19 (COVID-19) and has also been indicated to be associated with in-hospital mortality. Remdesivir has been authorized for the treatment of COVID-19. We conducted a systematic review to evaluate the incidence of AKI in hospitalized COVID-19 patients. The incidence of AKI in different subgroups was also investigated.

Methods: A thorough search was performed to find relevant studies in PubMed, Web of Science, medRxiv and EMBASE from 1 Jan 2020 until 1 June 2020. The systematic review was performed using the meta package in R (4.0.1).

Results: A total of 16,199 COVID-19 patients were included in our systematic review. The pooled estimated incidence of AKI in all hospitalized COVID-19 patients was 10.0% (95% CI: 7.0-12.0%). The pooled estimated proportion of COVID-19 patients who needed continuous renal replacement therapy (CRRT) was 4% (95% CI: 3-6%). According to our subgroup analysis, the incidence of AKI could be associated with age, disease severity and ethnicity. The incidence of AKI in hospitalized COVID-19 patients being treated with remdesivir was 7% (95% CI: 3-13%) in a total of 5 studies.

Conclusion: We found that AKI was not rare in hospitalized COVID-19 patients. The incidence of AKI could be associated with age, disease severity and ethnicity. Remdesivir probably did not induce AKI in COVID-19 patients. Our systematic review provides evidence that AKI might be closely associated with SARS-CoV-2 infection, which should be investigated in future studies.
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http://dx.doi.org/10.1186/s12882-021-02244-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863041PMC
February 2021

ISSLS prize in basic science 2021: a novel inducible system to regulate transgene expression of TIMP1.

Eur Spine J 2021 Feb 1. Epub 2021 Feb 1.

Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Purpose: Inflammatory and oxidative stress upregulates matrix metalloproteinase (MMP) activity, leading to intervertebral disc degeneration (IDD). Gene therapy using human tissue inhibitor of metalloproteinase 1 (hTIMP1) has effectively treated IDD in animal models. However, persistent unregulated transgene expression may have negative side effects. We developed a recombinant adeno-associated viral (AAV) gene vector, AAV-NFκB-hTIMP1, that only expresses the hTIMP1 transgene under conditions of stress.

Methods: Rabbit disc cells were transfected or transduced with AAV-CMV-hTIMP1, which constitutively expresses hTIMP1, or AAV-NFκB-hTIMP1. Disc cells were selectively treated with IL-1β. NFκB activation was verified by nuclear translocation. hTIMP1 mRNA and protein expression were measured by RT-PCR and ELISA, respectively. MMP activity was measured by following cleavage of a fluorogenic substrate.

Results: IL-1β stimulation activated NFκB demonstrating that IL-1β was a surrogate for inflammatory stress. Stimulating AAV-NFκB-hTIMP1 cells with IL-1β increased hTIMP1 expression compared to unstimulated cells. AAV-CMV-hTIMP1 cells demonstrated high levels of hTIMP1 expression regardless of IL-1β stimulation. hTIMP1 expression was comparable between IL-1β stimulated AAV-NFκB-hTIMP1 cells and AAV-CMV-hTIMP1 cells. MMP activity was decreased in AAV-NFκB-hTIMP1 cells compared to baseline levels or cells exposed to IL-1β.

Conclusion: AAV-NFκB-hTIMP1 is a novel inducible transgene delivery system. NFκB regulatory elements ensure that hTIMP1 expression occurs only with inflammation, which is central to IDD development. Unlike previous inducible systems, the AAV-NFκB-hTIMP1 construct is dependent on endogenous factors, which minimizes potential side effects caused by constitutive transgene overexpression. It also prevents the unnecessary production of transgene products in cells that do not require therapy.
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http://dx.doi.org/10.1007/s00586-021-06728-0DOI Listing
February 2021

Characterizing T cell subsets in the nasal mucosa of children with acute respiratory symptoms.

Pediatr Res 2021 Jan 27. Epub 2021 Jan 27.

Division of Emergency Medicine, Boston Children's Hospital, Boston, MA, USA.

Background: In infants admitted to an ICU with respiratory failure, there is an association between the ratio of CD8 to CD4 T cells within the upper respiratory tract and disease severity. Whether this ratio is associated with respiratory disease severity within children presenting to a pediatric emergency department is not known.

Methods: We studied a convenience sample of 63 children presenting to a pediatric emergency department with respiratory symptoms. T cell subsets in the nasal mucosa were analyzed by flow cytometry. We compared CD4 and CD8 T cells subsets in these samples and analyzed the proportion of these subsets that expressed markers associated with tissue residency.

Results: We were able to identify major subsets of CD8 and CD4 T cells within the nasal mucosa using flocked swabs. We found no difference in the ratio CD8 to CD4 T cells in children with upper or lower respiratory illness. A positive association between tissue-resident memory T cell frequency and patient age was identified.

Conclusions: In our patient populations, the CD8:CD4 ratio was not associated with disease severity. The majority of T cells collected on nasal swabs are antigen experienced, and there is an association between the frequency of tissue-resident T cells and age.

Impact: Immune cell populations from the nasal mucosa can be captured using flocked nasal swabs and analyzed by flow cytometry. Nasal CD8:CD4 ratio does not predict respiratory illness severity in children presenting to the emergency department. The frequency of CD8 and CD4 resident memory T cells within the nasal mucosa increases with age.
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http://dx.doi.org/10.1038/s41390-021-01364-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838854PMC
January 2021

PGC7 promotes tumor oncogenic dedifferentiation through remodeling DNA methylation pattern for key developmental transcription factors.

Cell Death Differ 2021 Jan 26. Epub 2021 Jan 26.

Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Hong Kong, China.

Poorly differentiated tumors usually exhibit phenotypes similar to that of their developmental precursor cells. Tumor cells that acquire the lineage progenitor cells feature usually exploit developmental signaling to potentiate cancer progression. However, the underlying molecular events remain elusive. In this study, based on analysis of an in vitro hepatocyte differentiation model, the maternal factor PGC7 (also known as DPPA3, STELLA) was found closely associated with liver development and tumor differentiation in hepatocellular carcinoma (HCC). Expression of PGC7 decreased during hepatocyte maturation and increased progressively from well-differentiated HCCs to poorly differentiated HCCs. Whole-genome methylation sequencing found that PGC7 could induce promoter demethylation of genes related to development. Pathway-based network analysis indicated that downstream targets of PGC7 might form networks associated with developmental transcription factor activation. Overexpression of PGC7 conferred progenitor-like features of HCC cells both in vitro and in vivo. Mechanism studies revealed that PGC7 could impede nuclear translocation of UHRF1, and thus facilitate promoter demethylation of GLI1 and MYCN, both of which are important regulators of HCC self-renewal and differentiation. Depletion or inhibition of GLI1 effectively downregulated MYCN, abolished the effect of PGC7, and sensitized HCC cells to sorafenib treatment. In addition, we found a significant correlation of PGC7 with GLI1/MYCN and lineage differentiation markers in clinical HCC patients. PGC7 expression might drive HCC toward a "dedifferentiated" progenitor lineage through facilitating promoter demethylation of key developmental transcription factors; further inhibition of PGC7/GLI1/MYCN might reverse poorly differentiated HCCs and provide novel therapeutic strategies.
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http://dx.doi.org/10.1038/s41418-020-00726-3DOI Listing
January 2021