Publications by authors named "Guojun Li"

315 Publications

Clustering single-cell RNA-seq data by rank constrained similarity learning.

Bioinformatics 2021 May 7. Epub 2021 May 7.

Department of Bioinformatics and Genomics, The University of North Carolina at Charlotte, Charlotte, NC 28223, USA.

Motivation: Recent breakthroughs of single-cell RNA sequencing (scRNA-seq) technologies offer an exciting opportunity to identify heterogeneous cell types in complex tissues. However, the unavoidable biological noise and technical artifacts in scRNA-seq data as well as the high dimensionality of expression vectors make the problem highly challenging. Consequently, although numerous tools have been developed, their accuracy remains to be improved.

Results: Here, we introduce a novel clustering algorithm and tool RCSL (Rank Constrained Similarity Learning) to accurately identify various cell types using scRNA-seq data from a complex tissue. RCSL considers both local similarity and global similarity among the cells to discern the subtle differences among cells of the same type as well as larger differences among cells of different types. RCSL uses Spearman's rank correlations of a cell's expression vector with those of other cells to measure its global similarity, and adaptively learns neighbour representation of a cell as its local similarity. The overall similarity of a cell to other cells is a linear combination of its global similarity and local similarity. RCSL automatically estimates the number of cell types defined in the similarity matrix, and identifies them by constructing a block-diagonal matrix, such that its distance to the similarity matrix is minimized. Each block-diagonal submatrix is a cell cluster/type, corresponding to a connected component in the cognate similarity graph. When tested on 16 benchmark scRNA-seq datasets in which the cell types are well-annotated, RCSL substantially outperformed six state-of-the-art methods in accuracy and robustness as measured by three metrics.

Availability: The RCSL algorithm is implemented in R and can be freely downloaded at https://cran.r-project.org/web/packages/RCSL/index.html.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab276DOI Listing
May 2021

Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: A multicenter, open-label, randomized trial.

Int Immunopharmacol 2021 Apr 21;97:107702. Epub 2021 Apr 21.

Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, China; Department of Infectious Disease, Peking University International Hospital, Beijing, China. Electronic address:

Background: The clinical characteristics and treatment of patients who tested positive for COVID-19 after recovery remained elusive. Effective antiviral therapy is important for tackling these patients. We assessed the efficacy and safety of favipiravir for treating these patients.

Methods: This is a multicenter, open-label, randomized controlled trial in SARS-CoV-2 RNA re-positive patients. Patients were randomly assigned in a 2:1 ratio to receive either favipiravir, in addition to standard care, or standard care alone. The primary outcome was time to achieve a consecutive twice (at intervals of more than 24 h) negative RT-PCR result for SARS-CoV-2 RNA in nasopharyngeal swab and sputum sample.

Results: Between March 27 and May 9, 2020, 55 patients underwent randomization; 36 were assigned to the favipiravir group and 19 were assigned to the control group. Favipiravir group had a significantly shorter time from start of study treatment to negative nasopharyngeal swab and sputum than control group (median 17 vs. 26 days); hazard ratio 2.1 (95% CI [1.1-4.0], p = 0.038). The proportion of virus shedding in favipiravir group was higher than control group (80.6% [29/36] vs. 52.6% [10/19], p = 0.030, respectively). C-reactive protein decreased significantly after treatment in the favipiravir group (p = 0.016). The adverse events were generally mild and self-limiting.

Conclusion: Favipiravir was safe and superior to control in shortening the duration of viral shedding in SARS-CoV-2 RNA recurrent positive after discharge. However, a larger scale and randomized, double-blind, placebo-controlled trial is required to confirm our conclusion.
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http://dx.doi.org/10.1016/j.intimp.2021.107702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059985PMC
April 2021

Substantial and stable magnetoresistance and spin conductance in phosphorene-based spintronic devices with Co electrodes.

Phys Chem Chem Phys 2021 May 27;23(17):10573-10579. Epub 2021 Apr 27.

School of Electronic Science and Applied Physics, Hefei University of Technology, Hefei, Anhui 230009, China.

Designing devices with excellent spin-polarized properties has been a challenge in physics and materials science. In this work, we report a theoretical investigation of the spin injection and spin-polarized transport properties of monolayer and bilayer phosphorene devices with Co electrodes. Based on the analysis of transmission coefficients, spin-polarized current, magnetoresistance (MR) (or tunnel MR) ratio and spin injection efficiency (SIE), both devices show superior spin-polarized transport properties. As phosphorene in the device is changed from monolayer to bilayer, the charge carrier type can be tuned from n-type to p-type. For the monolayer phosphorene device, the tunnel MR ratio reaches about 210% and the SIE is about 80.7% at zero bias. Notably, the SIE and tunnel MR ratio maintain almost constant values against bias voltage and gate voltage, which makes it suitable for magnetic sensors. As for the bilayer phosphorene device, it not only exhibits a considerable tunnel MR ratio, but also shows significantly enhanced conductance, beneficial to the sensitivity of spintronic devices. Further analysis shows that the improvement of conductance is attributed to the low barrier height between the bilayer phosphorene channel and Co electrodes. According to our results, the studied phosphorene devices with Co electrodes demonstrate superior spin injection and transport properties. We believe that these theoretical findings will be a strong asset for future experimental works in spintronics.
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http://dx.doi.org/10.1039/d1cp00070eDOI Listing
May 2021

Potential capacity of interferon-α to eliminate covalently closed circular DNA (cccDNA) in hepatocytes infected with hepatitis B virus.

Gut Pathog 2021 Apr 12;13(1):22. Epub 2021 Apr 12.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, National Clinical Research Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.

Interferon-alpha (IFN-α) and nucleot(s)ide analogs (NAs) are first-line drugs for the treatment of chronic hepatitis B virus (HBV) infections. Generally, NAs target the reverse transcription of HBV pregenomic RNA, but they cannot eliminate covalently-closed-circular DNA (cccDNA). Although effective treatment with NAs can dramatically decrease HBV proteins and DNA loads, and even promote serological conversion, cccDNA persists in the nucleus of hepatocytes due to the lack of effective anti-cccDNA drugs. Of the medications currently available, only IFN-α can potentially target cccDNA. However, the clinical effects of eradicating cccDNA using IFN-α in the hepatocytes of patients with HBV are not proficient as well as expected and are not well understood. Herein, we review the anti-HBV mechanisms of IFN-α involving cccDNA modification as the most promising approaches to cure HBV infection. We expect to find indications of promising areas of research that require further study to eliminate cccDNA of HBV in patients.
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http://dx.doi.org/10.1186/s13099-021-00421-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040234PMC
April 2021

Lactic dehydrogenase-lymphocyte ratio for predicting prognosis of severe COVID-19.

Medicine (Baltimore) 2021 Jan;100(4):e24441

Department of Gastroenterology, People's Hospital of Chongqing Hechuan, Chongqing, China.

Abstract: To develop a useful score for predicting the prognosis of severe corona virus disease 2019 (COVID-19) patients.We retrospectively analyzed patients with severe COVID-19 who were admitted from February 10, 2020 to April 5, 2020. First, all patients were randomly assigned to a training cohort or a validation cohort. By univariate analysis of the training cohort, we developed combination scores and screened the superior score for predicting the prognosis. Subsequently, we identified the independent factors influencing prognosis. Finally, we demonstrated the predictive efficiency of the score in validation cohort.A total of 145 patients were enrolled. In the training cohort, nonsurvivors had higher levels of lactic dehydrogenase than survivors. Among the 7 combination scores that were developed, lactic dehydrogenase-lymphocyte ratio (LLR) had the highest area under the curve (AUC) value for predicting prognosis, and it was associated with the incidence of liver injury, renal injury, and higher disseminated intravascular coagulation (DIC) score on admission. Univariate logistic regression analysis revealed that C-reactive protein, DIC score ≥2 and LLR >345 were the factors associated with prognosis. Multivariate analysis showed that only LLR >345 was an independent risk factor for prognosis (odds ratio [OR] = 9.176, 95% confidence interval [CI]: 2.674-31.487, P < .001). Lastly, we confirmed that LLR was also an independent risk factor for prognosis in severe COVID-19 patients in the validation cohort where the AUC was 0.857 (95% CI: 0.718-0.997).LLR is an accurate predictive score for poor prognosis of severe COVID-19 patients.
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http://dx.doi.org/10.1097/MD.0000000000024441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960489PMC
January 2021

Characterization of Glass Insulating Thick Films with Ag Conductors for Multilayer Packages.

Materials (Basel) 2021 Jan 21;14(3). Epub 2021 Jan 21.

College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing 211106, China.

In this paper, an insulating film was successfully prepared by sintering 35 wt % CaO-15 wt % AlO-10 wt % BO-40 wt % SiO glass at 875 °C. After sintering, the main component of the insulating film was glass-ceramics. The main crystal phase was CaAlSiO, and the crystallization activation energy was 189.76 kJ/mol. After preparing the insulating film, its color turned yellow, and the diffusion of Ag was found by XPS and XRD data. When the temperature increased to 875 °C, the color of the insulating film became lighter, and the silver content decreased. The adhesion of the multilayer structure could reach 875 N. The dielectric constant of the insulating film in the multilayer structure was approximately 5, and the dielectric loss was 0.0011. After sintering, the dielectric strength of the insulating film could reach 13.11 kV/mm, which fully meets the requirements of a complex packaging structure.
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http://dx.doi.org/10.3390/ma14030494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864519PMC
January 2021

Robust and ultrafast fiducial marker correspondence in electron tomography by a two-stage algorithm considering local constraints.

Bioinformatics 2021 Jan 8. Epub 2021 Jan 8.

Computational Bioscience Research Center (CBRC), Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia.

Motivation: Electron tomography (ET) has become an indispensable tool for structural biology studies. In ET, the tilt series alignment and the projection parameter calibration are the key steps towards high-resolution ultrastructure analysis. Usually, fiducial markers are embedded in the sample to aid the alignment. Despite the advances in developing algorithms to find correspondence of fiducial markers from different tilted micrographs, the error rate of the existing methods is still high such that manual correction has to be conducted. In addition, existing algorithms do not work well when the number of fiducial markers is high.

Results: In this paper, we try to completely solve the fiducial marker correspondence problem. We propose to divide the workflow of fiducial marker correspondence into two stages: (i) initial transformation determination, and (ii) local correspondence refinement. In the first stage, we model the transform estimation as a correspondence pair inquiry and verification problem. The local geometric constraints and invariant features are used to reduce the complexity of the problem. In the second stage, we encode the geometric distribution of the fiducial markers by a weighted Gaussian mixture model and introduce drift parameters to correct the effects of beam-induced motion and sample deformation. Comprehensive experiments on real-world datasets demonstrate the robustness, efficiency and effectiveness of the proposed algorithm. Especially, the proposed two-stage algorithm is able to produce an accurate tracking within an average of ≤ ms per image, even for micrographs with hundreds of fiducial markers, which makes the real-time ET data processing possible.

Availability: The code is available at https://github.com/icthrm/auto-tilt-pair . Additionally, the detailed original figures demonstrated in the experiments can be accessed at https://rb.gy/6adtk4.
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http://dx.doi.org/10.1093/bioinformatics/btaa1098DOI Listing
January 2021

Comet Assay Evaluation of Lanthanum Nitrate DNA Damage in C57-ras Transgenic Mice.

Biol Trace Elem Res 2021 Jan 5. Epub 2021 Jan 5.

Institute of Toxicology, Beijing Center for Disease Prevention and Control/Beijing Research Center for Preventive Medicine/Beijing Key Laboratory of Diagnostic and Traceablity Technologies for Food Poisoning, No. 16, Hepingli Middle Street, Dongcheng District, Beijing, 100013, China.

Due to the wide application of rare-earth elements (REEs) in the last decades, lanthanum has increasingly entered the environment and has gradually accumulated in the human body through the food chain. Lanthanum is worth paying attention in terms of food safety. Although the genotoxicity of lanthanum has been studied in vitro, data on its DNA damage in vivo rodent are limited, moreover, which have also presented some controversy. This study aimed to conduct an in vivo rodent alkaline comet assay, and as a companion test to the lanthanum nitrate carcinogenicity test. We conducted an oral gavage experiment for 180 days (26 weeks) to test for the persistence of DNA damage of long-term low-dose accumulation of lanthanum nitrate (12.5, 25, and 50 mg/kg body weight), in F1 hybrid C57-ras transgenic mice (CB6F1) by using alkaline comet assay in the blood and liver. The comet assay revealed that all the tested concentrations of lanthanum nitrate did not induce DNA damage in any of the tissues investigated, whereas DNA damage was induced in the positive control group. These results could indicate that lanthanum nitrate can accumulate in tissues and organs of the mice after exposure, and does not possess DNA damage in C57-ras transgenic mice after repeated treatments at oral doses up to 50 mg/kg·BW for 26 weeks; also, it did not cause pathological changes in the liver of the mice.
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http://dx.doi.org/10.1007/s12011-020-02500-5DOI Listing
January 2021

Facile synthesis of the Z-scheme graphite-like carbon nitride/silver/silver phosphate nanocomposite for photocatalytic oxidative removal of nitric oxides under visible light.

J Colloid Interface Sci 2021 Apr 31;588:110-121. Epub 2020 Dec 31.

School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, PR China. Electronic address:

In this study, a novel ternary Z-scheme Graphite-like Carbon Nitride (g-CN)/Silver (Ag)/Silver Phosphate (AgPO) photocatalyst was designed and prepared using a two-step method (sodium chloride (NaCl) template-assisted strategy plus selective deposition). Its photocatalysts performance against removing 400 ppm of Nitric Oxides (NOx) was then investigated. We found 50 wt% g-CN/Ag/AgPO(AP-CN 2:1) catalyst removes up to 74% of NO in 90 min under the illumination of visible light (>420 nm), which is respectively 3.5 and 1.8 times higher than using g-CN or AgPO, alone. This improved performance was attributed to the formation of Z-scheme g-CN/Ag/AgPO heterojunction, driven by the built-in electric field across the g-CN/Ag/AgPO interface. These separated the electron-hole but enhanced the original strong oxidation and reduction performance of related components. The superior performance is also attributed to the improved surface area, enhanced hydrophilicity (HO) and better visible-light-harvesting capability of the composite compound. More importantly, the AP-CN 2:1 sample maintained a NO removal rate of more than 73% even after four rounds of recycling. The photocatalytic oxidation removal mechanism was evaluated using the radical-capture experiments, electron spin resonance (ESR) and ion-exchange high-performance liquid chromatography (HPLC) analysis. The findings of this work offer a simple but effective design of a highly reactive and practical ternary Z-scheme heterojunction photocatalysts for the removal of toxic NO.
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http://dx.doi.org/10.1016/j.jcis.2020.12.063DOI Listing
April 2021

Integrating depth of invasion in T classification improves the prognostic performance of the American Joint Committee on Cancer primary tumor staging system for cutaneous squamous cell carcinoma of the head and neck.

Eur J Cancer 2021 Feb 22;144:169-177. Epub 2020 Dec 22.

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Background: The last revision of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual included a specific system for cutaneous squamous cell carcinoma (CSCC) of the head and neck. Here, we assessed the prognostic performance of six candidate modified T-classification models in head and neck CSCC patients.

Methods: Analysis of 916 patients with head and neck CSCC given treatment with curative intent at The University of Texas MD Anderson Cancer Center between 1995 and 2019 was performed. The main outcome was disease-specific survival (DSS), and the impact of depth of invasion (DOI) was analyzed using multivariable regression models. Candidate models were developed using the optimal DOI cut points for each AJCC T classification based on goodness of fit of the model and the simplicity of the model. Staging systems were compared using Harrell's concordance index.

Results: Median age was 70 years (range, 19-97years) and median follow-up time of 22 months (range, 1-250months). The median DOI was 6.0 mm (range, 0.1-70.0 mm). The five-year DSS rate was 80.7% (95%CI, 77.4-83.7%). We found significant association between DOI (hazard ratio, 1.21 [95%CI: 1.01-1.43]) and DSS on multivariable analysis. Based on a low Akaike information criterion score, improvement in the concordance index, and Kaplan-Meier curves, model 6 surpassed the AJCC staging system.

Conclusions: Incorporation of DOI in the current AJCC staging system improves discrimination of T classifications in head and neck CSCC patients.

Lay Summary: The current staging system for head and neck cutaneous squamous cell carcinoma demonstrates wide prognostic variability and provides suboptimal risk stratification. Incorporation of depth of invasion in the T-classification system improves risk prediction and patient counseling.

Precis: We propose improved head and neck cutaneous squamous cell carcinoma T staging that will include depth of invasion and should be considered in future versions of the American Joint Committee on Cancer after external validation.
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http://dx.doi.org/10.1016/j.ejca.2020.11.019DOI Listing
February 2021

Inclusion of extranodal extension in the lymph node classification of cutaneous squamous cell carcinoma of the head and neck.

Cancer 2021 Apr 15;127(8):1238-1245. Epub 2020 Dec 15.

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: The prognostic performance of the recently updated American Joint Committee on Cancer lymph node classification of cutaneous head and neck squamous cell carcinoma (HNSCC) has not been validated. The objective of this study was to assess the prognostic role of extranodal extension (ENE) in cutaneous HNSCC.

Methods: This was a retrospective analysis of 1258 patients with cutaneous HNSCC who underwent surgery with or without adjuvant therapy between 1995 and 2019 at The University of Texas MD Anderson Cancer Center. The primary outcome was disease-specific survival (DSS). Local, regional, and distant metastases-free survival were secondary outcomes. Recursive partitioning analysis (RPA) and a Cox proportional hazards regression model were used to assess the fitness of staging models.

Results: No significant differences in 5-year DSS were observed between patients with pathologic lymph node-negative (pN0) disease (67.4%) and those with pN-positive/ENE-negative disease (68.2%; hazard ratio, 1.02; 95% CI, 0.61-1.79) or between patients with pN-positive/ENE-negative disease and those with pN-positive/ENE-positive disease (52.7%; hazard ratio, 0.57; 95% CI, 0.31-1.01). The RPA-derived model achieved better stratification between high-risk patients (category III, ENE-positive with >2 positive lymph nodes) and low-risk patients (category I, pN0; category II, ENE-positive/pN1 and ENE-negative with >2 positive lymph nodes). The performance of the RPA-derived model was better than that of the pathologic TNM classification (Akaike information criterion score, 1167 compared with 1176; Bayesian information criterion score, 1175 compared with 1195).

Conclusions: The number of metastatic lymph nodes and the presence of ENE are independent prognostic factors for DSS in cutaneous HNSCC, and incorporation of these factors in staging systems improves the performance of the American Joint Committee on Cancer lymph node classification.
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http://dx.doi.org/10.1002/cncr.33373DOI Listing
April 2021

Serum Anion Gap Is Associated with All-Cause Mortality among Critically Ill Patients with Congestive Heart Failure.

Dis Markers 2020 16;2020:8833637. Epub 2020 Nov 16.

Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Background: Congestive heart failure (CHF) is a complex clinical syndrome, with high morbidity and mortality. Serum anion gap (SAG) is associated with the severity of various cardiovascular diseases. However, the role of SAG indicators in CHF is unclear.

Methods And Results: A retrospective analysis of data from Multiparameter Intelligent Monitoring in Intensive Care III version 1.4 was conducted in critically ill patients with CHF. The clinical information of each patient, including demographic data, comorbidities, vital signs, scores, and laboratory indicators, were successfully obtained. Cox proportional hazards models were used to determine the relationship between SAG and mortality in patients with CHF, the consistency of which was further verified by subgroup analysis.

Results: A total of 7426 subjects met the inclusion criteria. Multivariate analysis showed that after adjusting for age, gender, ethnicity, and other potential confounders, increased SAG was significantly related to an increase in 30- and 90-day all-cause mortalities of critically ill patients with CHF compared with decreased SAG (tertile 3 versus tertile 1: adjusted hazard ratio, 95% confidence interval: 1.74, 1.46-2.08; 1.53, 1.32-1.77). Subgroup analysis indicated that the association between SAG and all-cause mortality presented similarities in most strata.

Conclusion: SAG at admission could be a promising predictor of all-cause mortality in critically ill patients with CHF.
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http://dx.doi.org/10.1155/2020/8833637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688352PMC
November 2020

Clinical characteristics of recovered COVID-19 patients with re-detectable positive RNA test.

Ann Transl Med 2020 Sep;8(17):1084

Institute of Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, China.

Background: The characteristics, significance and potential cause of positive SARS-CoV-2 diagnoses in recovered coronavirus disease 2019 (COVID-19) patients post discharge (re-detectable positive, RP) remained elusive.

Methods: A total of 262 COVID-19 patients discharged from January 23 to February 25, 2020 were enrolled into this study. RP and non-RP (NRP) patients were grouped according to disease severity, and the characterization at re-admission was analyzed. SARS-CoV-2 RNA and plasma antibody levels were measured, and all patients were followed up for at least 14 days, with a cutoff date of March 10, 2020.

Results: A total of 14.5% of RP patients were detected. These patients were characterized as young and displayed mild and moderate conditions compared to NRP patients while no severe patients were RP. RP patients displayed fewer symptoms but similar plasma antibody levels during their hospitalization compared to NRP patients. Upon hospital readmission, these patients showed no obvious symptoms or disease progression. All 21 close contacts of RP patients were tested negative for viral RNA and showed no suspicious symptoms. Eighteen out of 24 of RNA-negative samples detected by the commercial kit were tested positive for viral RNA using a hyper-sensitive method, suggesting that these patients were potential carriers of the virus after recovery from COVID-19.

Conclusions: Our results indicated that young patients, with a mild diagnosis of COVID-19 are more likely to display RP status after discharge. These patients show no obvious symptoms or disease progression upon re-admission. More sensitive RNA detection methods are required to monitor these patients. Our findings provide information and evidence for the management of convalescent COVID-19 patients.
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http://dx.doi.org/10.21037/atm-20-5602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575971PMC
September 2020

BONZAI Proteins Control Global Osmotic Stress Responses in Plants.

Curr Biol 2020 Dec 8;30(24):4815-4825.e4. Epub 2020 Oct 8.

Shanghai Center for Plant Stress Biology and CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, Shanghai 200032, China; State Key Laboratory of Crop Stress Adaptation and Improvement, School of Life Sciences, Henan University, Kaifeng 475001, China. Electronic address:

Hyperosmotic stress caused by drought and salinity is a significant environmental threat that limits plant growth and agricultural productivity. Osmotic stress induces diverse responses in plants including Ca signaling, accumulation of the stress hormone abscisic acid (ABA), reprogramming of gene expression, and altering of growth. Despite intensive investigation, no global regulators of all of these responses have been identified. Here, we show that the Ca-responsive phospholipid-binding BONZAI (BON) proteins are critical for all of these osmotic stress responses. A Ca-imaging-based forward genetic screen identified a loss-of-function bon1 mutant with a reduced cytosolic Ca signal in response to hyperosmotic stress. The loss-of-function mutants of the BON1 gene family, bon1bon2bon3, are impaired in the induction of gene expression and ABA accumulation in response to osmotic stress. In addition, the bon mutants are hypersensitive to osmotic stress in growth inhibition. BON genes have been shown to negatively regulate plant immune responses mediated by intracellular immune receptor NLR genes including SNC1. We found that the defects of the bon mutants in osmotic stress responses were suppressed by mutations in the NLR gene SNC1 or the immunity regulator PAD4. Our findings indicate that NLR signaling represses osmotic stress responses and that BON proteins suppress NLR signaling to enable global osmotic stress responses in plants.
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http://dx.doi.org/10.1016/j.cub.2020.09.016DOI Listing
December 2020

An Overview of Cancer Prevention: Chemoprevention and Immunoprevention.

Authors:
Kyle J Gu Guojun Li

J Cancer Prev 2020 Sep;25(3):127-135

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Cancer prevention encompasses a broad spectrum of strategies designed to lower the chance of developing cancer and reduce the morbidity of established cancer. There are three levels of cancer prevention. Eliminating or mitigating cancer risk factors by adopting healthy behaviors and lifestyles, such as avoiding tobacco and alcohol use, exercising, eating a healthy diet, and applying sunscreen to protect against UV exposure, belongs to primary prevention and is the easiest and most effective way of preventing cancer for the general public. Secondary prevention includes screening to identify precancerous lesions and taking intervention measures to prevent disease progression to malignancy. Tertiary prevention refers to reducing or controlling the symptoms and morbidity of established cancer or the morbidity caused by cancer therapy. For high-risk populations, chemopreventive agents, such as selective estrogen receptor modulators (including tamoxifan and raloxifene) in breast cancer prevention and non-steroidal anti-inflammatory drugs (aspirin) in colorectal cancer prevention, and immunoprevention using human papillomavirus and hepatitis B virus vaccines in infection-related cancers have shown clear clinical benefits of reducing cancer incidences. In this review, we will summarize the current status of cancer prevention, focusing on the major agents that are clinically used for chemoprevention and immunoprevention.
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http://dx.doi.org/10.15430/JCP.2020.25.3.127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523034PMC
September 2020

The synergy of germline C634Y and V292M RET mutations in a northern Chinese family with multiple endocrine neoplasia type 2A.

J Cell Mol Med 2020 11 29;24(22):13163-13170. Epub 2020 Sep 29.

Department of Otolaryngology Head and Neck Surgery, Key Laboratory of Otolaryngology Head and Neck Surgery (Capital Medical University), Ministry of Education, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Genetic analysis for germline mutations of RET proto-oncogene has provided a basis for individual management of medullary thyroid carcinoma (MTC) and pheochromocytoma. Most of compound mutations have more aggressive phenotypes than single point mutations, but the compound C634Y/V292M variant in MTC has never been reported. Thus, we retrospectively investigated synergistic effect of C634Y and V292M RET germline mutations in family members with multiple endocrine neoplasia type 2A. Nine of 14 family members in a northern Chinese family underwent RET mutation screening using next-generation sequencing and PCR followed by direct bidirectional DNA sequencing. Clinical features of nine individuals were retrospectively carefully reviewed. In vitro, the scratch-wound assay was used to investigate the difference between the cells carrying different mutations. We find no patients died of MTC. All 3 carriers of the V292M variant were asymptomatic and did not have biochemical or structural evidence of disease (age: 82, 62 and 58). Among 4 C634Y mutation carriers, 2 patients had elevated calcitonin with the highest (156 pg/mL) in an 87-year-old male. Two carriers of compound C634Y/V292M trans variant had bilateral MTC with pheochromocytoma or lymph node metastasis (age: 54 and 41 years, respectively). Further, the compound C634Y/V292M variant had a faster migration rate than either single point mutation in vitro (P < .05). In conclusion, the V292M RET variant could be classified as 'likely benign' according to ACMG (2015). The compound variant V292M/C634Y was associated with both more aggressive clinical phenotype and faster cell growth in vitro than was either single mutation.
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http://dx.doi.org/10.1111/jcmm.15922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701567PMC
November 2020

Beneficial effects of sappanone A on lifespan and thermotolerance in Caenorhabditis elegans.

Eur J Pharmacol 2020 Dec 14;888:173558. Epub 2020 Sep 14.

Department of Toxicology, School of Public Health, Peking University, Beijing, 100191, China; Key Laboratory of State Administration of Traditional Chinese Medicine for Compatibility Toxicology, Beijing, 100191, China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, China. Electronic address:

Sappanone A (SA) is a homoisoflavonoid compound isolated from Caesalpinia sappan L. that selectively binds to inosine monophosphate dehydrogenase 2, a protein involved in aging. It is unknown if SA has an anti-aging effect and what is it mechanism. This study aimed to investigate the lifespan-extending and health-enhancing effects of SA, and the potential pharmacological mechanism in Caenorhabditis elegans (C. elegans). The worms were exposed to 0-50 μM SA. The effect on the lifespan was observed, and health status was evaluated by detecting motility, feeding, reproduction, thermotolerance, lipofuscin and ROS accumulation. To explore a possible mechanism, the transcription of the genes of the insulin/insulin-like growth factor-1 signalling pathway and heat stress response was detected by RT-qPCR. Moreover, subcellular distribution of green fluorescent protein-labeled DAF-16 was determined, and the interaction between SA and HSP-90 protein was simulated by molecular docking. We found that SA prolonged lifespan in C. elegans and enhanced motility and thermotolerance. The feeding and reproduction were not impacted. The ROS and lipofuscin accumulation was declined. Mechanistic study revealed that the gene expression levels of daf-16 and hsp-90 were up-regulated. Moreover, DAF-16 was translocated into the nucleus. SA was docked into the active pocket of HSP-90 in the simulation. SA (50 μM) can extend lifespan in C. elegans and decelerate aging by regulating the IIS pathway, and daf-16 is specifically important for the regulation of longevity. HSP-90 was involved in the enhancement of thermotolerance. Thus, SA may act as a promising candidate for the development of an anti-aging agent.
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http://dx.doi.org/10.1016/j.ejphar.2020.173558DOI Listing
December 2020

Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration.

Br J Cancer 2020 10 24;123(9):1456-1463. Epub 2020 Aug 24.

Institute of Oncology and Radiobiology, Havana, Cuba.

Background: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk.

Methods: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking.

Results: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx).

Conclusions: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.
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http://dx.doi.org/10.1038/s41416-020-01031-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592048PMC
October 2020

Comprehensive Analysis of SiNPs on the Genome-Wide Transcriptional Changes in .

Int J Nanomedicine 2020 23;15:5227-5237. Epub 2020 Jul 23.

Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, People's Republic of China.

Background: Large-scale production and application of amorphous silica nanoparticles (SiNPs) have enhanced the risk of human exposure to SiNPs. However, the toxic effects and the underlying biological mechanisms of SiNPs on remain largely unclear.

Purpose: This study was to investigate the genome-wide transcriptional alteration of SiNPs on .

Methods And Results: In this study, a total number of 3105 differentially expressed genes were identified in . Among them, 1398 genes were significantly upregulated and 1707 genes were notably downregulated in . Gene ontology analysis revealed that the significant change of gene functional categories triggered by SiNPs was focused on locomotion, determination of adult lifespan, reproduction, body morphogenesis, multicellular organism development, endoplasmic reticulum unfolded protein response, oocyte development, and nematode larval development. Meanwhile, we explored the regulated effects between microRNA and genes or signaling pathways. Pathway enrichment analysis and miRNA-gene-pathway-network displayed that 23 differential expression microRNA including , and could regulate the longevity-related pathways and inflammation signaling pathways, etc. Additionally, our data confirmed that SiNPs could disrupt the locomotion behavior and reduce the longevity by activating , and genes in .

Conclusion: Our study showed that SiNPs induced the change of the whole transcriptome in , and triggered negative effects on longevity, development, reproduction, and body morphogenesis. These data provide abundant clues to understand the molecular mechanisms of SiNPs in .
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http://dx.doi.org/10.2147/IJN.S251269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399461PMC
October 2020

Immune checkpoint targeting TIGIT in hepatocellular carcinoma.

Am J Transl Res 2020 15;12(7):3212-3224. Epub 2020 Jul 15.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, Zhejiang, China.

Hepatocellular carcinoma (HCC) has an extremely poor prognosis and is one of the most common malignancies worldwide. Immune checkpoint suppression has become the most effective treatment option for liver cancer. The strategies used for immune checkpoint inhibitor targeting cancer therapies have been affected by some significant successes, including blocking the advanced-stage malignant tumor by death protein 1 (PD-1)/programmed cell death ligand (PDL-1), and cytotoxic T-lymphocyte antigen-4 (CTLA4) pathways. T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) is an immune checkpoint that participates in tumor immune surveillance. Mainly expressed on T cells, natural killer (NK) cells, and other antigen-presenting cells (APCs), it diminishes cytokine production and exhibits strong suppressive properties. TIGIT achieves a more active antitumor immune response and highlights a pivotal role for cancer immunotherapy. Preclinical studies have found inhibitory effects using a targeted approach. Monotherapy targeting TIGIT or in combination with anti-PD-1/PD-L1 monoclonal antibodies for the treatment of patients with advanced solid malignancies have demonstrated improved antitumor immune responses. Due to the high tumor heterogeneity of liver cancer, immune checkpoint suppression therapy still needs further exploration. Therefore, we provide insights into the characteristics of TIGIT and the immune system in HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407725PMC
July 2020

KSP: an integrated method for predicting catalyzing kinases of phosphorylation sites in proteins.

BMC Genomics 2020 Aug 4;21(1):537. Epub 2020 Aug 4.

Department of Bioinformatics and Genomics, The University of North Carolina at Charlotte, Charlotte, NC 28223, USA.

Background: Protein phosphorylation by kinases plays crucial roles in various biological processes including signal transduction and tumorigenesis, thus a better understanding of protein phosphorylation events in cells is fundamental for studying protein functions and designing drugs to treat diseases caused by the malfunction of phosphorylation. Although a large number of phosphorylation sites in proteins have been identified using high-throughput phosphoproteomic technologies, their specific catalyzing kinases remain largely unknown. Therefore, computational methods are urgently needed to predict the kinases that catalyze the phosphorylation of these sites.

Results: We developed KSP, a new algorithm for predicting catalyzing kinases for experimentally identified phosphorylation sites in human proteins. KSP constructs a network based on known protein-protein interactions and kinase-substrate relationships. Based on the network, it computes an affinity score between a phosphorylation site and kinases, and returns the top-ranked kinases of the score as candidate catalyzing kinases. When tested on known kinase-substrate pairs, KSP outperforms existing methods including NetworKIN, iGPS, and PKIS.

Conclusions: We developed a novel accurate tool for predicting catalyzing kinases of known phosphorylation sites. It can work as a complementary network approach for sequence-based phosphorylation site predictors.
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http://dx.doi.org/10.1186/s12864-020-06895-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646512PMC
August 2020

Efficacy of Rebixiao Chinese herbal tablets and Chinese formula granules in acute gout arthritis patients: a randomized, multicenter, double-blind, controlled trial.

J Tradit Chin Med 2020 08;40(4):664-673

Department of Rheumatology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China.

Objective: To evaluate the clinical efficacy and safety of Rebixiao (RBX) Chinese herbal tablets (CHT) and Chinese formula granules (CFG) in the treatment of acute gout arthritis (AGA).

Methods: This randomized, multicenter, double-blind, controlled trial included 165 AGA patients with the damp-heat symptom pattern who were randomly divided into an RBX CHT group and an RBX CFG group and treated for 7 d at three centers. The total effective rates of the joint symptom score, Traditional Chinese Medicine (TCM) symptoms score, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were used to evaluate the clinical efficacy. Safety assessments were also performed.

Results: Of the 165 enrolled patients, 147 completed the clinical observation. There was no difference in baseline between the two groups. The total effective rates of the joint symptom score were 94.36% and 97.36%, and the total effective rates of the TCM symptoms score were 95.77% and 97.36% in the CFG group and CHT group, respectively. No statistical difference was found between the two groups (P > 0.05). Additionally, ESR and CRP were similar in both groups (P > 0.05). Furthermore, treatment efficacy regarding TCM and joint symptoms, the ESR, and CRP were consistent within each center and among the different centers (P > 0.05). In addition, the incidence of adverse events was 4.22% and 2.63% in the CFG group and CHT group, respectively, and no difference was observed between the two groups (P > 0.05).

Conclusion: RBX CFG and CHT have significant and similar efficacy in the treatment of AGA, and CFG did not increase adverse side effects.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2020.04.016DOI Listing
August 2020

RecBic: a fast and accurate algorithm recognizing trend-preserving biclusters.

Bioinformatics 2020 12;36(20):5054-5060

Research Center for Mathematics and Interdisciplinary Sciences.

Motivation: Biclustering has emerged as a powerful approach to identifying functional patterns in complex biological data. However, existing tools are limited by their accuracy and efficiency to recognize various kinds of complex biclusters submerged in ever large datasets. We introduce a novel fast and highly accurate algorithm RecBic to identify various forms of complex biclusters in gene expression datasets.

Results: We designed RecBic to identify various trend-preserving biclusters, particularly, those with narrow shapes, i.e. clusters where the number of genes is larger than the number of conditions/samples. Given a gene expression matrix, RecBic starts with a column seed, and grows it into a full-sized bicluster by simply repetitively comparing real numbers. When tested on simulated datasets in which the elements of implanted trend-preserving biclusters and those of the background matrix have the same distribution, RecBic was able to identify the implanted biclusters in a nearly perfect manner, outperforming all the compared salient tools in terms of accuracy and robustness to noise and overlaps between the clusters. Moreover, RecBic also showed superiority in identifying functionally related genes in real gene expression datasets.

Availability And Implementation: Code, sample input data and usage instructions are available at the following websites. Code: https://github.com/holyzews/RecBic/tree/master/RecBic/. Data: http://doi.org/10.5281/zenodo.3842717.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa630DOI Listing
December 2020

IL-23R in laryngeal cancer: a cancer immunoediting process that facilitates tumor cell proliferation and results in cisplatin resistance.

Carcinogenesis 2021 Feb;42(1):118-126

Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Oncogenic pathogens can disturb tissue homeostasis and initiate immune responses for oncogenicity clearance and homeostasis restoration, while failed clearance and chronic inflammation may result in tumorigenesis. The primary tumor development will undergo a cancer immunoediting process, including three phases, termed elimination, equilibrium and escape. Importantly, immune-edited tumor cells can not only reduce immunogenic molecular expression but also manipulate cytokines within the tumor environment (TME) for immune evasion and tumor proliferation. Many studies have revealed that IL-23R performed an essential role in mucous inflammation and tumorigenesis, and the role of IL-23R, either in tumor-infiltrating lymphocytes (TILs) or within immune-edited tumor cells, remained largely unknown in laryngeal cancer (LC). Here, we separately analyzed the IL-23R expression in LC TILs and tumor cells and found that high IL-23R expression in tumor cells was associated with moderate and poor tumor differentiation and an unfavorable prognosis. Furthermore, the real-time quantitative polymerase chain reaction analysis revealed that human LC tissues overexpress signal transducers and activators of transcription 3 (STAT3), and the relevance analysis found this STAT3 overexpression had a significant correlation with IL-23R expression. Besides, we isolated and cultured IL-23R+ human tumor cells from the postoperation tumor sample of three LC patients, and found that rhIL-23 could phosphorylate STAT3 (pSTAT3, residue Y705), which resulted in cancer cell proliferation and cisplatin resistance. These results indicate that IL-23R was a Hallmark of cancer immunoediting process, and targeting IL-23 should be considered as a therapeutic option for laryngeal function preservation and survival improvement.
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http://dx.doi.org/10.1093/carcin/bgaa058DOI Listing
February 2021

Effect of chronic exposure to nanopolystyrene on nematode Caenorhabditis elegans.

Chemosphere 2020 Oct 24;256:127172. Epub 2020 May 24.

Key Laboratory of Environmental Medicine Engineering of Ministry of Education, Medical School, Southeast University, Nanjing, 210009, China; Shenzhen Ruipuxun Academy for Stem Cell & Regenerative Medicine, Shenzhen, 518122, China. Electronic address:

Nanoplastic exposure could cause toxicity to Caenorhabditis elegans at various aspects. Nevertheless, the effects of chronic exposure to nanoplastics remain largely unclear in nematodes. In this study, we employed C. elegans as an animal model to determine the effects of nanopolystyrene (30 nm) exposure from adult day-1 for 8-day. After the exposure, only 1000 μg/L nanopolystyrene reduced the lifespan. In contrast, nanopolystyrene ≥1 μg/L decreased locomotion behavior and activated oxidative stress. Meanwhile, in 10 μg/L nanopolystyrene exposed nematodes, both expression of SOD-3, a Mn-SOD, and autophagy induction as indicated by LGG-1:GFP expression were significantly increased. RNAi knockdown of daf-2 encoding an insulin receptor enhanced the autophagy induction, and RNAi knockdown of daf-16 encoding a FOXO transcriptional factor in insulin signaling pathway suppressed the autophagy induction in 10 μg/L nanopolystyrene exposed nematodes. Moreover, DAF-16 acted upstream of LGG-1, an ortholog of Atg8/LC3, to regulate the toxicity of nanopolystyrene toxicity in inducing ROS production and in decreasing locomotion behavior at adult day-9. Our data implied the potential toxicity of chronic exposure to nanoplastics at predicted environmental concentrations on organisms.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127172DOI Listing
October 2020

A Genome-Wide Association Study Identifies Two Novel Susceptible Regions for Squamous Cell Carcinoma of the Head and Neck.

Cancer Res 2020 06 10;80(12):2451-2460. Epub 2020 Apr 10.

Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which, 434,839 typed and 7,423,250 imputed SNPs were used as the discovery. SNPs with < 1 × 10 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from databases of Genotypes and Phenotypes. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 ( = 2.96 × 10 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, ) and 6p21.33 (rs1265081, ) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 ( = 2.54 × 10 for the leading SNP rs142021700) was identified for hypopharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and expression quantitative trait loci analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of human leukocyte antigen loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN. SIGNIFICANCE: Two novel risk loci for SCCHN in non-Hispanic white individuals highlight the importance of immunologic mechanism in the disease etiology.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-2360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299763PMC
June 2020

Effect of up-regulation of circMATR3 on the proliferation, metastasis, progression and survival of hypopharyngeal carcinoma.

J Cell Mol Med 2020 04 12;24(8):4687-4697. Epub 2020 Mar 12.

Department of Otorhinolaryngology, Qilu Hospital, Shandong University, Key Laboratory of Otolaryngology, NHFPC (Shandong University), Shandong, China.

Increasing number of circular RNAs (circRNAs) have been reported to play important role in gene regulation, carcinogenesis and pathogenesis in various cancers. However, the biological functions and underlying molecular mechanisms of circRNAs in hypopharyngeal squamous cell carcinoma (HSCC) remain elusive. Thus, secondary circRNA-seq profiling was performed to identify the differentially expressed circRNAs between HSCC tissues and adjacent normal tissues, and the expression level of circMATR3 (derived from human gene matrin3 (MATR3), has_circRNA_0008922) was confirmed by qRT-PCR. Proliferation of HSCC cells was detected by cell counting kit-8 (CCK8) assay, apoptosis and the cell cycle were analysed by flow cytometry, and the migration and invasion of HSCC cells was determined by transwell assay. Bioinformatics analysis was conducted to predict possible pathways and potential miRNA targets of circMATR3. We found that circMATR3 was up-regulated in HSCC tissues, and abundant circMATR3 expression was markedly correlated with late T classification, advanced clinical stage, greater lymph node metastasis, and poor prognosis. Furthermore, knock-down of circMATR3 significantly inhibited proliferation, migration and invasion of HSCC cells, whereas silencing of circMATR3 induced cell apoptosis. Our analysis predicted that circMATR3 may participate in cancer-related pathways by serving as miRNA sponges. In conclusion, our findings first identified the oncogenic roles of circMATR3 in promoting the progression of HSCC and demonstrated that circMATR3 may be a novel prognostic marker and therapeutic target for HSCC.
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http://dx.doi.org/10.1111/jcmm.15134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176838PMC
April 2020

Angiotensin II triggers RIPK3-MLKL-mediated necroptosis by activating the Fas/FasL signaling pathway in renal tubular cells.

PLoS One 2020 5;15(3):e0228385. Epub 2020 Mar 5.

Department of Nephrology, the First Affiliated Hospital of Hainan Medical University, Haikou, China.

Our earlier studies proved that RIPK3-mediated necroptosis might be an important mode of renal tubular cell death in rats with chronic renal injury and the necroptotic cell death can be triggered by tumor necrosis factor-α (TNF-α) in vitro, but the triggering role of angiotensin II (AngII), which exerts notable effects on renal cells for the initiation and progression of renal tubulointerstitial fibrosis, is largely unknown. Here, we identified the presence of necroptotic cell death in the tubular cells of AngII-induced chronic renal injury and fibrosis mice and assessed the percentage of necroptotic renal tubular cell death with the disruption of this necroptosis by the addition of necrostatin-1 (Nec-1). Furthermore, the observation was further confirmed in HK-2 cells treated with AngII and RIPK1/3 or MLKL inhibitors. The detection of Fas and FasL proteins led us to investigate the contribution of the Fas/FasL signaling pathway to AngII-induced necroptosis. Disruption of FasL decreased the percentage of necroptotic cells, suggesting that Fas and FasL are likely key signal molecules in the necroptosis of HK-2 cells induced by AngII. Our data suggest that AngII exposure might trigger RIPK3-MLKL-mediated necroptosis in renal tubular epithelial cells by activating the Fas/FasL signaling pathway in vivo and in vitro.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228385PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058379PMC
June 2020

iPAC: a genome-guided assembler of isoforms via phasing and combing paths.

Bioinformatics 2020 05;36(9):2712-2717

School of Mathematics, Shandong University, Jinan 250100, China.

Motivation: Full-length transcript reconstruction is very important and quite challenging for the widely used RNA-seq data analysis. Currently, available RNA-seq assemblers generally suffered from serious limitations in practical applications, such as low assembly accuracy and incompatibility with latest alignment tools.

Results: We introduce iPAC, a new genome-guided assembler for reconstruction of isoforms, which revolutionizes the usage of paired-end and sequencing depth information via phasing and combing paths over a newly designed phasing graph. Tested on both simulated and real datasets, it is to some extent superior to all the salient assemblers of the same kind. Especially, iPAC is significantly powerful in recovery of lowly expressed transcripts while others are not.

Availability And Implementation: iPAC is freely available at http://sourceforge.net/projects/transassembly/files.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa052DOI Listing
May 2020

PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells.

J Cell Mol Med 2020 02 19;24(4):2444-2450. Epub 2020 Jan 19.

Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Radioresistance causes a major problem for improvement of outcomes of patients treated with radiation. Targeting for DNA repair deficient mechanisms is a hallmark of sensitization to resistance. We tested whether Olaparib, a (poly) ADP-ribose polymerase (PARP) inhibitor, can sensitize the radioresistant FaDu cells to radiotherapy. Radioresistant FaDu cells, called FaDu-RR cells, were used as the radioresistant hypopharyngeal cancer models. The expression of PARP1 was detected in both FaDu and FaDu-RR cells. The role of Olaparib in radiosensitization was analysed with several assays including clonogenic cell survival, cell proliferation and cell cycle, and radioresistant xenograft. High expression of PARP1 had a significant effect on enhancing radioresistance in FaDu-RR cells compared with FaDu cells. After treatment of Olaparib, FaDu-RR cells showed significantly less and smaller surviving colonies, lower proliferation ability and G2/M arrest than those in the group without treatment. Moreover, Olaparib significantly reduced growth of tumours in FaDu-RR cell xenografts treated with ionizing radiation. Olaparib can significantly inhibit PARP1 expression and consequently has significant effects on radiosensitization in FaDu-RR cells. These results indicate that Olaparib may help individualize treatment and improve their outcomes of hypopharyngeal cancer patients treated with radiation.
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http://dx.doi.org/10.1111/jcmm.14929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028864PMC
February 2020