Publications by authors named "Yue Qiu"

221 Publications

Aetiology of acute diarrhoea in children in Shanghai, 2015-2018.

PLoS One 2021 8;16(4):e0249888. Epub 2021 Apr 8.

Department of Infectious Diseases, Children's Hospital of Fudan University, Shanghai, China.

Diarrhoea remains a major cause of childhood morbidity and mortality worldwide. This study aimed to monitor the aetiology of acute diarrhoea in children in Shanghai. Paediatric outpatients with acute diarrhoea were enrolled in the study from Jan 2015 to Dec 2018. Faecal samples were collected for testing. Enteric bacteria were identified and typed by culture and serotyping, respectively. Enteric viruses were identified by real-time PCR. Enteric pathogens were identified in 1572 (58.4%) of the 2692 enrolled children with acute diarrhoea. Viruses were detected more frequently than bacteria (41.3% versus 25.0%). Nontyphoidal Salmonella spp. (NTS) was the most common (10.3%) bacteria isolated, followed by enteropathogenic Escherichia coli (EPEC) (6.5%), enteroaggregative Escherichia coli (EAEC) (6.2%), Campylobacter spp. (3.6%), enterotoxigenic Escherichia coli (ETEC) (1.1%), Shigella spp. (0.2%), and enterohemorrhagic Escherichia coli (EHEC) (0.1%). Rotavirus was the most common (16.0%) virus detected, followed by norovirus (15.5%), adenovirus (7.2%), sapovirus (3.0%) and astrovirus (2.7%). Rotavirus, norovirus and NTS were the major pathogens responsible for diarrhoea in Shanghainese children. Improving uptake of the rotavirus vaccine and strengthening foodborne-pathogen prevention will aid in reducing the burden of diarrhoeal disease in children in Shanghai.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249888PLOS
April 2021

N-Acetylcysteine Combined With Dexamethasone Treatment Improves Sudden Sensorineural Hearing Loss and Attenuates Hair Cell Death Caused by ROS Stress.

Front Cell Dev Biol 2021 18;9:659486. Epub 2021 Mar 18.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Sudden sensorineural hearing loss (SSNHL) is a common emergency in the world. Increasing evidence of imbalance of oxidant-antioxidant were found in SSNHL patients. Steroids combined with antioxidants may be a potential strategy for the treatment of SSNHL. In cochlear explant experiment, we found that N-acetylcysteine (NAC) combined with dexamethasone can effectively protect hair cells from oxidative stress when they were both at ineffective concentrations alone. A clinic trial was designed to explore whether oral NAC combined with intratympanic dexamethasone (ITD) as a salvage treatment has a better therapeutic effect. 41 patients with SSNHL were randomized to two groups. 23 patients in control group received ITD therapy alone, while 18 patient s in NAC group were treated with oral NAC and ITD. The patients were followed-up on day 1st (initiation of treatment) and day 14th. Overall, there was no statistical difference in final pure-tone threshold average (PTA) improvement between those two groups. However, a significant hearing gain at 8,000 Hz was observed in NAC group. Moreover, the hearing recovery rates of NAC group is much higher than that in control group. These results demonstrated that oral NAC in combination with ITD therapy is a more effective therapy for SSNHL than ITD alone.
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http://dx.doi.org/10.3389/fcell.2021.659486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014036PMC
March 2021

A deep learning framework for high-throughput mechanism-driven phenotype compound screening and its application to COVID-19 drug repurposing.

Nat Mach Intell 2021 Mar 1;3(3):247-257. Epub 2021 Feb 1.

Department of Computer Science and Engineering, The Ohio State University, Columbus, 43210, USA.

Phenotype-based compound screening has advantages over target-based drug discovery, but is unscalable and lacks understanding of mechanism. Chemical-induced gene expression profile provides a mechanistic signature of phenotypic response. However, the use of such data is limited by their sparseness, unreliability, and relatively low throughput. Few methods can perform phenotype-based chemical compound screening. Here, we propose a mechanism-driven neural network-based method DeepCE, which utilizes graph neural network and multi-head attention mechanism to model chemical substructure-gene and gene-gene associations, for predicting the differential gene expression profile perturbed by chemicals. Moreover, we propose a novel data augmentation method which extracts useful information from unreliable experiments in L1000 dataset. The experimental results show that DeepCE achieves superior performances to state-of-the-art methods. The effectiveness of gene expression profiles generated from DeepCE is further supported by comparing them with observed data for downstream classification tasks. To demonstrate the value of DeepCE, we apply it to drug repurposing of COVID-19, and generate novel lead compounds consistent with clinical evidence. Thus, DeepCE provides a potentially powerful framework for robust predictive modeling by utilizing noisy omics data and screening novel chemicals for the modulation of a systemic response to disease.
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http://dx.doi.org/10.1038/s42256-020-00285-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009091PMC
March 2021

Disease characteristics and neuropathological changes associated with cognitive dysfunction in obstructive sleep apnea.

Pediatr Investig 2021 Mar 22;5(1):52-57. Epub 2021 Mar 22.

Department of Otolaryngology, Head and Neck Surgery Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.

Obstructive sleep apnea (OSA) is a common sleep-disordered breathing disease that often leads to many comorbidities (e.g., cognitive dysfunction), which adversely affect the quality of life for patients with OSA. Thus far, the underlying mechanisms of this dysfunction remain unclear. Many studies have focused on OSA-related characteristics, including intermittent hypoxemia and sleep fragmentation. There is increasing emphasis on neuroimaging studies to explore underlying relationships between neuropathological changes and cognitive dysfunction. This article reviews recent research progress concerning cognitive dysfunction associated with OSA to reveal potential mechanisms that contribute to this dysfunction.
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http://dx.doi.org/10.1002/ped4.12247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984002PMC
March 2021

MSA-Regularized Protein Sequence Transformer toward Predicting Genome-Wide Chemical-Protein Interactions: Application to GPCRome Deorphanization.

J Chem Inf Model 2021 Mar 23. Epub 2021 Mar 23.

Ph.D. Program in Computer Science, The Graduate Center, The City University of New York, New York, New York 10016, United States.

Small molecules play a critical role in modulating biological systems. Knowledge of chemical-protein interactions helps address fundamental and practical questions in biology and medicine. However, with the rapid emergence of newly sequenced genes, the endogenous or surrogate ligands of a vast number of proteins remain unknown. Homology modeling and machine learning are two major methods for assigning new ligands to a protein but mostly fail when sequence homology between an unannotated protein and those with known functions or structures is low. In this study, we develop a new deep learning framework to predict chemical binding to evolutionary divergent unannotated proteins, whose ligand cannot be reliably predicted by existing methods. By incorporating evolutionary information into self-supervised learning of unlabeled protein sequences, we develop a novel method, distilled sequence alignment embedding (DISAE), for the protein sequence representation. DISAE can utilize all protein sequences and their multiple sequence alignment (MSA) to capture functional relationships between proteins without the knowledge of their structure and function. Followed by the DISAE pretraining, we devise a module-based fine-tuning strategy for the supervised learning of chemical-protein interactions. In the benchmark studies, DISAE significantly improves the generalizability of machine learning models and outperforms the state-of-the-art methods by a large margin. Comprehensive ablation studies suggest that the use of MSA, sequence distillation, and triplet pretraining critically contributes to the success of DISAE. The interpretability analysis of DISAE suggests that it learns biologically meaningful information. We further use DISAE to assign ligands to human orphan G-protein coupled receptors (GPCRs) and to cluster the human GPCRome by integrating their phylogenetic and ligand relationships. The promising results of DISAE open an avenue for exploring the chemical landscape of entire sequenced genomes.
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http://dx.doi.org/10.1021/acs.jcim.0c01285DOI Listing
March 2021

Hypoxia-induced microRNA-155 overexpression in extracellular vesicles promotes renal cell carcinoma progression by targeting .

Aging (Albany NY) 2021 Mar 19;13. Epub 2021 Mar 19.

Department of Urology, Qilu Hospital of Shandong University, Jinan 250000, China.

Renal cell carcinoma (RCC) is a form of cancer arising from the renal epithelium, with high mortality rates that have reached stable levels over the past decade. The tumor microenvironment is an essential regulator of tumor progression and survival, and extracellular vesicles (EVs) are an important facet of this microenvironment. Herein, we explored the impact of hypoxia-induced miR-155 expression in EVs on expression in RCC cells and their associated oncogenic activity. We found that RCC patients exhibited elevated miR-155 expression in EVs relative to healthy controls, suggesting that this miRNA may be important in the context of RCC progression. We then characterized EVs produced from RCC cell lines (Caki-1 and 786-O) under normoxic and hypoxic conditions, revealing that hypoxia-induced EVs contained higher levels of miR-155 and promoted cell proliferation. Then, we identified as a miR-155 target. Lastly, hypoxia-induced EVs were found to be able to significantly inhibit activation via facilitating miR-155 up-regulation. Together, these findings indicate that hypoxia can promote the upregulation of miR-155 in EVs and that this miRNA can act in RCC cells to suppress expression, thereby enhancing cellular tumor progression.
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http://dx.doi.org/10.18632/aging.202706DOI Listing
March 2021

Electronic Spin Moment As a Catalytic Descriptor for Fe Single-Atom Catalysts Supported on CN.

J Am Chem Soc 2021 Mar 11;143(11):4405-4413. Epub 2021 Mar 11.

Hefei National Laboratory for Physical Sciences at the Microscale, CAS Center for Excellence in Nanoscience, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.

The electrocatalytic activity of transition-metal-based compounds is strongly related to the spin states. However, the underlying relationship connecting spin to catalytic activity remains unclear. Herein, we carried out density functional theory calculations on oxygen reduction reaction (ORR) catalyzed by Fe single-atom supported on CN (CN-Fe) to shed light on this relationship. It is found that the change of electronic spin moments of Fe and O due to molecular-catalyst adsorption scales with the amount of electron transfer from Fe to O, which promotes the catalytic activity of CN-Fe for driving ORR. The nearly linear relationship between the catalytic activity and spin moment variation suggests electronic spin moment as a promising catalytic descriptor for Fe single-atom based catalysts. Following the revealed relationship, the ORR barrier on CN-Fe was tuned to be as low as 0.10 eV through judicious manipulation of spin states. These findings thus provide important insights into the relationship between catalytic activity and spin, leading to new strategies for designing transition metal single-atom catalysts.
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http://dx.doi.org/10.1021/jacs.1c00889DOI Listing
March 2021

Brain Function in Children with Obstructive Sleep Apnea: A Resting-State fMRI Study.

Sleep 2021 Mar 1. Epub 2021 Mar 1.

Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, People's Republic of China.

Objective: To explore the neural difference between children with obstructive sleep apnea (OSA) and healthy controls, together with the relation between this difference and cognitive dysfunction of children with OSA.

Methods: Twenty children with OSA (7.2 ± 3.1 years, apnea hypopnea index (AHI): 16.5 ± 16.6 events/h) and 29 healthy controls (7.7 ± 2.8 years, AHI: 1.7 ± 1.2 events/h) were recruited and matched with age, gender, and handedness. All children underwent resting-state fMRI (rs-fMRI) and T1-wighted imaging. Some children were sedated for MRI scanning. We compared amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) of children with OSA with those of healthy controls. During resting-state, the former reflects the intensity of the spontaneous neural activities, whereas the latter reflects temporal similarity of the spontaneous neural activities within a local brain region. Pearson correlation analysis was performed between these features of rs-fMRI and cognitive scores among children with OSA.

Results: Compared with controls, children with OSA showed decreased ALFF in the left angular gyrus but increased ALFF in the right insula, and decreased ReHo in the left medial superior frontal gyrus, right lingual gyrus and left precuneus. Additionally, among children with OSA, the ReHo value in the right lingual gyrus was negatively correlated with FIQ and VIQ, whereas that in the left medial superior frontal gyrus was positively correlated with VIQ.

Conclusions: Children with OSA presented abnormal neural activities in some brain regions and impaired cognitive functions with the former possibly being the neural mechanism of the latter.
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http://dx.doi.org/10.1093/sleep/zsab047DOI Listing
March 2021

Transcriptional regulation of the virulence genes and the biofilm formation associated operons in Vibrio parahaemolyticus.

Gut Pathog 2021 Mar 2;13(1):15. Epub 2021 Mar 2.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.

Background: The membrane fusion protein (mfp) gene locus of Vibrio parahaemolyticus consists of two operons, cpsQ-mfpABC and mfpABC, which are both required for biofilm formation. ToxR and CalR are required for the full virulence of V. parahaemolyticus, and their mutual regulation has been demonstrated. Moreover, cell density-dependent expression of toxR was previously observed in V. parahaemolyticus, but details about the related mechanisms remained unclear. QsvR can work with the master quorum sensing (QS) regulators AphA and OpaR to regulate virulence expression and biofilm formation.

Results: In the present work, we showed that QsvR bound to the promoter-proximal DNA regions of toxR and calR to repress their transcription as well as occupying the regulatory regions of cpsQ-mfpABC and mfpABC to activate their transcription. Thus, we reconstructed the QsvR-dependent promoter organization of toxR, calR, cpsQ-mfpABC, and mfpABC.

Conclusion: QsvR directly repressed toxR and calR transcription as well as directly activated cpsQ-mfpABC and mfpABC transcription. The data presented here promotes us to gain deeper knowledge of the regulatory network of the mfp locus in V. parahaemolyticus.
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http://dx.doi.org/10.1186/s13099-021-00410-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923509PMC
March 2021

CCDC154 Mutant Caused Abnormal Remodeling of the Otic Capsule and Hearing Loss in Mice.

Front Cell Dev Biol 2021 4;9:637011. Epub 2021 Feb 4.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Osteopetrosis is a rare inherited bone disease characterized by dysfunction of osteoclasts, causing impaired bone resorption and remodeling, which ultimately leads to increased bone mass and density. Hearing loss is one of the most common complications of osteopetrosis. However, the etiology and pathogenesis of auditory damage still need to be explored. In this study, we found that a spontaneous mutation of coiled-coil domain-containing 154 (CCDC154) gene, a new osteopetrosis-related gene, induced congenital deafness in mice. Homozygous mutant mice showed moderate to severe hearing loss, while heterozygous or wild-type (WT) littermates displayed normal hearing. Pathological observation showed that abnormal bony remodeling of the otic capsule, characterized by increased vascularization and multiple cavitary lesions, was found in homozygous mutant mice. Normal structure of the organ of Corti and no substantial hair cell or spiral ganglion neuron loss was observed in homozygous mutant mice. Our results indicate that mutation of the osteopetrosis-related gene CCDC154 can induce syndromic hereditary deafness in mice. Bony remodeling disorders of the auditory ossicles and otic capsule are involved in the hearing loss caused by CDCC154 mutation.
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http://dx.doi.org/10.3389/fcell.2021.637011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889813PMC
February 2021

CHBP induces stronger immunosuppressive CD127 M-MDSC via erythropoietin receptor.

Cell Death Dis 2021 Feb 12;12(2):177. Epub 2021 Feb 12.

Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Erythropoietin (EPO) is not only an erythropoiesis hormone but also an immune-regulatory cytokine. The receptors of EPO (EPOR) and tissue-protective receptor (TPR), mediate EPO's immune regulation. Our group firstly reported a non-erythropoietic peptide derivant of EPO, cyclic helix B peptide (CHBP), which could inhibit macrophages inflammation and dendritic cells (DCs) maturation. As a kind of innate immune regulatory cell, myeloid-derived suppressor cells (MDSCs) share a common myeloid progenitor with macrophages and DCs. In this study, we investigated the effects on MDSCs differentiation and immunosuppressive function via CHBP induction. CHBP promoted MDSCs differentiate toward M-MDSCs with enhanced immunosuppressive capability. Infusion of CHBP-induced M-MDSCs significantly prolonged murine skin allograft survival compared to its counterpart without CHBP stimulation. In addition, we found CHBP increased the proportion of CD11bLy6GLy6C CD127 M-MDSCs, which exerted a stronger immunosuppressive function compared to CD11bLy6GLy6C CD127 M-MDSCs. In CHBP induced M-MDSCs, we found that EPOR downstream signal proteins Jak2 and STAT3 were upregulated, which had a strong relationship with MDSC function. In addition, CHBP upregulated GATA-binding protein 3 (GATA-3) protein translation level, which was an upstream signal of CD127 and regulator of STAT3. These effects of CHBP could be reversed if Epor was deficient. Our novel findings identified a new subset of M-MDSCs with better immunosuppressive capability, which was induced by the EPOR-mediated Jak2/GATA3/STAT3 pathway. These results are beneficial for CHBP clinical translation and MDSC cell therapy in the future.
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http://dx.doi.org/10.1038/s41419-021-03448-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881243PMC
February 2021

Correlation between apparent diffusion coefficient and pathological characteristics of patients with invasive breast cancer.

Ann Transl Med 2021 Jan;9(2):143

Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China.

Background: There is insufficient research on the correlation between the apparent diffusion coefficient and clinicopathological characteristics of breast cancer patients. The present study is to investigate the correlation between the apparent diffusion coefficient and pathological characteristics of patients with invasive breast cancer.

Methods: From January 2019 to September 2020, 122 cases of invasive breast cancer and 21 cases of benign tumors were retrospectively enrolled. The apparent diffusion coefficient was compared between the two groups, and the correlation between the apparent diffusion coefficient and the pathological characteristics of the patients with invasive breast cancer were analyzed.

Results: Compared with the benign tumor group, the apparent diffusion coefficient in the invasive breast cancer group was significantly lower (0.89±0.17 1.47±0.27 10 mm/s, P=0.000). Using the apparent diffusion coefficient to diagnose patients with invasive breast cancer, the area under receiver operating characteristic (ROC) curve was 0.966±0.021 [95% confidence interval (CI): 0.924-1.000, P=0.000], and the best diagnostic cut-off value was 1.16 (10 mm/s), with sensitivity and specificity of 0.905 and 0.902, respectively. The apparent diffusion coefficient was used to diagnose vascular tumor thrombus in patients with invasive breast cancer. The area under the ROC curve was 0.641±0.068 (95% CI: 0.508-0.774, P=0.047), and the best diagnostic threshold was 0.835 (10 mm/s), with sensitivity and specificity of 0.676 and 0.650, respectively. The apparent diffusion coefficient in patients with high expression of Ki-67 (%) was significantly reduced (0.87±0.17 1.00±0.16 10 mm/s, P=0.000). The apparent diffusion coefficient was not significantly correlated with age, menopause, lesion size, estrogen receptor, progesterone receptor, or lymph node metastasis in patients with invasive breast cancer (P>0.05).

Conclusions: In patients with invasive breast cancer the apparent diffusion coefficient was significantly reduced. It was able to differentiate invasive breast cancer and vascular tumor thrombus, and was also related to Ki-67 (%) high expression.
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http://dx.doi.org/10.21037/atm-20-7746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867890PMC
January 2021

A method to screen left ventricular dysfunction through ECG based on convolutional neural network.

J Cardiovasc Electrophysiol 2021 Apr 15;32(4):1095-1102. Epub 2021 Feb 15.

Department of Cardiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.

Objective: This study aims to develop an artificial intelligence-based method to screen patients with left ventricular ejection fraction (LVEF) of 50% or lesser using electrocardiogram (ECG) data alone.

Methods: Convolutional neural network (CNN) is a class of deep neural networks, which has been widely used in medical image recognition. We collected standard 12-lead ECG and transthoracic echocardiogram (TTE) data including the LVEF value. Then, we paired the ECG and TTE data from the same individual. For multiple ECG-TTE pairs from a single individual, only the earliest data pair was included. All the ECG-TTE pairs were randomly divided into the training, validation, or testing data set in a ratio of 9:1:1 to create or evaluate the CNN model. Finally, we assessed the screening performance by overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value.

Results: We retrospectively enrolled a total of 26 786 ECG-TTE pairs and randomly divided them into training (n = 21 732), validation (n = 2 530), and testing data set (n = 2 530). In the testing set, the CNN algorithm showed an overall accuracy of 73.9%, sensitivity of 69.2%, specificity of 70.5%, positive predictive value of 70.1%, and negative predictive value of 69.9%.

Conclusion: Our results demonstrate that a well-trained CNN algorithm may be used as a low-cost and noninvasive method to identify patients with left ventricular dysfunction.
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http://dx.doi.org/10.1111/jce.14936DOI Listing
April 2021

A novel all-in-one strategy for purification and immobilization of β-1,3-xylanase directly from cell lysate as active and recyclable nanobiocatalyst.

Microb Cell Fact 2021 Feb 6;20(1):37. Epub 2021 Feb 6.

Department of Bioengineering and Biotechnology, Huaqiao University, Xiamen, 361021, Fujian, China.

Background: Exploring a simple and versatile technique for direct immobilization of target enzymes from cell lysate without prior purification is urgently needed. Thus, a novel all-in-one strategy for purification and immobilization of β-1,3-xylanase was proposed, the target enzymes were covalently immobilized on silica nanoparticles via elastin-like polypeptides (ELPs)-based biomimetic silicification and SpyTag/SpyCatcher spontaneous reaction. Thus, the functional carriers that did not require the time-consuming surface modification step were quickly and efficiently prepared. These carriers could specifically immobilize the SpyTag-fused target enzymes from the cell lysate without pre-purification.

Results: The ELPs-SpyCatcher hardly leaked from the carriers (0.5%), and the immobilization yield of enzyme was up to 96%. Immobilized enzyme retained 85.6% of the initial activity and showed 88.6% of the activity recovery. Compared with free ones, the immobilized β-1,3-xylanase showed improved thermal stability, elevated storage stability and good pH tolerance. It also retained more than 70.6% of initial activity after 12 reaction cycles, demonstrating its excellent reusability.

Conclusions: The results clearly highlighted the effectiveness of the novel enzyme immobilization method proposed here due to the improvement of overall performance of immobilized enzyme in respect to free form for the hydrolysis of macromolecular substrates. Thus, it may have great potential in the conversion of algae biomass as well as other related fields.
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http://dx.doi.org/10.1186/s12934-021-01530-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866670PMC
February 2021

A novel diphtheria toxin-based bivalent human EGF fusion toxin for treatment of head and neck squamous cell carcinoma.

Mol Oncol 2021 Apr 20;15(4):1054-1068. Epub 2021 Feb 20.

Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Epidermal growth factor receptor (EGFR) is often overexpressed in head and neck squamous cell carcinoma (HNSCC) and represents a top candidate for targeted HNSCC therapy. However, the clinical effectiveness of current Food and Drug Administration (FDA)-approved drugs targeting EGFR is moderate, and the overall survival rate for HNSCC patients remains low. Therefore, more effective treatments are urgently needed. In this study, we generated a novel diphtheria toxin-based bivalent human epidermal growth factor fusion toxin (bi-EGF-IT) to treat EGFR-expressing HNSCC. Bi-EGF-IT was tested for in vitro binding affinity, cytotoxicity, and specificity using 14 human EGFR-expressing HNSCC cell lines and three human EGFR-negative cancer cell lines. Bi-EGF-IT had increased binding affinity for EGFR-expressing HNSCC compared with the monovalent version (mono-EGF-IT), and both versions specifically depleted EGFR-positive HNSCC, but not EGFR-negative cell lines, in vitro. Bi-EGF-IT exhibited a comparable potency to that of the FDA-approved EGFR inhibitor, erlotinib, for inhibiting HNSCC tumor growth in vivo using both subcutaneous and orthotopic HNSCC xenograft mouse models. When tested in an experimental metastasis model, survival was significantly longer in the bi-EGF-IT treatment group than the erlotinib treatment group, with a significantly reduced number of metastases compared with mono-EGF-IT. In addition, in vivo off-target toxicities were significantly reduced in the bi-EGF-IT treatment group compared with the mono-EGF-IT group. These results demonstrate that bi-EGF-IT is more effective and markedly less toxic at inhibiting primary HNSCC tumor growth and metastasis than mono-EGF-IT and erlotinib. Thus, the novel bi-EGF-IT is a promising drug candidate for further development.
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http://dx.doi.org/10.1002/1878-0261.12919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024719PMC
April 2021

Prevalence and antimicrobial resistance patterns of bacteria isolated from cerebrospinal fluid among children with bacterial meningitis in China from 2016 to 2018: a multicenter retrospective study.

Antimicrob Resist Infect Control 2021 01 30;10(1):24. Epub 2021 Jan 30.

Department of Pediatrics, West China Second Hospital, Sichuan University and Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, No 20, 3rd Section of Renmin South Road, Chengdu, 610041, People's Republic of China.

Background: Pediatric bacterial meningitis (PBM) remains a devastating disease that causes substantial neurological morbidity and mortality worldwide. However, there are few large-scale studies on the pathogens causing PBM and their antimicrobial resistance (AMR) patterns in China. The present multicenter survey summarized the features of the etiological agents of PBM and characterized their AMR patterns.

Methods: Patients diagnosed with PBM were enrolled retrospectively at 13 children's hospitals in China from 2016 to 2018 and were screened based on a review of cerebrospinal fluid (CSF) microbiology results. Demographic characteristics, the causative organisms and their AMR patterns were systematically analyzed.

Results: Overall, 1193 CSF bacterial isolates from 1142 patients with PBM were obtained. The three leading pathogens causing PBM were Staphylococcus epidermidis (16.5%), Escherichia coli (12.4%) and Streptococcus pneumoniae (10.6%). In infants under 3 months of age, the top 3 pathogens were E. coli (116/523; 22.2%), Enterococcus faecium (75/523; 14.3%), and S. epidermidis (57/523; 10.9%). However, in children more than 3 months of age, the top 3 pathogens were S. epidermidis (140/670; 20.9%), S. pneumoniae (117/670; 17.5%), and Staphylococcus hominis (57/670; 8.5%). More than 93.0% of E. coli isolates were sensitive to cefoxitin, piperacillin/tazobactam, cefoperazone/sulbactam, amikacin and carbapenems, and the resistance rates to ceftriaxone, cefotaxime and ceftazidime were 49.4%, 49.2% and 26.4%, respectively. From 2016 to 2018, the proportion of methicillin-resistant coagulase-negative Staphylococcus isolates (MRCoNS) declined from 80.5 to 72.3%, and the frequency of penicillin-resistant S. pneumoniae isolates increased from 75.0 to 87.5%. The proportion of extended-spectrum β-lactamase (ESBL)-producing E. coli fluctuated between 44.4 and 49.2%, and the detection rate of ESBL production in Klebsiella pneumoniae ranged from 55.6 to 88.9%. The resistance of E. coli strains to carbapenems was 5.0%, but the overall prevalence of carbapenem-resistant K. pneumoniae (CRKP) was high (54.5%).

Conclusions: S. epidermidis, E. coli and S. pneumoniae were the predominant pathogens causing PBM in Chinese patients. The distribution of PBM causative organisms varied by age. The resistance of CoNS to methicillin and the high incidence of ESBL production among E. coli and K. pneumoniae isolates were concerning. CRKP poses a critical challenge for the treatment of PBM.
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http://dx.doi.org/10.1186/s13756-021-00895-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847565PMC
January 2021

Local Macrophage-Related Immune Response Is Involved in Cochlear Epithelial Damage in Distinct -Related Hereditary Deafness Models.

Front Cell Dev Biol 2020 11;8:597769. Epub 2021 Jan 11.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The macrophage-related immune response is an important component of the cochlear response to different exogenous stresses, including noise, ototoxic antibiotics, toxins, or viral infection. However, the role of the immune response in hereditary deafness caused by genetic mutations is rarely explored. , encoding connexin 26 (Cx26), is the most common deafness gene of hereditary deafness. In this study, two distinct Cx26-null mouse models were established to investigate the types and underlying mechanisms of immune responses. In a systemic Cx26-null model, macrophage recruitment was observed, associated with extensive cell degeneration of the cochlear epithelium. In a targeted-cell Cx26-null model, knockout of Cx26 was restricted to specific supporting cells (SCs), which led to preferential loss of local outer hair cells (OHCs). This local OHC loss can also induce a macrophage-related immune response. Common inflammatory factors, including TNF-α, IL-1β, Icam-1, Mif, Cx3cr1, Tlr4, Ccl2, and Ccr2, did not change significantly, while mRNA of Cx3cl1 was upregulated. Quantitative immunofluorescence showed that the protein expression of CX3CL1 in Deiters cells, a type of SC coupled with OHCs, increased significantly after OHC death. OHC loss caused the secondary death of spiral ganglion neurons (SGNs), while the remaining SGNs expressed high levels of CX3CL1 with infiltrated macrophages. Taken together, our results indicate that CX3CL1 signaling regulates macrophage recruitment and that enhancement of macrophage antigen-presenting function is associated with cell degeneration in Cx26-null mice.
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http://dx.doi.org/10.3389/fcell.2020.597769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829512PMC
January 2021

The efficacy and safety of montelukast in children with obstructive sleep apnea: a systematic review and meta-analysis.

Sleep Med 2021 Feb 10;78:193-201. Epub 2020 Nov 10.

Department of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, PR China. Electronic address:

Objective: The efficacy and safety of montelukast in children with obstructive sleep apnea (OSA) remain controversial. Therefore, the aims of this systemic review and meta-analysis are to verify this issue and further provide reference for clinical practice.

Methods: Seven databases were searched for randomized controlled trials (RCTs) up to September 30, 2019. The literature screening and data extraction were performed by two independent researchers. Adverse reactions from trials were also recorded. Meta-analysis was performed and analyzed heterogeneity. Methodological and evidence quality were followed by to evaluate according to Cochrane handbook.

Results: A total of 4 RCTs including 305 children with mild to moderate OSA were involved. Compared with placebo, we found that oral montelukast (OM) significantly improved polysomnography (PSG) monitoring parameters, typical and relevant symptoms including snoring and mouth breathing, and adenoid morphology in children with OSA. When compared with routine drugs, not only PSG monitoring parameters and adenoid morphology, but also sleep-disordered breathing (SDB)-related questionnaire scores were improved in patients with OSA treated by combination of OM and routine drugs. In addition, compared with single nasal spray of mometasone furoate, the present study also showed that OM combined with nasal spray of mometasone furoate significantly improved PSG monitoring parameters, symptoms of snoring and mouth breathing and reduced tonsil morphology in pediatric OSA. In terms of treatment safety, one study reported adverse reactions of OM such as headache, nausea and vomiting, while no adverse events were reported after OM treatment in another study.

Conclusion: As a classic leukotriene receptor antagonist, montelukast can be used to treat children with mild to moderate OSA in the short term and improve clinical characteristics. The promotion and application of OM in clinic is considered to be a noninvasive option to avoid surgical treatment.
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http://dx.doi.org/10.1016/j.sleep.2020.11.009DOI Listing
February 2021

Single-cell RNA Sequencing in Immunology.

Curr Genomics 2020 Dec;21(8):564-575

1Department of Urology, Zhongshan Hospital, Fudan University; Shanghai Key Laboratory of Organ Transplantation, Shanghai200032, China; 2Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai200032, China; 3Fudan Zhangjiang Institute of Fudan University, Shanghai201203, China.

The complex immune system is involved in multiple pathological processes. Single-cell RNA sequencing (scRNA-seq) is able to analyze complex cell mixtures correct to a single cell and single molecule, thus is qualified to analyze immune reactions in several diseases. In recent years, scRNA-seq has been applied in many researching fields and has presented many innovative results. In this review, we intend to provide an overview of single-cell RNA sequencing applications in immunology and a prospect of future directions.
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http://dx.doi.org/10.2174/1389202921999201020203249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770633PMC
December 2020

Snai1-induced partial epithelial-mesenchymal transition orchestrates p53-p21-mediated G2/M arrest in the progression of renal fibrosis via NF-κB-mediated inflammation.

Cell Death Dis 2021 Jan 5;12(1):44. Epub 2021 Jan 5.

Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.

Renal fibrosis is the common feature of all progressive kidney diseases and exerts great burden on public health worldwide. The maladaptive repair mechanism of tubular epithelial cells, an important mediator of renal fibrogenesis, manifests with partial epithelial-mesenchymal transition (EMT) and cell cycle arrest. The aim of this study is to investigate the possible correlation between partial EMT and cell cycle arrest, and elucidate the underlying mechanism. We examined human kidney allograft samples with interstitial fibrosis and three mice renal fibrosis models, unilateral ureter obstruction (UUO), ischemia-reperfusion injury, and Adriamycin nephropathy. The partial EMT process and p53-p21 axis were elevated in both human allograft with interstitial fibrosis, as well as three mice renal fibrosis models, and showed a time-dependent increase as fibrosis progressed in the UUO model. Snai1 controlled the partial EMT process, and led to parallel changes in renal fibrosis, G2/M arrest, and inflammation. p53-p21 axis arrested cell cycle at G2/M, and prompted partial EMT and fibrosis together with inflammation. NF-κB inhibitor Bay11-7082 disrupted the reciprocal loop between Snai1-induced partial EMT and p53-p21-mediated G2/M arrest. We demonstrated the reciprocal loop between partial EMT and G2/M arrest of TECs during renal fibrogenesis and revealed NF-κB-mediated inflammatory response as the underlying mechanism. This study suggests that targeting NF-κB might be a plausible therapeutic strategy to disrupt the reciprocal loop between partial EMT and G2/M arrest, therefore alleviating renal fibrosis.
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http://dx.doi.org/10.1038/s41419-020-03322-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790819PMC
January 2021

NKCC1 promotes proliferation, invasion and migration in human gastric cancer cells via activation of the MAPK-JNK/EMT signaling pathway.

J Cancer 2021 1;12(1):253-263. Epub 2021 Jan 1.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China.

This study aimed to explore the function of NKCC1 in the proliferation, migration and invasion of Gastric cancer (GC) cells. GC data extracted from the database was analyzed using molecular bioinformatics. The expression levels of NKCC1 in tissue samples from GC patients and GC cell lines were determined by Western blotting, qRT-PCR, and immunohistochemistry. Immunofluorescence was used to detect protein localization. The GC cell lines were transfected with NKCC1-shRNA or expression plasmid, and proliferation, invasion and migration were analyzed by the CCK8, wound healing and transwell tests. The NKCC1 mRNA level was significantly increased in GC tissues than that in normal gastric tissues ( = 0.0195). This phenomenon was further confirmed by the analysis of the TCGA-GTEx database that includes 408 gastric cancer tissues and 211 normal gastric tissues ( < 0.01). Furthermore, the increased level of NKCC1 was significantly correlated with Tumor size ( = 0.039), lymphatic node metastasis ( = 0.035) and tumor stage ( = 0.034). experiments confirmed that NKCC1 expression was higher in GC cells compared to that in GES-1 cells, and was mainly localized to the cytoplasm and membrane. NKCC1 silencing inhibited GC cell proliferation, invasion, migration and EMT, whereas its overexpression had the opposite effects. Furthermore, NKCC1 overexpression upregulated and activated JNK, and the targeted inhibition of JNK by SP600125 abrogated the pro-metastatic effects of NKCC1. NKCC1 promotes migration and invasion of GC cells by MAPK-JNK/EMT pathway and can be a potential therapeutic target.
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http://dx.doi.org/10.7150/jca.49709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738823PMC
January 2021

Expression and Prognostic Analysis of Integrins in Gastric Cancer.

J Oncol 2020 30;2020:8862228. Epub 2020 Nov 30.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China.

Background: Integrins are involved in the biological process of a variety of cancers, but their importance in the diagnosis and prognosis of gastric cancer (GC) is still unclear. Therefore, this study aimed at exploring the significance of ITG gene expression in GC to evaluate its diagnosis and prognosis.

Methods: GEPIA data were used to evaluate the mRNA expression of ITG genes in GC patients. The prognostic value of these genes was assessed by analyzing their mRNA expression using the Kaplan-Meier curve. The biological function of ITG genes was evaluated by GC tissue sequencing combined with GSEA bioinformatics. Based on the sequencing data, ITGA5 with the largest expression difference was selected for verification, and RT-PCR was used to verify its mRNA expression level in 40 pairs of GC and normal tissues.

Results: ITG (A2, A3, A4, A5, A6, A11, AE, AL, AM, AV, AX, B1, B2, B4, B5, B6, and B8) was highly expressed in GC tissues, while ITGA8 was low, compared with their expression in normal tissues. RNA-seq data shows that ITG (A2, A5, A11, AV, and B1) expression was associated with poor prognosis and overall survival. In addition, combined with the results of GC tissue mRNA sequencing, it was further found that the differentially expressed genes in the ITGs genes. ITGA5 was highly expressed in GC tissues compared with its expression in normal tissues, as evaluated by qRT-PCR ( < 0.001) and ROC ( < 0.001, AUC (95% CI) = 0.747 (0.641-0.851)), and confirmed that ITGA5 expression was a potential diagnostic marker for GC. Bioinformatics analysis revealed that the signaling pathway involved in ITGA5 was mainly enriched in focal adhesion, ECM-receptor interaction, and PI3K-AKT and was mainly involved in biological processes such as cell adhesion, extracellular matrix, and cell migration.

Conclusion: This study suggested that ITGs were associated with the diagnosis and prognosis of GC and discovered the prognostic value and biological role of ITGA5 in GC. Thus, ITGA5 might be used as a potential diagnostic marker for GC.
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http://dx.doi.org/10.1155/2020/8862228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722456PMC
November 2020

CRISPR/Cas9 Systems for the Development of Cell Factories.

Front Bioeng Biotechnol 2020 19;8:594347. Epub 2020 Nov 19.

Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.

Synthetic yeast cell factories provide a remarkable solution for the sustainable supply of a range of products, ranging from large-scale industrial chemicals to high-value pharmaceutical compounds. Synthetic biology is a field in which metabolic pathways are intensively studied and engineered. The clustered, regularly interspaced, short, palindromic repeat-associated (CRISPR)/CRISPR-associated protein 9 (Cas9) technology has emerged as the state-of-the-art gene editing technique for synthetic biology. Recently, the use of different CRISPR/Cas9 systems has been extended to the field of yeast engineering for single-nucleotide resolution editing, multiple-gene editing, transcriptional regulation, and genome-scale modifications. Such advancing systems have led to accelerated microbial engineering involving less labor and time and also enhanced the understanding of cellular genetics and physiology. This review provides a brief overview of the latest research progress and the use of CRISPR/Cas9 systems in genetic manipulation, with a focus on the applications of cell factory engineering.
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http://dx.doi.org/10.3389/fbioe.2020.594347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710542PMC
November 2020

Paying attention to tumor blood vessels: Cancer phototherapy assisted with nano delivery strategies.

Biomaterials 2021 Jan 24;268:120562. Epub 2020 Nov 24.

State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, Department of Pharmaceutics, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, China. Electronic address:

Cancer phototherapy has attracted increasing attention for its promising effectiveness and relative non-invasiveness. Over the past years, tremendous efforts have been made to develop better phototherapy strategies with various nano delivery systems. This review introduces cancer phototherapy strategies based on tumor blood vessels for improved therapeutic outcomes from the angle of direct tumor destruction and improved delivery process assisted with nano delivery designs. Latest directions and ideas of cancer phototherapy with translation potential are also discussed. Focusing on the double role of tumor vessels not only as an anti-tumor target but also as part of the delivery process, we highlight the crosstalk between photo-induced extensive effects and the complicated drug delivery process. Due to the heterogeneity of tumors, deeper investigations about the interconnection between tumor vessels and cancer phototherapy remain to be carried out. More delicate and intelligent nano delivery systems are expected to help realize the full potential of this therapeutic strategy.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120562DOI Listing
January 2021

Degradation of anthraquinone dye reactive blue 19 using persulfate activated with Fe/Mn modified biochar: Radical/non-radical mechanisms and fixed-bed reactor study.

Sci Total Environ 2021 Mar 17;758:143584. Epub 2020 Nov 17.

School of Civil Engineering and Architecture, Wuhan University of Technology, Wuhan 430070, PR China.

In this study, a heterogeneous activator was prepared via the Fe/Mn modification of sludge-derived biochar (Fe/MnBC) to achieve high-efficiency activation of persulfate (PS) for reactive blue 19 (RB19) degradation. The morphologies and chemical states of Fe/MnBC were examined by various characterizations. A comprehensive assessment was conducted to reveal the effects of biochar preparation conditions and system reaction conditions. According to the results of scavenger quenching experiments and electron paramagnetic resonance (EPR) testing, the mechanisms of Fe/MnBC combined PS system on RB19 degradation were proposed, including radical and non-radical mechanisms. The formation and involvement of sulfate radical (SO), hydroxyl radical (OH), and singlet oxygen (O) were proved in this system, and Fe(IV)/Mn(VII) was also speculated to participate in the non-radical degradation process. These findings give a new insight into the mechanisms of PS activated by metal-biochar composite. Besides, fixed-bed reactor (FBR) experiments indicated that the Fe/MnBC has considerable PS activation potential for dyes removal. The degradation process was further modeled by the central composite design (CCD-RSM) and artificial neural networks (ANN) methods. The statistical metrics and prediction indicated that the prediction results of ANN model were better than CCD-RSM model, and the ANN model could perfectly predict the reaction process of Fe/MnBC FBR for engineering applications.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143584DOI Listing
March 2021

Tim-3 is a potential regulator that inhibits monocyte inflammation in response to intermittent hypoxia in children with obstructive sleep apnea syndrome.

Clin Immunol 2021 Jan 30;222:108641. Epub 2020 Nov 30.

Department of Otolaryngology, Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. Electronic address:

The mechanism of the characteristic intermittent hypoxia (IH) of obstructive sleep apnea syndrome (OSAS) on monocyte remain unclear. Our study found that OSAS children had a significantly upregulated expression in circulating proinflammatory cytokines IL-6 and IL-12, and endothelial injury markers VEGF and ICAM1. Association analysis revealed that the plasma TNFα, IL-1β, IL-6, IL-10 and IL-12 concentration were negatively associated with the minimal SpO, a negative index for disease severity. OSAS monocytes presented an inflammatory phenotype with higher mRNA levels of inflammatory cytokines. Importantly, we noted a significant decrease in T-cell immunoglobulin and mucin domain (Tim)-3 expression in OSAS monocytes with the increase of the plasma proinflammatory cytokines. In vitro assay demonstrated that IH induced THP-1 cell overactivation via NF-κB dependent pathway was inhibited by the Tim-3 signal. Our results indicated that activation of monocyte inflammatory responses is closely related to OSAS-induced IH, and negatively mediated by a Tim-3 signaling pathway.
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http://dx.doi.org/10.1016/j.clim.2020.108641DOI Listing
January 2021

A "dual-guide" bioinspired drug delivery strategy of a macrophage-based carrier against postoperative triple-negative breast cancer recurrence.

J Control Release 2021 Jan 27;329:191-204. Epub 2020 Nov 27.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610064, PR China. Electronic address:

Recurrence after tumor resection is mainly caused by post-operative inflammation and residual cancer cells, which is a serious obstacle to breast cancer treatment. Traditional nanoparticles rely primarily on the enhanced permeability and retention (EPR) effect in well-vascularized tumors. In this study, a macrophage-based carrier is designed to enhance the efficiency of targeting to recurrent tumors through a "dual-guide" strategy. After tumor resection, a burst of inflammatory factors occurs in the resection wound, which can recruit monocytes/macrophages rapidly. Combined with the tropism of monocyte chemoattractant protein, a large number of macrophage-mediated carriers will be recruited to surgical recurrence sites. Octaarginine (RRRRRRRR, R8)-modified liposomes in macrophages contain two agents with different pharmacological mechanisms, paclitaxel (PTX) and resveratrol (Res), which have enhanced therapeutic effects. In vitro study demonstrated that macrophage-mediated carriers approach 4 T1 cells through an inflammatory gradient and reach recurrence tumors through a "dual-guide" strategy. Then, membrane fusion and inflammation-triggered release deliver the drug into the recurrent tumor cells. In vivo experiments show that macrophage-based carriers exhibit effective tumor-targeting ability, especially in post-operation situations. More importantly, macrophage-mediated liposomes encapsulated with PTX and Res inhibit tumor recurrence in both ectopic and orthotopic 4 T1 post-operative recurrence models.
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http://dx.doi.org/10.1016/j.jconrel.2020.11.039DOI Listing
January 2021

Visceral Fat Area, Not Subcutaneous Fat Area, is Associated with Cardiac Hemodynamics in Type 2 Diabetes.

Diabetes Metab Syndr Obes 2020 17;13:4413-4422. Epub 2020 Nov 17.

Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, People's Republic of China.

Background: This study was conducted in patients with type 2 diabetes mellitus (T2DM) to assess the association between visceral fat area (VFA) and cardiac hemodynamics.

Methods: A total of 568 patients with type 2 diabetes (mean age 54±12 years; 40.8% of women) were enrolled. Visceral fat area (VFA, m) and subcutaneous fat area (SFA, m) were evaluated by a bioelectrical impedance analyzer. Cardiac hemodynamics were measured by echocardiography, and other clinical and laboratory variables were also assessed and recorded. Patients were divided into those with VFA ≤ 100 (n=369) and those with VFA > 100 (n=199).

Results: VFA, SFA, LVMI (left ventricular mass index), left atrial diameter, left ventricular diastolic diameter (LvDd), interventricular septal thickness (IVST), left ventricular systolic diameter (LvSd), and posterior wall thickness (PWT) levels in high-V groups were significantly higher than those in low-V groups. Correlation analysis showed that VFA was positively correlated with LVMI (=0.120, =0.004), LVM (=0.249, <0.0001), left atrial diameter (=0.375, <0.0001), aortic root diameter (=0.243, <0.0001), left ventricular systolic diameter (LvSd) (=0.211, <0.0001) and negatively correlated with LVEF (=-0.107, =0.011). In multivariate linear regression analysis, VFA was the strongest independent determinant of LVMI (=0.04, =0.016), LVEF (=-0.01, =0.023), and left atrial diameter (=0.035, <0.0001), Internal diameter of the aortic root (=0.014, <0.0001) and LvSd (=0.017, <0.0001). In addition, the VFA also better predicted cardiovascular disease risk with AUC of 0.609 (95% CI:0.563-0.656), compared with SFA, waist-hip ratio (WHR), in a statistically significant manner.

Conclusion: We found a significant correlation between VFA (but not SFA) and cardiac hemodynamic parameters. The VFA has advantages as a predictor of visceral obesity and is significantly associated with the development of cardiovascular risk factors (CVD) in T2DM patients.
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http://dx.doi.org/10.2147/DMSO.S284420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680090PMC
November 2020

Immune-related lncRNAs as predictors of survival in breast cancer: a prognostic signature.

J Transl Med 2020 11 23;18(1):442. Epub 2020 Nov 23.

Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.

Background: Breast cancer is a highly heterogeneous disease, this poses challenges for classification and management. Long non-coding RNAs play acrucial role in the breast cancersdevelopment and progression, especially in tumor-related immune processes which have become the most rapidly investigated area. Therefore, we aimed at developing an immune-related lncRNA signature to improve the prognosis prediction of breast cancer.

Methods: We obtained breast cancer patient samples and corresponding clinical data from The Cancer Genome Atlas (TCGA) database. Immune-related lncRNAs were screened by co-expression analysis of immune-related genes which were downloaded from the Immunology Database and Analysis Portal (ImmPort). Clinical patient samples were randomly separated into training and testing sets. In the training set, univariate Cox regression analysis and LASSO regression were utilized to build a prognostic immune-related lncRNA signature. The signature was validated in the training set, testing set, and whole cohorts by the Kaplan-Meier log-rank test, time-dependent ROC curve analysis, principal component analysis, univariate andmultivariate Cox regression analyses.

Results: A total of 937 immune- related lncRNAs were identified, 15 candidate immune-related lncRNAs were significantly associated with overall survival (OS). Eight of these lncRNAs (OTUD6B-AS1, AL122010.1, AC136475.2, AL161646.1, AC245297.3, LINC00578, LINC01871, AP000442.2) were selected for establishment of the risk prediction model. The OS of patients in the low-risk group was higher than that of patients in the high-risk group (p = 1.215e - 06 in the training set; p = 0.0069 in the validation set; p = 1.233e - 07 in whole cohort). The time-dependent ROC curve analysis revealed that the AUCs for OS in the first, eighth, and tenth year were 0.812, 0.81, and 0.857, respectively, in the training set, 0.615, 0.68, 0.655 in the validation set, and 0.725, 0.742, 0.741 in the total cohort. Multivariate Cox regression analysis indicated the model was a reliable and independent indicator for the prognosis of breast cancer in the training set (HR = 1.432; 95% CI 1.204-1.702, p < 0.001), validation set (HR = 1.162; 95% CI 1.004-1.345, p = 0.044), and whole set (HR = 1.240; 95% CI 1.128-1.362, p < 0.001). GSEA analysis revealed a strong connection between the signature and immune-related biological processes and pathways.

Conclusions: We constructed and verified a robust signature of 8 immune-related lncRNAs for the prediction of breast cancer patient survival.
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http://dx.doi.org/10.1186/s12967-020-02522-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681988PMC
November 2020

Fur Represses Biofilm Formation Direct Regulation of , , , and Transcription.

Front Microbiol 2020 22;11:587159. Epub 2020 Oct 22.

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

Attached biofilms are essential for environmental persistence and infectivity. The loci (, -K, and ) are required for mature biofilm formation and are responsible for the synthesis of exopolysaccharide. Transcription of genes is activated by the signaling molecule bis-(3'-5')-cyclic di-GMP (c-di-GMP), whose metabolism is controlled by the proteins containing the GGDEF and/or EAL domains. The ferric uptake regulator (Fur) plays key roles in the transcription of many genes involved in iron metabolism and non-iron functions. However, roles for Fur in biofilm production have not been documented. In this study, phenotypic assays demonstrated that Fur, independent of iron, decreases c-di-GMP levels and inhibits biofilm formation by . The Fur box-like sequences were detected within the promoter-proximal DNA regions of , , , and , suggesting that transcription of these genes may be under the direct control of Fur. Indeed, the results of luminescence, quantitative PCR (qPCR), electrophoretic mobility shift assay (EMSA), and DNase I footprinting assays demonstrated Fur to bind to the promoter-proximal DNA regions of , , and to repress their transcription. In contrast, Fur activates the transcription of in a direct manner. The and encode proteins with GGDEF and EAL domains, respectively. Thus, data presented here highlight a new physiological role for Fur wherein it acts as a repressor of biofilm formation mediated by decreasing the production of exopolysaccharide and the intracellular levels of c-di-GMP.
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http://dx.doi.org/10.3389/fmicb.2020.587159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641913PMC
October 2020