Publications by authors named "Liang Chen"

3,575 Publications

  • Page 1 of 1

Effect of chlorhexidine-loaded poly(amido amine) dendrimer on matrix metalloproteinase activities and remineralization in etched human dentin in vitro.

J Mech Behav Biomed Mater 2021 Jun 10;121:104625. Epub 2021 Jun 10.

Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China. Electronic address:

To investigate the effect of chlorhexidine (CHX)-loaded carboxyl-terminated poly (amido amine) dendrimer (CHX-PAMAM-COOH) on matrix metalloproteinase (MMP) activities and remineralization in human dentin, CHX-PAMAM-COOH was prepared and characterized by Fourier-transform infrared spectroscopy. The inhibitory effects of CHX, PAMAM-COOH, and CHX-PAMAM-COOH on soluble recombinant human matrix metalloproteinase (rhMMP-2) and dentin-bound endogenous MMP activity were measured using an MMP Activity Assay Kit. In situ zymography was performed to evaluate the gelatinase activity in dentin pretreated with CHX, PAMAM-COOH, and CHX-PAMAM-COOH. The remineralization of etched dentin pretreated with CHX, PAMAM-COOH, and CHX-PAMAM-COOH was evaluated by field emission-scanning electron microscopy (SEM) and energy disperse spectroscopy (EDS) after incubation in artificial saliva for 14 days. The results of the rhMMP-2 activity assay showed that the MMP-2 activity in the CHX-PAMAM-COOH group and the CHX group decreased significantly to 5.58 ± 0.85% (P < 0.05) and 4.86 ± 1.12% (P < 0.05), respectively, but that in the PAMAM-COOH group increased significantly to 213.38 ± 0.11% (P < 0.05). The results of total MMP activity and in situ zymography showed a significant reduction in endogenous gelatinase activity in dentin in the CHX-PAMAM-COOH group and the CHX group. The SEM and EDS results showed that rod-like crystals were formed on the etched dentin surface in the PAMAM-COOH group and the CHX-PAMAM-COOH group, and their Ca/P ratios were 1.73 and 1.71, respectively. In conclusion, CHX-PAMAM-COOH can inhibit dentin-bound endogenous MMPs and induce remineralization in etched dentin simultaneously. However, it is important to note that the catalytic role of PAMAM dendrimers may have an undesired excitatory effect on MMP activity, which cannot be ignored if PAMAM dendrimers were used alone in the oral environment.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104625DOI Listing
June 2021

A Novel Prediction Model of COVID-19 Progression: A Retrospective Cohort Study.

Infect Dis Ther 2021 Jun 14. Epub 2021 Jun 14.

Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.

Introduction: Estimating the risk of disease progression is of utmost importance for planning appropriate setting of care and treatment for patients with coronavirus disease 2019 (COVID-19). This study aimed to develop and validate a novel prediction model of COVID-19 progression.

Methods: In total, 814 patients in the training set were included to develop a novel scoring system; and 420 patients in the validation set were included to validate the model.

Results: A prediction score, called ACCCDL, was developed on the basis of six risk factors associated with COVID-19 progression: age, comorbidity, CD4 T cell count, C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH). For predicting COVID-19 progression, the ACCCDL score yielded a significantly higher area under the receiver operating characteristic curve (AUROC) compared with the CALL score, CoLACD score, PH-COVID-19 score, neutrophil-lymphocyte ratio, and lymphocyte-monocyte ratio both in the training set (0.92, 0.84, 0.83, 0.83, 0.76, and 0.65, respectively) and in the validation set (0.97, 0.83, 0.83, 0.78, 0.74, and 0.60, respectively). Over 99% of patients with the ACCCDL score < 12 points will not progress to severe cases, and over 30% of patients with the ACCCDL score > 20 points will progress to severe cases.

Conclusion: The ACCCDL score could stratify patients with at risk of COVID-19 progression, and was useful in regulating the large flow of patients with COVID-19 between primary health care and tertiary centers.
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http://dx.doi.org/10.1007/s40121-021-00460-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202540PMC
June 2021

Genome-Wide Essentiality Analysis of by Saturated Transposon Mutagenesis and Deep Sequencing.

mBio 2021 Jun 15:e0104921. Epub 2021 Jun 15.

The Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

Mycobacterium abscessus is an emerging opportunistic human pathogen that naturally resists most major classes of antibiotics, making infections difficult to treat. Thus far, little is known about physiology, pathogenesis, and drug resistance. Genome-wide analyses have comprehensively catalogued genes with essential functions in Mycobacterium tuberculosis and Mycobacterium avium subsp. (here, ) but not in . By optimizing transduction conditions, we achieved full saturation of TA insertion sites with Himar1 transposon mutagenesis in the ATCC 19977 genome, as confirmed by deep sequencing prior to essentiality analyses of annotated genes and other genomic features. The overall densities of inserted TA sites (85.7%), unoccupied TA sites (14.3%), and nonpermissive TA sites (8.1%) were similar to results in and . Of the 4,920 annotated genes, 326 were identified as essential, 269 (83%) of which have mutual homology with essential genes, while 39 (12%) are homologous to genes that are not essential in and , and 11 (3.4%) only have homologs in . Interestingly, 7 (2.1%) essential genes have no homologs in either or , two of which were found in phage-like elements. Most essential genes are involved in DNA replication, RNA transcription and translation, and posttranslational events to synthesize important macromolecules. Some essential genes may be involved in pathogenesis and antibiotics response, including certain essential tRNAs and new short open reading frames. Our findings will help to pave the way for better understanding of and benefit development of novel bactericidal drugs against . Limited knowledge regarding pathogenesis and intrinsic resistance to most classes of antibiotics is a major obstacle to developing more effective strategies to prevent and mitigate disease. Using optimized procedures for Himar1 transposon mutagenesis and deep sequencing, we performed a comprehensive analysis to identify genetic elements essential for growth and compare them to similar data sets for and subsp. . Most essential genes have mutual homology with essential genes, providing a foundation for leveraging available knowledge from to develop more effective drugs and other interventions against . A small number of essential genes unique to deserve further attention to gain insights into what makes different from other mycobacteria. The essential genes and other genomic features such as short open reading frames and noncoding RNA identified here will provide useful information for future study of pathogenicity and new drug development.
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http://dx.doi.org/10.1128/mBio.01049-21DOI Listing
June 2021

A HO self-sufficient nanoplatform with domino effects for thermal-responsive enhanced chemodynamic therapy.

Chem Sci 2020 Jan 8;11(7):1926-1934. Epub 2020 Jan 8.

Key Laboratory of Flexible Electronics (KLOFE), Institute of Advanced Materials (IAM), School of Physical and Mathematical Sciences, Nanjing Tech University (NanjingTech) Nanjing 211800 China

Chemodynamic therapy (CDT), employing Fenton or Fenton-like catalysts to convert hydrogen peroxide (HO) into toxic hydroxyl radicals (˙OH) to kill cancer cells, holds high promise in tumor therapy due to its high selectivity. However, the anticancer efficacy is unsatisfactory owing to the limited concentration of endogenous HO. Herein, thermal responsive nanoparticles with HO self-sufficiency are fabricated by utilizing organic phase change materials (PCMs) to encapsulate iron-gallic acid nanoparticles (Fe-GA) and ultra-small CaO. PCMs, acting as the gatekeeper, could be melted down by the hyperthermia effect of Fe-GA under laser irradiation with a burst release of Fe-GA and CaO. The acidic tumor microenvironment would further trigger CaO to generate a large amount of HO and Ca. The self-supplied HO would be converted into ˙OH by participating in the Fenton reaction with Fe-GA. Meanwhile, generation of Ca could cause mitochondrial damage and lead to apoptosis of tumor cells. With efficient tumor accumulation illustrated in photoacoustic imaging, Fe-GA/[email protected] demonstrated a superior tumor-suppressive effect without inducing systemic toxicity. The study presents a unique domino effect approach of PCM based nanoparticles with thermal responsiveness, HO self-supply, and greatly enhanced CDT effects, showing bright prospects for highly efficient tumor treatment.
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http://dx.doi.org/10.1039/c9sc05506aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148300PMC
January 2020

A pH ratiometrically responsive surface enhanced resonance Raman scattering probe for tumor acidic margin delineation and image-guided surgery.

Chem Sci 2020 Apr 7;11(17):4397-4402. Epub 2020 Apr 7.

Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University Shanghai 201203 China

Surgery remains the mainstay for most solid tumor treatments. However, surgeons face challenges in intra-operatively identifying invasive tumor margins due to their infiltrative nature. Incomplete excision usually leads to early recurrence, while aggressive resection may injure adjacent functional tissues. Herein, we report a pH responsive ratiometric surface-enhanced Raman scattering (SERRS) probe that determined physiological pHs with a high sensitivity and tissue penetration depth an innovative mechanism named spatial orientation induced intramolecular energy transfer (SOIET). Due to the positive correlation between tumor acidity and malignancy, an acidic margin-guided surgery strategy was implemented in live animal models by intra-operatively assessing tissue pH/malignancy of the suspicious tissues in tumor cutting edges. This surgery remarkably extended the survival of animal models and minimized their post-surgical complications, showing promise in precisely identifying invasive tumor boundaries and achieving a balance between maximum tumor debulking and minimal functional impairment.
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http://dx.doi.org/10.1039/d0sc00844cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159485PMC
April 2020

Genomic evolution and virulence association of sequence type 37 (ribotype 017) in China.

Emerg Microbes Infect 2021 Jun 14:1-0. Epub 2021 Jun 14.

School of Laboratory Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, 310053, China.

sequence type (ST) 37 (ribotype 017) is one of the most prevalent genotypes circulating in China. However, its genomic evolution and virulence determinants were rarely explored. Whole-genome sequencing, phylogeographic and phylogenetic analyses were conducted for ST37 isolates. The 325 ST37 genomes from six continents, including North America (n=66), South America (n=4), Oceania (n=7), Africa (n=9), Europe (n=138) and Asia (n=101), were clustered into six major lineages, with region-dependent distributions, harbouring an array of antibiotic-resistance genes. The ST37 strains from China were divided into four distinct sublineages, showing five importation times and international sources. Isolates associated with severe infections exhibited significantly higher toxin productions, mRNA levels, and sporulation capacities (< 0.001). Kyoto Encyclopedia of Genes and Genomes analysis showed 10 metabolic pathways were significantly enriched in the mutations among isolates associated with severe CDI ( < 0.05). Gene mutations in glycometabolism, amino acid metabolism and biosynthesis virtually causing instability in protein activity were correlated positively to the transcription of and negatively to the expression of toxin repressor genes, and . In summary, our study firstly presented genomic insights into genetic characteristics and virulence association of ST37 in China. Gene mutations in certain important metabolic pathways are associated with severe symptoms and correlated with higher virulence in ST37 isolates.
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http://dx.doi.org/10.1080/22221751.2021.1943538DOI Listing
June 2021

Reprogramming the immunosuppressive microenvironment of IDH1 wild-type glioblastoma by blocking Wnt signaling between microglia and cancer cells.

Oncoimmunology 2021 Jun 6;10(1):1932061. Epub 2021 Jun 6.

Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China.

The vast majority (>90%) of glioblastoma (GBM) patients belong to the isocitrate dehydrogenase 1 wild type (IDH1) group which exhibits a poor prognosis with a median survival of less than 15 months. This study demonstrated numerous immunosuppressive genes as well as β-catenin gene, pivotal for Wnt/β-catenin signaling, were upregulated in 206 IDH1 glioma patients using the Chinese Glioma Genome Atlas (CGGA) database. The increase in microglia with an immunosuppressive phenotype and the overexpression of β-catenin protein were further verified in IDH1 GBM patients and IDH1 GL261 glioma allografts. Subsequently, we found that IDH1 GL261 cell-derived conditioned medium activated Wnt/β-catenin signaling in primary microglia and triggered their transition to an immunosuppressive phenotype. Blocking Wnt/β-catenin signaling not only attenuated microglial polarization to the immunosuppressive subtype but also reactivated immune responses in IDH1 GBM allografts by simultaneously enhancing cytotoxic CD8 T cell infiltration and downregulating regulatory T cells. Positron emission tomography imaging demonstrated enhanced proinflammatory activities in IDH1 GBM allografts after the blockade of Wnt signaling. Finally, gavage administration of a Wnt signaling inhibitor significantly restrained tumor proliferation and improved the survival of model mice bearing IDH1 GBM allografts. Depletion of CD8 T cells remarkably abrogated the therapeutic efficacy induced by the Wnt signaling inhibitor. Overall, the present work indicates that the crosstalk between IDH1 glioma cells and immunosuppressive microglia is important in maintaining the immunosuppressive glioma microenvironment. Blocking Wnt/β-catenin signaling is a promising complement for IDH1 GBM treatment by improving the hostile immunosuppressive microenvironment.
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http://dx.doi.org/10.1080/2162402X.2021.1932061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183516PMC
June 2021

NaHS or Lovastatin Attenuates Cyclosporine A-Induced Hypertension in Rats by Inhibiting Epithelial Sodium Channels.

Front Pharmacol 2021 26;12:665111. Epub 2021 May 26.

Department of Physiology, Emory University School of Medicine, Atlanta, GA, United States.

The use of cyclosporine A (CsA) in transplant recipients is limited due to its side effects of causing severe hypertension. We have previously shown that CsA increases the activity of the epithelial sodium channel (ENaC) in cultured distal nephron cells. However, it remains unknown whether ENaC mediates CsA-induced hypertension and how we could prevent hypertension. Our data show that the open probability of ENaC in principal cells of split-open cortical collecting ducts was significantly increased after treatment of rats with CsA; the increase was attenuated by lovastatin. Moreover, CsA also elevated the levels of intracellular cholesterol (Cho), intracellular reactive oxygen species (ROS) activation of NADPH oxidase p47, serum- and glucocorticoid-induced kinase isoform 1 (Sgk1), and phosphorylated neural precursor cell-expressed developmentally downregulated protein 4-2 (-Nedd4-2) in the kidney cortex. Lovastatin also abolished CsA-induced elevation of α-, -, and γ-ENaC expressions. CsA elevated systolic blood pressure in rats; the elevation was completely reversed by lovastatin (an inhibitor of cholesterol synthesis), NaHS (a donor of HS which ameliorated CsA-induced elevation of reactive oxygen species), or amiloride (a potent ENaC blocker). These results suggest that CsA elevates blood pressure by increasing ENaC activity via a signaling cascade associated with elevation of intracellular ROS, activation of Sgk1, and inactivation of Nedd4-2 in an intracellular cholesterol-dependent manner. Our data also show that NaHS ameliorates CsA-induced hypertension by inhibition of oxidative stress.
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http://dx.doi.org/10.3389/fphar.2021.665111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187945PMC
May 2021

Dietary amylose/amylopectin ratio influences the expression of amino acid transporters and enzyme activities for amino acid metabolism in the gastrointestinal tract of goats.

Br J Nutr 2021 Jun 14:1-31. Epub 2021 Jun 14.

CAS Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Key Laboratory of Animal Nutrition & Physiology and Metabolism, Institute of Subtropical Agriculture, the Chinese Academy of Sciences, Changsha 410125, P. R. China.

This study was designed to investigate the effects of dietary starch structure on muscle protein synthesis and gastrointestinal amino acid (AA) transport and metabolism of goats. Twenty-seven Xiangdong black female goats (average body weight = 9.00 ± 1.12 kg) were randomly assigned to three treatments, i.e., fed a T1 (normal corn 100%, high amylose corn 0%), T2 (normal corn 50%, high amylose corn 50%) and T3 (normal corn 0%, high amylose corn 100%) diet for 35 days, respectively. All amino acids in the ileal mucosa were decreased linearly as amylose/amylopectin increased in diets (P<0.05). The plasma valine (linear, P=0.03), leucine (linear, P=0.04), and total amino acids content (linear, P=0.03) increased linearly with the increase in the ratio of amylose in the diet. The relative mRNA levels of SLC38A1 (linear, P=0.01), SLC3A2 (linear, P=0.02), and SLC38A9 (linear, P=0.02) in the ileum increased linearly with the increase in the ratio of amylose in the diet. With the increase in the ratio of amylose/amylopectin in the diet, the mRNA levels of ACADSB (linear, P=0.04), BCAT1 (linear, P=0.02), and BCKDHB (linear, P=0.01) in the ileum decreased linearly. Our results revealed that the protein abundances of p-mTOR (P<0.001), p-4EBP1 (P<0.001), and p-S6K1 (P<0.001) of T2 and T3 were significantly higher than that of T1. In general, a diet with a high amylose ratio could reduce the consumption of amino acids in the intestine, allowing more amino acids to enter the blood to maintain higher muscle protein synthesis through the mTOR pathway.
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http://dx.doi.org/10.1017/S0007114521002087DOI Listing
June 2021

Recent developments in engineering protein-protein interactions using phage display.

Protein Eng Des Sel 2021 Feb;34

Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, 50 Stone Rd E, Guelph, Ontario N1G2W1, Canada.

Targeted inhibition of misregulated protein-protein interactions (PPIs) has been a promising area of investigation in drug discovery and development for human diseases. However, many constraints remain, including shallow binding surfaces and dynamic conformation changes upon interaction. A particularly challenging aspect is the undesirable off-target effects caused by inherent structural similarity among the protein families. To tackle this problem, phage display has been used to engineer PPIs for high-specificity binders with improved binding affinity and greatly reduced undesirable interactions with closely related proteins. Although general steps of phage display are standardized, library design is highly variable depending on experimental contexts. Here in this review, we examined recent advances in the structure-based combinatorial library design and the advantages and limitations of different approaches. The strategies described here can be explored for other protein-protein interactions and aid in designing new libraries or improving on previous libraries.
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http://dx.doi.org/10.1093/protein/gzab014DOI Listing
February 2021

Trifecta achievement in patients undergoing partial nephrectomy: a systematic review and meta-analysis of predictive factors.

Int Braz J Urol 2021 Apr 20;47. Epub 2021 Apr 20.

Department of Mongolian Medicine Urology, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao,China.

Purpose: The predictors of trifecta achievement in partial nephrectomy (PN) were poorly inquired and remained a controversial area of discovery. To evaluate predictive factors of trifecta achievement in patients undergoing PN.

Materials And Methods: A systematic literature search was performed to identify relevant articles. Only studies focusing on postoperative trifecta achievement and exploring its predictor with multivariable analyses were included. The trifecta achievement was defined as negative surgical margins, warm ischemia time <25 minutes, and no complications. Merged odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the predictive effect.

Results: Thirteen studies with 7066 patients meeting the inclusion criteria were included. The rate of trifecta achievement ranged from 43.3% to 78.6%. Merged results showed that preoperative eGFR (OR: 1.01, 95% CI: 1.00, 1.02, P=0.02), operative time (OR: 0.99, 95% CI: 0.99, 1.00, P=0.02), estimated blood loss (OR: 1.00, 95% CI: 1.00, 1.00, P <0.001), tumor size (OR: 0.70, 95% CI: 0.58, 0.84, P <0.001), medium (OR: 0.39, 95% CI: 0.18, 0.84, P=0.02) and high PADUA score (OR: 0.23, 95% CI: 0.08, 0.64, P=0.005) were independently associated with trifecta achievement. A publication bias was identified for tumor size. Sensitivity analysis confirmed the stability of result for tumor size.

Conclusions: Larger tumor size, medium and high PADUA score are associated with decreased probability of trifecta achievement. After verifying by further high-quality studies, these variables can be incorporated into tools to predict probability of trifecta achievement during clinical practice.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2021.0095DOI Listing
April 2021

Real-world antibiotic use in treating acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in China: Evidence from the ACURE study.

Front Pharmacol 2021 25;12:649884. Epub 2021 May 25.

Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.

The evidence for real-world antibiotic use in treating acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is insufficient. This study aimed to investigate real-world antibiotic use in the management of AECOPD in China. All hospitalized AECOPD patients from the acute exacerbation of chronic obstructive pulmonary disease inpatient registry (ACURE) study conducted at 163 sites between January 2018 and December 2019 were screened according to the eligible criteria. The eligible study population was divided into secondary and tertiary hospital groups. Patients' baseline characteristics, antibiotic use, and bacterial pathogen characteristics were retrieved and analyzed using SPSS 23.0. A total of 1663 patients were included in the study, including 194 patients from secondary hospitals and 1469 patients from tertiary hospitals. Among the 1663 AECOPD patients enrolled, 1434 (86.2%) received antibiotic treatment, comprising approximately 85.6% and 86.3% of patients in the secondary and tertiary hospital groups, respectively. The median antibiotic therapy duration was 9.0 (interquartile range [IQR]: 7.0 - 11.0)°days. Regarding the routes of antibiotic use, 1400 (97.6%) patients received intravenous antibiotics, 18 (1.3%) patients received oral antibiotics, 15 (1.0%) patients received both intravenous and oral antibiotics, and one (0.1%) patient received both oral and nebulized antibiotic treatment. In addition, cephalosporin, penicillin, and quinolone were the most commonly prescribed antibiotics (43.6%, 37.0%, and 34.2%, respectively). In total, 990 (56.5%) patients underwent pathogen examinations; the proportion of patients receiving pathogen examinations in the second hospital group was significantly lower than that in the tertiary hospital group (46.4% vs 61.3%, p < 0.001). This study demonstrates that an antibiotic overuse may exist in the treatment of AECOPD in China. Measures should be taken to prevent the overuse of antibiotics and potential antimicrobial resistance (AMR) in Chinese AECOPD patients.
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http://dx.doi.org/10.3389/fphar.2021.649884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185337PMC
May 2021

A novel predictive model for poor in-hospital outcomes in patients with acute kidney injury after cardiac surgery.

J Thorac Cardiovasc Surg 2021 May 11. Epub 2021 May 11.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:

Objective: Patients with cardiac surgery-associated acute kidney injury are at risk of renal replacement therapy and in-hospital death. We aimed to develop and validate a novel predictive model for poor in-hospital outcomes among patients with cardiac surgery-associated acute kidney injury.

Methods: A total of 196 patients diagnosed with cardiac surgery-associated acute kidney injury were enrolled in this study as the training cohort, and 32 blood cytokines were measured. Least absolute shrinkage and selection operator regression and random forest quantile-classifier were performed to identify the key blood predictors for in-hospital composite outcomes (requiring renal replacement therapy or in-hospital death). The logistic regression model incorporating the selected predictors was validated internally using bootstrapping and externally in an independent cohort (n = 52).

Results: A change in serum creatinine (delta serum creatinine) and interleukin 16 and interleukin 8 were selected as key predictors for composite outcomes. The logistic regression model incorporating interleukin 16, interleukin 8, and delta serum creatinine yielded the optimal performance, with decent discrimination (area under the receiver operating characteristic curve: 0.947; area under the precision-recall curve: 0.809) and excellent calibration (Brier score: 0.056, Hosmer-Lemeshow test P = .651). Application of the model in the validation cohort yielded good discrimination. A nomogram was generated for clinical use, and decision curve analysis demonstrated that the new model adds more net benefit than delta serum creatinine.

Conclusions: We developed and validated a promising predictive model for in-hospital composite outcomes among patients with cardiac surgery-associated acute kidney injury and demonstrated interleukin-16 and interleukin-8 as useful predictors to improve risk stratification for poor in-hospital outcomes among those with cardiac surgery-associated acute kidney injury.
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http://dx.doi.org/10.1016/j.jtcvs.2021.04.085DOI Listing
May 2021

Multi-Stage Degradation Homogenization for Super-Resolution of Face Images With Extreme Degradations.

IEEE Trans Image Process 2021 16;30:5600-5612. Epub 2021 Jun 16.

Face Super-Resolution (FSR) aims to infer High-Resolution (HR) face images from the captured Low-Resolution (LR) face image with the assistance of external information. Existing FSR methods are less effective for the LR face images captured with serious low-quality since the huge imaging/degradation gap caused by the different imaging scenarios (i.e., the complex practical imaging scenario that generates test LR images, the simple manual imaging degradation that generates the training LR images) is not considered in these algorithms. In this paper, we propose an image homogenization strategy via re-expression to solve this problem. In contrast to existing methods, we propose a homogenization projection in LR space and HR space as compensation for the classical LR/HR projection to formulate the FSR in a multi-stage framework. We then develop a re-expression process to bridge the gap between the complex degradation and the simple degradation, which can remove the heterogeneous factors such as serious noise and blur. To further improve the accuracy of the homogenization, we extract the image patch set that is invariant to degradation changes as Robust Neighbor Resources (RNR), with which these two homogenization projections re-express the input LR images and the initial inferred HR images successively. Both quantitative and qualitative results on the public datasets demonstrate the effectiveness of the proposed algorithm against the state-of-the-art methods.
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http://dx.doi.org/10.1109/TIP.2021.3086595DOI Listing
June 2021

Predicting Social Support Exchanging among Male Homosexuals Who are HIV-Positive in Social Media Context: The Role of Online Self-Disclosure.

J Homosex 2021 Jun 10:1-17. Epub 2021 Jun 10.

School of Journalism and Communication, Tsinghua University, Beijing, China.

This study investigated social support exchanges on social media among male homosexuals who are HIV-positive (MHHP) in China and explored how online self-disclosure relates to such activity. Analyses were based on 9,459 messages posted by 188 targeted users.Results showed that the informational and emotional support messages were prevalent in the Chinese context, and esteem social support was first found to be the most salient by the current investigation. Results of independent samples -tests suggested that MHHP who engaged in significant self-disclosure on tended to have more frequent social support exchanges than those who did not. In particular, MHHP who expressed sex-seeking intentions and companionship seeking intentions were likely to post more supportive messages than those who did not express such intentions. Moreover, MHHP who disclosed their concerns over discrimination tended to post more emotional, informational, and esteem support messages than those who did not express discrimination concerns.
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http://dx.doi.org/10.1080/00918369.2021.1935623DOI Listing
June 2021

Blocking SphK1/S1P/S1PR1 Signaling Pathway Alleviates Lung Injury Caused by Sepsis in Acute Ethanol Intoxication Mice.

Inflammation 2021 Jun 9. Epub 2021 Jun 9.

Jinling Clinical Medical College, Nanjing Medical University, 305 Zhongshan East Road, Xuanwu District, Nanjing City, 210002, Jiangsu Province, China.

Acute ethanol intoxication increases the risk of sepsis and aggravates the symptoms of sepsis and lung injury. Therefore, this study aimed to explore whether sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/S1P receptor 1 (S1PR1) signaling pathway functions in lung injury caused by acute ethanol intoxication-enhanced sepsis, as well as its underlying mechanism. The acute ethanol intoxication model was simulated by intraperitoneally administering mice with 32% ethanol solution, and cecal ligation and puncture (CLP) was used to construct the sepsis model. The lung tissue damage was observed by hematoxylin-eosin (H&E) staining, and the wet-to-dry (W/D) ratio was used to evaluate the degree of pulmonary edema. Inflammatory cell counting and protein concentration in bronchoalveolar lavage fluid (BALF) were, respectively, detected by hemocytometer and bicinchoninic acid (BCA) method. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-18 in BALF were detected by their commercial enzyme-linked immunosorbent assay (ELISA) kits. The myeloperoxidase (MPO) activity and expression of apoptosis-related proteins and SphK1/S1P/S1PR1 pathway-related proteins were, respectively, analyzed by MPO ELISA kit and Western blot analysis. The cell apoptosis in lung tissues was observed by TUNEL assay. Acute ethanol intoxication (EtOH) decreased the survival rate of mice and exacerbated the lung injury caused by sepsis through increasing pulmonary vascular permeability, neutrophil infiltration, release of inflammatory factors, and cell apoptosis. In addition, EtOH could activate the SphK1/S1P/S1PR1 pathway in CLP mice. However, PF-543, as a specific inhibitor of SphK1, could partially reverse the deleterious effects on lung injury of CLP mice. PF-543 alleviated lung injury caused by sepsis in acute ethanol intoxication rats by suppressing the SphK1/S1P/S1PR1 signaling pathway.
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http://dx.doi.org/10.1007/s10753-021-01490-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189277PMC
June 2021

Single-cell epigenomic landscape of peripheral immune cells reveals establishment of trained immunity in individuals convalescing from COVID-19.

Nat Cell Biol 2021 06 9;23(6):620-630. Epub 2021 Jun 9.

Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often causes severe complications and even death. However, asymptomatic infection has also been reported, highlighting the difference in immune responses among individuals. Here we performed single-cell chromatin accessibility and T cell-receptor analyses of peripheral blood mononuclear cells collected from individuals convalescing from COVID-19 and healthy donors. Chromatin remodelling was observed in both innate and adaptive immune cells in the individuals convalescing from COVID-19. Compared with healthy donors, recovered individuals contained abundant TBET-enriched CD16 and IRF1-enriched CD14 monocytes with sequential trained and activated epigenomic states. The B-cell lineage in recovered individuals exhibited an accelerated developmental programme from immature B cells to antibody-producing plasma cells. Finally, an integrated analysis of single-cell T cell-receptor clonality with the chromatin accessibility landscape revealed the expansion of putative SARS-CoV-2-specific CD8 T cells with epigenomic profiles that promote the differentiation of effector or memory cells. Overall, our data suggest that immune cells of individuals convalescing from COVID-19 exhibit global remodelling of the chromatin accessibility landscape, indicative of the establishment of immunological memory.
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http://dx.doi.org/10.1038/s41556-021-00690-1DOI Listing
June 2021

LncRNA PCBP1-AS1 correlated with the functional states of cancer cells and inhibited lung adenocarcinoma metastasis by suppressing the EMT progression.

Carcinogenesis 2021 Jun 9. Epub 2021 Jun 9.

Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

The development of single-cell RNA sequencing (scRNA-seq) provided us an unprecedented chance to identify novel oncogenes or tumor suppressors at single-cell resolution. Long non-coding RNAs (lncRNAs) related to the functional states of cancer cells might play vital roles in the progression of lung adenocarcinoma (LUAD). In this study, LncRNAs that were associated with the functional states of LUAD cells identified in scRNA-seq studies were screened based on the CancerSEA database. Differential gene expression analysis and survival analysis were performed in TCGA, GEO and our JSPH databases. Finally, transwell and tail vein metastasis assays were used to reveal the functions of our identified novel prognostic lncRNAs. A total of 849 lncRNAs were initially identified. Among them, 11 lncRNAs were found significantly associated with LUAD prognosis in the TCGA database. Two of them (PCBP1-AS1 and ZSCAN16-AS1) were further validated in independent GEO datasets. ScRNA-seq analysis showed that PCBP1-AS1 and ZSCAN16-AS1 were significantly negatively correlated with most of the functional states of LUAD cells, especially with metastasis. Functionally, PCBP1-AS1 was aberrantly downregulated in LUAD cells and tumor tissues. Knockdown of PCBP1-AS1 significantly promoted the migration and invasion of LUAD cells. Consistently, PCBP1-AS1 overexpression suppressed the metastasis of LUAD in vitro and in vivo. Besides, PCBP1-AS1 inhibition induced decreased E-cadherin expression and increased N-cadherin, Vimentin and Snail expression. In conclusion, PCBP1-AS1 could suppress the metastasis of LUAD by targeting the EMT (Epithelial-Mesenchymal Transition) pathway and might serve as a prognostic biomarker and a potential therapeutic target of LUAD.
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http://dx.doi.org/10.1093/carcin/bgab047DOI Listing
June 2021

Systematical review of interactions between microplastics and microorganisms in the soil environment.

J Hazard Mater 2021 Jun 1;418:126288. Epub 2021 Jun 1.

Faculty of Life Science and Technology, Central South University of Forestry and Technology, Changsha 410004, China; National Engineering Laboratory for Applied Forest Ecological Technology in Southern China, Changsha 410004, China; Laboratory of Urban Forest Ecology of Hunan Province, Changsha 410004, China. Electronic address:

Terrestrial ecosystems are widely contaminated by microplastics due to extensive usage and poor handling of plastic materials, but the subsequent fate and remediate strategy of these pollutants are far from fully understood. In soil environments, microplastics pose a potential threat to the survival, growth, and reproduction of soil microbiota that in turn threaten the biodiversity, function, and services of terrestrial ecosystems. Meanwhile, microorganisms are sensitive to microplastics due to the adaptability to changes in substrates and soil properties. Through the metabolic and mineralization processes, microorganisms are also crucial participator to the plastic biodegradation. In this review, we present current knowledges and research results of interactions between microplastics and microorganisms (both fungi and bacteria) in soil environments and mainly discuss the following: (1) effects of microplastics on microbial habitats via changes in soil physical, chemical, and biological properties; (2) effects of microplastics on soil microbial communities and functions; and (3) soil microbial-mediated plastic degradation with the likely mechanisms and potential remediation strategies. We aim to analyze the mechanisms driving these interactions and subsequent ecological effects, propose future directives for the study of microplastic in soils, and provide valuable information on the plastic bioremediation in contaminated soils.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126288DOI Listing
June 2021

Effects of graded levels of xylo-oligosaccharides on growth performance, serum parameters, intestinal morphology and intestinal barrier function in weaned piglets.

J Anim Sci 2021 Jun 7. Epub 2021 Jun 7.

Precision Livestock and Nutrition Unit, Gembloux Agro-Bio Tech, TERRA Teaching and Research Centre, Liège University, Passage des Déportés 2, 5030 Gembloux, Belgium.

The objective of this study was to investigate the effects of xylo-oligosaccharides (XOS) supplementation on growth performance, serum parameters, small intestinal morphology, intestinal mucosal integrity, and immune function in weaned piglets. A total of 240 weaned piglets with an average body weight (BW) of 8.82 ± 0.05 kg (28 d of age) were assigned randomly to 4 dietary treatments in a 28-d trial, including a control diet (CON), 3 diets with XOS supplementation at the concentration of 100, 500 and 1000 mg/kg (XOS100, XOS500, and XOS1000). There were 4 replicates per treatment with 15 pigs per pen. From d 1 to 14, there were no differences (P > 0.05) in average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F) during the different treatments. The different doses of XOS showed a quadratic effect on BW on d 28, ADG and G:F d 1-28 of piglets (P < 0.05). From d 15 to 28, ADG of pigs fed the XOS500 diet was higher (P < 0.05) than pigs fed the CON diet. During the overall period (d 1 to 28), pigs fed the XOS500 diet had a higher BW, ADG and G:F than pigs fed the CON diet (P < 0.05). In addition, compared with the CON group, the XOS500 group had significantly higher serum total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) and catalase (CAT) levels and lower malondialdehyde (MDA) levels on d 14 and 28 (P < 0.05). The serum immunoglobulin G (IgG) concentration in the XOS500 group was also significantly higher compared with the CON group on d 14 and 28 (P <0.05). However, serum immunoglobulin A (IgA) and immunoglobulin M (IgM) were not affected by the dietary treatments. Supplementation of XOS500 to the feed significantly increased the villus height (VH) and villus height to crypt depth ratio (VH:CD) in the jejunum and ileum in comparison with the CON and XOS1000 group. Moreover, the XOS500 group significantly elevated the expression levels of Occludin and zonula occludens protein-1 (ZO-1) in the ileum compared to the CON group. The ileal interleukin (IL)-1β, IL-8 and interferon (IFN)-γ mRNA expression levels in the XOS100 and XOS500 group were markedly lower than in the CON group. In contrast, the ileal IL-10 mRNA expression levels were remarkably higher in the XOS500 than CON group. In conclusion, xylo-oligosaccharides have a beneficial effect on growth performance by improving serum antioxidant defense system, serum IgG, small intestinal structure and intestinal barrier function in weaned piglets.
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http://dx.doi.org/10.1093/jas/skab183DOI Listing
June 2021

Exogenous hydrogen sulfide protects against hepatic ischemia/reperfusion injury by inhibiting endoplasmic reticulum stress and cell apoptosis.

Exp Ther Med 2021 Aug 25;22(2):799. Epub 2021 May 25.

Department of General Surgery, Affiliated Huadu Hospital of Southern Medical University (People's Hospital of Huadu District), Guangzhou, Guangdong 510800, P.R. China.

The aim of the present study was to explore the effect of exogenous hydrogen sulphide (HS) on endoplasmic reticulum (ER) stress (ERS) in a rat model of hepatic ischemia/reperfusion (I/R) injury. A total of 48 Sprague-Dawley rats were randomly divided into four groups (n=12/group) as follows: Sham, I/R, I/R preceded by NaHS (I/R-NaHS) and I/R preceded by L-C-propargylglycine (PAG), a HS inhibitor (I/R-PAG). With the exception of the sham group, the rats in the other groups were subjected to 30 min hepatic warm ischemia followed by reperfusion for 6 or 12 h. Hepatic function was evaluated by serum concentrations of alanine aminotransferase (ALT). Apoptosis of hepatic cells was assessed by TUNEL staining and measurement of caspase-12 expression. The expression levels of ERS-associated proteins and mRNAs of pancreatic ER eukaryotic translation initiation factor-2a kinase (PERK), activating transcription factor-6 (ATF6), glucose-regulated protein (GRP) 78, TNF-receptor-associated factor (TRAF)-2, C/EBP homologous protein (CHOP) and caspase-12 were also measured by western blotting and reverse transcription-quantitative PCR. The serum concentrations of ALT in the I/R and I/R-PAG groups were found to be significantly higher compared with those in the sham and I/R-NaHS groups after 6 h of reperfusion; in addition, the ALT level returned to normal in the I/R group, while it increased further in the I/R-PAG group after 12 h of reperfusion. A higher cell apoptosis rate was observed in the I/R and I/R-PAG groups and the highest cell apoptosis rate was observed in the I/R-PAG group; correspondingly, the expression of caspase-12 was increased in the I/R and I/R-PAG groups. HS appeared to significantly attenuate hepatic I/R-induced ERS response, as indicated by the decreased expression of ATF6, PERK, GRP78, TRAF2 and CHOP. Endogenous HS may serve a hepatoprotective function after I/R, and inhibition of endogenous HS results in aggravation of I/R damage. Exogenous HS was shown to inhibit ERS-related gene expression, leading to suppression of inflammatory reaction and improvement of I/R damage. Therefore, exogenous HS has therapeutic potential to alleviate hepatic I/R injury.
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http://dx.doi.org/10.3892/etm.2021.10231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170662PMC
August 2021

Effect of Different Nuclear Localization Signals on the Subcellular Localization and Anti-HIV-1 Function of the MxB Protein.

Front Microbiol 2021 20;12:675201. Epub 2021 May 20.

Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.

Interferon exerts its antiviral activity by stimulating the expression of antiviral proteins. These interferon stimulate genes (ISGs) often target a group of viruses with unique molecular mechanisms. One such ISG is myxovirus resistance B (MxB) that has been reported to inhibit human immunodeficiency virus type 1 (HIV-1) by targeting viral capsid and impairing nuclear import of viral DNA. The antiviral specificity of MxB is determined by its N-terminal 25 amino acids sequence which has the nuclear localization activity, therefore functions as a nuclear localization signal (NLS). In this study, we report that the bipartite NLS, but not the classic NLS, the PY-NLS, nor the arginine-rich NLS, when used to replace the N-terminal sequence of MxB, drastically suppress HIV-1 gene expression and virus production, thus creates a new anti-HIV-1 mechanism. MxB preserves its anti-HIV-1 activity when its N-terminal sequence is replaced by the arginine-rich NLS. Interestingly, the arginine-rich NLS allows MxB to inhibit HIV-1 CA mutants that are otherwise resistant to wild type MxB, which suggests sequence specific targeting of viral capsid. Together, these data implicate that it is not the nuclear import function itself, but rather the sequence and the mechanism of action of the NLS which define the antiviral property of MxB.
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http://dx.doi.org/10.3389/fmicb.2021.675201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173038PMC
May 2021

Role of C-X-C motif chemokine ligand 14 promoter region DNA methylation and single nucleotide polymorphism in influenza A severity.

Respir Med 2021 May 18;185:106462. Epub 2021 May 18.

Clinical Laboratory, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province 610072, China. Electronic address:

Objective: The purpose of our experiment is to discuss the function of DNA methylation and single nucleotide polymorphism (SNP) in C-X-C motif chemokine ligand 14 (CXCL14) promoter region in influenza A (H1N1) severity.

Methods: Clinic data and blood samples from H1N1 patients were collected. Blood routine indexes were measured. Levels of T lymphocytes were assessed. Importantly, CXCL14 expression and methylation in H1N1 patients and A549 cells were detected through functional assays. Additionally, rs2237061, rs2237062 and rs2547 of CXCL14 were genotyped to analyze the relation of CXCL14 SNP and H1N1 severity.

Results: The number of leukocytes, neutrophils and lymphocytes as well as T lymphocytes in H1N1 patients was lower than that in healthy subjects, and that was decreased in severe H1N1 patients compared with the mild H1N1 patients. In HIN1 patients, CXCL14 expression was decreased, while CXCL14 methylation was increased, and CXCL14 expression was further decreased and CXCL14 methylation was further increased in severe H1N1 patients. CXCL14 methylation was negatively correlated with T lymphocytes in H1N1 patients. CXCL14 methylation was elevated in H1N1-infected A549 cells. GA and AA genotypes of rs2547 in CXCL14 were risky genotypes for H1N1, and AA genotype was risky genotype for severe H1N1. Number of T lymphocytes was lower in H1N1 patients carrying AA genotype of rs2547 than that in GA + GG genotype.

Conclusion: CXCL14 promoter region DNA methylation and SNP were correlated with H1N1 severity.
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http://dx.doi.org/10.1016/j.rmed.2021.106462DOI Listing
May 2021

A new ferroptosis-related gene model for prognostic prediction of papillary thyroid carcinoma.

Bioengineered 2021 Dec;12(1):2341-2351

Department of Head and Neck Surgery, The First Hospital of Jiaxing, the First Affiliated Hospital of Jiaxing University,Jiaxing,China.

Papillary thyroid carcinoma (PTC) is a highly heterogeneous malignancy with diverse prognoses. Ferroptosis is a new type of cell death dependent on iron. Nevertheless, the predictive ability of ferroptosis-related genes for PTC is unclear. Based on the mRNA expression information from The Cancer Genome Atlas, we compared tumor and normal tissues in terms of the gene expression, for identifying differentially expressed genes (DEGs). Then, the risk score of a 5-gene signature was calculated and a prognostic model was established to test the predictive value of this gene signature by virtue of the LASSO Cox regression. The 5 genes were validated in PTC tissues by RT-qPCR.At last, functional analysis was implemented to investigate the underlying mechanisms. We found a total of 45 ferroptosis-related genes expressed differentially between tumor and normal tissues. 6 DEGs exhibited a significant relevance to the overall survival (OS) (< 0.05). We classified patients into group with high risk and group with low risk based on the median risk score of a 5-gene signature. Patients in the group with low risk presented a remarkably higher OS relative to the group with high risk (< 0.01). The Cox regression analysis displayed the independent predictive ability of the risk score. The receiver operating characteristic analysis helped to validate the predictive power owned by the gene signature. After validation, the 5 genes were abnormally expressed between PTC and normal tissues. Functional analysis showed two groups had different immune status. A new ferroptosis-related gene signature can predict the outcomes of PTC patients.
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http://dx.doi.org/10.1080/21655979.2021.1935400DOI Listing
December 2021

Novel Plasmid-Borne Fimbriae-Associated Gene Cluster Participates in Biofilm Formation in .

Microb Drug Resist 2021 Jun 1. Epub 2021 Jun 1.

National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine South China Agricultural University Guangzhou, China.

This study reported the involvement of a gene cluster from a conjugative plasmid in the biofilm formation of . We used a novel EZ-Tn transposon technique to generate a transposon library and used arbitrarily primed PCR to detect the insertion sites in biofilm formation-deficient mutants. To validate the function of candidate biofilm formation genes, the genes were cloned into plasmid pBluescript II SK (+) and transformed into DH5α. Biofilm production from the transformants was then assessed by phenotypic biofilm formation using Crystal Violet staining and microscopy. A total of 3,000 transposon mutants of DH5α-p253 were screened, of which 28 were found to be deficient in biofilm formation. Further characterization revealed that 24/28 mutations were detected with their insertions in chromosome, while the remaining 4 mutations were evidenced that the functional genes for biofilm formation were harbored in the plasmid. Interestingly, the plasmid sequencing showed that these four transposon mutations were all inserted into a fimbriae-associated gene cluster (-cluster). This -cluster is a hybrid segment spanning a 7,949 bp sequence, with a terminal inverted repeat sequence and two coding regions. In summary, we performed a high-efficiency screening to a library constructed with the EZ-Tn5-based transposon approach and identified the gene clusters responsible for the biofilm production of , especially the genes harbored in the plasmid. Further studies are needed to understand the spread of this novel plasmid-mediated biofilm formation gene in clinical isolates and the clinical impacts.
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http://dx.doi.org/10.1089/mdr.2020.0512DOI Listing
June 2021

Spatiotemporal 22q11.21 Protein Network Implicates DGCR8-Dependent MicroRNA Biogenesis as a Risk for Late-Fetal Cortical Development in Psychiatric Diseases.

Life (Basel) 2021 May 31;11(6). Epub 2021 May 31.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.

Chromosome 22q11.21 copy number variant (CNV) is a vital risk factor that can be a genetic predisposition to neurodevelopmental disorders (NDD). As 22q11.21 CNV affects multiple genes, causal disease genes and mechanisms affected are still poorly understood. Thus, we aimed to identify the most impactful 22q11.21 CNV genes and the potential impacted human brain regions, developmental stages, and signaling pathways. We constructed the spatiotemporal dynamic networks of 22q11.21 CNV genes using the brain developmental transcriptome and physical protein-protein interactions. The affected brain regions, developmental stages, driver genes, and pathways were subsequently investigated via integrated bioinformatics analysis. As a result, we first identified that 22q11.21 CNV genes affect cortical area mainly during late-fetal periods. Interestingly, we observed that connections between a driver gene and its interacting partners, MECP2 and CUL3, also network hubs, only existed in the network of late-fetal period within cortical region, suggesting their functional specificity during brain development. We also confirmed the physical interaction result between DGCR8 and CUL3 by liquid chromatography-tandem mass spectrometry. As a whole, our results could suggest that the disruption of DGCR8-dependent microRNA biogenesis plays a vital role in NDD for late-fetal cortical development.
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http://dx.doi.org/10.3390/life11060514DOI Listing
May 2021

Prestimulus dynamics blend with the stimulus in neural variability quenching.

Neuroimage 2021 May 28;238:118160. Epub 2021 May 28.

University of Ottawa Institute of Mental Health Research, Ottawa, Canada; Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada.

Neural responses to the same stimulus show significant variability over trials, with this variability typically reduced (quenched) after a stimulus is presented. This trial-to-trial variability (TTV) has been much studied, however how this neural variability quenching is influenced by the ongoing dynamics of the prestimulus period is unknown. Utilizing a human intracranial stereo-electroencephalography (sEEG) data set, we investigate how prestimulus dynamics, as operationalized by standard deviation (SD), shapes poststimulus activity through trial-to-trial variability (TTV). We first observed greater poststimulus variability quenching in those real trials exhibiting high prestimulus variability as observed in all frequency bands. Next, we found that the relative effect of the stimulus was higher in the later (300-600ms) than the earlier (0-300ms) poststimulus period. Lastly, we replicate our findings in a separate EEG dataset and extend them by finding that trials with high prestimulus variability in the theta and alpha bands had faster reaction times. Together, our results demonstrate that stimulus-related activity, including its variability, is a blend of two factors: 1) the effects of the external stimulus itself, and 2) the effects of the ongoing dynamics spilling over from the prestimulus period - the state at stimulus onset - with the second dwarfing the influence of the first.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118160DOI Listing
May 2021

Preoperative interventional artery embolization for the treatment of a giant malignant phyllodes tumor: A case report.

Mol Clin Oncol 2021 Jul 11;15(1):133. Epub 2021 May 11.

First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.

Phyllodes tumors (PTs) are rare but complex fibroepithelial lesions of the breast. The present report describes an unusual case of a giant malignant PT with a rich blood supply treated with dominant blood supply internal thoracic artery interventional embolization before surgery. A 41-year-old woman without underlying systemic disease presented with a tumor >20 cm in diameter growing rapidly in the left breast. Radiological results indicated a giant circular tumor with a clear boundary occupying the whole breast, possible invasion of the major pectoralis muscle and several enlarged lymph nodes in the left axillary region. Computed tomography angiography showed a large mass with a rich and powerful blood vessel supply and preoperative interventional embolization was performed to block the internal thoracic artery. Three days after artery embolization, mastectomy and grade I axillary lymph node dissection were performed. The giant tumor measured 17x16x11 cm. The surgery successfully treated the pain and tumor necrosis and the patient received chemotherapy and local radiotherapy. No recurrence was found at the 14-month follow-up.
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http://dx.doi.org/10.3892/mco.2021.2295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138852PMC
July 2021

Cholesterol Stimulates the Transient Receptor Potential Melastatin 4 Channel in mpkCCD Cells.

Front Pharmacol 2021 14;12:627875. Epub 2021 May 14.

Department of Physiology, Emory University School of Medicine, Atlanta, GA, United States.

We have shown that cholesterol regulates the activity of ion channels in mouse cortical collecting duct (CCD) mpkCCD cells and that the transient receptor potential melastatin 4 (TRPM4) channel is expressed in these cells. However, whether TRPM4 channel is regulated by cholesterol remains unclear. Here, we performed inside-out patch-clamp experiments and found that inhibition of cholesterol biosynthesis by lovastatin significantly decreased, whereas enrichment of cholesterol with exogenous cholesterol significantly increased, TRPM4 channel open probability () by regulating its sensitivity to Ca in mpkCCD cells. In addition, inside-out patch-clamp data show that acute depletion of cholesterol in the membrane inner leaflet by methyl-β-cyclodextrin (MβCD) significantly reduced TRPM4 , which was reversed by exogenous cholesterol. Moreover, immunofluorescence microscopy, Western blot, cell-surface biotinylation, and patch clamp analysis show that neither inhibition of intracellular cholesterol biosynthesis with lovastatin nor application of exogenous cholesterol had effect on TRPM4 channel protein abundance in the plasma membrane of mpkCCD cells. Sucrose density gradient centrifugation studies demonstrate that TRPM4 was mainly located in cholesterol-rich lipid rafts. Lipid-protein overlay experiments show that TRPM4 directly interacted with several anionic phospholipids, including PI(4,5)P. Depletion of PI(4,5)P with either wortmannin or PGE2 abrogated the stimulatory effects of exogenous cholesterol on TRPM4 activity, whereas exogenous PI(4,5)P (diC8-PI(4,5)P, a water-soluble analog) increased the effects. These results suggest that cholesterol stimulates TRPM4 via a PI(4,5)P-dependent mechanism.
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http://dx.doi.org/10.3389/fphar.2021.627875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160378PMC
May 2021

Distribution of antibiotic resistance genes in the environment.

Environ Pollut 2021 May 19;285:117402. Epub 2021 May 19.

Biotechnology and Food Engineering Program, Guangdong Technion - Israel Institute of Technology, Shantou, 515063, China; Faculty of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, Israel. Electronic address:

The prevalence of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in the microbiome is a major public health concern globally. Many habitats in the environment are under threat due to excessive use of antibiotics and evolutionary changes occurring in the resistome. ARB and ARGs from farms, cities and hospitals, wastewater treatment plants (WWTPs) or as water runoffs, may accumulate in water, soil, and air. We present a global picture of the resistome by examining ARG-related papers retrieved from PubMed and published in the last 30 years (1990-2020). Natural Language Processing (NLP) was used to retrieve 496,640 papers, out of which 9374 passed the filtering test and were further analyzed to determine the distribution and diversity of ARG subtypes. The papers revealed seven major antibiotic families together with their respective ARG subtypes in different habitats on six continents. Asia, especially China, had the highest number of ARGs related papers compared to other countries/regions/continents. ARGs belonging to multidrug, glycopeptide, and β-lactam families were the most common in reports from hospitals and sulfonamide and tetracycline families were common in reports from farms, WWTPs, water and soil. We also highlight the 'omics' tools used in resistome research, describe some factors that shape the development of resistome, and suggest future work needed to better understand the resistome. The goal was to show the global nature of ARB and ARGs in order to encourage collaborate research efforts aimed at reducing the negative impacts of antibiotic resistance on the One Health concept.
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http://dx.doi.org/10.1016/j.envpol.2021.117402DOI Listing
May 2021