Publications by authors named "Yang Liang"

767 Publications

Development and Quantitation of Biofilms after Cultivation in Flow-reactors.

Bio Protoc 2021 Aug 20;11(16):e4126. Epub 2021 Aug 20.

College of Life Sciences, Northwest University, Xi'an, ShaanXi, China.

Characterization of biofilm formation and metabolic activities is critical to investigating biofilm interactions with environmental factors and illustrating biofilm regulatory mechanisms. An appropriate model that mimics biofilm habitats therefore demands accurate quantitation and investigation of biofilm-associated activities. Current methodologies commonly involve static biofilm setups (such as biofilm assays in microplates, bead biofilms, or biofilms on glass-slides) and fluidic flow biofilm systems (such as drip-flow biofilm reactors, 3-channel biofilm reactors, or tubing biofilm reactors). Continuous flow systems take into consideration the contribution of hydrodynamic shear forces, nutrient supply, and physical transport of dispersed cells, which define the habitat for biofilm development in most natural and engineered systems. This protocol describes the assembly of 3 flow-system setups to cultivate PAO1 and MR-1 model biofilms, including the respective quantitation and observation approaches. The standardized flow systems promise productive and reproducible biofilm experimental results, which can be further modified according to specific research projects.
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http://dx.doi.org/10.21769/BioProtoc.4126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413656PMC
August 2021

Corrigendum: Bioactive Sr/Feco-substituted hydroxyapatite in cryogenically 3D printed porous scaffolds for bone tissue engineering. Liang Yang 2021  035007.

Biofabrication 2021 Sep 16. Epub 2021 Sep 16.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430000, CHINA.

Developing multi-doped bioceramics that possess biological multifunctionality is becoming increasingly attractive and promising for bone tissue engineering. In this view innovative Sr/Feco-substituted nano-hydroxyapatite with gradient doping concentrations fixed at 10 mol% has been deliberately designed previously. Herein, to evaluate their therapeutic potentials for bone healing, novel gradient SrFeHA/PCL scaffolds are fabricated by extrusion cryogenic 3D printing technology with subsequent lyophilization. The obtained scaffolds exhibit desired 3D interconnected porous structure and rough microsurface, along with appreciable release of bioactive Sr/Fefrom SrFeHA components. These favorable physicochemical properties render printed scaffolds realizing effective biological applications both in vitro and in vivo, particularly the moderate co-substituted Sr7.5Fe2.5HA and Sr5Fe5HA groups exhibit remarkably enhanced bioactivity that not only promotes the functions of MC3T3 osteoblasts and HUVECs directly, but also energetically manipulates favorable macrophages activation to concurrently facilitate osteogenesis/angiogenesis. Moreover, in vivo subcutaneous implantation and cranial defects repair outcomes further confirm their superior capacity to dictate immune reaction, implants vascularization and in situ bone regeneration, mainly dependent on the synergetic effects of released Sr/Fe. Accordingly, for the first time, present study highlights the great potential of Sr7.5Fe2.5HA and Sr5Fe5HA for ameliorating bone regeneration process by coupling of immunomodulation with enhanced angio- and osteogenesis and hence may provide a new promising alternative for future bone tissue engineering.
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http://dx.doi.org/10.1088/1758-5090/ac278aDOI Listing
September 2021

Protecting carbohydrates with ethers, acetals and orthoesters under basic conditions.

Org Biomol Chem 2021 Sep 15;19(35):7598-7601. Epub 2021 Sep 15.

Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen O, Denmark.

Chlorinated ethyl and vinyl ethers are introduced at various positions of carbohydrates. Depending on the relative stereochemistry, vinylethers, acetals or orthoesters are formed under basic conditions. The products are stable, but are easily deprotected after dechlorination. The scope of the intramolecular protection is studied using common pentoses and hexoses.
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http://dx.doi.org/10.1039/d1ob01467fDOI Listing
September 2021

Role of the Extracellular Matrix in Alzheimer's Disease.

Front Aging Neurosci 2021 27;13:707466. Epub 2021 Aug 27.

College of Life Sciences and Research Center for Resource Peptide Drugs, Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yanan University, Yanan, China.

Alzheimer's disease (AD) is a neurodegenerative disease with complex pathological characteristics, whose etiology and pathogenesis are still unclear. Over the past few decades, the role of the extracellular matrix (ECM) has gained importance in neurodegenerative disease. In this review, we describe the role of the ECM in AD, focusing on the aspects of synaptic transmission, amyloid-β-plaque generation and degradation, Tau-protein production, oxidative-stress response, and inflammatory response. The function of ECM in the pathological process of AD will inform future research on the etiology and pathogenesis of AD.
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http://dx.doi.org/10.3389/fnagi.2021.707466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430252PMC
August 2021

Predictors of acute kidney injury in patients with acute decompensated heart failure in emergency departments in China.

J Int Med Res 2021 Sep;49(9):3000605211016208

Emergency Department, Peking University Third Hospital, No. 49 North Garden Road, Hai-dian District, Beijing, China.

Objective: This retrospective multicentre observational study was performed to assess the predictors of acute kidney injury (AKI) in patients with acute decompensated heart failure (ADHF) in emergency departments in China.

Methods: In total, 1743 consecutive patients with ADHF were recruited from August 2017 to January 2018. Clinical characteristics and outcomes were compared between patients with and without AKI. Predictors of AKI occurrence and underdiagnosis were assessed in multivariate regression analyses.

Results: Of the 1743 patients, 593 (34.0%) had AKI. AKI was partly associated with short-term all-cause mortality and cost. Cardiovascular comorbidities such as coronary heart disease, diabetes mellitus, and hypertension remained significant predictors of AKI in the univariate analysis. AKI was significantly more likely to occur in patients with a lower arterial pH, lower albumin concentration, higher creatinine concentration, and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Patients treated with inotropic agents were significantly more likely to develop AKI during their hospital stay.

Conclusion: This study suggests that cardiovascular comorbidities, arterial pH, the albumin concentration, the creatinine concentration, the NT-proBNP concentration, and use of inotropic agents are predictors of AKI in patients with ADHF.
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http://dx.doi.org/10.1177/03000605211016208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442502PMC
September 2021

Dietary Supplementation of Inulin Ameliorates Subclinical Mastitis via Regulation of Rumen Microbial Community and Metabolites in Dairy Cows.

Microbiol Spectr 2021 Sep 8:e0010521. Epub 2021 Sep 8.

State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.

Subclinical mastitis (SCM) is one of the highly infectious diseases in dairy cows with the characteristics of high incidence and nonvisible clinical symptoms. The gastrointestinal microbiota is closely related to mastitis. Inulin is a prebiotic fiber with functions in improving intestinal microbial communities and enhancing the host's immunity. However, the impact of dietary inulin on the rumen inner environment remains unknown. The current study investigated whether inulin could relieve SCM by affecting the profiles of ruminal bacterial and metabolites in dairy cows. Inulin inclusion rates were 0, 100, 200, 300, and 400 g/day per cow, respectively. Inulin increased milk yield, milk protein, and lactose and reduced the somatic cell counts (SCC) in milk. In serum, the concentration of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-8, tumor necrosis factor α (TNF-α), and malondialdehyde (MDA) were decreased, and IL-4 and superoxide dismutase (SOD) were increased. Meanwhile, inulin increased the concentration of propionate, butyrate, and lactic acid (LA), while it decreased NH-N in rumen. The propionate- and butyrate-producing bacteria (e.g., and ) and several beneficial commensal bacteria (e.g., and ) as well as metabolites related to energy and amino acid metabolism (e.g., melibiose and l-glutamate) were increased. However, several proinflammatory bacteria (e.g., , Streptococcus, and Escherichia) were decreased, accompanied by the downregulation of lipid proinflammatory metabolites, for example, ceramide(d18:0/15:0) [Cer(d18:0/15:0)] and 17-phenyl-18,19,20-trinor-prostaglandin E. In the current study, the above indicators showed the best response in the 300 g/day inulin group. Overall, dietary supplementation of inulin could alleviate inflammatory responses in cows with SCM through improving the rumen inner environment. The correlation between mastitis and the gastrointestinal microbiome in dairy cows has been demonstrated. Regulating the profile of rumen microorganisms may contribute to remission of subclinical mastitis (SCM). Supplementation of inulin in the diets of cows with SCM could increase the abundance of short-chain fatty acid (SCFA)-producing bacteria and beneficial commensal bacteria in rumen and meanwhile the levels of amino acids and energy metabolism. Conversely, the abundance of ruminal bacteria and metabolites with proinflammatory effects were decreased. Our study suggests that the improvement of the rumen internal environment by inulin supplementation could ameliorate inflammatory responses during SCM in dairy cows and thus improve lactation performance and milk quality. Our results provide a theoretical basis for regulation measures of SCM in dairy cows.
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http://dx.doi.org/10.1128/Spectrum.00105-21DOI Listing
September 2021

Adversarial Neural Network with Sentiment-Aware Attention for Detecting Adverse Drug Reactions.

J Biomed Inform 2021 Sep 3:103896. Epub 2021 Sep 3.

Dalian Minzu University, Dalian, China.

Adverse drug reaction (ADR) detection is an important issue in drug safety. ADRs are health threats caused by medication. Identifying ADRs in a timely manner can reduce harm to patients and can also assist doctors in the rational use of drugs. Many studies have investigated potential ADRs based on social media due to the openness and timeliness of this resource; however, they have ignored the fine-grained emotional expression in social media text. In addition, the benchmark datasets from social media are usually small, which can result in the problem of over-fitting. In this paper, we propose the Adversarial Neural Network with Sentiment-aware Attention (ANNSA) model, which enhances the sentimental element in social media and improves the performance of neural networks via data augmentation. Specifically, a sentiment-aware attention mechanism is proposed to extract the word-level sentiment features associated with sentiment words and learn task-related information by optimizing a task-specific loss. For low-resource datasets, we use an adversarial training approach to generate perturbations of the word embeddings via an implicit regularization technique. ANNSA was tested on three social media ADR detection datasets, namely, Twitter, TwiMed (Twitter) and CADEC. The experimental results indicated the ability to achieve F1 values of 48.84%, 64.18% and 83.06%, respectively, comparable to the best results reported for state-of-the-art methods. Our study demonstrates that sentiment words are highly correlated with ADRs and that word-level sentiment features can assist in detecting ADRs from social media datasets.
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http://dx.doi.org/10.1016/j.jbi.2021.103896DOI Listing
September 2021

CISD2 Promotes Resistance to Sorafenib-Induced Ferroptosis by Regulating Autophagy in Hepatocellular Carcinoma.

Front Oncol 2021 16;11:657723. Epub 2021 Aug 16.

Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.

Purpose: Sorafenib is a multi-kinase inhibitor that is used as a standard treatment for advanced hepatocellular carcinoma (HCC). However, the mechanism of sorafenib resistance in HCC is still unclear. It has been shown that CISD2 expression is related to the progression and poor prognosis of HCC. Here, we show a new role for CISD2 in sorafenib resistance in HCC.

Methods: Bioinformatic analysis was used to detect the expression of negative regulatory genes of ferroptosis in sorafenib-resistant samples. The concentration gradient method was used to establish sorafenib-resistant HCC cells. Western blot was used to detect the protein expression of CISD2, LC3, ERK, PI3K, AKT, mTOR, and Beclin1 in HCC samples. Quantitative real-time PCR (qPCR) was used to detect gene expression. CISD2 shRNA and Beclin1 shRNA were transfected to knock down the expression of the corresponding genes. Cell viability was detected by a CCK-8 assay. ROS were detected by DCFH-DA staining, and MDA and GSH were detected with a Lipid Peroxidation MDA Assay Kit and Micro Reduced Glutathione (GSH) Assay Kit, respectively. Flow cytometry was used to detect apoptosis and the levels of ROS and iron ions.

Results: CISD2 was highly expressed in HCC cells compared with normal cells and was associated with poor prognosis in patients. Knockdown of CISD2 promoted a decrease in the viability of drug-resistant HCC cells. CISD2 knockdown promoted sorafenib-induced ferroptosis in resistant HCC cells. The levels of ROS, MDA, and iron ions increased, but the change in GSH was not obvious. Knockdown of CISD2 promoted uncontrolled autophagy in resistant HCC cells. Inhibition of autophagy attenuated CISD2 knockdown-induced ferroptosis. The autophagy promoted by CISD2 knockdown was related to Beclin1. When CISD2 and Beclin1 were inhibited, the effect on ferroptosis was correspondingly weakened.

Conclusion: Inhibition of CISD2 promoted sorafenib-induced ferroptosis in resistant cells, and this process promoted excessive iron ion accumulation through autophagy, leading to ferroptosis. The combination of CISD2 inhibition and sorafenib treatment is an effective therapeutic strategy for resistant HCC.
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http://dx.doi.org/10.3389/fonc.2021.657723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415543PMC
August 2021

The role of natural polymers in bone tissue engineering.

J Control Release 2021 Sep 2;338:571-582. Epub 2021 Sep 2.

Department of Public Health, Jiamusi University, Jiamusi, 154000, China. Electronic address:

Bone is a dynamic self-healing organ and a continuous remodeling ensures the restoration of the bone structure and function over time. However, bone remodeling is not able to repair large traumatic injuries. Therefore, surgical interventions and bone substitutes are required. The aim of bone tissue engineering is to repair and regenerate tissues and engineered a bone graft as a bone substitute. To met this goal, several natural or synthetic polymers have been used to develop a biocompatible and biodegradable polymeric construct. Among the polymers, natural polymers have higher biocompatibility, excellent biodegradability, and no toxicity. So far, collagen, chitosan, gelatin, silk fibroin, alginate, cellulose, and starch, alone or in combination, have been widely used in bone tissue engineering. These polymers have been used as scaffolds, hydrogels, and micro-nanospheres. The functionalization of the polymer with growth factors and bioactive glasses increases the potential use of polymers for bone regeneration. As bone is a dynamic highly vascularized tissue, the vascularization of the polymeric scaffolds is vital for successful bone regeneration. Several in vivo and in vitro strategies have been used to vascularize the polymeric scaffolds. In this review, the application of the most commonly used natural polymers is discussed.
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http://dx.doi.org/10.1016/j.jconrel.2021.08.055DOI Listing
September 2021

Short-form OPA1 is a molecular chaperone in mitochondrial intermembrane space.

Sci China Life Sci 2021 Aug 31. Epub 2021 Aug 31.

Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, 510530, China.

Mitochondria, double-membrane organelles, are known to participate in a variety of metabolic and signal transduction pathways. The intermembrane space (IMS) of mitochondria is proposed to subject to multiple damages emanating from the respiratory chain. The optic atrophy 1 (OPA1), an important protein for mitochondrial fusion, is cleaved into soluble short-form (S-OPA1) under stresses. Here we report that S-OPA1 could function as a molecular chaperone in IMS. We purified the S-OPA1 (amino acid sequence after OPA1 isoform 5 S1 site) protein and showed it protected substrate proteins from thermally and chemically induced aggregation and strengthened the thermotolerance of Escherichia coli (E. coli). We also showed that S-OPA1 conferred thermotolerance on IMS proteins, e.g., neurolysin. The chaperone activity of S-OPA1 may be required for maintaining IMS homeostasis in mitochondria.
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http://dx.doi.org/10.1007/s11427-021-1962-0DOI Listing
August 2021

Disruption of the Pseudomonas aeruginosa Tat system perturbs PQS-dependent quorum sensing and biofilm maturation through lack of the Rieske cytochrome bc1 sub-unit.

PLoS Pathog 2021 Aug 30;17(8):e1009425. Epub 2021 Aug 30.

Biodiscovery Institute, National Biofilms Innovation Centre and School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.

Extracellular DNA (eDNA) is a major constituent of the extracellular matrix of Pseudomonas aeruginosa biofilms and its release is regulated via pseudomonas quinolone signal (PQS) dependent quorum sensing (QS). By screening a P. aeruginosa transposon library to identify factors required for DNA release, mutants with insertions in the twin-arginine translocation (Tat) pathway were identified as exhibiting reduced eDNA release, and defective biofilm architecture with enhanced susceptibility to tobramycin. P. aeruginosa tat mutants showed substantial reductions in pyocyanin, rhamnolipid and membrane vesicle (MV) production consistent with perturbation of PQS-dependent QS as demonstrated by changes in pqsA expression and 2-alkyl-4-quinolone (AQ) production. Provision of exogenous PQS to the tat mutants did not return pqsA, rhlA or phzA1 expression or pyocyanin production to wild type levels. However, transformation of the tat mutants with the AQ-independent pqs effector pqsE restored phzA1 expression and pyocyanin production. Since mutation or inhibition of Tat prevented PQS-driven auto-induction, we sought to identify the Tat substrate(s) responsible. A pqsA::lux fusion was introduced into each of 34 validated P. aeruginosa Tat substrate deletion mutants. Analysis of each mutant for reduced bioluminescence revealed that the primary signalling defect was associated with the Rieske iron-sulfur subunit of the cytochrome bc1 complex. In common with the parent strain, a Rieske mutant exhibited defective PQS signalling, AQ production, rhlA expression and eDNA release that could be restored by genetic complementation. This defect was also phenocopied by deletion of cytB or cytC1. Thus, either lack of the Rieske sub-unit or mutation of cytochrome bc1 genes results in the perturbation of PQS-dependent autoinduction resulting in eDNA deficient biofilms, reduced antibiotic tolerance and compromised virulence factor production.
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http://dx.doi.org/10.1371/journal.ppat.1009425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432897PMC
August 2021

miR-425 regulates lipophagy via SIRT1 to promote sorafenib resistance in liver cancer.

Oncol Lett 2021 Oct 2;22(4):695. Epub 2021 Aug 2.

Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, Liaoning 110032, P.R. China.

Liver cancer is one of the most malignant cancer, with poor outcomes and a high incidence rate, and current treatment approaches to prevent tumor progression and development remain unsatisfactory. Therefore, it is urgent to explore novel methods to inhibit tumor growth and metastasis. Autophagy is a highly conserved process associated with metastasis and drug resistance. Lipids are selectively recognized and degraded via autophagy; thus, autophagy is a crucial process to maintain tumor self-protection. MicroRNA (miR)-425 is a tumor-associated gene involved in liver cancer development that can induce cell proliferation and drug resistance. Using Cell Counting Kit-8 assays, western blot analysis and immunofluorescence assays, the present study revealed that inhibition of miR-425 promoted lipophagy by mediating the autophagy process, which in turn helps to promote sorafenib resistance. Using a bioinformatics website, it was revealed that autophagy promoted lipophagy by targeting silent information regulator 2 homolog 1 (SIRT1). The results of luciferase reporter assays supported this finding, and rescue experiments provided additional evidence. Overall, the current results suggested that inhibition of miR-425 expression increased SIRT1 expression to promote lipophagy, leading to the inhibition of liver cancer cell proliferation.
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http://dx.doi.org/10.3892/ol.2021.12956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358621PMC
October 2021

Caffeic Acid in Tobacco Root Exudate Defends Tobacco Plants From Infection by .

Front Plant Sci 2021 12;12:690586. Epub 2021 Aug 12.

Laboratory of Natural Products Pesticides, College of Plant Protection, Southwest University, Chongqing, China.

In rhizospheres, chemical barrier-forming natural compounds play a key role in preventing pathogenic bacteria from infecting plant roots. Here, we sought to identify specific phenolic exudates in tobacco () plants infected by the soil-borne pathogen that may exhibit antibacterial activity and promote plant resistance against pathogens. Among detected phenolic acids, only caffeic acid was significantly induced in infected plants by relative to healthy plants, and the concentration of caffeic acid reached 1.95 μg/mL. , caffeic acid at 200 μg/mL was highly active against and obviously damaged the membrane structure of the cells, resulting in the thinning of the cell membrane and irregular cavities in cells. Moreover, caffeic acid significantly inhibited biofilm formation by repressing the expression of the and genes. , caffeic acid could effectively activate phenylalanine ammonia-lyase (PAL) and peroxidase (POD) and promote the accumulation of lignin and hydroxyproline. In pot and field experiments, exogenous applications of caffeic acid significantly reduced and delayed the incidence of tobacco bacterial wilt. Taken together, all these results suggest that caffeic acid played a crucial role in defending against infection and was a potential and effective antibacterial agent for controlling bacterial wilt.
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http://dx.doi.org/10.3389/fpls.2021.690586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387680PMC
August 2021

WS6 Induces Adult Hippocampal Neurogenesis in Correlation to its Antidepressant Effect on the Alleviation of Depressive-like Behaviors of Rats.

Neuroscience 2021 Oct 26;473:119-129. Epub 2021 Aug 26.

Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China. Electronic address:

Major depressive disorder (MDD) is one of the most common psychiatric disorders. However, the effective drugs for MDD have not yet been developed. WS6 is originally designed with a similar structure as Resveratrol and Pterostilbene. The present study aims to investigate the neuroprotective and ameliorating effects of WS6 treatment in a rat model of chronic unpredictable mild stress (CUMS) induced depression. The results show that CUMS is effective in producing depressive-like behavior in rats as indicated by decreased responses in the locomotor activity, sucrose preference test and increased immobility time. However, WS6 treatment significantly ameliorated these behavioral alterations associated with CUMS-induced depression. Moreover, the reduction in neurogenesis, GABAergic neurons, dendrite complexity, spine density and synaptic plasticity-associate protein 95 (PSD95) by CUMS can be reversed by treatment with WS6. Taken together, this study highlights the neuroprotective and antidepressant-like effects of WS6 against CUMS-induced depression, and suggest a possible mechanism for this protection via changes in neurogenesis within the hippocampus. These finding reveal the therapeutic protection of WS6 for use in clinical trials in the treatment of neuronal deterioration in MDD.
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http://dx.doi.org/10.1016/j.neuroscience.2021.08.020DOI Listing
October 2021

3D-printed smartphone-based device for fluorimetric diagnosis of ketosis by acetone-responsive dye marker and red emissive carbon dots.

Mikrochim Acta 2021 Aug 27;188(9):306. Epub 2021 Aug 27.

Institute of Solid State Physics, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, Anhui, China.

A portable smartphone device is reported that uses 3D printing technology for the primary diagnosis of diseases by detecting acetone. The key part of the device consists of red carbon dots (RCDs), which are used as internal standards, and a sensing reagent (3-N,N-(diacethydrazide)-9-ethylcarbazole (2-HCA)) for acetone. With an excitation wavelength of 360 nm, the emission wavelengths of 2-HCA and RCDs are 443 nm and 619 nm, respectively. 2-HCA effectively captures acetone to form a nonfluorescent acylhydrazone via a condensation reaction occurring in aqueous solution, resulting in obvious color changes from blue-violet to dark red. The detection limit for acetone is 2.62 μM (~ 0.24 ppm). This is far lower than the ketone content in normal human blood (≤ 0.50 mM) and the acetone content in human respiratory gas (≤ 1.80 ppm). The device has good recovery rates for acetone detection in blood and exhaled breath, which are 90.56-109.98% (RSD ≤ 5.48) and 92.80-108.00% (RSD ≤ 5.07), respectively. The method designed here provides a reliable way to provide health warnings by visually detecting markers of ketosis/diabetes in blood or exhaled breath. The portable smart phone device visually detects ketosis/diabetes markers in the blood or exhaled breath through the nucleophilic addition reaction, which effectively captures acetone to form nonfluorescent acyl groups. This will be a reliable tool to warn human health.
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http://dx.doi.org/10.1007/s00604-021-04965-0DOI Listing
August 2021

Femtosecond laser-induced periodic grooves and nanopore clusters make a synergistic effect on osteogenic differentiation.

Colloids Surf B Biointerfaces 2021 Aug 4;208:112021. Epub 2021 Aug 4.

Department of Orthopedics/Sports Medicine Center, The First Affiliated Hospital of Army Medical University of Chinese PLA, Chongqing, 400038, PR China. Electronic address:

Polyether-ether-ketone (PEEK) materials have good biocompatibility, excellent corrosion resistance, chemical stability and an elastic modulus close to that of natural bone. However, due to its biological inertness, PEEK may affect osteogenic differentiation and leads to osseointegration failure, though PEEK is expected to improve osseointegration. In this work, by changing the power of femtosecond laser, micro-grooves are made on the PEEK surface. As observed by scanning electron microscopy, the trench has a periodic structure, the micro shape is neat, and the trench is also covered with nanometer-level pore clusters. In the in vitro culture experiments, through the proliferation experiment of mouse bone marrow mesenchymalstem cells (mBMSCs), cell viability analysis and alkaline phosphatase activity analysis, it is proven that after femtosecond laser treatment of the PEEK surface, the micro-grooves on the surface and the nanopore clusters due to laser energy ablation can produce a synergistic effect, enhancing the osteogenic differentiation ability of cells, and improving the bone integration ability of PEEK materials.
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http://dx.doi.org/10.1016/j.colsurfb.2021.112021DOI Listing
August 2021

The Gene Acts as a Positive Regulator of NaCl Signaling during Seed Germination.

Int J Mol Sci 2021 Aug 20;22(16). Epub 2021 Aug 20.

Jilin Province Engineering Laboratory of Plant Genetic Improvement, College of Plant Science, Jilin University, Changchun 130062, China.

Phytochromobilin (PΦB) participates in the regulation of plant growth and development as an important synthetase of photoreceptor phytochromes (phy). In addition, long hypocotyl 2 (HY2) appropriately works as a key PΦB synthetase. However, whether takes part in the plant stress response signal network remains unknown. Here, we described the function of HY2 in NaCl signaling. The mutant was NaCl-insensitive, whereas HY2-overexpressing lines showed NaCl-hypersensitive phenotypes during seed germination. The exogenous NaCl induced the transcription and the protein level of , which positively mediated the expression of downstream stress-related genes of , , and . Further quantitative proteomics showed the patterns of 7391 proteins under salt stress. HY2 was then found to specifically mediate 215 differentially regulated proteins (DRPs), which, according to GO enrichment analysis, were mainly involved in ion homeostasis, flavonoid biosynthetic and metabolic pathways, hormone response (SA, JA, ABA, ethylene), the reactive oxygen species (ROS) metabolic pathway, photosynthesis, and detoxification pathways to respond to salt stress. More importantly, ANNAT1-ANNAT2-ANNAT3-ANNAT4 and GSTU19-GSTF10-RPL5A-RPL5B-AT2G32060, two protein interaction networks specifically regulated by HY2, jointly participated in the salt stress response. These results direct the pathway of participating in salt stress, and provide new insights for the plant to resist salt stress.
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http://dx.doi.org/10.3390/ijms22169009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396667PMC
August 2021

Profound Treg perturbations correlate with COVID-19 severity.

Proc Natl Acad Sci U S A 2021 09;118(37)

Department of Immunology, Harvard Medical School, Boston, MA 02115;

The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We hypothesized that perturbations in FoxP3 T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, correlating with poor outcomes. These Tregs showed a distinct transcriptional signature, with overexpression of several suppressive effectors, but also proinflammatory molecules like interleukin (IL)-32, and a striking similarity to tumor-infiltrating Tregs that suppress antitumor responses. Most marked during acute severe disease, these traits persisted somewhat in convalescent patients. A screen for candidate agents revealed that IL-6 and IL-18 may individually contribute different facets of these COVID-19-linked perturbations. These results suggest that Tregs may play nefarious roles in COVID-19, by suppressing antiviral T cell responses during the severe phase of the disease, and by a direct proinflammatory role.
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http://dx.doi.org/10.1073/pnas.2111315118DOI Listing
September 2021

A life-cycle assessment framework for quantifying the carbon footprint of rural households based on survey data.

MethodsX 2021 9;8:101411. Epub 2021 Jun 9.

Institute of Geography, Center for Earth System Research and Sustainability (CEN), University of Hamburg, Germany.

This paper presents the development of a life-cycle assessment (LCA) framework for quantifying the carbon footprint of individual households based on detailed household survey data. According to household consumption and production patterns, the comprehensive life-cycle assessment framework is designed with clarified life-cycle boundaries. The framework covers eight types of specific living activities of rural households generated from a large-scale household survey in the Three Gorges Reservoir area in China. Both carbon emissions and carbon sequestrations of households' consumption and production activities can be assessed, and eventually the integrative carbon footprint is evaluated. The LCA framework enables comprehensive and relatively precise assessment of carbon footprint at a household level and thus adds value to studies in the fields of carbon emission reduction, carbon neutrality and climate policies.
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http://dx.doi.org/10.1016/j.mex.2021.101411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374513PMC
June 2021

Preliminary Studies on the Antibacterial Mechanism of a New Plant-Derived Compound, 7-Methoxycoumarin, Against .

Front Microbiol 2021 6;12:697911. Epub 2021 Aug 6.

Laboratory of Natural Products Pesticides, College of Plant Protection, Southwest University, Chongqing, China.

() is one of the most devastating plant bacterial pathogens and leads to serious economic losses in crops worldwide. In this study, the antibacterial mechanism of 7-methoxycoumarin, a new coumarin antibiotic, was preliminarily investigated by the observation of symptoms and physical and biochemical analyses. The results showed that 7-methoxycoumarin significantly suppressed bacterial growth of , with the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) values of 75 and 175 mg/L, respectively. Electron microscopy observations showed that the bacterial cell membrane was destroyed after 7-methoxycoumarin treatment. Biofilm formation of was significantly suppressed by 7-methoxycoumarin at concentrations ranging from 25 to 100 mg/L. Furthermore, virulence-associated genes , , and of were significantly inhibited by 7-methoxycoumarin. The application of 7-methoxycoumarin effectively suppressed tobacco bacterial wilt progress in pot experiments, with relative control efficiencies of 83.61, 68.78, and 58.11% at 6, 8, and 10 days post inoculation, respectively.
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http://dx.doi.org/10.3389/fmicb.2021.697911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377673PMC
August 2021

Prevalence, Risk Factors, and Clinical Correlates of Insomnia in China College Student During the COVID-19.

Front Psychiatry 2021 6;12:694051. Epub 2021 Aug 6.

Ningbo Key Laboratory of Sleep Medicine, Ningbo Kangning Hospital, Ningbo, China.

The 2019 novel coronavirus disease (COVID-19) broke out in Hubei Province and spread rapidly to the whole country, causing huge public health problems. College students are a special group, and there is no survey on insomnia among college students. The purpose of this study was to investigate the incidence and related factors of insomnia in college students during the period of COVID-19. A total of 1,086 college students conducted a cross-sectional study through the questionnaire star platform. The survey time was from February 15 to February 22, 2020. The collected information included demographic informatics and mental health scale, Athens Insomnia Scale (AIS) to assess sleep quality, Self-Reporting Questionnaire-20 (SRQ-20) to assess general psychological symptoms, Chinese perceived stress scale (CPSS) to assess stress. We used logistic regression to analyze the correlation between related factors and insomnia symptoms. The prevalence of insomnia, general psychological symptoms and stress were 16.67, 5.8, and 40.70%, respectively. Multivariate logistic regression analysis showed that gender ( = 1.55, = 0.044, 95% = 1.00-2.41), general psychological symptoms ( = 1.49, < 0.01, 95% = 1.40-1.60) and living in an isolation unit ( = 2.21, = 0.014, 95% = 1.17-4.16) were risk factors for insomnia of college students. Our results show that the insomnia is very common among college students during the outbreak of covid-19, and the related factors include gender, general psychological symptoms and isolation environment. It is necessary to intervene the insomnia of college students and warrants attention for mental well-being of college students.
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http://dx.doi.org/10.3389/fpsyt.2021.694051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377355PMC
August 2021

Let-7a-5p regulated by lncRNA-MEG3 promotes functional differentiation to Schwann cells from adipose derived stem cells via directly inhibiting RBPJ-mediating Notch pathway.

Apoptosis 2021 Aug 18. Epub 2021 Aug 18.

Department of Neurosurgery, The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Changsha, 410078, Hunan, China.

Schwann cells (SCs) have important roles in supporting and repairing peripheral neurons, and thus have great potential for nerve injury treatment. Adipose tissue-derived stem cells (ADSCs) can be reliably induced to differentiate into SCs. However, the underlying molecular mechanisms are unclear. We explored the roles of MEG3/let-7a-5p/RBPJ axis in the differentiation into SCs from ADSCs. Primary ADSCs were induced to differentiate into SCs by appropriate reagents. ELISA, immunostaining, Western blotting, and qRT-PCR were employed to examine levels of SC-markers such as S100, GFAP, SOX10, p75NTR, GAP43, MPZ, β-NGF, BDNF, and NCAM and let-7 family, MEG3, RBPJ, and Notch signaling related proteins. Dual luciferase assay and RNA immunoprecipitation were performed to validate interactions of let-7a-5p/RBPJ mRNA and MEG3/let-7a-5p. Cultured ADSCs could be induced to differentiate into functional SCs. Let-7a-5p and let-7d-5p were elevated during the differentiation while MEG3 and RBPJ/Notch-signaling were suppressed. Let-7a-5p mimics promoted ADSC differentiation into SCs and up-regulated the levels of SC-related markers including S100, GFAP, SOX10, p75NTR, GAP43, MPZ, β-NGF, and NCAM, while RBPJ or MEG3 overexpression retarded the differentiation and reduced those levels. Let-7a-5p directly targeted RBPJ and MEG3 disinhibited Notch-RBPJ signaling via sponging let-7a-5p. RBPJ overexpression reversed the acceleration of let-7a-5p mimics on SC differentiation while let-7a-5p mimics blocked MEG3-mediated suppression on SC differentiation. Let-7a-5p sponged by MEG3 promotes differentiation of ADSCs into SCs via suppressing Notch signaling by targeting RBPJ. These findings shed light on mechanisms underlying the differentiation of ADSCs to SCs and provide avenues to accelerate the process.
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http://dx.doi.org/10.1007/s10495-021-01685-xDOI Listing
August 2021

METTL3-mediated m6A methylation of ASPM drives hepatocellular carcinoma cells growth and metastasis.

J Clin Lab Anal 2021 Sep 16;35(9):e23931. Epub 2021 Aug 16.

Department of General Surgery, Ningbo First Hospital, Ningbo, China.

Background: Abnormal spindle-like microcephaly (ASPM) has been proved to participate in tumor progression. However, the underlying mechanism of ASPM in liver hepatocellular carcinoma (LIHC) remains elusive.

Methods: The mRNA and protein expression were determined using Western blot and qRT-PCR, and the capacities of cells proliferation, migration, and invasion were evaluated by CCK-8, colony formation, wound healing, and transwell. MeRIP was performed to validate the interaction between ASPM and methyltransferase-like 3 (METTL3).

Results: Herein, we found that ASPM was significantly upregulated in LIHC, and the high expression of ASPM was associated with poor LIHC prognosis. Furthermore, ASPM knockdown could suppress LIHC cells proliferation, migration, and invasion, while ASPM overexpression exerted reverse effect. Mechanistically, we revealed that the N6-methyladenosine (m6A) modification of ASPM mRNA mediated by METTL3 promoted its expression in LIHC. More importantly, silencing METTL3 suppressed LIHC cells proliferation, migration, and invasion, which could be retained by ASPM overexpression.

Conclusion: Collectively, our findings suggested that METTL3/ASPM axis could serve as a novel promising therapeutic candidate for LIHC.
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http://dx.doi.org/10.1002/jcla.23931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418466PMC
September 2021

Improving prediction accuracy in acute myeloid leukaemia: micro-environment, immune and metabolic models.

Leukemia 2021 Aug 7. Epub 2021 Aug 7.

Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China.

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http://dx.doi.org/10.1038/s41375-021-01377-0DOI Listing
August 2021

Intervertebral Disc Degeneration Models for Pathophysiology and Regenerative Therapy -Benefits and Limitations.

J Invest Surg 2021 Jul 26:1-18. Epub 2021 Jul 26.

The Second Clinical Medical College, Lanzhou University, Lanzhou, P.R. China.

This review summarized the recent intervertebral disc degeneration (IDD) models and described their advantages and potential disadvantages, aiming to provide an overview for the current condition of IDD model establishment and new ideas for new strategies development of the treatment and prevention of IDD.The database of PubMed was searched up to May 2021 with the following search terms: nucleus pulposus, annulus fibrosus, cartilage endplate, intervertebral disc(IVD), intervertebral disc degeneration, animal model, organ culture, bioreactor, inflammatory reaction, mechanical stress, pathophysiology, epidemiology. Any IDD model-related articles were collected and summarized.The best IDD model should have the features of repeatability, measurability and controllability. There are a lot of aspects to be considered in the selection of animals. Mice, rats and rabbits are low-cost and easy to access. However, their IVD size and shape are more different from human anatomy than pigs, cattle, sheep and goats. Organ culture models and animal models are two options in model establishment for IDD. The IVD organ culture model can put the studying variables into the controllable system for transitional research. Unlike the animal model, the organ culture model can only be used to evaluate the short-term effects and it is not applicable in simulating the complex process of IDD. Similarly, the animal models induced by different methods also have their advantages and disadvantages. For studying the mechanism of IDD and the corresponding treatment and prevention strategies, the selection of model should be individualized based on the purpose of each study.Various models have different characteristics and scope of application due to their different rationales and methods of construction. Currently, there is no experimental model that can perfectly mimic the degenerative process of human IVD. Personalized selection of appropriate model based on study purpose and experimental designing can enhance the possibility to obtain reliable and real results.
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http://dx.doi.org/10.1080/08941939.2021.1953640DOI Listing
July 2021

Discovery of a novel plant-derived agent against Ralstonia solanacearum by targeting the bacterial division protein FtsZ.

Pestic Biochem Physiol 2021 Aug 5;177:104892. Epub 2021 Jun 5.

Laboratory of Natural Products Pesticides, College of Plant Protection, Southwest University, Chongqing 400715, China. Electronic address:

Ralstonia solanacearum (R. solanacearum) is one of the most devastating bacterial pathogens and leads to serious economic losses in crops worldwide. In this study, the antibacterial activities of novel plant-derived coumarins against R. solanacearum and their underlying mechanisms were initially investigated. The bioactivity assay results showed that certain coumarins had significant in vitro inhibitory effects against R. solanacearum. Notably, 6-methylcoumarin showed the best in vitro antibacterial activity with 76.79%. Interestingly, 6-methylcoumarin was found to cause cell elongation, disrupt cell division, and suppress the expression of the bacterial division protein coding genes ftsZ. Compared with the control treatment, the ∆ftsZ mutant inhibited bacterial growth and caused the bacteria to be more sensitive to 6-methylcoumarin. The application of 6-methylcoumarin effectively suppressed the development of tobacco bacterial wilt in pot and field experiments, and significantly reduced the bacterial population in tobacco stems. The control efficiency of 6-methylcoumarin treatment was 35.76%, 40.51%, 38.99% at 10, 11, and 12 weeks after tobacco transplantation in field condition. All of these results demonstrate that 6-methylcoumarin has potential as an eco-friendly and target specificity agent for controlling tobacco bacterial wilt.
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http://dx.doi.org/10.1016/j.pestbp.2021.104892DOI Listing
August 2021

Shared Steering Control for Lane Keeping and Obstacle Avoidance Based on Multi-Objective MPC.

Sensors (Basel) 2021 Jul 8;21(14). Epub 2021 Jul 8.

School of Automotive Engineering, Wuhan University of Technology, Wuhan 430070, China.

This paper presents a shared steering control framework for lane keeping and obstacle avoidance based on multi-objective model predictive control. One of the control objectives is to track the reference trajectory, which is updated continuously by the trajectory planning module; whereas the other is to track the driver's current steering command, so as to consider the driver's intention. By adding the two control objectives to the cost function of an MPC shared controller, a smooth combination of the commands of the driver and the automation can be achieved through the optimization. The authority of the driver and the automation is allocated by adjusting the weights of the objective terms in the cost function, which is determined by the proposed situation assessment method considering the longitudinal and lateral risks simultaneously. The results of the CarSim-Matlab/Simulink joint simulations show that the proposed shared controller can assist the driver to complete the tasks of lane keeping and obstacle avoidance smoothly while maintaining a good level of vehicle stability.
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http://dx.doi.org/10.3390/s21144671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309538PMC
July 2021

Toward the Cure of Acute Lymphoblastic Leukemia in Children in China.

JCO Glob Oncol 2021 07;7:1176-1186

Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

This study explored results of therapy of children with acute lymphoblastic leukemia (ALL) in China, recent progress, and challenges. Included are a survey of therapy outcomes of ALL in Chinese children nationwide, comparison of these data with global ALL therapy outcomes, analyses of obstacles to improving outcomes, and suggestions of how progress can be achieved. Therapy outcomes at many Chinese pediatric cancer centers are approaching those of resource-rich countries. However, nationwide outcomes still need improvement. Obstacles include suboptimal clinical trials participation, children without adequate health care funding, human resource shortages, especially physicians expert in pediatric hematology and oncology, and social-economic disparities. We suggest how these obstacles have been and continue to be remedied including expanded access to protocol-based therapy, improved supportive care, health care reforms, recruitment of trained personnel, and international collaborations. China has made substantial progress treating children with ALL. We envision even better outcomes in the near future.
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http://dx.doi.org/10.1200/GO.21.00049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457838PMC
July 2021

rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure.

Cell Biosci 2021 Jul 21;11(1):138. Epub 2021 Jul 21.

School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, People's Republic of China.

Background: Pseudomonas aeruginosa is a notorious opportunistic pathogen causing various types of biofilm-related infections. Biofilm formation is a unique microbial strategy that allows P. aeruginosa to survive adverse conditions such as antibiotic treatment and human immune clearance.

Results: In this study, we experimentally evolved P. aeruginosa PAO1 biofilms for cyclic treatment in the presence of high dose of imipenem, and enriched hyperbiofilm mutants within six cycles in two independent lineages. The competition assay showed that the evolved hyperbiofilm mutants can outcompete the ancestral strain within biofilms but not in planktonic cultures. Whole-genome sequencing analysis revealed the hyperbiofilm phenotype is caused by point mutations in rpoS gene in all independently evolved mutants and the same mutation was found in P. aeruginosa clinical isolates. We further showed that mutation in rpoS gene increased the intracellular c-di-GMP level by turning on the expression of the diguanylate cyclases. Mutation in rpoS increased pyocyanin production and virulence in hyperbiofilm variants.

Conclusion: Here, our study revealed that antibiotic treatment of biofilm-related P. aeruginosa infections might induce a hyperbiofilm phenotype via rpoS mutation, which might partially explain antimicrobial treatment failure of many P. aeruginosa biofilm-related infections.
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http://dx.doi.org/10.1186/s13578-021-00655-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293535PMC
July 2021

rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure.

Cell Biosci 2021 Jul 21;11(1):138. Epub 2021 Jul 21.

School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, People's Republic of China.

Background: Pseudomonas aeruginosa is a notorious opportunistic pathogen causing various types of biofilm-related infections. Biofilm formation is a unique microbial strategy that allows P. aeruginosa to survive adverse conditions such as antibiotic treatment and human immune clearance.

Results: In this study, we experimentally evolved P. aeruginosa PAO1 biofilms for cyclic treatment in the presence of high dose of imipenem, and enriched hyperbiofilm mutants within six cycles in two independent lineages. The competition assay showed that the evolved hyperbiofilm mutants can outcompete the ancestral strain within biofilms but not in planktonic cultures. Whole-genome sequencing analysis revealed the hyperbiofilm phenotype is caused by point mutations in rpoS gene in all independently evolved mutants and the same mutation was found in P. aeruginosa clinical isolates. We further showed that mutation in rpoS gene increased the intracellular c-di-GMP level by turning on the expression of the diguanylate cyclases. Mutation in rpoS increased pyocyanin production and virulence in hyperbiofilm variants.

Conclusion: Here, our study revealed that antibiotic treatment of biofilm-related P. aeruginosa infections might induce a hyperbiofilm phenotype via rpoS mutation, which might partially explain antimicrobial treatment failure of many P. aeruginosa biofilm-related infections.
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http://dx.doi.org/10.1186/s13578-021-00655-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293535PMC
July 2021
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