Publications by authors named "Bin Cao"

555 Publications

Key considerations on the development of biodegradable biomaterials for clinical translation of medical devices: With cartilage repair products as an example.

Bioact Mater 2022 Mar 3;9:332-342. Epub 2021 Aug 3.

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, PR China.

With the interdisciplinary convergence of biology, medicine and materials science, both research and clinical translation of biomaterials are progressing at a rapid pace. However, there is still a huge gap between applied basic research on biomaterials and their translational products - medical devices, where two significantly different perspectives and mindsets often work independently and non-synergistically, which in turn significantly increases financial costs and research effort. Although this gap is well-known and often criticized in the biopharmaceutical industry, it is gradually widening. In this article, we critically examine the developmental pipeline of biodegradable biomaterials and biomaterial-based medical device products. Then based on clinical needs, market analysis, and relevant regulations, some ideas are proposed to integrate the two different mindsets to guide applied basic research and translation of biomaterial-based products, from the material and technical perspectives. Cartilage repair substitutes are discussed here as an example. Hopefully, this will lay a strong foundation for biomaterial research and clinical translation, while reducing the amount of extra research effort and funding required due to the dissonance between innovative basic research and commercialization pipeline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioactmat.2021.07.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586440PMC
March 2022

Extracellular DNA in environmental samples: Occurrence, extraction, quantification, and impact on microbial biodiversity assessment.

Appl Environ Microbiol 2021 Nov 24:AEM0184521. Epub 2021 Nov 24.

Singapore Centre for Environmental Life Sciences Engineering, Interdisciplinary Graduate Program, Nanyang Technological University, Singapore.

Environmental DNA, i.e., DNA directly extracted from environmental samples, has been applied to understand microbial communities in the environments and to monitor contemporary biodiversity in the conservation context. Environmental DNA often contains both intracellular DNA (iDNA) and extracellular DNA (eDNA). eDNA can persist in the environment and complicate environmental DNA sequencing-based analyses of microbial communities and biodiversity. Although several studies acknowledged the impact of eDNA on DNA-based profiling of environmental communities, eDNA is still being neglected or ignored in most studies dealing with environmental samples. In this article, we summarize key findings on eDNA in environmental samples and discuss the methods used to extract and quantify eDNA as well as the importance of eDNA on the interpretation of experimental results. We then suggest several factors to consider when designing experiments and analyzing data to negate or determine the contribution of eDNA to environmental DNA-based community analyses. This field of research will be driven forward by: (i) carefully designing environmental DNA extraction pipelines by taking into consideration technical details in methods for eDNA extraction/removal and membrane-based filtration and concentration; (ii) quantifying eDNA in extracted environmental DNA using multiple methods including qPCR and fluorescent DNA binding dyes; (iii) carefully interpretating effect of eDNA on DNA-based community analyses at different taxonomic levels; and (iv) when possible, removing eDNA from environmental samples for DNA-based community analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AEM.01845-21DOI Listing
November 2021

Long-term Ozone Exposure and Small Airways Dysfunction: The China Pulmonary Health (CPH) Study.

Am J Respir Crit Care Med 2021 Nov 23. Epub 2021 Nov 23.

Sichuan University West China Hospital, 34753, Chengdu, China.

Rationale: It remains unknown whether long-term ozone exposure can impair lung function.

Objectives: To investigate the associations between long-term ozone exposure and adult lung function in China.

Methods: Lung function results and diagnosis of small airways dysfunction (SAD) were collected from a cross-sectional study, China Pulmonary Health Study (N=50,991). We used multivariate linear and logistic regression models to examine the associations of long-term ozone exposure with lung function parameters and SAD, respectively, adjusting for demographic characteristics, individual risk factors, and longitudinal trend. We then performed a stratification analysis by chronic obstructive pulmonary disease (COPD).

Measurements And Main Results: We observed each 1-standard deviation (SD, 4.9 ppb) increase in warm-season ozone concentrations was associated with a 14.2 mL/s [95% confidence interval (CI): 8.8, 19.6] decrease in forced expiratory flow at 75th percentile of vital capacity and a 29.5 mL/s (95% CI: 19.6, 39.5) decrease in mean forced expiratory flow between the 25th and 75th percentile of vital capacity. The odds ratio of SAD was 1.09 (95% CI: 1.06, 1.11) for a 1-SD increase in warm-season ozone concentrations. Meanwhile, we observed a significant association with a decreased ratio of expiratory volume in 1 second to forced vital capacity (FEV1/FVC) but not with FEV1 or FVC. The association estimates were greater in the COPD group than in the non-COPD group.

Conclusion: We found independent associations of long-term ozone exposure with impaired small airways function and higher SAD risks, while the associations with airflow obstruction were weak. COPD patients appear to be more vulnerable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202107-1599OCDOI Listing
November 2021

Sirolimus Combined with Oseltamivir and Corticosteroid Treatment for a Puerpera with Severe Pneumonia Caused by 2009 Pandemic H1N1:A Case Report.

Biosaf Health 2021 Nov 14. Epub 2021 Nov 14.

Department of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, Tsinghua University-Peking University Joint Center for Life Sciences, Beijing 100029, China.

Severe pneumonia in patients infected with the 2009 pandemic H1N1 (pH1N1) virus was partially attributed to excessive immune response. Anti-virus treatment for these patients was insufficient. Here we reported the therapy effect of sirolimus, an immunosuppressor, combined with oseltamivir and corticosteroid for a puerpera with severe pneumonia caused by pH1N1 virus. This patient has infected with the pH1N1 virus in late pregnancy, and antiviral therapy was not implemented timely. She developed severe pneumonia and ARDS rapidly and need receive a cesarean section on the 39th week after pregnancy. Oseltamivir, sirolimus, and corticosteroid were administrated after the operation, and the patient's condition improved in the following days. Moreover, the cytokines in serum and viral loads in BALF decreased significantly. She recovered without infectious symptoms and was discharged. Sirolimus combined with oseltamivir and corticosteroid is likely responsible for lowering the viral loads, reducing the patient's cytokine level, and further improving her clinical outcomes. It provides evidence that adjuvant treatment was beneficial to patients with severe pneumonia induced by the pH1N1 virus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bsheal.2021.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590738PMC
November 2021

Long-term effects on survivors with COVID-19 - Authors' reply.

Lancet 2021 11;398(10314):1872-1873

Department of Pulmonary and Critical Care Medicine, National Centre for Respiratory Medicine, Centre of Respiratory Medicine, National Clinical Research Centre for Respiratory Diseases, China-Japan Friendship Hospital, Beijing 100029, China; Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China; Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China; Tsinghua University-Peking University Joint Centre for Life Sciences, Beijing, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(21)02324-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601684PMC
November 2021

Prospective Evaluation of a Rapid Clinical Metagenomics Test for Bacterial Pneumonia.

Front Cell Infect Microbiol 2021 19;11:684965. Epub 2021 Oct 19.

China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, China.

Background: The diagnosis of bacterial pathogens in lower respiratory tract infections (LRI) using conventional culture methods remains challenging and time-consuming.

Objectives: To evaluate the clinical performance of a rapid nanopore-sequencing based metagenomics test for diagnosis of bacterial pathogens in common LRIs through a large-scale prospective study.

Methods: We enrolled 292 hospitalized patients suspected to have LRIs between November 2018 and June 2019 in a single-center, prospective cohort study. Rapid clinical metagenomics test was performed on-site, and the results were compared with those of routine microbiology tests.

Results: 171 bronchoalveolar lavage fluid (BAL) and 121 sputum samples were collected from patients with six kinds of LRIs. The turnaround time (from sample registration to result) for the rapid metagenomics test was 6.4 ± 1.4 hours, compared to 94.8 ± 34.9 hours for routine culture. Compared with culture and real-time PCR validation tests, rapid metagenomics achieved 96.6% sensitivity and 88.0% specificity and identified pathogens in 63 out of 161 (39.1%) culture-negative samples. Correlation between enriched anaerobes and lung abscess was observed by Gene Set Enrichment Analysis. Moreover, 38 anaerobic species failed in culture was identified by metagenomics sequencing. The hypothetical impact of metagenomics test proposed antibiotic de-escalation in 34 patients compared to 1 using routine culture.

Conclusions: Rapid clinical metagenomics test improved pathogen detection yield in the diagnosis of LRI. Empirical antimicrobial therapy could be de-escalated if rapid metagenomics test results were hypothetically applied to clinical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2021.684965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560692PMC
November 2021

Battling COVID-19 Using Lessons Learned from 100 Years of Fighting Against Influenza.

Authors:
Xiaohui Zou Bin Cao

China CDC Wkly 2020 Oct;2(44):867-869

China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Clinical Center for Pulmonary Infections, Capital Medical University.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.46234/ccdcw2020.230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543720PMC
October 2020

Serum CD203c+ Extracellular Vesicle Serves as a Novel Diagnostic and Prognostic Biomarker for Succinylated Gelatin Induced Perioperative Hypersensitive Reaction.

Front Immunol 2021 28;12:732209. Epub 2021 Sep 28.

Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Perioperative hypersensitivity reaction (HR) is an IgE-FcϵRI-mediated hypersensitivity reaction with degranulation and activation of mast cells and basophils. Several studies have focused on assessing the degranulation and activation of mast cells and basophils to diagnose and predict the prognosis of drug induced HR. However, it is challenging to isolate sufficiently pure mast cells and basophils from human sources to investigate. Effective biomarkers to assess mast cells and basophils activation could potentially have high diagnostic and prognostic values. In the present study, we investigated EVs pelleted from serum in patients with succinylated gelatin induced HR.

Methods: Extracellular vesicles (EVs) were isolated using a total exosome isolation kit and ultracentrifugation, characterized by Western blot, transmission electron microscopy, and nanoparticle tracking analysis. Basophils were isolated from fresh peripheral blood by negative selection using Basophil Isolation Kit II. Human mast cell line was stimulated with IL4. The expression levels of proteins related to the hypersensitive response were evaluated by Western blotting and flow Cytometer. Histamine and tryptase levels were tested using a commercial ELISA kit, and gene expression of inflammatory mediators was evaluated by qRT-PCR. The receiver operating characteristic (ROC) curve was used to evaluate the specificity and sensitivity of biomarker in predicting HR.

Results: The concentration of EVs and protein expression level of CD63, FcϵRI, CD203c and tryptase were significantly (< 0.05) increased in HR samples. The expression level of mast cell/basophil specific CD203c were significantly increased in EVs derived from serum and basophils of HR patients, and the CD203c-EVs production in mast cells is dramatically increased in the presence of IL4, which positively correlated with histamine, tryptase and inflammatory mediators. Moreover, the ROC curve of EVs concentration and CD203c expression indicated that CD203c-EVs had a strong diagnostic ability for HR.

Conclusion: Serum CD203c+-EVs serves as a novel diagnostic and prognostic biomarker for HR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.732209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505883PMC
September 2021

Synthesis and Structural Characterization of Ricin Inhibitors Targeting Ribosome Binding Using Fragment-Based Methods and Structure-Based Design.

J Med Chem 2021 10 14;64(20):15334-15348. Epub 2021 Oct 14.

Department of Plant Biology, Rutgers, The State University of New Jersey, 59 Dudley Road, New Brunswick, New Jersey 08901, United States.

Ricin toxin A subunit (RTA) is the catalytic subunit of ricin, which depurinates an adenine from the sarcin/ricin loop in eukaryotic ribosomes. There are no approved inhibitors against ricin. We used a new strategy to disrupt RTA-ribosome interactions by fragment screening using surface plasmon resonance. Here, using a structure-guided approach, we improved the affinity and inhibitory activity of small-molecular-weight lead compounds and obtained improved compounds with over an order of magnitude higher efficiency. Four advanced compounds were characterized by X-ray crystallography. They bind at the RTA-ribosome binding site as the original compound but in a distinctive manner. These inhibitors bind remotely from the catalytic site and cause local conformational changes with no alteration of the catalytic site geometry. Yet they inhibit depurination by ricin holotoxin and inhibit the cytotoxicity of ricin in mammalian cells. They are the first agents that protect against ricin holotoxin by acting directly on RTA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.1c01370DOI Listing
October 2021

Volumetric interferometric lattice light-sheet imaging.

Nat Biotechnol 2021 Nov 11;39(11):1385-1393. Epub 2021 Oct 11.

Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Live cell imaging with high spatiotemporal resolution and high detection sensitivity facilitates the study of the dynamics of cellular structure and function. However, extracting high-resolution 4D (3D space plus time) information from live cells remains challenging, because current methods are slow, require high peak excitation intensities or suffer from high out-of-focus background. Here we present 3D interferometric lattice light-sheet (3D-iLLS) imaging, a technique that requires low excitation light levels and provides high background suppression and substantially improved volumetric resolution by combining 4Pi interferometry with selective plane illumination. We demonstrate that 3D-iLLS has an axial resolution and single-particle localization precision of 100 nm (FWHM) and <10 nm (1σ), respectively. We illustrate the performance of 3D-iLLS in a range of systems: single messenger RNA molecules, nanoscale assemblies of transcription regulators in the nucleus, the microtubule cytoskeleton and mitochondria organelles. The enhanced 4D resolution and increased signal-to-noise ratio of 3D-iLLS will facilitate the analysis of biological processes at the sub-cellular level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41587-021-01042-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595582PMC
November 2021

Selection of Imipenem Resistance Among Ceftazidime-Avibactam-Resistant, Imipenem-Susceptible Isolate With KPC-33 Carbapenemase.

Front Microbiol 2021 23;12:727946. Epub 2021 Sep 23.

Laboratory of Clinical Microbiology and Infectious Diseases, China-Japan Friendship Hospital, Department of Pulmonary and Critical Care Medicine, Beijing, China.

We describe evolution of carbapenem and ceftazidime-avibactam resistance by analyzing four longitudinal clinical isolates from a patient with pneumonia following antimicrobial treatment. The patient had fever, cough associated with expectoration, and new infiltration was found on the chest CT. Antimicrobial susceptibility was determined, and whole genome sequencing (WGS) was performed to investigate its dynamic change of resistance phenotype. Population analysis profile was performed to investigate the population of . The infection started with a KPC-2-producing (ZRKP01, ceftazidime-avibactam-S/carbapenem-R). Then, after ceftazidime-avibactam treatment, the strain switched to D179Y mutant that is KPC-33 (ZRKP02, ceftazidime-avibactam-R/carbapenem-S), which restored carbapenem susceptibility. However, the restored carbapenem susceptibility was not stable and the subsequent use of imipenem against KPC-33-producing infection resulted in a reversion of KPC-2 producers (ZRKP03 and ZRKP04, ceftazidime-avibactam-S/carbapenem-R). Genetic analysis demonstrated that all four isolates belonged to sequence type 11and had identical capsular polysaccharide (KL47), identical porin genes, and same plasmid replicon types. Phylogenetic analysis indicated that four isolates showed a high degree of relatedness. Single nucleotide polymorphisms analysis indicated that the number of mutations observed in the KPC-33 isolate was more than in the wild-type KPC-2 isolates and the four KPC-Kp isolates evolved from a longitudinal evolution of harboring gene. This is the first report to observe the evolution of wild-type KPC-2 to KPC-33 and then the reversion to its original wild-type KPC-2. Through WGS, we demonstrated the role of selective pressure of antibiotic in the mutation and reversion of genes, which leading to the dynamic change of KPC enzymes and the dynamic emergence of resistance to ceftazidime-avibactam and carbapenems. Recently, studies reported the emergence of ceftazidime-avibactam-resistant strains. The KPC mutations mediating ceftazidime-avibactam resistance are generally associated with the restoration of carbapenem susceptibility. However, clinical significance of this observation is unclear. In this manuscript, we demonstrate the role of selective pressure of antibiotic in the mutation and reversion of genes, which leading to the dynamic change of KPC enzymes and the dynamic emergence of resistance to ceftazidime-avibactam and carbapenems. To the best of our knowledge, this is the first report to observe the evolution of wild-type KPC-2 to KPC-33 and then the reversion to its original wild-type KPC-2. It should be noted that understanding the clinical significance of this observation is of critical importance, and reversion to carbapenem susceptibility would not imply a potential role for carbapenems monotherapy. We hope our study will draw attention to clinicians, so that this agent can be used most effectively for the longest period of time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.727946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496447PMC
September 2021

Single-detecting-path high-resolution displacement sensor based onself-interference effect of a single submicrometer grating.

Appl Opt 2021 Sep;60(25):7518-7522

On the basis of the self-interference effect between ±1 st-order diffraction beams from a single optical submicrometer grating, we demonstrate a single-detecting-path optical displacement sensor with high resolution. Using a quadrant optoelectronic detector, a single-detecting-path system without any wave plates is realized experimentally. Combined with an interpolation circuit, we demonstrate the system for displacement measurement within a range of 200 µm. The results indicate a detecting sensitivity of 905.4°/µm and an accuracy of ±1.9µ. It is worth mentioning that, considering a maximum subdividing factor of 9674 used in experiment, the resolution goes down to 41.1 pm in principle. We demonstrate a compact optical sensor with high resolution, which is promising in developing miniaturized displacement systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/AO.430262DOI Listing
September 2021

Increased Arterial Stiffness as a Predictor for Onset and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus.

J Diabetes Res 2021 23;2021:9124656. Epub 2021 Sep 23.

Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, China.

Introduction: Brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, has been demonstrated to be associated with type 2 diabetes mellitus (T2DM) and its vascular complications. This study was aimed at investigating the correlations of baPWV with both the presence and severity of diabetic retinopathy (DR) at baseline and at exploring the predictive role of baPWV in the new onset/progression of DR in the follow-up analysis.

Methods: The prospective cohort study recruited 2,473 Chinese patients with T2DM, of whom 663 participants were finally included in the follow-up analysis. The presence and grading of DR were performed by the modified Early Treatment Diabetic Retinopathy Study. Uni- or multivariate linear and logistic regression models and Cox proportional-hazards regression analysis were conducted.

Results: Of 2,473 patients with T2DM at baseline, 734 individuals were assessed to have DR and further categorized into 630 with non-sight-threatening DR (NSTDR) and 104 with STDR. In addition to the positive relationship between increased baPWV and the presence of DR, multinominal logistic regression analysis revealed that higher tertiles of baPWV were significantly related to the NSTDR (T2: OR = 1.62 (1.22, 2.15), < 0.001, and T3: OR = 2.58 (1.86, 3.58), < 0.001) and STDR group (T3: OR = 3.87 (1.87, 8.02), < 0.001). During a follow-up (mean period of 16.4 months), 111 participants had new onset/progression of DR. The cox regressions showed that high baseline baPWV was correlated with increased risk of development/progression of DR (HR = 2.24, 95% CI (1.24, 4.03), = 0.007, for T2 baPWV and HR = 2.90, 95% CI (1.49, 5.64), = 0.002, for T3 baPWV) after adjustments for multiple factors.

Conclusions: Our results demonstrated that baseline baPWV might be an independent predictor in new onset/worsening of DR, suggesting that increased arterial stiffness might be involved in the development of DR. Follow-up studies with a longer duration are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/9124656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486550PMC
September 2021

C-reactive protein or procalcitonin combined with rhinorrhea for discrimination of viral from bacterial infections in hospitalized adults in non-intensive care units with lower respiratory tract infections.

BMC Pulm Med 2021 Sep 28;21(1):308. Epub 2021 Sep 28.

Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China.

Background: Whether procalcitonin (PCT) or C-reactive protein (CRP) combined with certain clinical characteristics can better distinguish viral from bacterial infections remains unclear. The aim of the study was to assess the ability of PCT or CRP combined with clinical characteristics to distinguish between viral and bacterial infections in hospitalized non-intensive care unit (ICU) adults with lower respiratory tract infection (LRTI).

Methods: This was a post-hoc analysis of a randomized clinical trial previously conducted among LRTI patients. The ability of PCT, CRP and PCT or CRP combined with clinical symptoms to discriminate between viral and bacterial infection were assessed by portraying receiver operating characteristic (ROC) curves among patients with only a viral or a typical bacterial infection.

Results: In total, 209 infected patients (viral 69%, bacterial 31%) were included in the study. When using CRP or PCT to discriminate between viral and bacterial LRTI, the optimal cut-off points were 22 mg/L and 0.18 ng/mL, respectively. When the optimal cut-off for CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) combined with rhinorrhea was used to discriminate viral from bacterial LRTI, the AUCs were 0.81 (95% CI: 0.75-0.87) and 0.80 (95% CI: 0.74-0.86), which was statistically significantly better than when CRP or PCT used alone (p < 0.001). When CRP ≤ 22 mg/L, PCT ≤ 0.18 ng/mL and rhinorrhea were combined, the AUC was 0.86 (95% CI: 0.80-0.91), which was statistically significantly higher than when CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) was combined with rhinorrhea (p = 0.011 and p = 0.021).

Conclusions: Either CRP ≤ 22 mg/L or PCT ≤ 0.18 ng/mL combined with rhinorrhea could help distinguish viral from bacterial infections in hospitalized non-ICU adults with LRTI. When rhinorrhea was combined together, discrimination ability was further improved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12890-021-01672-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478003PMC
September 2021

MOF-Derived ZnS Nanodots/TiCT MXene Hybrids Boosting Superior Lithium Storage Performance.

Nanomicro Lett 2021 Sep 26;13(1):202. Epub 2021 Sep 26.

State Key Laboratory of Organic-Inorganic Composites, Beijing Key Laboratory of Electrochemical Process and Technology for Materials, Beijing University of Chemical Technology, Beijing, 100029, People's Republic of China.

ZnS has great potentials as an anode for lithium storage because of its high theoretical capacity and resource abundance; however, the large volume expansion accompanied with structural collapse and low conductivity of ZnS cause severe capacity fading and inferior rate capability during lithium storage. Herein, 0D-2D ZnS nanodots/TiCT MXene hybrids are prepared by anchoring ZnS nanodots on TiCT MXene nanosheets through coordination modulation between MXene and MOF precursor (ZIF-8) followed with sulfidation. The MXene substrate coupled with the ZnS nanodots can synergistically accommodate volume variation of ZnS over charge-discharge to realize stable cyclability. As revealed by XPS characterizations and DFT calculations, the strong interfacial interaction between ZnS nanodots and MXene nanosheets can boost fast electron/lithium-ion transfer to achieve excellent electrochemical activity and kinetics for lithium storage. Thereby, the as-prepared ZnS nanodots/MXene hybrid exhibits a high capacity of 726.8 mAh g at 30 mA g, superior cyclic stability (462.8 mAh g after 1000 cycles at 0.5 A g), and excellent rate performance. The present results provide new insights into the understanding of the lithium storage mechanism of ZnS and the revealing of the effects of interfacial interaction on lithium storage performance enhancement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40820-021-00728-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473522PMC
September 2021

Dynamics of the Upper Respiratory Tract Microbiota and its Association with Mortality in COVID-19.

Am J Respir Crit Care Med 2021 Sep 17. Epub 2021 Sep 17.

Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China;

Rationale: Alteration of human respiratory microbiota had been observed in COVID-19. How the microbiota is associated with the prognosis in COVID-19 is unclear.

Objectives: To characterize the feature and dynamics of the respiratory microbiota and its associations with clinical features in COVID-19 patients. Methods:We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 COVID-19 patients (including 39 deceased patients), and 95 healthy controls from the same geographic area. Meanwhile, the concentration of 27 cytokines and chemokines in plasma was measured for COVID-19 patients.

Measurements And Main Results: The upper respiratory tract (URT) microbiota in COVID-19 patients differed from that in healthy controls, while deceased patients possessed a more distinct microbiota, both on admission and before discharge/death. The alteration of URT microbiota showed a significant correlation with the concentration of proinflammatory cytokines and mortality. Specifically, Streptococcus-dominated microbiota was enriched in recovered patients, and show high temporal stability and resistance against pathogens. In contrast, the microbiota in deceased patients was more susceptible to secondary infections, and became more deviated from the normality after admission. Moreover, the abundance of S. parasanguinis on admission was significantly correlated with prognosis in non-severe patients (lower vs. higher abundance, odds ratio=7.80, [95% CI 1.70-42.05]). Conclusions:URT microbiota dysbiosis is a remarkable manifestation of COVID-19; its association with mortality suggests it may reflect the interplay between pathogens, symbionts, and the host immune status. Whether URT microbiota could be used as a biomarker for the diagnosis and prognosis of respiratory diseases merits further investigation. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.202103-0814OCDOI Listing
September 2021

Dipeptidyl peptidase-4 (DPP4) inhibitor sitagliptin alleviates liver inflammation of diabetic mice by acting as a ROS scavenger and inhibiting the NFκB pathway.

Cell Death Discov 2021 Sep 7;7(1):236. Epub 2021 Sep 7.

Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, China.

As a common chronic metabolic disease, the development of diabetes mellitus (DM) may also be accompanied by liver damage and inflammatory disorders. Sitagliptin is an inhibitor of dipeptidyl peptidase-4 (DPP4, also known as CD26), which is clinically used for DM treatment. However, the mechanism of sitagliptin's efficiency in liver diseases is largely unknown. In this study, mice suffering from streptozotocin (STZ) exhibit elevated liver DPP4 expression and activity, as well as inflammatory and chronic liver injury phenotype, whereas specifically inhibiting the activity of DPP4 in mouse liver tissues and hepatocytes by sitagliptin contributes to decreased cytokines, oxidative stress, cell apoptosis, and inflammation in STZ-induced diabetic mice. Moreover, sitagliptin reduced TNFα or LPS-induced cellular reactive oxygen species (ROS) level, cell apoptosis, and protein expression in the NFκB signaling pathway in HepG2 cells or primary mouse hepatocytes. Altogether, our study confirms that sitagliptin may protect liver tissue by alleviating ROS production and NFκB signaling activation, providing a putative mechanism for preventing the development of diabetic liver disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41420-021-00625-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423797PMC
September 2021

Toward On-Device Federated Learning: A Direct Acyclic Graph-Based Blockchain Approach.

IEEE Trans Neural Netw Learn Syst 2021 Aug 30;PP. Epub 2021 Aug 30.

Due to the distributed characteristics of federated learning (FL), the vulnerability of the global model and the coordination of devices are the main obstacle. As a promising solution of decentralization, scalability, and security, leveraging the blockchain in FL has attracted much attention in recent years. However, the traditional consensus mechanisms designed for blockchain-like proof of work (PoW) would cause extreme resource consumption, which reduces the efficiency of FL greatly, especially when the participating devices are wireless and resource-limited. In order to address device asynchrony and anomaly detection in FL while avoiding the extra resource consumption caused by blockchain, this article introduces a framework for empowering FL using direct acyclic graph (DAG)-based blockchain systematically (DAG-FL). Accordingly, DAG-FL is first introduced from a three-layer architecture in detail, and then, two algorithms DAG-FL Controlling and DAG-FL Updating are designed running on different nodes to elaborate the operation of the DAG-FL consensus mechanism. After that, a Poisson process model is formulated to discuss that how to set deployment parameters to maintain DAG-FL stably in different FL tasks. The extensive simulations and experiments show that DAG-FL can achieve better performance in terms of training efficiency and model accuracy compared with the typical existing on-device FL systems as the benchmarks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TNNLS.2021.3105810DOI Listing
August 2021

LC-MS/MS determination of guanabenz E/Z isomers and its application to in vitro and in vivo DMPK profiling studies.

J Pharm Biomed Anal 2021 Oct 18;205:114331. Epub 2021 Aug 18.

Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

Endoplasmic reticulum (ER) stress underlies a variety of disorders involving inflammation, such as diabetes, neurodegenerative diseases. Guanabenz acetate (Wytensin®, GA), a clinically approved antihypertensive drug, efficiently counteracts ER stress. The entirety of clinically used GA is the E-isomer, while the Z-isomer is known to lack significant hypotensive properties. We recently discovered that the Z-isomer retains anti-ER stress activity. Coupled with its lack of sedative effects, (Z)-GA is well positioned as a potential therapeutic for a host of ER stress-related disorders. We set forth to characterize the metabolism and pharmacokinetics (DMPK) of (Z)-GA in vitro and in vivo. Toward this end, a reliable and sensitive LC-MS/MS method for simultaneous determination of the (E)- and (Z)-guanabenz was developed. Chromatographic separation of the isomers was achieved on a C18 reverse phase column with a gradient elution. Tandem mass spectrometric detection was conducted using an AB Sciex 5500 QTrap mass spectrometer with positive electrospray ionization. Full validation of the method was performed in mouse plasma with a simple and low plasma volume protein precipitation procedure. The method demonstrated good linearity, reproducibility, and accuracy over a range of 0.5-1000 nM with minimal matrix effect and excellent extraction efficiency. In addition, the developed method was successfully applied to DMPK studies of the GA isomers in vitro and in vivo. Results of these studies revealed for the first time that the DMPK profile of (Z)-guanabenz is distinct from that of (E)-guanabenz, with higher apparent volume of distribution (V) and clearance, presumably due to lower plasma protein binding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpba.2021.114331DOI Listing
October 2021

1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study.

Lancet 2021 08;398(10302):747-758

Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China; Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China. Electronic address:

Background: The full range of long-term health consequences of COVID-19 in patients who are discharged from hospital is largely unclear. The aim of our study was to comprehensively compare consequences between 6 months and 12 months after symptom onset among hospital survivors with COVID-19.

Methods: We undertook an ambidirectional cohort study of COVID-19 survivors who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. At 6-month and 12-month follow-up visit, survivors were interviewed with questionnaires on symptoms and health-related quality of life (HRQoL), and received a physical examination, a 6-min walking test, and laboratory tests. They were required to report their health-care use after discharge and work status at the 12-month visit. Survivors who had completed pulmonary function tests or had lung radiographic abnormality at 6 months were given the corresponding tests at 12 months. Non-COVID-19 participants (controls) matched for age, sex, and comorbidities were interviewed and completed questionnaires to assess prevalent symptoms and HRQoL. The primary outcomes were symptoms, modified British Medical Research Council (mMRC) score, HRQoL, and distance walked in 6 min (6MWD). Multivariable adjusted logistic regression models were used to evaluate the risk factors of 12-month outcomes.

Findings: 1276 COVID-19 survivors completed both visits. The median age of patients was 59·0 years (IQR 49·0-67·0) and 681 (53%) were men. The median follow-up time was 185·0 days (IQR 175·0-198·0) for the 6-month visit and 349·0 days (337·0-361·0) for the 12-month visit after symptom onset. The proportion of patients with at least one sequelae symptom decreased from 68% (831/1227) at 6 months to 49% (620/1272) at 12 months (p<0·0001). The proportion of patients with dyspnoea, characterised by mMRC score of 1 or more, slightly increased from 26% (313/1185) at 6-month visit to 30% (380/1271) at 12-month visit (p=0·014). Additionally, more patients had anxiety or depression at 12-month visit (26% [331/1271] at 12-month visit vs 23% [274/1187] at 6-month visit; p=0·015). No significant difference on 6MWD was observed between 6 months and 12 months. 88% (422/479) of patients who were employed before COVID-19 had returned to their original work at 12 months. Compared with men, women had an odds ratio of 1·43 (95% CI 1·04-1·96) for fatigue or muscle weakness, 2·00 (1·48-2·69) for anxiety or depression, and 2·97 (1·50-5·88) for diffusion impairment. Matched COVID-19 survivors at 12 months had more problems with mobility, pain or discomfort, and anxiety or depression, and had more prevalent symptoms than did controls.

Interpretation: Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work and life. The health status in our cohort of COVID-19 survivors at 12 months was still lower than that in the control population.

Funding: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(21)01755-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389999PMC
August 2021

SARS-CoV-2 vaccination for immune-comprised patients: More is required.

Lancet Reg Health Eur 2021 Oct 18;9:100191. Epub 2021 Aug 18.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lanepe.2021.100191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372430PMC
October 2021

Increased gene expression and copy number of mutated bla lead to high-level ceftazidime/avibactam resistance in Klebsiella pneumoniae.

BMC Microbiol 2021 08 19;21(1):230. Epub 2021 Aug 19.

National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Capital Medical University, Beijing, China.

Background: Resistance to ceftazidime-avibactam was reported, and it is important to investigate the mechanisms of ceftazidime/avibactam resistance in K. pneumoniae with mutations in bla.

Results: We report the mutated bla is not the only mechanism related to CZA resistance, and investigate the role of outer porin defects, efflux pump, and relative gene expression and copy number of bla and ompk35/36. Four ceftazidime/avibactam-sensitive isolates detected wild type bla, while 4 ceftazidime/avibactam-resistant isolates detected mutated bla (bla, bla, and bla). Compared with other ceftazidime/avibactam-resistant isolates with the minimal inhibitory concentration of ceftazidime/avibactam ranging 128-256 mg/L, the relative gene expression and copy number of bla was increased in the isolate which carried bla and also showed the highest minimal inhibitory concentration of ceftazidime/avibactam at 2048 mg/L. The truncated Ompk35 contributes rare to ceftazidime/avibactam resistance in our isolates. No significant difference in minimal inhibitory concentration of ceftazidime/avibactam was observed after the addition of PABN.

Conclusions: Increased gene expression and copy number of mutated bla can cause high-level ceftazidime/avibactam resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12866-021-02293-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375111PMC
August 2021

Procalcitonin-guided initiation of antibiotics in AECOPD inpatients: study protocol for a multicenter randomised controlled trial.

BMJ Open 2021 08 5;11(8):e049515. Epub 2021 Aug 5.

Department of Pulmonary and Critical Care Medicine, Capital Medical University, Beijing, China

Introduction: Current antibiotic prescription for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is generally based on the Anthonisen criteria in The Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guideline that have a potential risk of antibiotics overuse. The dilemma is to identify patients who are most likely to benefit from antibiotics while avoiding unnecessary antibiotic use. Procalcitonin (PCT), a more sensitive and specific biomarker of bacterial infection than other conventional laboratory tests, has the potential to determine those patients in whom antibiotics would be beneficial. It is unclear whether PCT-guided antibiotic therapy is safe and effective for patients hospitalised with AECOPD. The study hypothesis is that PCT-guided antibiotic therapy could reduce the antibiotic prescription rate for AECOPD, compared with the GOLD guideline recommendations, without negatively impacting the treatment success rate.

Methods And Analysis: In this multicenter, open-label, randomised controlled trial, we aim to enrol 500 hospitalised patients with AECOPD that will be randomly assigned to either a PCT-guided group or a GOLD guideline-guided group. The coprimary endpoints are antibiotic prescription rate for AECOPD within 30 days post randomisation and treatment success rate at day 30 post randomisation. The secondary outcomes include: antibiotic prescription rate at day 1 post randomisation; hospital antibiotic exposure; length of hospital stay; rate of subsequent exacerbation and hospital readmission; overall mortality within 30 days post randomisation; changes in lung function and the score of COPD assessment test and modified Medical Research Council; and rate of intensive care unit admission.

Ethics And Dissemination: This trial has been approved by the ethic committee of China-Japan Friendship Hospital. The findings of the study will be disseminated in peer-reviewed journals. If the results of the study are positive, PCT-guided antibiotic therapy is likely to change the guidelines for antibiotic recommendations for patients with AECOPD.

Trial Registration Number: ClinicalTrials.gov: NCT04682899.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2021-049515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344287PMC
August 2021

Lessons learnt from hydroxychloroquine/azithromycin in treatment of COVID-19.

Authors:
Jiuyang Xu Bin Cao

Eur Respir J 2021 Jul 29. Epub 2021 Jul 29.

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Beijing, China

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.02002-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340617PMC
July 2021

Analysis of the comprehensive non-pharmaceutical interventions and measures in containing the COVID-19 epidemic in Shenzhen: a retrospective study.

BMJ Open 2021 07 26;11(7):e044940. Epub 2021 Jul 26.

Department of Communicable Disease Control and Prevention, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China

Objective: To analyse the epidemiological characteristics of family clusters of COVID-19 and the three stages of the comprehensive non-pharmaceutical interventions and measures implemented in Shenzhen.

Methods: The epidemic curve of COVID-19 was drawn and the impact of the comprehensive non-pharmaceutical interventions and measures was analysed by the different periods of the epidemic.

Results: A total of 427 cases (417 confirmed cases and 10 asymptomatic infectious cases) were reported in Shenzhen, of which 259 (60.7%) were clustered cases. 97 cluster events were drawn and most cluster events (97.3%) occurred in families. There were three stages of the COVID-19 epidemic in Shenzhen. The epidemic increased rapidly, but the peak lasted for a short time, while the decline in incidence was rapid and large.

Conclusions: Family clusters were the main feature of the COVID-19 outbreak in Shenzhen in 2020, and the Shenzhen government rolled out a quick response to the epidemic. Non-pharmaceutical interventions and measures were proven to have effectively contained community transmission, limit the transmission to aggregation and reduce the scale of transmission within a household.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-044940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316694PMC
July 2021

Clinical factors associated with composition of lung microbiota and important taxa predicting clinical prognosis in patients with severe community-acquired pneumonia.

Front Med 2021 Jul 24. Epub 2021 Jul 24.

China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, 100029, China.

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R = 0.033; P = 0.018), followed by acute kidney injury (AKI; R = 0.032; P = 0.011) and plasma MIP-1β level (R = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11684-021-0856-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302972PMC
July 2021

Ficolin A exacerbates severe H1N1 influenza virus infection-induced acute lung immunopathological injury via excessive complement activation.

Cell Mol Immunol 2021 Sep 23;18(9):2278-2280. Epub 2021 Jul 23.

Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41423-021-00737-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298942PMC
September 2021

Serum Extracellular Vesicle-Derived miR-124-3p as a Diagnostic and Predictive Marker for Early-Stage Acute Ischemic Stroke.

Front Mol Biosci 2021 1;8:685088. Epub 2021 Jul 1.

Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

A delay in the diagnosis of acute ischemic stroke (AIS) reduces the eligibility and outcome of patients for thrombolytic therapy. Therefore, early diagnosis and treatment of AIS are crucial. The present study evaluated the sensitivity and accuracy of serum extracellular vesicle (EV)-derived in the diagnosis and prediction of AIS. An miRNA expression profile was downloaded from Gene Expression Omnibus (GEO) database and analyzed by R software. EVs were harvested from the serum of AIS patients using a total exosome isolation kit and characterized by Western blotting, a transmission electron microscope, and the nanoparticle tracking analysis. BV2 microglia were pre-stimulated with lipopolysaccharide (LPS), followed by treatment for 24 h and subsequent analysis of viability, apoptosis, and migration (scratch assay), and Western blotting. The relative expression of the selected genes was assessed by qRT-PCR. The phosphorylation of Erk1/2, PI3K/Akt, and p38MAPK in BV2 microglia cells was evaluated by Western blotting, while the luciferase reporter gene assay detected the correlation between key genes involved in the pro-inflammatory signaling pathways and . was downregulated in AIS serum compared to the non-AIS serum ( < 0.05), and the gene expression of in EVs was negatively correlated with serum pro-inflammatory cytokines and the NIHSS ( < 0.05). In addition, promoted the viability and inhibited the apoptosis of LPS-induced BV2 microglia. Furthermore, reduced the phosphorylation of Erk1/2, PI3K/Akt, and p38MAPK, and promoted the migration in LPS-induced BV2 microglia ( < 0.05). Serum EV-derived serves as a diagnostic and predictive marker for early-stage AIS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2021.685088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280338PMC
July 2021

In-hospital complications associated with COVID-19.

Authors:
Xiaoying Gu Bin Cao

Lancet 2021 07;398(10296):188-190

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing 100029, China; National Center for Respiratory Medicine, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China; Department of Respiratory Medicine, Capital Medical University, Beijing, China; Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(21)00983-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285113PMC
July 2021

Synergistic Activity of Colistin Combined With Auranofin Against Colistin-Resistant Gram-Negative Bacteria.

Front Microbiol 2021 25;12:676414. Epub 2021 Jun 25.

Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Colistin-resistant (Col-R) bacteria are steadily increasing, and are extremely difficult to treat. New drugs or therapies are urgently needed to treat infections caused by these pathogens. Combination therapy with colistin and other old drugs, is an important way to restore the activity of colistin. This study aimed to investigate the activity of colistin in combination with the anti-rheumatic drug auranofin against Col-R Gram-negative bacteria. The results of checkerboard analysis demonstrated that auranofin synergized with colistin against Col-R Gram-negative bacteria. Time-kill assays showed significant synergistic antimicrobial activity of colistin combined with auranofin. Electron microscopy revealed that the combination resulted in more cellular structural alterations compared to each drug alone. Auranofin enhanced the therapeutic effectiveness of colistin in mouse peritoneal infection models. These results suggested that the combination of colistin and auranofin might be a potential alternative for the treatment of Col-R Gram-negative bacterial infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.676414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267823PMC
June 2021
-->