Publications by authors named "Ke Bai"

30 Publications

  • Page 1 of 1

Preclinical study of a novel therapeutic vaccine for recurrent respiratory papillomatosis.

NPJ Vaccines 2021 Jun 18;6(1):86. Epub 2021 Jun 18.

Section on Translational Tumor Immunology, National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health, Bethesda, MD, USA.

Activation of antigen-specific T-lymphocyte responses may be needed to cure disorders caused by chronic infection with low-risk human papillomavirus (lrHPV). Safe and effective adjuvant therapies for such disorders are needed. The safety and efficacy of a novel gorilla adenovirus vaccine expressing a protein designed to elicit immune responses directed against HPV6 and HPV11, PRGN-2012, was studied using in vitro stimulation of T lymphocytes from patients with recurrent respiratory papillomatosis, in vivo vaccination studies, and therapeutic studies in mice bearing tumors expressing lrHPV antigen. PRGN-2012 treatment induces lrHPV antigen-specific responses in patient T lymphocytes. Vaccination of wild-type mice induces E6-specific T-lymphocyte responses without toxicity. In vivo therapeutic vaccination of mice bearing established HPV6 E6 expressing tumors results in HPV6 E6-specific CD8+ T-lymphocyte immunity of sufficient magnitude to induce tumor growth delay. The clinical study of PRGN-2012 in patients with disorders caused by chronic infection with lrHPV is warranted.
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http://dx.doi.org/10.1038/s41541-021-00348-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213691PMC
June 2021

Cu-Ag Bimetallic Core-shell Nanoparticles in Pores of a Membrane Microreactor for Enhanced Synergistic Catalysis.

ACS Appl Mater Interfaces 2021 Jun 19;13(21):24795-24803. Epub 2021 May 19.

Sichuan University, No. 24 South Section 1, Yihuan Road, 610065 Chengdu, China.

A bimetallic catalytic membrane microreactor (CMMR) with bimetallic nanoparticles in membrane pores has been fabricated via flowing synthesis. The bimetallic nanoparticle is successfully immobilized in membrane pores along its thickness direction. Enhanced synergistic catalysis can be expected in this CMMR. As a concept-of-proof, Cu-Ag core-shell nanoparticles have been fabricated and immobilized in membrane pores for -nitrophenol (-NP) hydrogenation. Transmission electron microscopy (TEM) for the characterization of the bimetallic core-shell nanostructure and X-ray photoelectron spectroscopy (XPS) for the characterization of the electron transfer behavior between Cu-Ag bimetal have been performed. The Ag shell on the core of Cu can improve the utilization of Ag atoms, and electron transfer between bimetallic components can promote the formation of high electron density active sites as well as active hydrogen with strong reducing properties on the Ag surface. The dispersed membrane pore can prevent nanoparticle aggregation, and the contact between the reaction fluid and catalyst is enhanced. The enhanced mass transfer can be achieved by the plug-flow mode during the process of hydrogenation catalysis. The -NP conversion rate being over 95% can be obtained under the condition of a membrane flux of 1.59 mL·cm·min. This Cu-Ag/PES CMMR has good stability and has a potential application in industry.
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http://dx.doi.org/10.1021/acsami.1c04155DOI Listing
June 2021

A Cluster-Based Energy Optimization Algorithm in Wireless Sensor Networks with Mobile Sink.

Sensors (Basel) 2021 Apr 4;21(7). Epub 2021 Apr 4.

School of Artificial Intelligence, Henan University, Kaifeng 475004, China.

Aiming at high network energy consumption and data delay induced by mobile sink in wireless sensor networks (WSNs), this paper proposes a cluster-based energy optimization algorithm called Cluster-Based Energy Optimization with Mobile Sink (CEOMS). CEOMS algorithm constructs the energy density function of network nodes firstly and then assigns sensor nodes with higher remaining energy as cluster heads according to energy density function. Meanwhile, the directivity motion performance function of mobile sink is constructed to enhance the probability of remote sensor nodes being assigned as cluster heads. Secondly, based on Low Energy Adaptive Clustering Hierarchy Protocol (LEACH) architecture, the energy density function and the motion performance function are introduced into the cluster head selection process to avoid random assignment of cluster head. Finally, an adaptive adjustment function is designed to improve the adaptability of cluster head selection by percentage of network nodes death and the density of all surviving nodes of the entire network. The simulation results show that the proposed CEOMS algorithm improves the cluster head selection self-adaptability, extends the network life, reduces the data delay, and balances the network load.
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http://dx.doi.org/10.3390/s21072523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038497PMC
April 2021

Rapidly deployable and morphable 3D mesostructures with applications in multimodal biomedical devices.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208;

Structures that significantly and rapidly change their shapes and sizes upon external stimuli have widespread applications in a diversity of areas. The ability to miniaturize these deployable and morphable structures is essential for applications in fields that require high-spatial resolution or minimal invasiveness, such as biomechanics sensing, surgery, and biopsy. Despite intensive studies on the actuation mechanisms and material/structure strategies, it remains challenging to realize deployable and morphable structures in high-performance inorganic materials at small scales (e.g., several millimeters, comparable to the feature size of many biological tissues). The difficulty in integrating actuation materials increases as the size scales down, and many types of actuation forces become too small compared to the structure rigidity at millimeter scales. Here, we present schemes of electromagnetic actuation and design strategies to overcome this challenge, by exploiting the mechanics-guided three-dimensional (3D) assembly to enable integration of current-carrying metallic or magnetic films into millimeter-scale structures that generate controlled Lorentz forces or magnetic forces under an external magnetic field. Tailored designs guided by quantitative modeling and developed scaling laws allow formation of low-rigidity 3D architectures that deform significantly, reversibly, and rapidly by remotely controlled electromagnetic actuation. Reconfigurable mesostructures with multiple stable states can be also achieved, in which distinct 3D configurations are maintained after removal of the magnetic field. Demonstration of a functional device that combines the deep and shallow sensing for simultaneous measurements of thermal conductivities in bilayer films suggests the promising potential of the proposed strategy toward multimodal sensing of biomedical signals.
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http://dx.doi.org/10.1073/pnas.2026414118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980465PMC
March 2021

How Enhancing Immunity to Low-Risk HPV Could Cure Recurrent Respiratory Papillomatosis.

Authors:
Ke Bai Clint Allen

Laryngoscope 2021 Mar 15. Epub 2021 Mar 15.

Section on Translation Tumor Immunology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, U.S.A.

Recurrent respiratory papillomatosis (RRP) is currently treated with repeat surgical resection of papillomatous disease that does not address the fundamental underlying issue of chronic infection with low-risk human papillomavirus. Here, we review the biology and immunology of low-risk human papillomavirus (HPV) infections. Antiviral or antiangiogenic adjuvant treatments similarly address the papillomatous disease itself but do not activate HPV immunity. It is likely that only through immune-mediated clearance of low-risk HPV infection can patients with RRP be cured. In some patients, this occurs spontaneously. In others with more aggressive disease, adjuvant immunotherapy to activate immunity may be needed. Based on current understanding of antiviral immune responses, the only rational strategy to clear HPV-infected epithelial cells is through activation of the T-lymphocyte arm of the adaptive immune response. Translation of immunotherapies that are Food and Drug Administration-approved or under clinical study for cancer, such as immune checkpoint blockade or engineered therapeutic vaccines, may provide a path toward tolerable and efficacious adjuvant immunotherapy for RRP. LEVEL OF EVIDENCE: NA Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29153DOI Listing
March 2021

Glial Fibrillary Acidic Protein Astrocytopathy in Pediatric Patients: A Retrospective Study.

Front Pediatr 2020 25;8:626564. Epub 2021 Jan 25.

Intensive Care Unit, Key Medical Laboratory of Pediatrics, Chongqing Health Bureau, Ministry of Education, Chongqing, China.

Autoimmune glial fibrillary acidic protein astrocytopathy is a novel form of autoimmune meningoencephalitis related to GFAP autoantibodies. This condition is still being characterized, and few pediatric patients have been identified. Here, we report three patients presenting with fever, nausea, and headache, following progressive disturbance of consciousness, limb weakness, dyspnea, or urine retention. MRI analysis revealed that T2-hyperintense lesions, or enhancement of the meninges and spinal cord. CSF and serum analyses revealed they were positive for GFAP antibody, confirming GFAP astrocytopathy diagnosis. Treating the patients with IVIG, with or without intravenous steroids, gradually improved their clinical symptoms. Our findings indicate that GFAP astrocytopathy should be considered in children who are clinically diagnosed with meningoencephalitis, whether or not myelitis is present, and if the MRI reveals enhancement of meninges or spinal cord, T2-hyperintense lesions, or a pattern of linear perivascular gadolinium enhancement. Suspected cases should be tested for GFAP antibody as soon as possible because these patients may benefit from immunotherapy.
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http://dx.doi.org/10.3389/fped.2020.626564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868541PMC
January 2021

Ecthyma gangrenosum due to Pseudomonas aeruginosa sepsis as initial manifestation of X-linked agammaglobulinemia: a case report.

BMC Pediatr 2020 12 1;20(1):540. Epub 2020 Dec 1.

Intensive Care Unit, Key Medical Laboratory of Pediatrics, Key Laboratory of Child Development and Disorders, Chongqing Health Bureau, Ministry of Education, Children's Hospital of Chongqing Medical University, 136#, Zhong Shan 2nd Rord, Yuzhong District, Chongqing, People's Republic of China.

Background: X-linked agammaglobulinemia (XLA, OMIM#300,300), caused by mutations in the Bruton tyrosine kinase (BTK) gene, is a rare monogenic inheritable immunodeficiency disorder. Ecthyma gangrenosum is a cutaneous lesion caused by Pseudomonas aeruginosa that typically occurs in patients with XLA and other immunodeficiencies.

Case Presentation: We report the case of a 20-month-old boy who presented with fever, vomiting, diarrhea, and ecthyma gangrenosum. Blood, stool, and skin lesion culture samples were positive for P. aeruginosa. A diagnosis of XLA was established, and the c.262G > T mutation in exon 4 of BTK was identified with Sanger sequencing. Symptoms improved following treatment with antibiotics and immunoglobulin infusion.

Conclusions: Primary immunodeficiency (i.e., XLA) should be suspected in male infants with P. aeruginosa sepsis, highlighting the importance of genetic and immune testing in these patients.
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http://dx.doi.org/10.1186/s12887-020-02436-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704585PMC
December 2020

Chemicals orchestrate reprogramming with hierarchical activation of master transcription factors primed by endogenous Sox17 activation.

Commun Biol 2020 10 30;3(1):629. Epub 2020 Oct 30.

State Key Laboratory of Natural and Biomimetic Drugs, MOE Key Laboratory of Cell Proliferation and Differentiation, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, 100871, Beijing, China.

Mouse somatic cells can be chemically reprogrammed into pluripotent stem cells (CiPSCs) through an intermediate extraembryonic endoderm (XEN)-like state. However, it is elusive how the chemicals orchestrate the cell fate alteration. In this study, we analyze molecular dynamics in chemical reprogramming from fibroblasts to a XEN-like state. We find that Sox17 is initially activated by the chemical cocktails, and XEN cell fate specialization is subsequently mediated by Sox17 activated expression of other XEN master genes, such as Sall4 and Gata4. Furthermore, this stepwise process is differentially regulated. The core reprogramming chemicals CHIR99021, 616452 and Forskolin are all necessary for Sox17 activation, while differently required for Gata4 and Sall4 expression. The addition of chemical boosters in different phases further improves the generation efficiency of XEN-like cells. Taken together, our work demonstrates that chemical reprogramming is regulated in 3 distinct "prime-specify-transit" phases initiated with endogenous Sox17 activation, providing a new framework to understand cell fate determination.
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http://dx.doi.org/10.1038/s42003-020-01346-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603307PMC
October 2020

Geometrically reconfigurable 3D mesostructures and electromagnetic devices through a rational bottom-up design strategy.

Sci Adv 2020 Jul 22;6(30):eabb7417. Epub 2020 Jul 22.

AML, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, P.R. China.

Microelectronic devices with reconfigurable three-dimensional (3D) microarchitecture that can be repetitively switched among different geometrical and/or working states have promising applications in widespread areas. Traditional approaches usually rely on stimulated deformations of active materials under external electric/magnetic fields, which could potentially introduce parasitic side effects and lower device performances. Development of a rational strategy that allows access to high-performance 3D microdevices with multiple stable geometric configurations remains challenging. We introduce a mechanically guided scheme to build geometrically reconfigurable 3D mesostructures through a bottom-up design strategy based on a class of elementary reconfigurable structures with the simplest ribbon geometries. Quantitative mechanics modeling of the structural reconfigurability allows for the development of phase diagrams and design maps. Demonstrations of ~30 reconfigurable mesostructures with diverse geometric topologies and characteristic dimensions illustrate the versatile applicability. The multimode nature enables customized distinct beamforming and discrete beam scanning using a single antenna capable of on-demand reconfiguration.
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http://dx.doi.org/10.1126/sciadv.abb7417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439572PMC
July 2020

Infection in the Pediatric Population: A Retrospective Study.

Front Pediatr 2020 10;8:362. Epub 2020 Jul 10.

Intensive Care Unit, Children's Hospital of Chongqing Medical University, Chongqing, China.

is a pathogen causing an increasing number of pediatric infections. The objective of this study was to investigate the clinical characteristics of infections in children. As a retrospective analysis, clinical features and drug susceptibility data of the five cases were analyzed and related literature was reviewed. A total of 14 cases (eight females, six males) were analyzed: nine cases were retrieved from PubMed, Web of Science, and three domestic databases; five cases occurred in our hospital. The primary diseases of the older children were mainly of neoplastic and immune origin, while cases of infants and young children were mostly complicated by congenital malformation. Fever was the main symptom, and neonatal infection was mainly manifested by dyspnea and hypoxemia, with multiple skin flushes, systemic erythema, and leukocytosis. Of the 14 cases, six were ventilator-assisted, five had indwelling urethral catheters, three had surgical treatment or chemotherapy, and one had multiple rounds of continuous renal replacement therapy (CRRT). Blood infection is the main route of infection in children. Skin flushing and systemic erythema might be positive clues for newborn infection. Patients with multiple congenital abnormalities are susceptible to infection. Tumors, immune deficiency, and invasive operations increase the risk of infection. Blood culture was the main method of disease identification. Based on the drug susceptibility results, the preferred antibiotics are third generations of cephalosporins, carbapenems, quinolone, and aminoglycoside. Lastly, patients with sepsis mostly have poor prognosis.
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http://dx.doi.org/10.3389/fped.2020.00362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366290PMC
July 2020

Ventricular Septal Rupture After Blunt Chest Trauma in an Infant: A Case Report and Mini-Review.

Front Pediatr 2020 19;8:316. Epub 2020 Jun 19.

Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorder, Chongqing, China.

Ventricular septal rupture (VSR) due to blunt chest trauma (BCT) is rare in infants. Traumatic VSR should be considered in infants with acute congestive cardiac failure following blunt trauma to the chest. Echocardiography is the method of choice for diagnosis and guiding the management of VSR. In this case report, we present a case of VSR caused by BCT in a 1-year and 9-month-old infant, who was diagnosed by emergency bedside echocardiography. We also provide a mini-review of literatures on BCT-induced VSR in children.
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http://dx.doi.org/10.3389/fped.2020.00316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325629PMC
June 2020

Clinical Analysis of 25 COVID-19 Infections in Children.

Pediatr Infect Dis J 2020 07;39(7):e100-e103

Qianjiang Central Hospital, China.

Background: To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing.

Methods: All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiologic history of these patients were retrospectively collected and analyzed.

Results: The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 × 10/L and 2 cases (8%) less than 4 × 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 ± 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital.

Conclusions: The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.
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http://dx.doi.org/10.1097/INF.0000000000002740DOI Listing
July 2020

Bioinformatic identification of hub genes and key pathways in neutrophils of patients with acute respiratory distress syndrome.

Medicine (Baltimore) 2020 Apr;99(15):e19820

Department of Intensive Care Unit, Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders (Chongqing); China International Science and Technology Cooperation base of Child development and Critical Disorders; Children's Hospital of Chongqing Medical University.

Acute respiratory distress syndrome (ARDS) is characterized as a neutrophil-dominant disorder without effective pharmacological interventions. Knowledge of neutrophils in ARDS patients at the transcriptome level is still limited. We aimed to identify the hub genes and key pathways in neutrophils of patients with ARDS. The transcriptional profiles of neutrophils from ARDS patients and healthy volunteers were obtained from the GSE76293 dataset. The differentially expressed genes (DEGs) between ARDS and healthy samples were screened using the limma R package. Subsequently, functional and pathway enrichment analyses were performed based on the database for annotation, visualization, and integrated discovery (DAVID). The construction of a protein-protein interaction network was carried out using the search tool for the retrieval of interacting genes (STRING) database and the network was visualized by Cytoscape software. The Cytoscape plugins cytoHubba and MCODE were used to identify hub genes and significant modules. Finally, 136 upregulated genes and 95 downregulated genes were identified. Gene ontology analyses revealed MHC class II plays a major role in functional annotations. SLC11A1, ARG1, CHI3L1, HP, LCN2, and MMP8 were identified as hub genes, and they were all involved in the neutrophil degranulation pathway. The MAPK and neutrophil degranulation pathways in neutrophils were considered as key pathways in the pathogenesis of ARDS. This study improves our understanding of the biological characteristics of neutrophils and the mechanisms underlying ARDS, and key pathways and hub genes identified in this work can serve as targets for novel ARDS treatment strategies.
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http://dx.doi.org/10.1097/MD.0000000000019820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220668PMC
April 2020

Citrate-Based Self-Circulation Anticoagulation Protocol for Discontinuity of Continuous Renal Replacement Therapy.

Blood Purif 2020 4;49(4):394-399. Epub 2020 Feb 4.

Intensive Care Unit, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Children Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China.

Background/aims: Continuous renal replacement therapy (CRRT) has been used widely in the treatment of critically ill children for its continuity. However, sometimes we have to interrupt the continuity for necessary surgeries or blood transfusions. Our objective was to demonstrate a feasible self-circulation anticoagulation protocol based on citrate (CSAP) to address discontinuity during CRRT.

Methods: We conducted a prospective observational study of 57 pediatric patients undergoing 88 CRRT sessions that were receiving CSAP during the treatment discontinuity period by using an anticoagulation regimen containing 5 mL 4% sodium citrate in 50 mL of saline to maintain the continuity. We documented the reasons for CSAP and the total duration of the treatment. We assessed the in-line pressure recordings, blood routine examination, blood electrolytes, and blood gas analysis before, throughout, and after the period of CSAP.

Results: The average duration of CSAP was 118.5 ± 45.3 min. There was no significant increase in arterial pressures, venous pressures, and transmembrane pressures and no significant decreases in blood cell counts observed at the end of the CSAP, compared to the data recorded at the beginning of the CSAP. Compared to before the CSAP, there was no significant change in the ratio of total to ionized calcium, Na+, HCO3-, and pH value after CSAP.

Conclusions: CSAP might be a safe, effective, and easy approach for use during the treatment discontinuity of CRRT in children.
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http://dx.doi.org/10.1159/000504562DOI Listing
May 2021

Regional citrate anticoagulation with a substitute containing calcium for continuous hemofiltration in children.

Medicine (Baltimore) 2019 Oct;98(40):e17421

Intensive Care Unit, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Children Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, P.R. China.

Regional citrate anticoagulation (RCA) was recommended as the first treatment option for adults by the Kidney Disease Improving Global Outcomes Kidney Foundation in 2012, for the characteristic of sufficient anticoagulation in vitro, but almost no anticoagulation in vivo. Traditionally, the substitute for RCA is calcium-free. This study investigated a simplified protocol of RCA for continuous hemofiltration (CHF) in children using a commercially available substitute containing calcium.An analytical, observational, retrospective study assessed 59 pediatric patients with 106 sessions and 3580 hours of CHF. Values before and after treatment were compared, including Na, ionic calcium (iCa) and HCO3 concentrations, pH, and the ratio of total calcium to iCa (T/iCa). In addition, in vivo and in vitro iCa, treatment time, sessions with continuous transmembrane pressure >200 mm Hg, and sessions with clotting and bleeding were recorded.The average treatment time was 33.8 ± 10.1 hours. In vitro, 88.5% of iCa achieved the target (0.25-0.35 mmol/L), and in vivo, 95.4% of iCa achieved the target (1.0-1.35 mmol/L). There were 8 sessions with a transmembrane pressure >200 mm Hg and 3 sessions with filters clotted. After treatment, there were 2, 1, and 2 sessions with T/iCa > 2.5 (implying citrate accumulation), iCa < 0.9 mmol/L, and iCa > 1.35 mmol/L. No sodium disorders were recorded. There were fewer cases of acidemia and more cases of alkalemia after treatment compared to before.RCA-CHF with a substitute containing calcium and close monitoring could be a safe and effective treatment for children. In addition, the calcium test site in vitro and the adjustment of citrate should be given strict attention.
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http://dx.doi.org/10.1097/MD.0000000000017421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783142PMC
October 2019

The impact of admission serum lactate on children with moderate to severe traumatic brain injury.

PLoS One 2019 19;14(9):e0222591. Epub 2019 Sep 19.

Department of Critical Care Medicine, Children's Hospital, Chongqing Medical University, Chongqing, China.

Background: Lactate is used to evaluate the prognosis of adult patients with trauma. However, the prognostic significance of admission serum lactate in the setting of pediatric traumatic brain injury (TBI) is still unclear. We aim to investigate the impact of admission lactate on the outcome in children with moderate to severe TBI.

Methods: This retrospective study was conducted in a tertiary pediatric hospital between May 2012 and Jun 2018 included children with an admission Glasgow Coma Scale (GCS) of ≤13. Two hundred and thirteen patients were included in the analysis and 45 patients died in hospital.

Results: Admission lactate and glucose were significantly higher in non-survivors than those in survivors (P < 0.05). Admission lactate was positively correlated with admission glucose and negatively correlated with GCS in all patients (n = 213), subgroup of isolated TBI (n = 112) and subgroup of GCS ≤ 8 (n = 133), respectively. AUCs of lactate could significantly predict the mortality and were higher than those of glucose in all patients, subgroup of isolated TBI and subgroup of GCS ≤ 8, respectively. Multivariate logistic regression showed that admission lactate (Adjusted OR = 1.189; 95% CI: 1.002-1.410; P = 0.047) was independently associated with mortality, while admission glucose (Adjusted OR = 1.077; 95% CI: 0.978-1.186; P = 0.133) wasn't an independent risk factor of death. Elevated admission lactate (> 2 mmol/L) was associated with death, reduced 14-day ventilation-free days, 14-day ICU-free days and 28-day hospital-free days.

Conclusions: Admission serum lactate can effectively predict the mortality of children with moderate to severe TBI. Elevated admission lactate is associated with death, reduced ventilator-free, ICU-free, and hospital-free days. Admission serum lactate could be used as a prognostic biomarker of mortality in children with moderate to severe TBI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222591PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752785PMC
March 2020

Design and Fabrication of Heterogeneous, Deformable Substrates for the Mechanically Guided 3D Assembly.

ACS Appl Mater Interfaces 2019 Jan 8;11(3):3482-3492. Epub 2019 Jan 8.

Center for Flexible Electronics Technology; AML, Department of Engineering Mechanics , Tsinghua University , Beijing 100084 , P. R. China.

Development of schemes to form complex three-dimensional (3D) mesostructures in functional materials is a topic of broad interest, thanks to the ubiquitous applications across a diversity of technologies. Recently established schemes in the mechanically guided 3D assembly allow deterministic transformation of two-dimensional structures into sophisticated 3D architectures by controlled compressive buckling resulted from strain release of prestretched elastomer substrates. Existing studies mostly exploited supporting substrates made of homogeneous elastomeric material with uniform thickness, which produces relatively uniform strain field to drive the 3D assembly, thus posing limitations to the geometric diversity of resultant 3D mesostructures. To offer nonuniform strains with desired spatial distributions in the 3D assembly, this paper introduces a versatile set of concepts in the design of engineered substrates with heterogeneous integration of materials of different moduli. Such heterogeneous, deformable substrates can achieve large strain gradients and efficient strain isolation/magnification, which are difficult to realize using the previously reported strategies. Theoretical and experimental studies on the underlying mechanics offer a viable route to the design of heterogeneous, deformable substrates to yield favorable strain fields. A broad collection of 3D mesostructures and associated heterogeneous substrates is fabricated and demonstrated, including examples that resemble windmills, scorpions, and manta rays and those that have application potentials in tunable inductors and vibrational microsystems.
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http://dx.doi.org/10.1021/acsami.8b19187DOI Listing
January 2019

A TCR mechanotransduction signaling loop induces negative selection in the thymus.

Nat Immunol 2018 12 12;19(12):1379-1390. Epub 2018 Nov 12.

Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.

The T cell antigen receptor (TCR) expressed on thymocytes interacts with self-peptide major histocompatibility complex (pMHC) ligands to signal apoptosis or survival. Here, we found that negative-selection ligands induced thymocytes to exert forces on the TCR and the co-receptor CD8 and formed cooperative TCR-pMHC-CD8 trimolecular 'catch bonds', whereas positive-selection ligands induced less sustained thymocyte forces on TCR and CD8 and formed shorter-lived, independent TCR-pMHC and pMHC-CD8 bimolecular 'slip bonds'. Catch bonds were not intrinsic to either the TCR-pMHC or the pMHC-CD8 arm of the trans (cross-junctional) heterodimer but resulted from coupling of the extracellular pMHC-CD8 interaction to the intracellular interaction of CD8 with TCR-CD3 via associated kinases to form a cis (lateral) heterodimer capable of inside-out signaling. We suggest that the coupled trans-cis heterodimeric interactions form a mechanotransduction loop that reinforces negative-selection signaling that is distinct from positive-selection signaling in the thymus.
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http://dx.doi.org/10.1038/s41590-018-0259-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452639PMC
December 2018

A Genetically Encoded Protein Polymer for Uranyl Binding and Extraction Based on the SpyTag-SpyCatcher Chemistry.

ACS Synth Biol 2018 10 1;7(10):2331-2339. Epub 2018 Oct 1.

Center for Quantitative Biology and Peking-Tsinghua Joint Center for Life Sciences , Peking University , Beijing , 100871 , China.

A defining goal of synthetic biology is to develop biomaterials with superior performance and versatility. Here we introduce a purely genetically encoded and self-assembling biopolymer based on the SpyTag-SpyCatcher chemistry. We show the application of this polymer for highly efficient uranyl binding and extraction from aqueous solutions, by embedding two functional modules-the superuranyl binding protein and the monomeric streptavidin-to the polymer via genetic fusion. We further provide a modeling strategy for predicting the polymer's physical properties, and experimentally demonstrate the autosecretion of component monomers from bacterial cells. The potential of multifunctionalization, in conjunction with the genetic design and production pipeline, underscores the advantage of the SpyTag-SpyCatcher biopolymers for applications beyond trace metal enrichment and environmental remediation.
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http://dx.doi.org/10.1021/acssynbio.8b00223DOI Listing
October 2018

A Novel Fault Diagnosis Method of Rolling Bearings Based on AFEWT-KDEMI.

Entropy (Basel) 2018 Jun 11;20(6). Epub 2018 Jun 11.

School of Electrical Engineering, Zhengzhou University, Zhengzhou 50001, China.

According to the dynamic characteristics of the rolling bearing vibration signal and the distribution characteristics of its noise, a fault identification method based on the adaptive filtering empirical wavelet transform (AFEWT) and kernel density estimation mutual information (KDEMI) classifier is proposed. First, we use AFEWT to extract the feature of the rolling bearing vibration signal. The hypothesis test of the Gaussian distribution is carried out for the sub-modes that are obtained by the twice decomposition of EWT, and Gaussian noise is filtered out according to the test results. In this way, we can overcome the noise interference and avoid the mode selection problem when we extract the feature of the signal. Then we combine the advantages of kernel density estimation (KDE) and mutual information (MI) and put forward a KDEMI classifier. The mutual information of the probability density combining the unknown signal feature vector and the probability density of the known type signal is calculated. The type of the unknown signal is determined via the value of the mutual information, so as to achieve the purpose of fault identification of the rolling bearing. In order to verify the effectiveness of AFEWT in feature extraction, we extract signal features using three methods, AFEWT, EWT, and EMD, and then use the same classifier to identify fault signals. Experimental results show that the fault signal has the highest recognition rate by using AFEWT for feature extraction. At the same time, in order to verify the performance of the AFEWT-KDEMI method, we compare two classical fault signal identification methods, SVM and BP neural network, with the AFEWT-KDEMI method. Through experimental analysis, we found that the AFEWT-KDEMI method is more stable and effective.
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http://dx.doi.org/10.3390/e20060455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7512972PMC
June 2018

High-throughput light sheet tomography platform for automated fast imaging of whole mouse brain.

J Biophotonics 2018 09 8;11(9):e201800047. Epub 2018 Jun 8.

Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China.

Acquiring information of the neural structures in the whole-brain level is vital for systematically exploring mechanisms and principles of brain function and dysfunction. Most methods for whole brain imaging, while capable of capturing the complete morphology of neurons, usually involve complex sample preparation and several days of image acquisition. The whole process including optical clearing or resin embedding is time consuming for a quick survey of the distribution of specific neural circuits in the whole brain. Here, we develop a high-throughput light-sheet tomography platform (HLTP), which requires minimum sample preparation. This method does not require optical clearing for block face light sheet imaging. After fixation using paraformaldehyde, an aligned 3 dimensional image dataset of a whole mouse brain can be obtained within 5 hours at a voxel size of 1.30 × 1.30 × 0.92 μm. HLTP could be a very efficient tool for quick exploration and visualization of brain-wide distribution of specific neurons or neural circuits.
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http://dx.doi.org/10.1002/jbio.201800047DOI Listing
September 2018

Morphable 3D mesostructures and microelectronic devices by multistable buckling mechanics.

Nat Mater 2018 03 29;17(3):268-276. Epub 2018 Jan 29.

Departments of Materials Science and Engineering, Biomedical Engineering, Neurological Surgery, Chemistry, Mechanical Engineering, Electrical Engineering and Computer Science; Center for Bio-Integrated Electronics; and Simpson Querrey Institute for BioNanotechnology, Northwestern University, Evanston, IL, USA.

Three-dimensional (3D) structures capable of reversible transformations in their geometrical layouts have important applications across a broad range of areas. Most morphable 3D systems rely on concepts inspired by origami/kirigami or techniques of 3D printing with responsive materials. The development of schemes that can simultaneously apply across a wide range of size scales and with classes of advanced materials found in state-of-the-art microsystem technologies remains challenging. Here, we introduce a set of concepts for morphable 3D mesostructures in diverse materials and fully formed planar devices spanning length scales from micrometres to millimetres. The approaches rely on elastomer platforms deformed in different time sequences to elastically alter the 3D geometries of supported mesostructures via nonlinear mechanical buckling. Over 20 examples have been experimentally and theoretically investigated, including mesostructures that can be reshaped between different geometries as well as those that can morph into three or more distinct states. An adaptive radiofrequency circuit and a concealable electromagnetic device provide examples of functionally reconfigurable microelectronic devices.
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http://dx.doi.org/10.1038/s41563-017-0011-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877475PMC
March 2018

High axial resolution imaging system for large volume tissues using combination of inclined selective plane illumination and mechanical sectioning.

Biomed Opt Express 2017 Dec 27;8(12):5767-5775. Epub 2017 Nov 27.

Collaborative Innovation Center for Biomedical Engineering, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.

To resolve fine structures of biological systems like neurons, it is required to realize microscopic imaging with sufficient spatial resolution in three dimensional systems. With regular optical imaging systems, high lateral resolution is accessible while high axial resolution is hard to achieve in a large volume. We introduce an imaging system for high 3D resolution fluorescence imaging of large volume tissues. Selective plane illumination was adopted to provide high axial resolution. A scientific CMOS working in sub-array mode kept the imaging area in the sample surface, which restrained the adverse effect of aberrations caused by inclined illumination. Plastic embedding and precise mechanical sectioning extended the axial range and eliminated distortion during the whole imaging process. The combination of these techniques enabled 3D high resolution imaging of large tissues. Fluorescent bead imaging showed resolutions of 0.59 μm, 0.47μm, and 0.59 μm in the x, y, and z directions, respectively. Data acquired from the volume sample of brain tissue demonstrated the applicability of this imaging system. Imaging of different depths showed uniform performance where details could be recognized in either the near-soma area or terminal area, and fine structures of neurons could be seen in both the xy and xz sections.
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http://dx.doi.org/10.1364/BOE.8.005767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745118PMC
December 2017

Pediatric non-diabetic ketoacidosis: a case-series report.

BMC Pediatr 2017 Dec 19;17(1):209. Epub 2017 Dec 19.

Department of Endocrinology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Children Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Labortory of Pediatrics, Chongqing, 400014, People's Republic of China.

Background: This study is to explore the clinical characteristics, laboratory diagnosis, and treatment outcomes in pediatric patients with non-diabetic ketoacidosis.

Methods: Retrospective patient chart review was performed between March 2009 to March 2015. Cases were included if they met the selection criteria for non-diabetic ketoacidosis, which were: 1) Age ≤ 18 years; 2) urine ketone positive ++ or >8.0 mmol/L; 3) blood ketone >3.1 mmol/L; 4) acidosis (pH < 7.3) and/or HCO < 15 mmol/L; 5) random blood glucose level < 11.1 mmol/L. Patients who met the criteria 1, 4, 5, plus either 2 or 3, were defined as non-diabetic ketoacidosis and were included in the report.

Results: Five patients with 7 episodes of non-diabetic ketoacidosis were identified. They all presented with dehydration, poor appetite, and Kussmaul breathing. Patients treated with insulin plus glucose supplementation had a quicker recovery from acidosis, in comparison to those treated with bicarbonate infusion and continuous renal replacement therapy. Two patients treated with bicarbonate infusion developed transient coma and seizures during the treatment.

Conclusion: Despite normal or low blood glucose levels, patients with non-diabetic ketoacidosis should receive insulin administration with glucose supplementation to correct ketoacidosis.
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http://dx.doi.org/10.1186/s12887-017-0960-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735941PMC
December 2017

Pre-TCR ligand binding impacts thymocyte development before αβTCR expression.

Proc Natl Acad Sci U S A 2015 Jul 8;112(27):8373-8. Epub 2015 Jun 8.

Department of Medical Oncology, Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115; Department of Medicine, Harvard Medical School, Boston, MA 02115;

Adaptive cellular immunity requires accurate self- vs. nonself-discrimination to protect against infections and tumorous transformations while at the same time excluding autoimmunity. This vital capability is programmed in the thymus through selection of αβT-cell receptors (αβTCRs) recognizing peptides bound to MHC molecules (pMHC). Here, we show that the pre-TCR (preTCR), a pTα-β heterodimer appearing before αβTCR expression, directs a previously unappreciated initial phase of repertoire selection. Contrasting with the ligand-independent model of preTCR function, we reveal through NMR and bioforce-probe analyses that the β-subunit binds pMHC using Vβ complementarity-determining regions as well as an exposed hydrophobic Vβ patch characteristic of the preTCR. Force-regulated single bonds akin to those of αβTCRs but with more promiscuous ligand specificity trigger calcium flux. Thus, thymic development involves sequential β- and then, αβ-repertoire tuning, whereby preTCR interactions with self pMHC modulate early thymocyte expansion, with implications for β-selection, immunodominant peptide recognition, and germ line-encoded MHC interaction.
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http://dx.doi.org/10.1073/pnas.1504971112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500245PMC
July 2015

Microcapsules functionalized with neuraminidase can enter vascular endothelial cells in vitro.

J R Soc Interface 2014 Dec;11(101):20141027

Institute of Bioengineering, Queen Mary University of London, London E1 4NS, UK School of Engineering and Materials Science, Queen Mary University of London, London E1 4NS, UK

Microcapsules made of polyelectrolyte multilayers exhibit no or low toxicity, appropriate mechanical stability, variable controllable degradation and can incorporate remote release mechanisms triggered by various stimuli, making them well suited for targeted drug delivery to live cells. This study investigates interactions between microcapsules made of synthetic (i.e. polystyrenesulfonate sodium salt/polyallylamine hydrochloride) or natural (i.e. dextran sulfate/poly-L-arginine) polyelectrolyte and human umbilical vein endothelial cells with particular focus on the effect of the glycocalyx layer on the intake of microcapsules by endothelial cells. Neuraminidase cleaves N-acetyl neuraminic acid residues of glycoproteins and targets the sialic acid component of the glycocalyx on the cell membrane. Three-dimensional confocal images reveal that microcapsules, functionalized with neuraminidase, can be internalized by endothelial cells. Capsules without neuraminidase are blocked by the glycocalyx layer. Uptake of the microcapsules is most significant in the first 2 h. Following their internalization by endothelial cells, biodegradable DS/PArg capsules rupture by day 5; however, there is no obvious change in the shape and integrity of PSS/PAH capsules within the period of observation. Results from the study support our hypothesis that the glycocalyx functions as an endothelial barrier to cross-membrane movement of microcapsules. Neuraminidase-loaded microcapsules can enter endothelial cells by localized cleavage of glycocalyx components with minimum disruption of the glycocalyx layer and therefore have high potential to act as drug delivery vehicles to reach tissues beyond the endothelial barrier of blood vessels.
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http://dx.doi.org/10.1098/rsif.2014.1027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223926PMC
December 2014

Shear stress-induced redistribution of the glycocalyx on endothelial cells in vitro.

Authors:
Ke Bai Wen Wang

Biomech Model Mechanobiol 2014 Apr 29;13(2):303-11. Epub 2013 May 29.

Institute of Bioengineering, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.

The glycocalyx is the inner most layer of the endothelium that is in direct contact with the circulating blood. Shear stress affects its synthesis and reorganization. This study focuses on changes in the spatial distribution of the glycocalyx caused by shear stimulation and its recovery following the removal of the shear stress. Sialic acid components of the glycocalyx on human umbilical vain endothelial cells are observed using confocal microscopy. The percentage area of the cell membrane covered by the glycocalyx, as well as the average fluorescence intensity ratio between the apical and edge areas of the cell is used to assess the spatial distribution of the glycocalyx on the cell membrane. Our results show that following 24 h shear stimulation, the glycocalyx relocates near the edge of endothelial cells (i.e., cell-cell junction regions). Following the removal of the shear stress, the glycocalyx redistributes and gradually appears in the apical region of the cell membrane. This redistribution is faster in the early hours (<4 h) after shear stimulation than that in the later stage (e.g., between 8 and 24 h). We further investigate the recovery of the glycocalyx after its enzyme degradation under either static or shear flow conditions. Our results show that following 24 h recovery under shear flow, the glycocalyx reappears predominantly near the edge of endothelial cells. Static and shear flow conditions result in notable changes in the spatial recovery of the glycocalyx, but the difference is not statistically significant. We hypothesize that newly synthesized glycocalyx is not structurally well developed. Its weak interaction with flow results in less than significant redistribution, contrary to what has been observed for a well-developed glycocalyx layer.
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http://dx.doi.org/10.1007/s10237-013-0502-3DOI Listing
April 2014

Spatio-temporal development of the endothelial glycocalyx layer and its mechanical property in vitro.

Authors:
Ke Bai Wen Wang

J R Soc Interface 2012 Sep 14;9(74):2290-8. Epub 2012 Mar 14.

Institute for Bioengineering, Queen Mary University of London, London, UK.

The endothelial glycocalyx is a thin layer of polysaccharide matrix on the luminal surface of endothelial cells (ECs), which contains sulphated proteoglycans and glycoproteins. It is a mechanotransducer and functions as an amplifier of the shear stress on ECs. It controls the vessel permeability and mediates the blood-endothelium interaction. This study investigates the spatial distribution and temporal development of the glycocalyx on cultured ECs, and evaluates mechanical properties of the glycocalyx using atomic force microscopy (AFM) nano-indentation. The glycocalyx on human umbilical vein endothelial cells (HUVECs) is observed under a confocal microscope. Manipulation of the glycocalyx is achieved using heparanase or neuraminidase. The Young's modulus of the cell membrane is calculated from the force-distance curve during AFM indentation. Results show that the glycocalyx appears predominantly on the edge of cells in the early days in culture, e.g. up to day 5 after seeding. On day 7, the glycocalyx is also seen in the apical area of the cell membrane. The thickness of the glycocalyx is approximately 300 nm-1 μm. AFM indentation reveals the Young's modulus of the cell membrane decreases from day 3 (2.93 ± 1.16 kPa) to day 14 (0.35 ± 0.15 kPa) and remains unchanged to day 21 (0.33 ± 0.19 kPa). Significant difference in the Young's modulus is also seen between the apical (1.54 ± 0.58 kPa) and the edge (0.69 ± 0.55 kPa) of cells at day 7. By contrast, neuraminidase-treated cells (i.e. without the glycocalyx) have similar values between day 3 (3.18 ± 0.88 kPa), day 14 (2.12 ± 0.78 kPa) and day 21 (2.15 ± 0.48 kPa). The endothelial glycocalyx in vitro shows temporal development in the early days in culture. It covers predominantly the edge of cells initially and appears on the apical membrane of cells as time progresses. The Young's modulus of the glycocalyx is deduced from Young's moduli of cell membranes with and without the glycocalyx layer. Our results show the glycocalyx on cultured HUVECs has a Young's modulus of approximately 0.39 kPa.
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http://dx.doi.org/10.1098/rsif.2011.0901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405740PMC
September 2012

Effect of fluid shear stress on cardiomyogenic differentiation of rat bone marrow mesenchymal stem cells.

Arch Med Res 2010 Oct;41(7):497-505

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Yue Yuan Road no. 37, Beijing, China.

Background And Aims: Bone marrow mesenchymal stem cells (BMSCs) are a potential source of material for the construction of tissue-engineered cardiac grafts because of their potential to transdifferentiate into cardiomyocytes after chemical treatment or co-culture with cardiomyocytes. Recent evidence has shown that mechanical loads could regulate the BMSC differentiation into osteoblasts and endothelial cells through various signaling pathways. We investigated whether fluid shear stress (FSS), which is a mechanical load generated by fluid flow, can regulate rat BMSC (rBMSC) differentiation into cardiomyocytes.

Methods: rBMSCs were isolated from marrow of rat femur and tibia using density gradient centrifugation combined with adhesion method and identified with surface marker, proliferation character and differentiation potential in vitro. Cultured rBMSCs with or without 5-azacytidine (5-aza) treatment were exposed to laminar shear stress with a parallel plate-type device and analyzed by RT-PCR, immunocytochemistry, FACS and Western-blotting for the cardiomyogenic differentiation.

Results: Appropriate FSS treatment alone induced cardiomyogenic differentiation of rBMSCs, as confirmed by the expression of cardiomyocyte-related markers at both mRNA and protein levels. Furthermore, when rBMSC cultures were exposed to both FSS and 5-aza, expression levels of cardiomyocyte-related markers significantly increased to a degree suggestive of a synergistic interaction.

Conclusions: The results demonstrate that FSS is an important factor affecting cardiomyogenic differentiation of rBMSCs. This provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated cells.
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http://dx.doi.org/10.1016/j.arcmed.2010.10.002DOI Listing
October 2010

Endothelium oriented differentiation of bone marrow mesenchymal stem cells under chemical and mechanical stimulations.

J Biomech 2010 Apr 22;43(6):1176-81. Epub 2009 Dec 22.

School of Biological Science and Medical Engineering, Beijing University of Aeronautics and Astronautics, No 37 Xueyuan Road, Beijing 100191, China.

Bone marrow mesenchymal stem cells (MSCs) have multi-differentiation capability. Their endothelial cell (EC) oriented differentiation is the key to vasculogenesis, in which both mechanical and chemical stimulations play important roles. Most previous studies reported individual effects of VEGF or fluid shear stress (SS), when MSCs were subjected to shear stress of 10-15 dyn/cm(2) over 24hr. In this paper, we investigated responses of MSCs from young Sprague Dawley rats to shear stress, VEGF and the combination of the two stimuli. Our study showed that the combined stimulation of shear stress and VEGF resulted in more profound EC oriented differentiation of MSCs in comparison to any individual stimulation. Furthermore, we subjected MSCs to prolonged period of fluid shear stimulation, i.e. 48 hr rather than 24hr, and increased the magnitude of the shear stress from 10 dyn/cm(2) to 15, 20 and 25 dyn/cm(2). We found that without VEGF, the endothelium oriented differentiation of MSCs that was seen following 24hr of shear stimulation was largely abolished if we extended the shear stimulation to 48hr. A similar sharp decrease in MSC differentiation was also observed when the magnitude of the shear stress was increased from 10-15 dyn/cm(2) to 20-25 dyn/cm(2) in 24hr shear stimulation studies. However, with combined VEGF and fluid shear stimulation, most of the endothelial differentiation was retained following an extended period, i.e. at 48 hr, of shear stimulation. Our study demonstrates that chemical and mechanical stimulations work together in determining MSC differentiation dynamics.
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http://dx.doi.org/10.1016/j.jbiomech.2009.11.030DOI Listing
April 2010
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