Publications by authors named "Yubo Fan"

591 Publications

Human locomotion-control brain networks detected with independent component analysis.

J Integr Neurosci 2021 Sep;20(3):695-701

Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, 100083 Beijing, China.

Walking is a fundamental movement skill in humans. However, how the brain controls walking is not fully understood. In this functional magnetic resonance imaging study, the rhythmic, bilaterally alternating ankle movements were used as paradigm to simulate walking. In addition to the resting state, several motor tasks with different speeds were tested. Independent component analysis was performed to detect four components shared by all task conditions and the resting state. According to the distributed brain regions, these independent components were the cerebellum, primary auditory cortex-secondary somatosensory cortex-inferior parietal cortex-presupplementary motor area, medial primary sensorimotor cortex-supplementary area-premotor cortex-superior parietal lobule, and lateral primary somatosensory cortex-superior parietal lobule-dorsal premotor cortex networks, which coordinated limb movements, controlled the rhythm, differentiated speed, and performed a function as a basic actor network, respectively. These brain networks may be used as biomarkers of the neural control of normal human walking and as targets for neural modulation to improve different aspects of walking, such as rhythm and speed.
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http://dx.doi.org/10.31083/j.jin2003074DOI Listing
September 2021

Multiomics Analysis Reveals the Prognostic Non-tumor Cell Landscape in Glioblastoma Niches.

Front Genet 2021 16;12:741325. Epub 2021 Sep 16.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Engineering Medicine, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.

A comprehensive characterization of non-tumor cells in the niches of primary glioblastoma is not fully established yet. This study aims to present an overview of non-malignant cells in the complex microenvironment of glioblastoma with detailed characterizations of their prognostic effects. We curate 540 gene signatures covering a total of 64 non-tumor cell types. Cell type-specific expression patterns are interrogated by normalized enrichment score across four large gene expression profiling cohorts of glioblastoma with a total number of 967 cases. The glioblastoma multiforms (GBMs) in each cohort are hierarchically clustered into negative or positive immune response classes with significantly different overall survival. Our results show that astrocytes, macrophages, monocytes, NKTs, and MSC are risk factors, while CD8 T cells, CD8 naive T cells, and plasma cells are protective factors. Moreover, we find that the immune system and organogenesis are uniformly enriched in negative immune response clusters, in contrast to the enrichment of nervous system in positive immune response clusters. Mesenchymal differentiation is also observed in the negative immune response clusters. High enrichment status of macrophages in negative immune response clusters is independently validated by analyzing scRNA-seq data from eight high-grade gliomas, revealing that negative immune response samples comprised 46.63 to 55.12% of macrophages, whereas positive immune response samples comprised only 1.70 to 8.12%, with IHC staining of samples from six short-term and six long-term survivors of GBMs confirming the results.
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http://dx.doi.org/10.3389/fgene.2021.741325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481948PMC
September 2021

A biomimetic hierarchical small intestinal submucosa-chitosan sponge/chitosan hydrogel scaffold with a micro/nano structure for dural repair.

J Mater Chem B 2021 Sep 29;9(37):7821-7834. Epub 2021 Sep 29.

Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China.

The dura mater is an essential barrier to protect the brain tissue and the dural defects caused by accidents can lead to serious complications. Various materials have been applied to dural repair, but it remains a challenge to perfectly match the structure and properties of the natural dura mater. Small intestinal submucosa has been developed for dural repair because of its excellent biocompatibility and biological activity, but its application is tremendously limited by the rapid degradation rate. Chitosan has also been broadly investigated in tissue repair, but the traditional chitosan hydrogels exhibit poor mechanical properties. A nanofiber chitosan hydrogel can be constructed based on an alkaline solvent, which is equipped with surprisingly high strength. Therefore, based on the bilayer structure of the natural dura mater, a biomimetic hierarchical small intestinal submucosa-chitosan sponge/chitosan hydrogel scaffold with a micro/nano structure was fabricated, which possessed a microporous structure in the upper sponge and a nanofiber structure in the lower hydrogel. The degradation rate was remarkably reduced compared with that of the small intestinal submucosa in the enzymatic degradation experiment . Meanwhile, the chitosan nanofibers brought high mechanical strength to the bilayer scaffold. Moreover, the hierarchical micro/nano structure and the active factors in the small intestinal submucosa have a fantastic effect on promoting the proliferation of fibroblasts and vascular endothelial cells. The bilayer scaffold showed good histocompatibility in the experiment of subcutaneous implantation in rats. Thus, the biomimetic hierarchical small intestinal submucosa-chitosan sponge/chitosan hydrogel scaffold with micro/nano structure simulates the structure of the natural dura mater and possesses properties with excellent performance, which has high practical value for dural repair.
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http://dx.doi.org/10.1039/d1tb00948fDOI Listing
September 2021

The differences between surface degradation and bulk degradation of FEM on the prediction of the degradation time for poly (lactic-co-glycolic acid) stent.

Comput Methods Biomech Biomed Engin 2021 Sep 28:1-8. Epub 2021 Sep 28.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.

The degradation time is a crucial factor in evaluating the performance of poly (lactic-co-glycolic acid) (PLGA) stents. Bulk degradation mode was commonly used to analyze the stent degradation behavior by finite element approach. However, the PLGA stents may present surface degradation more than bulk degradation under certain conditions, which will greatly affect the degradation time after implantation. In this study, the degradation processes of the poly (lactic-co-glycolic acid) stent were reproduced utilizing finite element analysis. Both bulk degradation and surface degradation modes were considered. The correlation between tensile stress and degradation rate was investigated. The degradation time was analyzed selectively. The stress distribution, fracture, and mass loss were also compared between bulk degradation mode and surface degradation mode. The simulation results showed that, in both evolution modes, the degradation began at the 'peak-valley' region and fracture occurred at the cross of links and rings. Additionally, high levels of Von-Mises stress were observed in these two regions. Compared with bulk degradation, the fracture time of the stent was delayed by 63% in the surface degradation mode. In conclusion, the mass loss rate and scaffolding period showed great differences between surface degradation and bulk degradation. Based on this study, it is suggested that bulk degradation mode is not applicable to the case of inadequate water uptake mode, such as the tracheal stent degradation process. More experimental research should be carried out to accurately predict the scaffolding period after implantation. The mechanical properties of the fracture zone should be strengthened.
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http://dx.doi.org/10.1080/10255842.2021.1931846DOI Listing
September 2021

A micropore array-based solid lift-off method for highly efficient and controllable cell alignment and spreading.

Microsyst Nanoeng 2020 7;6:86. Epub 2020 Sep 7.

Institute of Microelectronics, Peking University, 100871 Beijing, China.

Interpretation of cell-cell and cell-microenvironment interactions is critical for both advancing knowledge of basic biology and promoting applications of regenerative medicine. Cell patterning has been widely investigated in previous studies. However, the reported methods cannot simultaneously realize precise control of cell alignment and adhesion/spreading with a high efficiency at a high throughput. Here, a novel solid lift-off method with a micropore array as a shadow mask was proposed. Efficient and precise control of cell alignment and adhesion/spreading are simultaneously achieved via an ingeniously designed shadow mask, which contains large micropores (capture pores) in central areas and small micropores (spreading pores) in surrounding areas contributing to capture/alignment and adhesion/spreading control, respectively. The solid lift-off functions as follows: (1) protein micropattern generates through both the capture and spreading pores, (2) cell capture/alignment control is realized through the capture pores, and (3) cell adhesion/spreading is controlled through previously generated protein micropatterns after lift-off of the shadow mask. High-throughput (2.4-3.2 × 10 cells/cm) cell alignments were achieved with high efficiencies (86.2 ± 3.2%, 56.7 ± 9.4% and 51.1 ± 4.0% for single-cell, double-cell, and triple-cell alignments, respectively). Precise control of cell spreading and applications for regulating cell skeletons and cell-cell junctions were investigated and verified using murine skeletal muscle myoblasts. To the best of our knowledge, this is the first report to demonstrate highly efficient and controllable multicell alignment and adhesion/spreading simultaneously via a simple solid lift-off operation. This study successfully fills a gap in literatures and promotes the effective and reproducible application of cell patterning in the fields of both basic mechanism studies and applied medicine.
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http://dx.doi.org/10.1038/s41378-020-00191-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433473PMC
September 2020

Vascular transplantation with dual-biofunctional ePTFE vascular grafts in a porcine model.

J Mater Chem B 2021 Sep 22;9(36):7409-7422. Epub 2021 Sep 22.

Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, P. R. China.

Cardiovascular disease (CVD) poses serious health concerns worldwide. The lack of transplantable vascular grafts is an unmet clinical need in the surgical treatment of CVD. Although expanded polytetrafluoroethylene (ePTFE) vascular grafts have been used in clinical practice, a low long-term patency rate in small-diameter transplantation application is still the biggest challenge. Thus, surface modification of ePTFE is sought after. In this study, polydopamine (PDA) was used to improve the hydrophilia and provide immobilization sites in ePTFE. Bivalirudin (BVLD), a direct thrombin inhibitor, was used to enhance the anti-thrombotic activity of ePTFE. The peptides derived from extracellular matrix proteins were used to elevate the bioactivity of ePTFE. The morphology, chemical composition, peptide modified strength, wettability, and hemocompatibility of modified ePTFE vascular grafts were investigated. Then, an endothelial cell proliferation assay was used to evaluate the best co-modification strategy of the ePTFE vascular graft . Since a large animal could relatively better mimic human physiology, we chose a porcine carotid artery replacement model in the current study. The results showed that the BVLD/REDV co-modified ePTFE vascular grafts had a satisfactory patency rate (66.7%) and a higher endothelial cell coverage ratio (70%) at 12 weeks after implantation. This may offer an opportunity to produce a multi-biofunctional ePTFE vascular graft, thereby yielding a potent product to meet the clinical needs.
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http://dx.doi.org/10.1039/d1tb01398jDOI Listing
September 2021

Effect of intermittent pneumatic compression with different inflation pressures on the distal microvascular responses of the foot in people with type 2 diabetes mellitus.

Int Wound J 2021 Sep 15. Epub 2021 Sep 15.

Key Laboratory for Biomechanics and Mechanobiology of Chinese Education Ministry, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.

Intermittent pneumatic compression (IPC) is commonly used to improve peripheral circulation of the lower extremity. However, its therapeutic dosage for people with type 2 diabetes mellitus (DM) at risk for ulcers is not well established. This study explored the effect of IPC with different inflation pressures on the distal microvascular responses of the foot in people with type 2 DM. Twenty-four subjects with and without DM were recruited. Three IPC protocols with inflation pressures of 60, 90, and 120 mmHg were applied to the foot. The foot skin blood flow (SBF) responses were measured by laser Doppler flowmetry during and after IPC interventions. Results show that all three IPC interventions significantly increased foot SBF of IPC stage in healthy subjects, but only 90 and 120 mmHg IPC significantly improved SBF in diabetic subjects. IPC with 90 and 120 mmHg showed a greater effect than 60 mmHg in both groups, but 120 mmHg IPC was more effective for diabetic subjects. This study demonstrates that 90 and 120 mmHg are effective dosages of IPC for improving blood flow in healthy people, and 120 mmHg IPC may be more suitable for people with type 2 DM.
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http://dx.doi.org/10.1111/iwj.13693DOI Listing
September 2021

Label-free visible colorimetric biosensor for detection of multiple pathogenic bacteria based on engineered polydiacetylene liposomes.

J Colloid Interface Sci 2021 Aug 13;606(Pt 2):1684-1694. Epub 2021 Aug 13.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China; Beijing Advanced Innovation Centre for Biomedical Engineering, Beihang University, Beijing, 102402, China. Electronic address:

Bacterial infections are considered as a critical healthcare concern worldwide. Timely infection detection is crucial to effective antibiotic administration which can reduce the severity of infection and the occurrence of antibiotic resistance. We have developed label-free polydiacetylene (PDA) liposome-based colorimetric biosensor to detect and identify bacterial cultures at the genus and species level with naked eyes by simple color change. We found that among the various liposomal systems, moderate concentration of PDA, phospholipids and cholesterol in liposome assemblies can greatly influence the sensitivity to different bacteria, exhibiting unique chromatic properties of each bacterial strain. The strikingly different chromatic color change was due to the various mechanisms of interactions between bacterial toxins and biomimetic lipid bilayers. Furthermore, increase of cholesterol in liposome assemblies greatly enhanced the sensitivity of bacterial strains related to membrane destruction mediated by pore-formation mechanism such as S. aureus and E.coli, whereas the detection of the two bacterial strains was believed to rely on the specific recognition elements coupled with PDA moiety. As a proof of concept, a colorimetric finger-print array for distinguishing 6 bacterial species was studied. Particularly, the proposed bacterial detection platform is achieved through the interaction between bacterially secreted toxins and liposome bilayers instead of specific recognition of receptors-ligands. The results of both response time and sensitivity of label-free-liposome-based system show superior to previous reports on chromatic bacterial detection assays. By combing these results, the label-free-liposome-based colorimetric sensing platform shows great importance as a bacterial-sensing and discrimination platform.
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http://dx.doi.org/10.1016/j.jcis.2021.07.155DOI Listing
August 2021

A surface-eroding poly(1,3-trimethylene carbonate) coating for magnesium based cardiovascular stents with stable drug release and improved corrosion resistance.

Bioact Mater 2022 Jan 6;7:144-153. Epub 2021 Jun 6.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, 10083, China.

Magnesium alloys with integration of degradability and good mechanical performance are desired for vascular stent application. Drug-eluting coatings may optimize the corrosion profiles of magnesium substrate and reduce the incidence of restenosis simultaneously. In this paper, poly (trimethylene carbonate) (PTMC) with different molecular weight (50,000 g/mol named as PTMC5 and 350,000 g/mol named as PTMC35) was applied as drug-eluting coatings on magnesium alloys. A conventional antiproliferative drug, paclitaxel (PTX), was incorporated in the PTMC coating. The adhesive strength, corrosion behavior, drug release and biocompatibility were investigated. Compared with the PLGA control group, PTMC coating was uniform and gradually degraded from surface to inside, which could provide long-term protection for the magnesium substrate. PTMC35 coated samples exhibited much slower corrosion rate 0.05 μA/cm in comparison with 0.11 μA/cm and 0.13 μA/cm for PLGA and PTMC5 coated counterparts. In addition, PTMC35 coating showed more stable and sustained drug release ability and effectively inhibited the proliferation of human umbilical vein vascular smooth muscle cells. Hemocompatibility test indicated that few platelets were adhered on PTMC5 and PTMC35 coatings. PTMC35 coating, exhibiting surface erosion behavior, stable drug release and good biocompatibility, could be a good candidate as a drug-eluting coating for magnesium-based stent.
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http://dx.doi.org/10.1016/j.bioactmat.2021.05.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379472PMC
January 2022

Preparation of Magnetic-Luminescent Bifunctional Rapeseed Pod-Like Drug Delivery System for Sequential Release of Dual Drugs.

Pharmaceutics 2021 Jul 22;13(8). Epub 2021 Jul 22.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.

Drug delivery systems (DDSs) limited to a single function or single-drug loading are struggling to meet the requirements of clinical medical applications. It is of great significance to fabricate DDSs with multiple functions such as magnetic targeting or fluorescent labeling, as well as with multiple-drug loading for enhancing drug efficacy and accelerating actions. In this study, inspired by the dual-chamber structure of rapeseed pods, biomimetic magnetic-luminescent bifunctional drug delivery carriers (DDCs) of 1.9 ± 0.3 μm diameter and 19.6 ± 4.4 μm length for dual drug release were fabricated via double-needle electrospraying. Morphological images showed that the rapeseed pod-like DDCs had a rod-like morphology and Janus dual-chamber structure. Magnetic nanoparticles and luminescent materials were elaborately designed to be dispersed in two different chambers to endow the DDCs with excellent magnetic and luminescent properties. Synchronously, the Janus structure of DDCs promoted the luminescent intensity by at least threefold compared to single-chamber DDCs. The results of the hemolysis experiment and cytotoxicity assay suggested the great blood and cell compatibilities of DDCs. Further inspired by the core-shell structure of rapeseeds containing oil wrapped in rapeseed pods, DDCs were fabricated to carry benzimidazole molecules and [email protected] nanoparticles in different chambers, realizing the sequential release of benzimidazole within 12 h and of doxorubicin from day 3 to day 18. These rapeseed pod-like DDSs with excellent magnetic and luminescent properties and sequential release of dual drugs have potential for biomedical applications such as targeted drug delivery, bioimaging, and sustained treatment of diseases.
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http://dx.doi.org/10.3390/pharmaceutics13081116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398606PMC
July 2021

A Bioresorbable Dynamic Pressure Sensor for Cardiovascular Postoperative Care.

Adv Mater 2021 Oct 8;33(39):e2102302. Epub 2021 Aug 8.

CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 100083, China.

Bioresorbable electronics that can be absorbed and become part of the organism after their service life are a new trend to avoid secondary invasive surgery. However, the material limitation is a significant challenge. There are fewer biodegradable materials with pressure-sensitive properties. Here, a pressure sensor based on the triboelectric effect between bioabsorbable materials is reported. This effect is available in almost all materials. The bioresorbable triboelectric sensor (BTS) can directly convert ambient pressure changes into electrical signals. This device successfully identifies abnormal vascular occlusion events in large animals (dogs). The service life of the BTS reaches 5 days with a high service efficiency (5.95%). The BTS offers excellent sensitivity (11 mV mmHg ), linearity (R  = 0.993), and good durability (450 000 cycles). The antibacterial bioresorbable materials (poly(lactic acid)-(chitosan 4%)) for the BTS can achieve 99% sterilization. Triboelectric devices are expected to be applied in postoperative care as bioresorbable electronics.
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http://dx.doi.org/10.1002/adma.202102302DOI Listing
October 2021

Biomechanics of adjacent segment after three-level lumbar fusion, hybrid single-level semi-rigid fixation with two-level lumbar fusion.

Comput Methods Biomech Biomed Engin 2021 Aug 2:1-9. Epub 2021 Aug 2.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, P. R. China.

Multi-level spinal fusion has been reported in some cases to lead to adjacent segment disease (ASD) and proximal junctional kyphosis (PJK). The purpose of this study was to demonstrate a polyether-ether-ketone (PEEK) rod fixation system implanted adjacent to a two-level lumbar fusion would have a lower risk of PJK than three-level lumbar fusion, which was investigated by comparing the biomechanical effects on the adjacent level after surgical procedures. Four finite element (FE) models of the lumbar-sacral spine (intact model (INT), L4-S1 fusion model (L4-S1 FUS), L3-S1 fusion model (L3-S1 FUS), and single-level PEEK rod semi-rigid fixation adjacent to L4-S1 fusion model (FUSPRF)) were established. Displacement-controlled finite element (FE) analysis was used during the simulation. Compared with the two-level fusion model (L4-S1 FUS), both three-level implanted models (L3-S1 FUS and FUSPRF) showed an increase intersegmental rotation angle, and maximum von-Mises stress on the disc annulus. The results also showed that the intersegmental rotation, stress on the disc annulus and maximum stress on the rod were lower in the FUSPRF model than the L3-S1 FUS model. Though the maximum screw stress was higher in the FUSPRF model than the L3-S1 FUS model under all moments except for torsion, the maximum screw stress in the two models were far below the yield strength of titanium alloy. As the parameters above have been indicated as risk factors for PJK, it can be concluded that hybrid single-level PEEK rod semi-rigid fixation and two-level lumbar fusion have a lower risk of PJK than three-level lumbar fusion.
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http://dx.doi.org/10.1080/10255842.2021.1959557DOI Listing
August 2021

Stereotactic technology for 3D bioprinting: from the perspective of robot mechanism.

Biofabrication 2021 08 13;13(4). Epub 2021 Aug 13.

Key Laboratory for Biomechanics and Mechanobiology of Chinese Education Ministry, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, People's Republic of China.

Three-dimensional (3D) bioprinting has been widely applied in the field of biomedical engineering because of its rapidly individualized fabrication and precisely geometric designability. The emerging demand for bioprinted tissues/organs with bio-inspired anisotropic property is stimulating new bioprinting strategies. Stereotactic bioprinting is regarded as a preferable strategy for this purpose, which can perform bioprinting at the target position from any desired orientation in 3D space. In this work, based on the motion characteristics analysis of the stacked bioprinting technologies, mechanism configurations and path planning methods for robotic stereotactic bioprinting were investigated and a prototype system based on the double parallelogram mechanism was introduced in detail. Moreover, the influence of the time dimension on stereotactic bioprinting was discussed. Finally, technical challenges and future trends of stereotactic bioprinting within the field of biomedical engineering were summarized.
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http://dx.doi.org/10.1088/1758-5090/ac1846DOI Listing
August 2021

An Index From Transcranial Doppler Signals for Evaluation of Stroke Rehabilitation Using External Counterpulsation.

IEEE Trans Neural Syst Rehabil Eng 2021 29;29:1487-1493. Epub 2021 Jul 29.

This study aimed to develop a sensitive index from transcranial Doppler (TCD) signals for quantitatively evaluating the effects of long-term external counterpulsation (ECP) treatment on stroke rehabilitation. We recruited 27 patients with unilateral ischemic stroke and a good acoustic window within 7 days of stroke onset. 15 of them received 35 daily 1-hour ECP treatment (ECP group) and the others underwent conventional therapy without ECP treatment (No-ECP group). We monitored blood flow in middle cerebral arteries on both sides by TCD, and analyzed them via discrete wavelet analysis method. The overall changes of National Institutes of Health Stroke Scale (NIHSS) and Barthel Index were assessed. A 'big-wave' phenomenon was observed in TCD signals of patients in ECP group after 35 days' treatment, with significant fluctuation in frequency interval from 0.010 to 0.034 Hz as main feature. A new index, which was denoted as I , was derived from this phenomenon. The I was significantly higher for patients in ECP group than that for patients in No-ECP group after 35-days' treatment ( 0.01). And the I was positively correlated with NIHSS change in ECP group ( ). The new index could be used as an effective indicator for evaluating enhancement of endothelial metabolism and neurogenic activity after long-term ECP treatment.
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http://dx.doi.org/10.1109/TNSRE.2021.3099203DOI Listing
August 2021

neoDL: a novel neoantigen intrinsic feature-based deep learning model identifies IDH wild-type glioblastomas with the longest survival.

BMC Bioinformatics 2021 Jul 23;22(1):382. Epub 2021 Jul 23.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Engineering Medicine, School of Biological Science and Medical Engineering, Beihang University, No.37 Xueyuan Road, Haidian District, Beijing, 100083, People's Republic of China.

Background: Neoantigen based personalized immune therapies achieve promising results in melanoma and lung cancer, but few neoantigen based models perform well in IDH wild-type GBM, and the association between neoantigen intrinsic features and prognosis remain unclear in IDH wild-type GBM. We presented a novel neoantigen intrinsic feature-based deep learning model (neoDL) to stratify IDH wild-type GBMs into subgroups with different survivals.

Results: We first derived intrinsic features for each neoantigen associated with survival, followed by applying neoDL in TCGA data cohort(AUC = 0.988, p value < 0.0001). Leave one out cross validation (LOOCV) in TCGA demonstrated that neoDL successfully classified IDH wild-type GBMs into different prognostic subgroups, which was further validated in an independent data cohort from Asian population. Long-term survival IDH wild-type GBMs identified by neoDL were found characterized by 12 protective neoantigen intrinsic features and enriched in development and cell cycle.

Conclusions: The model can be therapeutically exploited to identify IDH wild-type GBM with good prognosis who will most likely benefit from neoantigen based personalized immunetherapy. Furthermore, the prognostic intrinsic features of the neoantigens inferred from this study can be used for identifying neoantigens with high potentials of immunogenicity.
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http://dx.doi.org/10.1186/s12859-021-04301-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299600PMC
July 2021

Hydrogel Loaded with VEGF/TFEB-Engineered Extracellular Vesicles for Rescuing Critical Limb Ischemia by a Dual-Pathway Activation Strategy.

Adv Healthc Mater 2021 Jul 23:e2100334. Epub 2021 Jul 23.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, P. R. China.

Critical limb ischemia (CLI) is the most severe clinical manifestation of peripheral arterial disease, which causes many amputations and deaths. Conventional treatment strategies for CLI (e.g., stent implantation and vascular surgery) bring surgical risk, which are not suitable for each patient. Extracellular vesicles (EVs) can be a potential solution for CLI. Herein, vascular endothelial growth factor (VEGF; i.e., a crucial molecule related to angiogenesis) and transcription factor EB (TFEB; i.e., a pivotal regulator of autophagy) are chosen as the target gene to improve the bioactivity of EVs derived from endothelial cells. The VEGF/TFEB-engineered EVs (Engineered-EVs) are fabricated by genetically engineering the parent cells, and their versatile functions are confirmed using three cell models (human umbilical vein endothelial cells, myoblast, and monocytes). Injectable thermal-responsive hydrogel are then combined with Engineered-EVs to combat CLI. These results reveal that the hydrogel can enhance the stability of Engineered-EVs in vivo and release EVs at different temperatures. Moreover, the results of animal studies indicate that Engineered-EV/Hydrogel can significantly improve neovascularization, attenuate muscle injury, and recover limb function after CLI. Finally, mechanistic studies shed light on the therapeutic effect of Engineered-EV/Hydrogel due to the activated VEGF/VEGFR pathway and autophagy-lysosomal pathway.
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http://dx.doi.org/10.1002/adhm.202100334DOI Listing
July 2021

Macrophage Polarization in Response to Biomaterials for Vascularization.

Ann Biomed Eng 2021 Sep 19;49(9):1992-2005. Epub 2021 Jul 19.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, People's Republic of China.

Vascularization of tissue engineering constructs is an urgent need for delivering oxygen and nutrients and promoting tissue remodeling. As we all know, almost all implanted biomaterials elicit immune responses. Interestingly, the immunomodulatory biomaterials can utilize the inherent regenerative capability of endogenous cells and stem cells recruited by the activated immune cells to facilitate anagenesis and tissue remodeling. Macrophages, as almost ones of the first responses upon the implantation of biomaterials, play a vital role in guiding vascular formation and tissue remodeling. The polarization of macrophages can be influenced by the physical and chemical properties of biomaterials and thus they display diverse function states. Here, this review focus on the macrophage polarization in response to biomaterials and the interactions between them. It also summarizes the current strategies to promote vascularization of tissue engineering constructs through macrophage responses.
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http://dx.doi.org/10.1007/s10439-021-02832-wDOI Listing
September 2021

Two-dimensional dynamic walking stability of elderly females with a history of falls.

Med Biol Eng Comput 2021 Aug 15;59(7-8):1575-1583. Epub 2021 Jul 15.

Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Haidian District, No. 37, Xueyuan Road, Beijing, 100191, China.

Injuries related with falls are a major health risk for the elderly. Accurate evaluation of the dynamic walking stability of elderly people is the key to fall prevention. A two-dimensional (2-D) model is proposed in this study given that the custom method is mainly focused on the dynamic walking stability along the antero-posterior axis. An inverted pendulum model was utilised to calculate the region of stability at toe-off, and stability conditions were evaluated first along the antero-posterior and medio-lateral axes. The analysis was then extended to the 2-D plane. In the 2-D case, the region of stability was determined based on the use of the information of the envelope of the foot. Twenty-four female participants, categorised as healthy young, healthy elderly, and elderly with a history of falls, were examined. Significant differences among the three groups were demonstrated with the 2-D analysis method, but not in the antero-posterior or medio-lateral analyses. The centre-of-masses of elderly fallers were significantly closer to the foot-supporting boundary compared with that of healthy young and elderly adults at toe-off. A 2-D analysis method using the envelope-of-foot could evaluate the dynamic stability of elderly females based on a more accurate scale.
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http://dx.doi.org/10.1007/s11517-021-02410-1DOI Listing
August 2021

Investigation of failure modes of explanted porcine valves in the mitral position.

J Thorac Dis 2021 May;13(5):2858-2866

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.

Background: Porcine valves are used for mitral valve replacement, but the limited long-term durability has restricted the application in younger patients. Degenerated porcine mitral valves were explanted to analyze the failure modes and damage characteristics.

Methods: Twelve porcine valves were explanted via secondary mitral valve replacement surgery. Microcomputed tomography scanning, morphological and pathological examinations were performed to classify the cusp tears, calcification, and pannus formation. The causes of valve deterioration were subsequently analyzed.

Results: The mean age at first implantation was 45.42±19.58 years (range, 11-64 years). The mean duration of implantation was 9.39±4.14 years (range, 4.25-18.75 years). The indications for first surgery were rheumatic heart disease in 8 patients (66.67%), infective endocarditis in 2 patients (16.67%), degenerative valvular disease in one patient (8.33%), and congenital heart disease in one patient (8.33%). Type I cusp tears and commissural dehiscence that occurred near the stent post position were found in 6 (50%) and 5 (41.67%) valves, respectively. Calcification was detected in 6 (50%) cases, and pannus was found in most valves (91.67%).

Conclusions: Leaflet damage occurred near the stent posts area was the main failure mode of porcine mitral valves in this study. Patients who undergo the first surgery at younger age, the higher prevalence rate of rheumatic heart disease, the structure of bioprosthetic porcine valve, and left ventricular stresses could be considered as the main factors causing valve deterioration.
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http://dx.doi.org/10.21037/jtd-20-3578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182507PMC
May 2021

degradation, biocompatibility and antibacterial properties of pure zinc: assessing the potential of Zn as a guided bone regeneration membrane.

J Mater Chem B 2021 06;9(25):5114-5127

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.

Membrane exposure is a common complication after the guided bone regeneration (GBR) procedure and has a detrimental influence on the bone regeneration outcomes, while the commercially available GBR membranes show limited exposure tolerance. Recently, zinc (Zn) has been suggested as a promising material to be used as a barrier membrane in GBR therapy for bone augmentation. In this study, the degradation behavior in artificial saliva solution, cytotoxicity and antibacterial activity of pure Zn were investigated to explore its degradation and associated biocompatibility in the case of premature membrane exposure. The results indicated that the degradation rate of Zn in artificial saliva solution was about 31.42 μm year-1 after 28 days of immersion. The corrosion products on the Zn surface were mainly composed of Zn3(PO4)2, Ca3(PO4)2, CaHPO4, Zn5(CO3)2(OH)6 and ZnO. Besides, Zn presented an acceptable in vitro HGF cytocompatibility and a high antibacterial activity against Porphyromonas gingivalis. The preliminary results demonstrate that pure Zn exhibits appropriate degradation behavior, adequate cell compatibility and favorable antibacterial properties in the oral environment and is thus believed to sustain profitable function when membrane exposure occurs. The results provided new insights for understanding the exposure tolerance of Zn based membranes and are beneficial to their clinical applications.
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http://dx.doi.org/10.1039/d1tb00596kDOI Listing
June 2021

The characteristics of distal tears affect false lumen thrombosis rate after thoracic endovascular aortic repair for acute type B dissection.

Interact Cardiovasc Thorac Surg 2021 Jun 14. Epub 2021 Jun 14.

Beijing Advanced Innovation Center of Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.

Objectives: A low false lumen thrombosis rate (FLTR) is common in patients with type B aortic dissection after they have undergone thoracic endovascular aortic repair, which indicates a poor long-term prognosis. This study aimed to establish a quantitative linear regression model to predict false lumen (FL) thrombosis accurately using morphological parameters.

Methods: In this retrospective study, we included 59 patients diagnosed with acute type B aortic dissection between 2014 and 2017. Morphological parameters were measured. Univariable and multivariable linear regression analyses were performed, and a linear regression model relating FLTR with the number of re-entry tears was proposed. Ten patients were further chosen to validate the linear relationship, and idealized aortic dissection models were adopted for haemodynamic analysis.

Results: Only the total area and number of re-entry tears were negatively correlated with FL thrombosis (P < 0.001). Moreover, based on the univariable regression, the number of re-entry tears played a more crucial role in FLTR (R2 = 0.509 vs R2 = 0.298), and the linear relationship model was created as follows: thrombosis rate (%) = -11.25 × distal tear number + 105.24. This model was perfectly matched in 10 patients (concordance correlation coefficient = 0.880, P = 0.947). Moreover, when the total area of re-entry tears was constant, the net blood flow increased rapidly with an increase in the tear count.

Conclusions: The number of re-entry tears could be a crucial related factor of FL thrombosis; the larger the number of re-entry tears is, the lower the possibility of thrombosis is.
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http://dx.doi.org/10.1093/icvts/ivab166DOI Listing
June 2021

A biomimetic triple-layered biocomposite with effective multifunction for dura repair.

Acta Biomater 2021 08 10;130:248-267. Epub 2021 Jun 10.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. Electronic address:

Dura mater defect and subsequent cerebrospinal fluid (CSF) leakage usually appear in trauma or neurosurgical procedures and are followed by a series of serious complications and even death. The use of a qualified dura mater substitute with multifunction of leakage blockade, adhesion prevention, and dura reconstruction is one of the promising treatment methods. However, even though some products have been used in the clinic, none of the substitutes achieved the required multifunction. In this study, we aimed to design and fabricate a dura repair composite with the ideal multifunction. By biomimicking the structure and component of natural dura, we applied poly(L-lactic acid) (PLLA), chitosan (CS), gelatin, and acellular small intestinal submucosa (SIS) powders to successfully prepare a triple-layered composite. Then, a series of specific devices and techniques were developed to investigate the performance. The results revealed that satisfactory structural stability could be realized under good synergistic interactions among the components. In addition, all the findings suggested that the bionic triple-layered composite showed satisfactory multifunction of leakage blockade, adhesion prevention, antibacterial property, and dura reconstruction potential, and thus, it might be a promising candidate for dura repair. STATEMENT OF SIGNIFICANCE: Developing qualified dura mater substitutes with multifunction of leakage blockade, adhesion prevention, and dura reconstruction is crucial for treating dura mater defect and subsequent cerebrospinal fluid (CSF) leakage that appear in trauma or neurosurgical procedures. In this study, we designed and fabricated a triple-layered dura repair biocomposite with satisfactory structural stability and desired multifunction based on biomimicking of the structure and component of natural dura. Moreover, a series of specific devices and techniques were developed to investigate the relevant performance. Overall, the developed hydrogel electrospinning system exhibited excellent advantages in achieving multifunction and could be applied widely in the future to achieve multifunctional tissue repair materials.
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http://dx.doi.org/10.1016/j.actbio.2021.06.003DOI Listing
August 2021

A Review: Optimization for Poly(glycerol sebacate) and Fabrication Techniques for Its Centered Scaffolds.

Macromol Biosci 2021 Sep 12;21(9):e2100022. Epub 2021 Jun 12.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China.

Poly(glycerol sebacate) (PGS), an emerging promising thermosetting polymer synthesized from sebacic acid and glycerol, has attracted considerable attention due to its elasticity, biocompatibility, and tunable biodegradation properties. But it also has some drawbacks such as harsh synthesis conditions, rapid degradation rates, and low stiffness. To overcome these challenges and optimize PGS performance, various modification methods and fabrication techniques for PGS-based scaffolds have been developed in recent years. Outlining the current modification approaches of PGS and summarizing the fabrication techniques for PGS-based scaffolds are of great importance to accelerate the development of new materials and enable them to be appropriately used in potential applications. Thus, this review comprehensively overviews PGS derivatives, PGS composites, PGS blends, processing for PGS-based scaffolds, and their related applications. It is envisioned that this review could instruct and inspire the design of the PGS-based materials and facilitate tissue engineering advances into clinical practice.
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http://dx.doi.org/10.1002/mabi.202100022DOI Listing
September 2021

Cyclic Strain and Electrical Co-stimulation Improve Neural Differentiation of Marrow-Derived Mesenchymal Stem Cells.

Front Cell Dev Biol 2021 11;9:624755. Epub 2021 May 11.

Beijing Advanced Innovation Center for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Chinese Education Ministry, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.

The current study investigated the combinatorial effect of cyclic strain and electrical stimulation on neural differentiation potential of rat bone marrow-derived mesenchymal stem cells (BMSCs) under epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2) inductions . We developed a prototype device which can provide cyclic strain and electrical signal synchronously. Using this system, we demonstrated that cyclic strain and electrical co-stimulation promote the differentiation of BMCSs into neural cells with more branches and longer neurites than strain or electrical stimulation alone. Strain and electrical co-stimulation can also induce a higher expression of neural markers in terms of transcription and protein level. Neurotrophic factors and the intracellular cyclic AMP (cAMP) are also upregulated with co-stimulation. Importantly, the co-stimulation further enhances the calcium influx of neural differentiated BMSCs when responding to acetylcholine and potassium chloride (KCl). Finally, the phosphorylation of extracellular-signal-regulated kinase (ERK) 1 and 2 and protein kinase B (AKT) was elevated under co-stimulation treatment. The present work suggests a synergistic effect of the combination of cyclic strain and electrical stimulation on BMSC neuronal differentiation and provides an alternative approach to physically manipulate stem cell differentiation into mature and functional neural cells .
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http://dx.doi.org/10.3389/fcell.2021.624755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150581PMC
May 2021

Dynamic real-time imaging of living cell traction force by piezo-phototronic light nano-antenna array.

Sci Adv 2021 May 26;7(22). Epub 2021 May 26.

CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, 100083 Beijing, China.

Dynamic mapping of the cell-generated force of cardiomyocytes will help provide an intrinsic understanding of the heart. However, a real-time, dynamic, and high-resolution mapping of the force distribution across a single living cell remains a challenge. Here, we established a force mapping method based on a "light nano-antenna" array with the use of piezo-phototronic effect. A spatial resolution of 800 nm and a temporal resolution of 333 ms have been demonstrated for force mapping. The dynamic mapping of cell force of live cardiomyocytes was directly derived by locating the antennas' positions and quantifying the light intensities of the piezo-phototronic light nano-antenna array. This study presents a rapid and ultrahigh-resolution methodology for the fundamental study of cardiomyocyte behavior at the cell or subcellular level. It can provide valuable information about disease detection, drug screening, and tissue engineering for heart-related studies.
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http://dx.doi.org/10.1126/sciadv.abe7738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153726PMC
May 2021

Hydrogel-based therapeutic angiogenesis: An alternative treatment strategy for critical limb ischemia.

Biomaterials 2021 07 7;274:120872. Epub 2021 May 7.

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, PR China. Electronic address:

Critical limb ischemia (CLI) is the most severe clinical manifestation of peripheral arterial disease (PAD), resulting in the total or partial loss of limb function. Although the conventional treatment strategy of CLI (e.g., medical treatment and surgery) can improve blood perfusion and restore limb function, many patients are unsuitable for these strategies and they still face the threats of amputation or death. Therapeutic angiogenesis, as a potential solution for these problems, attempts to manipulate blood vessel growth in vivo for augment perfusion without the help of extra pharmaceutics and surgery. With the rise of interdisciplinary research, regenerative medicine strategies provide new possibilities for treating many clinical diseases. Hydrogel, as an excellent biocompatibility material, is an ideal candidate for delivering bioactive molecules and cells for therapeutic angiogenesis. Besides, hydrogel could precisely deliver, control release, and keep the bioactivity of cargos, making hydrogel-based therapeutic angiogenesis a new strategy for CLI therapy. In this review, we comprehensively discuss the approaches of hydrogel-based strategy for CLI treatment as well as their challenges, and future directions.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120872DOI Listing
July 2021

Electrical Stimulation Promotes Stem Cell Neural Differentiation in Tissue Engineering.

Stem Cells Int 2021 20;2021:6697574. Epub 2021 Apr 20.

Beijing Advanced Innovation Center for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Chinese Education Ministry, School of Biological Science and Medical Engineering, Beihang University, No. 37, Xueyuan Road, Haidian District, Beijing 100083, China.

Nerve injuries and neurodegenerative disorders remain serious challenges, owing to the poor treatment outcomes of neural stem cell regeneration. The most promising treatment for such injuries and disorders is stem cell-based therapies, but there remain obstacles in controlling the differentiation of stem cells into fully functional neuronal cells. Various biochemical and physical approaches have been explored to improve stem cell-based neural tissue engineering, among which electrical stimulation has been validated as a promising one both in vitro and in vivo. Here, we summarize the most basic waveforms of electrical stimulation and the conductive materials used for the fabrication of electroactive substrates or scaffolds in neural tissue engineering. Various intensities and patterns of electrical current result in different biological effects, such as enhancing the proliferation, migration, and differentiation of stem cells into neural cells. Moreover, conductive materials can be used in delivering electrical stimulation to manipulate the migration and differentiation of stem cells and the outgrowth of neurites on two- and three-dimensional scaffolds. Finally, we also discuss the possible mechanisms in enhancing stem cell neural differentiation using electrical stimulation. We believe that stem cell-based therapies using biocompatible conductive scaffolds under electrical stimulation and biochemical induction are promising for neural regeneration.
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http://dx.doi.org/10.1155/2021/6697574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081629PMC
April 2021

[Estimation of lung recruitment characteristics using the static pressure-volume curve of lungs].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2021 Apr;38(2):326-332

Beijing Advanced Innovation Center for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, P.R. China.

Mechanical ventilation is an importmant life-sustaining treatment for patients with acute respiratory distress syndrome. Its clinical outcomes depend on patients' characteristics of lung recruitment. Estimation of lung recruitment characteristics is valuable for the determination of ventilatory maneurvers and ventilator parameters. There is no easily-used, bedside method to assess lung recruitment characteristics. The present paper proposed a method to estimate lung recruitment characteristics from the static pressure-volume curve of lungs. The method was evaluated by comparing with published experimental data. Results of lung recruitment derived from the presented method were in high agreement with the published data, suggesting that the proposed method is capable to estimate lung recruitment characteristics. Since some advanced ventilators are capable to measure the static pressure-volume curve automatedly, the presented method is potential to be used at bedside, and it is helpful for clinicians to individualize ventilatory manuevers and the correpsonding ventilator parameters.
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http://dx.doi.org/10.7507/1001-5515.202008061DOI Listing
April 2021

Gastrointestinal Microenvironment and the Gut-Lung Axis in the Immune Responses of Severe COVID-19.

Front Mol Biosci 2021 12;8:647508. Epub 2021 Apr 12.

Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing, China.

The global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an unprecedented threat to the human health. A close association of the digestive tract is implied by the high frequency of gastrointestinal syndromes among COVID-19 patients. A better understanding of the role of intestinal microenvironment in COVID-19 immunopathology will be helpful to improve the control of COVID-19 associated morbidity and mortality. This review summarizes the immune responses associated with the severity of COVID-19, the current evidence of SARS-CoV-2 intestinal tropism, and the potential involvement of gut microenvironment in COVID-19 severity. Additionally, we discuss the therapeutic potential of probiotics as an alternative medicine to prevent or alleviate severe COVID-19 outcome.
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http://dx.doi.org/10.3389/fmolb.2021.647508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071853PMC
April 2021

Microfluidic Model to Mimic Initial Event of Neovascularization.

J Vis Exp 2021 04 10(170). Epub 2021 Apr 10.

Beijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Chinese Education Ministry, School of Biological Science and Medical Engineering, Beihang University; School of Engineering Medicine, Beihang University;

Neovascularization is usually initialized from an existing normal vasculature and the biomechanical microenvironment of endothelial cells (ECs) in the initial stage varies dramatically from the following process of neovascularization. Although there are plenty of models to simulate different stages of neovascularization, an in vitro 3D model that capitulates the initial process of neovascularization under the corresponding stimulations of normal vasculature microenvironments is still lacking. Here, we reconstructed an in vitro 3D model that mimics the initial event of neovascularization (MIEN). The MIEN model contains a microfluidic sprouting chip and an automatic control, highly efficient circulation system. A functional, perfusable microchannel coated with endothelium was formed and the process of sprouting was simulated in the microfluidic sprouting chip. The initially physiological microenvironment of neovascularization was recapitulated with the microfluidic control system, by which ECs would be exposed to high luminal shear stress, physiological transendothelial flow, and various vascular endothelial growth factor (VEGF) distributions simultaneously. The MIEN model can be readily applied to the study of neovascularization mechanism and holds a potential promise as a low-cost platform for drug screening and toxicology applications.
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http://dx.doi.org/10.3791/62003DOI Listing
April 2021
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