Publications by authors named "Bowen Zhang"

168 Publications

Vertical stability of different orthognathic treatments for correcting skeletal anterior open bite: a systematic review and meta-analysis.

Eur J Orthod 2021 Apr 3. Epub 2021 Apr 3.

Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.

Background: Several orthognathic procedures have been applied to correct skeletal anterior open bites (SAOB). Which method is most stable has been debated and no consensus has been reached and there is no conclusive evidence for clinicians to use.

Objective: To analyse whether maxillary, mandibular, or bimaxillary surgery provides a better stability.

Materials And Methods: A systematic search was conducted up to December 2020 using PubMed, EMBASE, Medline, Scopus, Web of Science, Cochrane CENTRAL, and Google Scholar. We made direct comparisons among the controlled trials and also made indirect comparisons via subgroup analysis on the aspects of occlusional, skeletal, and dento-alveolar stability to assess the overall stability of each method.

Results: Finally 16 cohort studies were identified. At the occlusional level, pooled change in overbite was 0.21 mm in maxillary surgery, 0.37 mm in bimaxillary surgery, and -0.32 mm in mandibular surgery. At the skeletal level, pooled sella-nasion-Point A angle (SNA) was -0.12 degrees in bimaxillary surgery, -0.37 degrees in maxillary surgery and -0.20 degrees in mandibular surgery. The sella-nasion to palatal plane angle (SNPP) relapsed to a statistically significant degree in all samples received single maxillary surgery. Relapse of the sella-nasion-Point B angle (SNB) was 0.47 degrees in mandibular setback, -1.8 degrees in mandibular advancement, and -0.48 degrees in maxillary surgery. The Sella-Nasion to mandibular plane angle (SNMP) relapsed more in procedures involving bilateral sagittal split osteotomy than in other procedures. As for dento-alveolar changes, intrusion of molars and extrusion of incisors took place in most patients.

Conclusions: Bimaxillary surgery produced the most beneficial post-operative increase in overbite, maxillary surgery led to a lesser but still positive overbite change, and mandibular surgery correlated with some extent of relapse. Skeletally, bimaxillary surgery was more stable than maxillary surgery at both SNA and SNPP; SNB was more stable in mandibular setback than advancement; and SNMP was unstable in both mandibular and bimaxillary surgeries versus maxillary surgery with comparable surgical changes. Dento-alveolar compensation helped maintain a positive overbite.

Registration Number: CRD42020198088.
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http://dx.doi.org/10.1093/ejo/cjab011DOI Listing
April 2021

Pollution characteristics and ecological risks associated with heavy metals in the Fuyang river system in North China.

Environ Pollut 2021 Mar 29;281:116994. Epub 2021 Mar 29.

CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, & CAS-HKU Joint Laboratory of Metallomics on Health and Environment, & Beijing Metallomics Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.

The Fuyang River system (FRS) in north China, for a long time, is seriously polluted with organic compounds and heavy metals due to industrialization. However, the information on heavy metal pollution in this area is still limited, and health risks raised by trace elements are neglected up to now. To characterize the heavy metal pollutants and assess their potential ecological risks scientifically in FRS, surface sediments were collected from 66 sampling sites selected according to the hydrological and anthropogenic conditions along the river. A total of twelve metal pollutants (e.g., Cr, As, and Hg) in the sediments were detected among the distributaries. A combining application of geoaccumulation index (I), ratio of secondary phase and primary phase (RSP), and the ecological risk factor (Er) in this study gave systematic assessment results of single or combined pollution status raised by heavy metals in this area. The results show that Cr, Ni, Cu, As, Cd, Co, and Sn are mainly dispersed in the river reaches of Xingtai City and pose potential health risks in midstream, as per the geoaccumulation index and Pearson's correlation analyses. In particular, Cd accumulates strongly in sediments of Ming River and Aixinzhuang dam from Xingtai City. In upstream and downstream of FRS, the potential ecological risk is low, except in Yongnian County where high ecological risk was caused by Cd and Hg. These findings provide new insights into the pollution characteristics and assessment of the potential ecological risks induced by heavy metals along FRS, which suggest new directions should strategically tend to typical pollutants control by policy formulation and taking effective measures to prevent and manage heavy metal pollution in North China.
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http://dx.doi.org/10.1016/j.envpol.2021.116994DOI Listing
March 2021

Analysis of Immune Gene Expression Subtypes Reveals Osteosarcoma Immune Heterogeneity.

J Oncol 2021 1;2021:6649412. Epub 2021 Mar 1.

Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, Beijing Research Institute of Traumatology and Orthopaedics, Beijing JiShuiTan Hospital, Beijing 100035, China.

Background: Osteosarcoma (OS) patients have a poor response to immunotherapy due to the sheer complexity of the immune system and the nuances of the tumor-immune microenvironment. . To gain insights into the immune heterogeneity of OS, we identified robust clusters of patients based on the immune gene expression profiles of OS patients in the TARGET database and assessed their reproducibility in an independent cohort collected from the GEO database. The association of comprehensive molecular characterization with reproducible immune subtypes was accessed with ANOVA. Furthermore, we visualized the distribution of individual patients in a tree structure by the graph structure learning-based dimensionality reduction algorithm.

Results: We found that 87 OS samples can be divided into 5 immune subtypes, and each of them was associated with distinct clinical outcomes. The immune subtypes also demonstrated widely different patterns in tumor genetic aberrations, tumor-infiltrating, immune cell composition, and cytokine profiles. The immune landscape of OS uncovered the significant intracluster heterogeneity within each subtype and depicted a continuous immune spectrum across patients.

Conclusion: The established five immune subtypes in our study suggested immune heterogeneity in OS patients and may provide optimal individual immunotherapy for patients exhibiting OS.
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http://dx.doi.org/10.1155/2021/6649412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939746PMC
March 2021

Experimental demonstration of an optical quantizer with ENOB of 3.31 bit by using a cascaded step-size MMI.

Opt Express 2021 Jan;29(2):2555-2563

We experimentally demonstrated an optical phase shifted quantizer using a cascade step-size MMI (CS-MMI), which was fabricated on a commercially available 220-nm SOI platform via multi-project wafer (MPW) process. An experimental setup was built to test the ability of the CS-MMI acting as a quantizer. The experimental results show that the proposed CS-MMI-based quantizer has an effective number of bit (ENOB) of 3.31bit, which is a little slighter than the ideal ENOB of 3.32bit. The operation range is 12 nm for ENOB≥3 bit. Moreover, the insertion loss of the CS-MMI is -1.26 dB at 1560 nm, the performance of the fabricated device agrees well with simulation results.
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http://dx.doi.org/10.1364/OE.413799DOI Listing
January 2021

Tetrahedral DNA nanostructure improves transport efficiency and anti-fungal effect of histatin 5 against Candida albicans.

Cell Prolif 2021 Mar 11:e13020. Epub 2021 Mar 11.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Objectives: Anti-microbial peptides (AMPs) have been comprehensively investigated as a novel alternative to traditional antibiotics against microorganisms. Meanwhile, Tetrahedral DNA nanostructures (TDNs) have gained attention in the field of biomedicine for their premium biological effects and transportation efficiency as delivery vehicles. Hence, in this study, TDN/Histatin 5 (His-5) was synthesized and the transport efficiency and anti-fungal effect were measured to evaluate the promotion of His-5 modified by TDNs.

Materials And Methods: Tetrahedral DNA nanostructures/His-5 complex was prepared via electrostatic attraction and characterized by transmission electron microscopy (TEM), polyacrylamide gel electrophoresis (PAGE), dynamic light scattering (DLS) and electrophoretic light scattering (ELS). The anti-fungal effect of the TDN/His-5 complex was evaluated by determining the growth curve and colony-forming units of C. albicans. The morphological transformation of C. albicans was observed by light microscope and scanning electron microscope (SEM). Immunofluorescence was performed, and potassium efflux was detected to mechanistically demonstrate the efficacy of TDN/His-5.

Results: The results showed that Histatin 5 modified by TDNs had preferable stability in serum and was effectively transported into C. albicans, leading to the increased formation of intracellular reactive oxygen species, higher potassium efflux and enhanced anti-fungal effect against C. albicans.

Conclusions: Our study showed that TDN/His-5 was synthesized successfully. And by the modification of TDNs, His-5 showed increased transport efficiency and improved anti-fungal effect.
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http://dx.doi.org/10.1111/cpr.13020DOI Listing
March 2021

Prosaposin mediates inflammation in atherosclerosis.

Sci Transl Med 2021 Mar;13(584)

Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Macrophages play a central role in the pathogenesis of atherosclerosis. The inflammatory properties of these cells are dictated by their metabolism, of which the mechanistic target of rapamycin (mTOR) signaling pathway is a key regulator. Using myeloid cell-specific nanobiologics in apolipoprotein E-deficient () mice, we found that targeting the mTOR and ribosomal protein S6 kinase-1 (S6K1) signaling pathways rapidly diminished plaque macrophages' inflammatory activity. By investigating transcriptome modifications, we identified , a gene encoding the lysosomal protein prosaposin, as closely related with mTOR signaling. Subsequent in vitro experiments revealed that inhibition suppressed both glycolysis and oxidative phosphorylation. Transplantation of bone marrow to low-density lipoprotein receptor knockout () mice led to a reduction in atherosclerosis development and plaque inflammation. Last, we confirmed the relationship between expression and inflammation in human carotid atherosclerotic plaques. Our findings provide mechanistic insights into the development of atherosclerosis and identify prosaposin as a potential therapeutic target.
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http://dx.doi.org/10.1126/scitranslmed.abe1433DOI Listing
March 2021

Large-scale generation of megakaryocytes from human embryonic stem cells using transgene-free and stepwise defined suspension culture conditions.

Cell Prolif 2021 Apr 21;54(4):e13002. Epub 2021 Feb 21.

Experimental Hematology and Biochemistry Lab, Beijing Institute of Radiation Medicine, Beijing, China.

Objectives: Ex vivo engineered production of megakaryocytes (MKs) and platelets (PLTs) from human pluripotent stem cells is an alternative approach to solve shortage of donor-donated PLTs in clinics and to provide induced PLTs for transfusion. However, low production yields are observed and the generation of clinically applicable MKs and PLTs from human pluripotent stem cells without genetic modifications still needs to be improved.

Materials And Methods: We defined an optimal, stepwise and completely xeno-free culture protocol for the generation of MKs from human embryonic stem cells (hESCs). To generate MKs from hESCs on a large scale, we improved the monolayer induction manner to define three-dimensional (3D) and sphere-like differentiation systems for MKs by using a special polystyrene CellSTACK culture chamber.

Results: The 3D manufacturing system could efficiently generate large numbers of MKs from hESCs within 16-18 days of continuous culturing. Each CellSTACK culture chamber could collect on an average 3.4 × 10 CD41 MKs after a three-stage orderly induction process. MKs obtained from hESCs via 3D induction showed significant secretion of IL-8, thrombospondin-1 and MMP9. The induced cells derived from hESCs in our culture system were shown to have the characteristics of MKs as well as the function to form proPLTs and release PLTs. Furthermore, we generated clinically applicable MKs from clinical-grade hESC lines and confirmed the biosafety of these cells.

Conclusions: We developed a simple, stepwise, 3D and completely xeno-free/feeder-free/transgene-free induction system for the generation of MKs from hESCs. hESC-derived MKs were shown to have typical MK characteristics and PLT formation ability. This study further enhances the clinical applications of MKs or PLTs derived from pluripotent stem cells.
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http://dx.doi.org/10.1111/cpr.13002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016648PMC
April 2021

High-Temperature Stability and Phase Transformations of Titanium Carbide (Ti3C2Tx) MXene.

J Phys Condens Matter 2021 Feb 18. Epub 2021 Feb 18.

Department of Mechanical and Energy Engineering, Indiana University Purdue University at Indianapolis School of Engineering and Technology, 723 W. Michigan Street, SL 260, Indianapolis, Indianapolis, Indiana, 46202-5160, UNITED STATES.

Two-dimensional (2D) transition metal carbides, nitrides, and carbonitrides, known as MXenes, are under increasing pressure to meet technological demands in high-temperature applications, as MXenes can be considered as one of the few high temperature 2D materials. Although there are studies on the stability of their surface functionalities, there is a gap in fundamental understanding of the phase stability and transformation of the metal carbide core at high temperatures (> 700 °C) in an inert environment. In this study, we conduct systematic annealing of TiCTMXene films in which we present the 2D MXene flake phase transformation to ordered vacancy superstructure of a bulk three-dimensional (3D) TiC phase and 3D bulk TiCcrystals at 700 ᵒC ≤ T ≤ 1000 ºC with subsequent transformation to disordered carbon vacancy cubic TiCduring annealing at higher temperatures (T > 1000 ºC). We annealed TiCTMXene films made from the delaminated MXene single-flakes as well as the multi-layer MXene clay powder in a controlled environment through the use of in-situ hot stage x-ray diffraction (XRD) paired with a 2D detector (XRD) up to 1000 °C and ex-situ annealing in a tube furnace and spark plasma sintering up to 1500 °C. Our XRDanalysis paired with cross-sectional scanning electron microscope imaging indicated the resulting nano-sized lamellar and micron-sized cubic grain morphology of the 3D crystals depend on the starting TiCTform. While annealing the multi-layer MXene create TiCgrains with cubic and irregular morphology, the grains of 3D TiC and TiCformed by annealing the TiCTMXene single-flake films keep the lamellar morphology. The ultrathin lamellar nature of the 3D grains formed at temperatures >1000 °C can pave way for applications of MXenes as a stable carbide material 2D additive for high-temperature applications.
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http://dx.doi.org/10.1088/1361-648X/abe793DOI Listing
February 2021

Erythromycin loaded by tetrahedral framework nucleic acids are more antimicrobial sensitive against .

Bioact Mater 2021 Aug 23;6(8):2281-2290. Epub 2021 Jan 23.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.

Erythromycin is a commonly used broad-spectrum antibiotic, but resistance to this antibiotic makes its use less effective. Considerable efforts, beside finding alternatives, are needed to enhance its antimicrobial effect and stability against bacteria. Tetrahedral framework nucleic acids (tFNAs), a novel delivery vehicle with a three-dimensional nanostructure, have been studied as a carrying platform of antineoplastic drugs. In this study, the use of tFNAs in delivering erythromycin into () was investigated for the first time. The tFNAs vehicle increased the bacterial uptake of erythromycin and promoted membrane destabilization. Moreover, it increased the permeability of the bacterial cell wall, and reduced drug resistance by improving the movement of the drug across the membrane. The tFNAs-based delivery system enhanced the effects of erythromycin against . It may therefore provide an effective delivery vehicle for erythromycin in targeting antibiotic-resistant bacteria with thick cell wall.
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http://dx.doi.org/10.1016/j.bioactmat.2020.12.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841501PMC
August 2021

Identification of Novel Population-Specific Cell Subsets in Chinese Ulcerative Colitis Patients Using Single-Cell RNA Sequencing.

Cell Mol Gastroenterol Hepatol 2021 Feb 2. Epub 2021 Feb 2.

Centre for Individualised Infection Medicine and TWINCORE, joint ventures between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.

Background & Aims: Genome-wide association studies (GWAS) and transcriptome analyses have been performed to better understand the pathogenesis of ulcerative colitis (UC). However, current studies mainly focus on European ancestry, highlighting a great need to identify the key genes, pathways and cell types in colonic mucosal cells of adult UC patients from other ancestries. Here we aimed to identify key genes and cell types in colonic mucosal of UC.

Methods: We performed Single-cell RNA sequencing (scRNA-seq) analysis of 12 colon biopsies of UC patients and healthy controls from Chinese Han ancestry.

Results: Two novel plasma subsets were identified. Five epithelial/stromal and three immune cell subsets show significant difference in abundance between inflamed and non-inflamed samples. In general, UC risk genes show consistent expression alteration in both Immune cells of inflamed and non-inflamed tissues. As one of the exceptions, IgA defection, marking the signal of immune dysfunction, is specific to the inflamed area. Moreover, Th17 derived activation was observed in both epithelial cell lineage and immune cell lineage of UC patients as compared to controls , suggesting a systemic change of immune activities driven by Th17. The UC risk genes show enrichment in progenitors, glial cells and immune cells, and drug-target genes are differentially expressed in antigen presenting cells.

Conclusions: Our work identifies novel population-specific plasma cell molecular signatures of UC. The transcriptional signature of UC is shared in immune cells from both inflamed and non-inflamed tissues, whereas the transcriptional response to disease is a local effect only in inflamed epithelial/stromal cells.
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http://dx.doi.org/10.1016/j.jcmgh.2021.01.020DOI Listing
February 2021

Roles of peptidyl-prolyl isomerase Pin1 in disease pathogenesis.

Theranostics 2021 19;11(7):3348-3358. Epub 2021 Jan 19.

The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, Sichuan, China.

Pin1 belongs to the peptidyl-prolyl cis-trans isomerases (PPIases) superfamily and catalyzes the cis-trans conversion of proline in target substrates to modulate diverse cellular functions including cell cycle progression, cell motility, and apoptosis. Dysregulation of Pin1 has wide-ranging influences on the fate of cells; therefore, it is closely related to the occurrence and development of various diseases. This review summarizes the current knowledge of Pin1 in disease pathogenesis.
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http://dx.doi.org/10.7150/thno.45889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847688PMC
January 2021

WITH OR WITHOUT INTERNAL LIMITING MEMBRANE PEELING FOR IDIOPATHIC EPIRETINAL MEMBRANE: A Meta-Analysis of Randomized Controlled Trials.

Retina 2020 Dec 19;Publish Ahead of Print. Epub 2020 Dec 19.

Department of Ophthalmology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China. Department of Ophthalmology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, 410005, China. Surgical Department, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.

Purpose: To clarify whether internal limiting membrane (ILM) peeling provides better outcomes for patients with idiopathic epiretinal membrane (ERM).

Methods: Randomized controlled trials (RCTs) comparing ERM removal with and without ILM peeling were searched in Embase, PubMed, Web of Science, Cochrane Library and CNKI before 15 April 2020. The pooled mean difference (MD) for best corrected visual acuity (BCVA), central macular thickness (CMT), and odds ratio (OR) for recurrence were calculated.

Results: 8 RCTs involving 422 eyes were included. No significant difference in BCVA (final follow-up: MD 0.03 logarithm of the minimum angle of resolution [1.5 Early Treatment Diabetic Retinopathy Study letters]; 95% CI -0.04 to 0.09 [-4.5 to 2 Early Treatment Diabetic Retinopathy Study letters]; P=0.40) or recurrence rate (OR, 0.21; 95% CI 0.04 to 1.05; P=0.06) between the groups was observed. However, patients with ILM peeling presented thicker CMT at 3 months (MD, 16.36; 95% CI 1.26 to 31.46; P=0.03), 6 months (MD, 22.64; 95% CI 10.29 to 34.98; P=0.0003) and the final follow-up (MD, 25.87; 95% CI 13.96 to 37.79; P<0.0001).

Conclusion: ILM peeling did not significantly improve the postoperative visual outcome or decrease recurrence, but result in thicker CMT, indicating inessential for idiopathic ERM.
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http://dx.doi.org/10.1097/IAE.0000000000003076DOI Listing
December 2020

Comparison of different transcatheter interventions for treatment of mitral regurgitation: A protocol for a network meta-analysis.

Medicine (Baltimore) 2020 Dec;99(50):e23623

Department of Thoracic Surgery, First Hospital of Lanzhou University, Lanzhou, China.

Background: The arrival of transcatheter mitral valve therapies has provided feasible and safe alternatives to medical and surgical treatments for mitral regurgitation. The aim of this study is to estimate the relative efficacy and safety of different transcatheter mitral valve therapies for mitral regurgitation patients through network meta-analysis.

Methods: A systematic search will be performed using PubMed, EMBASE, the Cochrane Library, Web of Science, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure to include random controlled trials and nonrandom controlled trials comparing the efficacy and safety of different transcatheter mitral valve techniques. The risk of bias for the included nonrandom controlled studies will be evaluated according to Risk of Bias in Non-randomized Studies - of Interventions. For random controlled trials, we will use Cochrane Handbook version 5.1.0 as the risk of bias tool. A Bayesian network meta-analysis will be conducted using R-4.0.3 software. Grading of recommendations assessment, development, and evaluation will be used to assess the quality of evidence.

Results: The results of this network meta-analysis will be submitted to a peer-reviewed journal for publication.

Conclusion: This study will provide broad evidence of efficacy and safety of different transcatheter mitral valve therapies for treatment of mitral regurgitation and provide suggestions for clinical practice and future research.

Protocol Registration Number: INPLASY2020110034.
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http://dx.doi.org/10.1097/MD.0000000000023623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738030PMC
December 2020

A Differential Evolution-Based Consistency Improvement Method in AHP With an Optimal Allocation of Information Granularity.

IEEE Trans Cybern 2020 Dec 7;PP. Epub 2020 Dec 7.

In the analytic hierarchy process (AHP), the reciprocal matrix is generated based on the pairwise comparisons completed among all the alternatives or attributes under consideration. To ensure reliability and validity of the decision solution, a certain modification of entries of the matrix is usually needed to improve the consistency of the reciprocal matrix. This study aims to present a consistency improvement method by admitting some level of information granularity in the evaluation process. This gives rise to a granular rather than numeric matrix of pairwise comparisons. First, with a given average level of information granularity, we present an optimal granularity model that is characterized by maximal consistency. One can maximize the consistency degree by invoking a process of allocation of information granularity across the corresponding modifications of the reciprocal matrix. Based on the optimal granularity model, an interactive consistency improvement process is presented with the involvement of the decision maker. Then, an adaptive differential evolution algorithm is applied to optimize entries of the modified reciprocal matrix. Detailed experiments along with a thorough comparative analysis are completed to demonstrate the effectiveness of the proposed method.
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http://dx.doi.org/10.1109/TCYB.2020.3035909DOI Listing
December 2020

Startup and performance of a novel single-stage partial nitritation/anammox system for reject water treatment.

Bioresour Technol 2021 Feb 20;321:124432. Epub 2020 Nov 20.

School of Environmental and Municipal Engineering, Tianjin Chengjian University, Tianjin 300384, China; Joint Research Centre for Protective Infrastructure Technology and Environmental Green Bioprocess, School of Environmental and Municipal Engineering, Tianjin 300384, China; Tianjin Key Laboratory of Aqueous Science and Technology, Tianjin 300384, China.

A novel internal circulation contact oxidation membrane bioreactor (ICCOMBR) was constructed to investigate a three steps startup strategy of single-stage partial nitritation-anammox (SPNA) system. A stable nitrite accumulation rate (NAR) of 86.60% was achieved with NH-N over 250 mg/L in nitritation process. The partial nitritation process could be effectively achieved by reducing the aeration rate (AR) by about 50% in the nitritation process, with an effluent NO-N/NH-N ratio of 1.15 ± 0.04. The SPNA system was started up in 27 days following the inoculated anammox granular sludge. A total nitrogen removal efficiencies of 82% was achieved at a NLR of 0.60 gN/L/d and dissolved oxygen (DO) concentration below 0.55 mg/L. Anammox function genus (Ca.Kuenenia and Ca. Anammoximicrobium) abundance accounted for 20.77% in the biofilm, which is approximately equal to 22.2% in the suspended sludge. Nitrosomon as the dominant AOB genera, was detected in the biofilm (6.5%) and suspended sludge (13.3%).
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http://dx.doi.org/10.1016/j.biortech.2020.124432DOI Listing
February 2021

Human decellularized adipose matrix derived hydrogel assists mesenchymal stem cells delivery and accelerates chronic wound healing.

J Biomed Mater Res A 2020 Nov 30. Epub 2020 Nov 30.

Department of Plastic and Reconstructive Surgery, The First Medical, Chinese PLA General Hospital Centre, Beijing, China.

Biological scaffolds based stem cell delivery methods have emerged as a promising approach for tissue repair and regeneration. Here we developed a hydrogel biological scaffold from human decellularized adipose matrix (hDAM) for human adipose-derived stem cells (hASCs) delivery to accelerate chronic wound healing. The hDAM hydrogel was prepared by pepsin mediated digestion and pH controlled neutralization. The morphology, survival, proliferation, and angiogenic paracrine activity of hASCs cultured in the hydrogel were assessed. Moreover, the therapeutic efficacy of the hASCs-hydrogel composite for impaired wound healing was evaluated by using a full-thickness wound model on diabetic mouse. The developed hDAM hydrogel was a thermosensitive hydrogel, presented the biochemical complexity of native extracellular matrix and formed a porous nanofiber structure after gelation. The hydrogel can support hASCs adhesion, survival, and proliferation. Compared to standard culture condition, hASCs cultured in the hydrogel exhibited enhanced paracrine activity with increased secretion of hepatocyte growth factor. In the diabetic mice model with excisional full-thickness skin wounds, mice treated with the hASCs-hydrogel composite displayed accelerated wound closure and increased neovascularization. Our results suggested that the developed hDAM hydrogel can provide a favorable microenvironment for hASCs with augmented regeneration potential to accelerate chronic wound healing.
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http://dx.doi.org/10.1002/jbm.a.37133DOI Listing
November 2020

Meltblown fabric nanofiber membrane, which is better for fabricating personal protective equipments.

Chin J Chem Eng 2020 Nov 23. Epub 2020 Nov 23.

State Key Laboratory of Materials-Oriented Chemical Engineering, National Engineering Research Center for Special Separation Membrane, Nanjing Tech University, Nanjing 210009, China.

The coronavirus disease 2019 (COVID-19) pandemic has led to a great demand on the personal protection products such as reusable masks. As a key raw material for masks, meltblown fabrics play an important role in rejection of aerosols. However, the electrostatic dominated aerosol rejection mechanism of meltblown fabrics prevents the mask from maintaining the desired protective effect after the static charge degradation. Herein, novel reusable masks with high aerosols rejection efficiency were fabricated by the introduction of spider-web bionic nanofiber membrane (nano cobweb-biomimetic membrane). The reuse stability of meltblown and nanofiber membrane mask was separately evaluated by infiltrating water, 75% alcohol solution, and exposing under ultraviolet (UV) light. After the water immersion test, the filtration efficiency of meltblown mask was decreased to about 79%, while the nanofiber membrane was maintained at 99%. The same phenomenon could be observed after the 75% alcohol treatment, a high filtration efficiency of 99% was maintained in nanofiber membrane, but obvious negative effect was observed in meltblown mask, which decreased to about 50%. In addition, after long-term expose under UV light, no filtration efficiency decrease was observed in nanofiber membrane, which provide a suitable way to disinfect the potential carried virus. This work successfully achieved the daily disinfection and reuse of masks, which effectively alleviate the shortage of masks during this special period.
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http://dx.doi.org/10.1016/j.cjche.2020.10.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682934PMC
November 2020

A Comparison of Frozen Elephant Trunk, Aortic Balloon Occlusion, and Hybrid Repair for Total Arch Replacement.

Semin Thorac Cardiovasc Surg 2020 Nov 23. Epub 2020 Nov 23.

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

This study aimed to compare clinical outcomes of patients treated by total arch replacement (TAR) with frozen elephant trunk (FET), aortic balloon occlusion (ABO) technique and hybrid arch repair (HAR). Between January 2017 and July 2019, 643 consecutive patients with aortic arch diseases were eligible for TAR, including 356 in conventional FET, 112 in ABO based on FET, and 175 in HAR. A retrospective cohort analysis of perioperative results was undertaken, performed with inverse probability weighting. The primary endpoint was composite endpoints included 30-day mortality, stroke, paraplegia, hemodialysis, reintubation, and intra-aortic balloon pump or extracorporeal membrane oxygenation support, and visceral dysfunction was secondary endpoint. Overall in-hospital mortality was 2.2% (FET = 2.5% vs ABO = 0 vs HAR = 2.9%, P= 0.210). Parallel early outcomes were demonstrated among three groups. ABO group was associated with significantly shorter circulatory arrest time (5, IQR 3-7 vs 16, IQR 14-18 minutes, P < 0.001), and a lower incidence of visceral dysfunction compared with FET group (25.1% vs 47.3%, P= 0.003). Patients receiving ABO suffered a significantly lower rate of prolonged ventilation (more than 72 hours; P= 0.014). Furthermore, a tendency toward decreasing composite endpoints was suggested in ABO (7.2%) compared with FET (15.5%, P= 0.061) and HAR (19.8%, P= 0.032). ABO technique obtains considerable early clinical outcomes for TAR compared with conventional FET and HAR, which could be a feasible and effective approach for patients with aortic arch diseases.
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http://dx.doi.org/10.1053/j.semtcvs.2020.11.020DOI Listing
November 2020

The Fission Yeast RNA-Binding Protein Meu5 Is Involved in Outer Forespore Membrane Breakdown during Spore Formation.

J Fungi (Basel) 2020 Nov 13;6(4). Epub 2020 Nov 13.

Department of Biology, Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka 558-8585, Japan.

In , the spore wall confers strong resistance against external stress. During meiosis II, the double-layered intracellular forespore membrane (FSM) forms de novo and encapsulates the nucleus. Eventually, the inner FSM layer becomes the plasma membrane of the spore, while the outer layer breaks down. However, the molecular mechanism and biological significance of this membrane breakdown remain unknown. Here, by genetic investigation of an mutant (E22) with normal prespore formation but abnormal spores, we showed that Meu5, an RNA-binding protein known to bind to and stabilize more than 80 transcripts, is involved in this process. We confirmed that the E22 mutant does not produce Meu5 protein, while overexpression of in E22 restores the sporulation defect. Furthermore, electron microscopy revealed that the outer membrane of the FSM persisted in ∆ spores. Investigation of the target genes of showed that a mutant of encoding cytochrome also showed a severe defect in outer FSM breakdown. Lastly, we determined that outer FSM breakdown occurs coincident with or after formation of the outermost Isp3 layer of the spore wall. Collectively, our data provide novel insights into the molecular mechanism of spore formation.
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http://dx.doi.org/10.3390/jof6040284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712723PMC
November 2020

Reprogramming of bone marrow myeloid progenitor cells in patients with severe coronary artery disease.

Elife 2020 11 10;9. Epub 2020 Nov 10.

Department of Internal Medicine and Radboud Institute for Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, Netherlands.

Atherosclerosis is the major cause of cardiovascular disease (CVD). Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. In patients with atherosclerotic CVD, leukocytes have a hyperinflammatory phenotype. We hypothesize that immune cell reprogramming in these patients occurs at the level of myeloid progenitors. We included 13 patients with coronary artery disease due to severe atherosclerosis and 13 subjects without atherosclerosis in an exploratory study. Cytokine production capacity after stimulation of peripheral blood mononuclear cells (MNCs) and bone marrow MNCs was higher in patients with atherosclerosis. In BM-MNCs this was associated with increased glycolysis and oxidative phosphorylation. The BM composition was skewed towards myelopoiesis and transcriptome analysis of HSC/GMP cell populations revealed enrichment of neutrophil- and monocyte-related pathways. These results show that in patients with atherosclerosis, activation of innate immune cells occurs at the level of myeloid progenitors, which adds exciting opportunities for novel treatment strategies.
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http://dx.doi.org/10.7554/eLife.60939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665893PMC
November 2020

Ultrafast carrier relaxation dynamics of photoexcited GaAs and GaAs/AlGaAs nanowire array.

Phys Chem Chem Phys 2020 Nov;22(44):25819-25826

State Key Laboratory of High-Power Semiconductor Laser, School of Science, Changchun University of Science and Technology, 7089 Wei-Xing Road, Changchun 130022, China.

Femtosecond optical pump-probe spectroscopy is employed to elucidate the ultrafast carrier nonradiative relaxation dynamics of bare GaAs and a core-shell GaAs/AlGaAs semiconductor nanowire array. Different from the single nanowire conventionally used for the study of ultrafast dynamics, a simple spin coating and peeling off method was performed to prepare transparent organic films containing a vertical oriented nanowire array for transient absorption measurement. The transient experiment provides the direct observation of carrier thermalization, carrier cooling, thermal dissipation and band-gap energy evolutions along with the carrier relaxations. Carrier thermalization occurs within sub-0.5 ps and proceeds almost independently on the AlGaAs-coating, while the time constants of carrier cooling and thermal dissipation are increased by an order of magnitude due to the AlGaAs-coating effect. The concomitant band-gap evolutions in GaAs and GaAs/AlGaAs include an initial rapid red-shift in thermalization period, followed by a slow blue and/or red shift in carrier cooling, and then by an even slower blue shift in thermal dissipation. The evolution is explained by the competition of band-gap renormalization, plasma screening and band-filling. These findings are significant for understanding the basic physics of carrier scattering, and also for the development of flexible optoelectronic devices.
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http://dx.doi.org/10.1039/d0cp04250aDOI Listing
November 2020

Molecular detection of opportunistic pathogens and insights into microbial diversity in private well water and premise plumbing.

J Water Health 2020 Oct;18(5):820-834

Department of Environmental Health Sciences, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, 70112, USA E-mail:

Private well water systems in rural areas that are improperly maintained will result in poor drinking water quality, loss of water supply, and pose human health risk. The purpose of this study was to investigate the occurrence of fecal indicator bacteria (FIB) and opportunistic pathogens in private well water in rural areas surrounding New Orleans, Louisiana. Our results confirmed the ubiquitous nature of Legionella (86.7%) and mycobacteria (68.1%) in private well water in the study area, with gene concentration ranged from 0.60 to 5.53 and 0.67 to 5.95 Log of GC/100 mL, respectively. Naegleria fowleri target sequence was detected in 16.8% and Escherichia coli was detected in 43.4% of the water samples. Total coliform, as well as Legionella and mycobacteria genetic markers' concentrations were significantly reduced by 3-minute flushing. Next-generation sequencing (NGS) data indicated that the abundance of bacterial species was significantly increased in water collected in kitchens compared with samples from wells directly. This study provided integrated knowledge on the persistence of pathogenic organisms in private well water. Further study is needed to explore the presence of clinical species of those opportunistic pathogens in private well water systems to elucidate the health risk.
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http://dx.doi.org/10.2166/wh.2020.271DOI Listing
October 2020

Metabolites from Fungi and Their Biological Activities.

J Fungi (Basel) 2020 Oct 16;6(4). Epub 2020 Oct 16.

Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China.

(teleomorph: ) fungi are well known to produce a variety of secondary metabolites with various biological activities to show their pharmaceutical and agrochemical applications. Up to now, at least 229 secondary metabolites, mainly including 84 nitrogen-containing metabolites, 85 polyketides, 40 terpenoids, and 20 other metabolites, have been reported. Many of these compounds exhibit biological activities, such as cytotoxic, antimicrobial, antileishmanial, antimalarial activities. This mini-review aims to summarize the diversity of the secondary metabolites as well as their occurrences in fungi and biological activities.
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http://dx.doi.org/10.3390/jof6040229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712584PMC
October 2020

Massively Parallel Sequencingof the Filaggrin Gene Reveals an Association Between FLG Loss-of-function Mutations and Leprosy.

Acta Derm Venereol 2020 Oct 21;100(17):adv00299. Epub 2020 Oct 21.

Shandong Provincial Hospital for Skin Diseases and Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University and Shandong Academy of Medical Sciences, 27397 Jingshi Lu, Jinan 250022, China.

Filaggrin, encoded by the FLG gene, plays a crucial role in the barrier function of epidermis, but the association between FLG loss-of-function mutations and infectious skin diseases has not been systematically studied. FLG coding sequences from 945 patients with leprosy and 916 healthy controls were captured and enriched using an array-based high-throughput system, and subjected to next-generation sequencing. The loss-of-function mutations found were further validated by Sanger sequencing. A total of 21 loss-of-function mutations were found in 945 patients with leprosy, with a carrier rate of 17.53%, while the prevalence of these mutations in 916 healthy controls was 14.77%, which was significantly lower than in patients. Two individual FLG loss-of-function mutations (K4022X and Q1790X) were found to be significantly associated with leprosy. These results suggest a possible role for filaggrin in defending against leprosy pathogens.
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http://dx.doi.org/10.2340/00015555-3663DOI Listing
October 2020

Effect of surface properties on the electrochemical response of cynarin by electro-synthesized functionalized-polybithiophene/MWCNT/GNP.

Mater Sci Eng C Mater Biol Appl 2020 Sep 11;114:111067. Epub 2020 May 11.

Henan International Joint Laboratory of Medicinal Plants Utilization, College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, China. Electronic address:

Cynarin is one of the biologically active functional components present a wide range of pharmacological applications. Herein, we reported the fabrication and surface properties investigation of a new highly sensitive electrochemical sensor for the detection of cynarin. The electrochemical sensors were fabricated in several steps; the first being the synthesis of bi-thiophene derivatives-based monomers 3,3'-bithiophen (M1); 2-methoxy-5-carbaldehyde-[3,3'-bithiophene] (M2) and 2-((2-methoxy-[3,3'-bithiophen]-5-yl)methylene)malononitrile) (M3) followed by electrochemical polymerization on a glassy carbon electrode after which multi-walled carbon nanotube (MWCNT) and gold nanoparticles (GNP's) were electrodeposited layer-by-layer on the polymer coating to obtain multilayer electrochemical sensors. The morphological properties of the formed polymers were evaluated using SEM analysis and the apparent contact angles to preview the changes in surface properties after the functionalization of monomers and therefore their effects on the detection of cynarin. Analytical parameters such as the accumulation time and pH of the PBS solution which influence the sensitivity of the electrochemical sensors were optimized. Under the optimal conditions the GCE/P3/MWCNT/GNP's showed a wide range of analyte concentrations (1 to 100 μM and 0.01 to 1 μM) and detection limit of 0.0095 using pulse differential voltammetry. In addition, the electrochemical sensors showed good reproducibility, stability and selectivity and they were used successfully for the determination of cynarin in real solutions.
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http://dx.doi.org/10.1016/j.msec.2020.111067DOI Listing
September 2020

Revealing the Structure and Oxygen Transport at Interfaces in Complex Oxide Heterostructures via O NMR Spectroscopy.

Chem Mater 2020 Sep 19;32(18):7921-7931. Epub 2020 Aug 19.

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, United Kingdom.

Vertically aligned nanocomposite (VAN) films, comprising nanopillars of one phase embedded in a matrix of another, have shown great promise for a range of applications due to their high interfacial areas oriented perpendicular to the substrate. In particular, oxide VANs show enhanced oxide-ion conductivity in directions that are orthogonal to those found in more conventional thin-film heterostructures; however, the structure of the interfaces and its influence on conductivity remain unclear. In this work, O NMR spectroscopy is used to study CeO-SrTiO VAN thin films: selective isotopic enrichment is combined with a lift-off technique to remove the substrate, facilitating detection of the O NMR signal from single atomic layer interfaces. By performing the isotopic enrichment at variable temperatures, the superior oxide-ion conductivity of the VAN films compared to the bulk materials is shown to arise from enhanced oxygen mobility at this interface; oxygen motion at the interface is further identified from O relaxometry experiments. The structure of this interface is solved by calculating the NMR parameters using density functional theory combined with random structure searching, allowing the chemistry underpinning the enhanced oxide-ion transport to be proposed. Finally, a comparison is made with 1% Gd-doped CeO-SrTiO VAN films, for which greater NMR signal can be obtained due to paramagnetic relaxation enhancement, while the relative oxide-ion conductivities of the phases remain similar. These results highlight the information that can be obtained on interfacial structure and dynamics with solid-state NMR spectroscopy, in this and other nanostructured systems, our methodology being generally applicable to overcome sensitivity limitations in thin-film studies.
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http://dx.doi.org/10.1021/acs.chemmater.0c02698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513580PMC
September 2020

Dynamic Experimental Study on the Paraffin Deposition Prevention Performance of Tungsten Alloy Coating Pipe in Simulating Vertical Wellbore.

ACS Omega 2020 Sep 31;5(36):23284-23288. Epub 2020 Aug 31.

School of Petroleum Engineering, China University of Petroleum (East China), Qingdao 266580, China.

In this study, a self-designed apparatus was used to provide a quantitative evaluation of the wax prevention effect of tungsten alloy-coated tubing compared with ordinary tubing in oil production. The paraffin deposition of both pipes at different temperatures and different flow rates was studied. The efficiency of paraffin deposition prevention of the tungsten alloy coating pipe was analyzed. The results show that using this apparatus can efficiently and accurately calculate the wax prevention rate and can accurately obtain the wax deposit and wax thickness of the inner wall. The paraffin deposition of both pipes reaches the highest point at 290.15 K, and it reduces with the increase of flow rate. The use of the tungsten alloy coating pipe results in about 30% reduction in paraffin deposition. It provides a promising method for the paraffin inhibition to extend the wax removal cycle.
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http://dx.doi.org/10.1021/acsomega.0c03002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495718PMC
September 2020

Clinical features and surgical outcomes of type A intramural hematoma.

J Thorac Dis 2020 Aug;12(8):3964-3975

Department of Cardiovascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Data on the clinical features and surgical outcomes of type A intramural hematoma (IMH) in Chinese patients are very limited. We aimed to present the surgical experiences on type A IMH in our center, and report early and late outcomes.

Methods: From February 2012 to April 2018, 106 consecutive patients underwent open surgery for type A IMH at our hospital. We adopted emergent operation for patients with cardiac tamponade or other severe complications, and recommended initial medical treatment followed by elective surgery for stable patients. The composite endpoints included operative mortality, permanent nerve damage (stroke, paraplegia), and new-onset renal failure necessitating hemodialysis. Risk factors for operative mortality and the composite endpoints were identified using univariable and multivariable logistic regression model analysis. The survival and freedom from aortic events were analyzed using a Kaplan-Meier surviving curve and a log-rank test.

Results: Except 1 patient receiving emergent surgery (within 24 hours from onset) because of cardiac tamponade and cerebral malperfusion, all patients received initial medical treatment and delayed surgery. Two patient developed pericardial tamponade while waiting for surgery, and then received emergent surgery. Preoperative conversion to aortic dissection (AD) was noted in no patient. The operative techniques included ascending aorta replacement in 9 patients, hemiarch replacement in 18 patients, total arch replacement (TAR) with frozen elephant trunk (FET) in 45 patient and hybrid aortic arch repair in 34 patients. The mean cardiopulmonary bypass (CPB) time and cross-clamp time were 138.7±41.6 and 79.3±27.8 min, respectively. The operative mortality was 1.9% (2/106). And the composite endpoints occurred in 7 patients. Multivariable logistic regression analysis showed CPB time ≥200 min and chronic kidney disease were risk factors for the composite endpoints. The follow-up data were available in 97 survivors, with the mean follow-up time of 30.8±16.2 months. Three patients died and 5 patients developed aortic events during the follow-up. The overall survival at 1-, 3- and 5-year were 97.0%, 95.3%, and 79.4%, respectively. And freedom from aortic events at 1-, 3- and 5-year were 97.7%, 95.3% and 89.4%, respectively.

Conclusions: Our strategy had got low mortality and excellent mid-term survival in patients with type A IMH. Therefore, our strategy was suitable for the surgical repair of type A IMH in Chinese population.
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http://dx.doi.org/10.21037/jtd-20-748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475568PMC
August 2020

Implementation and evaluation of a novel real-time multiplex assay for SARS-CoV-2: in-field learnings from a clinical microbiology laboratory.

Pathology 2020 Dec 1;52(7):754-759. Epub 2020 Sep 1.

Department of Microbiology, Royal Melbourne Hospital, Melbourne, Vic, Australia; Victorian Infectious Diseases Reference Laboratory, The Peter Doherty Institute for Infection and Immunity, Melbourne, Vic, Australia; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Vic, Australia.

The unprecedented scale of testing required to effectively control the coronavirus disease (COVID-19) pandemic has necessitated urgent implementation of rapid testing in clinical microbiology laboratories. To date, there are limited data available on the analytical performance of emerging commercially available assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and integration of these assays into laboratory workflows. Here, we performed a prospective validation study of a commercially available assay, the AusDiagnostics Coronavirus Typing (8-well) assay. Respiratory tract samples for SARS-CoV-2 testing were collected between 1 March and 25 March 2020. All positive samples and a random subset of negative samples were sent to a reference laboratory for confirmation. In total, 2673 samples were analysed using the Coronavirus Typing assay. The predominant sample type was a combined nasopharyngeal/throat swab (2640/2673; 98.8%). Fifty-four patients were positive for SARS-CoV-2 (2.0%) using the Coronavirus Typing assay; 53/54 (98.1%) positive results and 621/621 (100%) negative results were concordant with the reference laboratory. Compared to the reference laboratory gold standard, sensitivity of the Coronavirus Typing assay for SARS-CoV-2 was 100% (95% CI 93.2-100%), specificity 99.8% (95% CI 99.1-100%), positive predictive value 98.1% (95% CI 90.2-99.7%) and negative predictive value 100% (95% CI 99.4-100%). In many countries, standard regulatory requirements for the introduction of new assays have been replaced by emergency authorisations and it is critical that laboratories share their post-market validation experiences, as the consequences of widespread introduction of a suboptimal assay for SARS-CoV-2 are profound. Here, we share our in-field experience, and encourage other laboratories to follow suit.
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http://dx.doi.org/10.1016/j.pathol.2020.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462582PMC
December 2020

Generation of hypoimmunogenic human pluripotent stem cells via expression of membrane-bound and secreted β2m-HLA-G fusion proteins.

Stem Cells 2020 11 15;38(11):1423-1437. Epub 2020 Sep 15.

Brain and Spinal Cord Clinical Research Center, Tongji University School of Medicine, Shanghai, People's Republic of China.

Allogeneic immune rejection is a major barrier for the application of human pluripotent stem cells (hPSCs) in regenerative medicine. A broad spectrum of immune cells, including T cells, natural killer (NK) cells, and antigen-presenting cells, which either cause direct cell killing or constitute an immunogenic environment, are involved in allograft immune rejection. A strategy to protect donor cells from cytotoxicity while decreasing the secretion of inflammatory cytokines of lymphocytes is still lacking. Here, we engineered hPSCs with no surface expression of classical human leukocyte antigen (HLA) class I proteins via beta-2 microglobulin (B2M) knockout or biallelic knockin of HLA-G1 within the frame of endogenous B2M loci. Elimination of the surface expression of HLA class I proteins protected the engineered hPSCs from cytotoxicity mediated by T cells. However, this lack of surface expression also resulted in missing-self response and NK cell activation, which were largely compromised by expression of β2m-HLA-G1 fusion proteins. We also proved that the engineered β2m-HLA-G5 fusion proteins were soluble, secretable, and capable of safeguarding low immunogenic environments by lowering inflammatory cytokines secretion in allografts. Our current study reveals a novel strategy that may offer unique advantages to construct hypoimmunogenic hPSCs via the expression of membrane-bound and secreted β2m-HLA-G fusion proteins. These engineered hPSCs are expected to serve as an unlimited cell source for generating universally compatible "off-the-shelf" cell grafts in the future.
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http://dx.doi.org/10.1002/stem.3269DOI Listing
November 2020