Publications by authors named "Fang Gao"

329 Publications

Rational Design of Dendritic Mesoporous Silica Nanoparticles' Surface Chemistry for Quantum Dot Enrichment and an Ultrasensitive Lateral Flow Immunoassay.

ACS Appl Mater Interfaces 2021 May 3. Epub 2021 May 3.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.

Lateral flow immunoassays (LFIAs) have drawn much attention in point-of-care diagnostic applications, and the development of high-performance label materials is the key. In this study, the impact of the surface chemistry of dendritic mesoporous silica nanoparticles (DMSNs) on their enrichment performance toward quantum dots (QDs) and signal amplification of the resultant DMSNs-QDs as label materials have been investigated. A series of DMSNs with controllable amino/thiol group densities have been synthesized. It is demonstrated that the amino groups are beneficial for QD fluorescence preservation, owing to the amino-based surface passivation, while the thiol groups are responsible for increasing the loading capacity of QDs due to the thiol-metal coordination. The optimized DMSNs-QDs labels with an amino density of 153 μmol g and a thiol density of 218 μmol g displayed sufficient QD fluorescence preservation (89.4%) and high QD loading capacity (1.55 g g). Ultrasensitive detection of serum amyloid A (SAA) with a detection limit of 10 pg mL with the naked eye was achieved, which is 1 order of magnitude higher than that reported in the literature. This study provides insights into the development of advanced label materials and an ultrasensitive LFIA for future bioassay applications.
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http://dx.doi.org/10.1021/acsami.1c02149DOI Listing
May 2021

Glycoconjugate vaccines against serovars and species: existing and emerging methods for their analysis.

Biophys Rev 2021 Apr 10:1-26. Epub 2021 Apr 10.

School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, LE12 5RD UK.

The global spread of enteric disease, the increasingly limited options for antimicrobial treatment and the need for effective eradication programs have resulted in an increased demand for glycoconjugate enteric vaccines, made with carbohydrate-based membrane components of the pathogen, and their precise characterisation. A set of physico-chemical and immunological tests are employed for complete vaccine characterisation and to ensure their consistency, potency, safety and stability, following the relevant World Health Organization and Pharmacopoeia guidelines. Variable requirements for analytical methods are linked to conjugate structure, carrier protein nature and size and acetyl content of polysaccharide. We investigated a key stability-indicating method which measures the percent free saccharide of subspecies serovar Typhi capsular polysaccharide, by detergent precipitation, depolymerisation and HPAEC-PAD quantitation. Together with modern computational approaches, a more precise design of glycoconjugates is possible, allowing for improvements in solubility, structural conformation and stability, and immunogenicity of antigens, which may be applicable to a broad spectrum of vaccines. More validation experiments are required to establish the most effective and suitable methods for glycoconjugate analysis to bring uniformity to the existing protocols, although the need for product-specific approaches will apply, especially for the more complex vaccines. An overview of current and emerging analytical approaches for the characterisation of vaccines against Typhi and species is described in this paper. This study should aid the development and licensing of new glycoconjugate vaccines aimed at the prevention of enteric diseases.
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http://dx.doi.org/10.1007/s12551-021-00791-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035613PMC
April 2021

Shed antigen-induced blocking effect on CAR-T cells targeting Glypican-3 in Hepatocellular Carcinoma.

J Immunother Cancer 2021 Apr;9(4)

Key Laboratory of Human Functional Genomics of Jiangsu Province, National Health Commission Key Laboratory of Antibody Techniques, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China

Background: Glypican-3 (GPC3), a cell surface glycoprotein that is pathologically highly expressed in hepatocellular carcinoma (HCC), is an attractive target for immunotherapies, including chimeric antigen receptor (CAR) T cells. The serum GPC3 is frequently elevated in HCC patients due to the shedding effect of cell surface GPC3. The shed GPC3 (sGPC3) is reported to block the function of cell-surface GPC3 as a negative regulator. Therefore, it would be worth investigating the potential influence of antigen shedding in anti-GPC3 CAR-T therapy for HCC.

Methods: In this study, we constructed two types of CAR-T cells targeting distinct epitopes of GPC3 to examine how sGPC3 influences the activation and cytotoxicity of CAR-T cells in vitro and in vivo by introducing sGPC3 positive patient serum or recombinant sGPC3 proteins into HCC cells or by using sGPC3-overexpressing HCC cell lines.

Results: Both humanized YP7 CAR-T cells and 32A9 CAR-T cells showed GPC3-specific antitumor functions in vitro and in vivo. The existence of sGPC3 significantly inhibited the release of cytokines and the cytotoxicity of anti-GPC3 CAR-T cells in vitro. In animal models, mice carrying Hep3B xenograft tumors expressing sGPC3 exhibited a worse response to the treatment with CAR-T cells under both a low and high tumor burden. sGPC3 bound to CAR-T cells but failed to induce the effective activation of CAR-T cells. Therefore, sGPC3 acted as dominant negative regulators when competed with cell surface GPC3 to bind anti-GPC3 CAR-T cells, leading to an inhibitory effect on CAR-T cells in HCC.

Conclusions: We provide a proof-of-concept study demonstrating that GPC3 shedding might cause worse response to CAR-T cell treatment by competing with cell surface GPC3 for CAR-T cell binding, which revealed a new mechanism of tumor immune escape in HCC, providing a novel biomarker for patient enrolment in future clinical trials and/or treatments with GPC3-targeted CAR-T cells.
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http://dx.doi.org/10.1136/jitc-2020-001875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039282PMC
April 2021

Endocannabinoid system in the neurodevelopment of GABAergic interneurons: implications for neurological and psychiatric disorders.

Rev Neurosci 2021 Mar 30. Epub 2021 Mar 30.

Department of Neurobiology and Institute of Neurosciences, Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, 169 Chang Le Xi Road, Xi'an710032, Shaanxi, China.

In mature mammalian brains, the endocannabinoid system (ECS) plays an important role in the regulation of synaptic plasticity and the functioning of neural networks. Besides, the ECS also contributes to the neurodevelopment of the central nervous system. Due to the increase in the medical and recreational use of cannabis, it is inevitable and essential to elaborate the roles of the ECS on neurodevelopment. GABAergic interneurons represent a group of inhibitory neurons that are vital in controlling neural network activity. However, the role of the ECS in the neurodevelopment of GABAergic interneurons remains to be fully elucidated. In this review, we provide a brief introduction of the ECS and interneuron diversity. We focus on the process of interneuron development and the role of ECS in the modulation of interneuron development, from the expansion of the neural stem/progenitor cells to the migration, specification and maturation of interneurons. We further discuss the potential implications of the ECS and interneurons in the pathogenesis of neurological and psychiatric disorders, including epilepsy, schizophrenia, major depressive disorder and autism spectrum disorder.
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http://dx.doi.org/10.1515/revneuro-2020-0134DOI Listing
March 2021

Regulating effect of spraying stage of ethephon on the formation of source-sink in peanut.

Ying Yong Sheng Tai Xue Bao 2021 Mar;32(3):951-958

College of Agronomy, Shandong Agricultural University/State Key Laboratory of Crop Biology, Tai'an 271018, Shandong, China.

To solve the problem of uncoordinated source-sink relationship that limits the increase of peanut yield, we investigated the regulating effects of ethephon on the formation of source-sink in cultivar Shanhua 9 by spraying at 10, 20, and 30 d after anthesis in a field experiment. The results showed that spraying ethephon at 10 d and 20 d after anthesis significantly reduced the number of flowers, pegs and young pods, but increased the number of immature pods and mature pods. Spraying at 30 d after anthesis did not affect the number of flowers, pegs and young pods. Spraying ethephon could improve the leaf area per plant. Spraying at 10 d after anthesis achieved the highest leaf area per plant and the increment amplitude decreased with the delay of spraying stage. Spraying ethephon at 10 d and 20 d after anthesis significantly improved the photosynthetic performance of peanut, whereas spraying at 30 days after anthesis increased the photosynthesis only in the short-term and had no effect at late growth period. In terms of the comprehensive characters of source and sink, spraying ethephon at 20 d after anthesis achieved the most harmonious source-sink relationship, which could promote the transport of photosynthate to pods and increase the economic pods ratio, pod fullness, and the yield. Therefore, spraying ethephon is an effective practice to solve the problems of "more flowers but less pegs" and "more pods but less kernels" in peanut. The optimum spraying stage of ethephon to regulate flowering should be at 20 d after anthesis.
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http://dx.doi.org/10.13287/j.1001-9332.202103.029DOI Listing
March 2021

Identification of low-frequency variants of UGT1A3 associated with bladder cancer risk by next-generation sequencing.

Oncogene 2021 Apr 3;40(13):2382-2394. Epub 2021 Mar 3.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.

Although genome-wide association studies (GWASs) have successfully revealed many common risk variants for bladder cancer, the heritability is still largely unexplained. We hypothesized that low-frequency variants involved in bladder cancer risk could reveal the unexplained heritability. Next-generation sequencing of 113 patients and 118 controls was conducted on 81 genes/regions of known bladder cancer GWAS loci. A two-stage validation comprising 3,350 cases and 4,005 controls was performed to evaluate the effects of low-frequency variants on bladder cancer risk. Biological experiments and techniques, including electrophoretic mobility shift assays, CRISPR/Cas9, RNA-Seq, and bioinformatics approaches, were performed to assess the potential functions of low-frequency variants. The low-frequency variant rs28898617 was located in the first exon of UGT1A3 and was significantly associated with increased bladder cancer risk (odds ratio = 1.50, P = 3.10 × 10). Intriguingly, rs28898617 was only observed in the Asian population, but monomorphism was observed in the European population. The risk-associated G allele of rs28898617 increased UGT1A3 expression, facilitated UGT1A3 transcriptional activity, and enhanced the binding activity. In addition, UGT1A3 deletion significantly inhibited the proliferation, invasion, and migration of bladder cancer cells and xenograft tumor growth. Mechanistically, UGT1A3 induced LAMC2 expression by binding CBP and promoting histone acetylation, which remarkably promoted the progression of bladder cancer. This is the first targeted sequencing study to reveal that the novel low-frequency variant rs28898617 and its associated gene UGT1A3 are involved in bladder cancer development, providing new insights into the genetic architecture of bladder cancer.
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http://dx.doi.org/10.1038/s41388-021-01672-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016664PMC
April 2021

Saccharide dosage content of meningococcal polysaccharide conjugate vaccines determined using WHO International Standards for serogroup A, C, W, Y and X polysaccharides.

Biologicals 2021 Apr 29;70:53-58. Epub 2021 Jan 29.

Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, Potters Bar, Hertfordshire, EN6 3QG, UK.

Potency of meningococcal polysaccharide-protein conjugate vaccines relies on the polysaccharide content to prevent meningitis. NIBSC, as the official national control laboratory in UK, analysed ten different mono- and multi-meningococcal conjugate vaccines, using established International Standards for meningococcal serogroups A, C, W, Y and X, by resorcinol or HPAEC-PAD assay. Most saccharide contents were within ±20% of their claimed content for licensure with taking different O-acetylation levels into consideration, with only MenC content in two vaccines below (by 60% and 54%) the labelled value, however, previous study showed different dosage was not necessarily correlated to the immunogenicity of those vaccines. This study demonstrated the use of International Standards to quantify saccharide content in polysaccharide-based vaccines with different percentage of O-acetylation. These International Standards are suitable to serve as either quantitative standard or calibrator of in-house standards, with supplied stability data.
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http://dx.doi.org/10.1016/j.biologicals.2021.01.001DOI Listing
April 2021

Bulbar Palsy as the Initial Manifestation of Multiple Myeloma: A Case Report.

J Natl Med Assoc 2021 Jan 18. Epub 2021 Jan 18.

Department of Neurology, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.

Multiple Myeloma (MM) is a neoplastic disorder derived from the malignant proliferation of monoclonal plasma cells. It is characterized by the overproduction of immunoglobulins (Ig). We report a rare case in which bulbar palsy was the initial manifestation of IgG-MM. A 66-year-old woman initially presented with progressive dysphagia and dysarthria for half a year. Physical examination demonstrated a deviation of the uvula, difficulty in protruding tongue, and bilateral tongue atrophy. Laboratory assessments revealed anemia and prominent monoclonal elevation of IgG levels both in serum and cerebrospinal fluid (CSF). The diagnosis of IgG-MM was confirmed by the identification of plasmacytosis in bone marrow aspiration and biopsy and elevation of γ-M protein in serum protein electrophoresis (SPEP). Therefore, the patient began to receive the chemotherapy with PAD (bortezomib-doxorubicin-dexamethasone) regimen. Her condition had been under control. MM as a hematological malignancy can affect cranial nerves and present as chronic progressive bulbar palsy.
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http://dx.doi.org/10.1016/j.jnma.2020.12.007DOI Listing
January 2021

Effects of Soil Tillage, Management Practices, and Mulching Film Application on Soil Health and Peanut Yield in a Continuous Cropping System.

Front Microbiol 2020 23;11:570924. Epub 2020 Dec 23.

State Key Laboratory of Crop Biology, Agronomy College of Shandong Agricultural University, Tai'an, China.

Our objective was to optimize soil management practices to improve soil health to increase peanut ( L.) yield. We studied the effects of using rotary tillage with mulching film or without [rotary tillage with no mulching (RTNM)], plow tillage with mulching film or without, and green manure with mulching film (GMMF) or without [green manure with no mulching (GMNM)] over 3 years in Tai'an, China. Results showed that compared with RTNM treatment, GMNM and GMMF treatments significantly ( < 0.05) increased soil organic carbon, enzymatic activity, and the available nitrogen, phosphorus, and potassium content. The dominant bacterial phyla in the soil across all treatments were Proteobacteria, Acidobacteria, and Actinobacteria. Bacterial richness and diversity in the soil were significantly ( < 0.05) enhanced after GMMF and GMNM treatments compared with those after RTNM treatment. The linear discriminant analysis effect size analysis indicated that Chloroflexi abundance in the 0-10 and 10-20 cm soil layers changed significantly ( < 0.05) after rotary tillage with mulching film and RTNM treatments, respectively, whereas that of Bacteroidetes changed significantly ( < 0.05) in the 0-10 layer after GMNM treatment. The abundance of the family of Proteobacteria in both soil layers changed significantly ( < 0.05) after GMNM and GMMF treatments. Redundancy analysis revealed that soil physical (soil bulk density and water content), chemical (soil organic carbon, available nitrogen, phosphorus, and potassium), and biological (soil enzymatic activity and nutrient content) characteristics affect the soil bacterial community. Changed soil quality indices may be favorable for leaf photo-assimilate accumulation. Compared with RTNM treatment, GMNM and GMMF treatments significantly increased photosynthesis rate in the peanut leaf and decreased intercellular carbon dioxide concentration. Our results showed that compared with that after RTNM treatment, the average pod yield after GMMF and GMNM treatments increased by 27.85 and 21.26%, respectively, due to increases in the pods per plant and plant numbers. The highest yield of all treatments was obtained from the GMMF-treated plot, followed by that from the GMNM-treated plots. Thus, taking into consideration the residual pollution caused by plastic films, we propose GMNM as a suitable strategy to improve soil physicochemical and microbial properties and to increase the peanut pod yield.
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http://dx.doi.org/10.3389/fmicb.2020.570924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785755PMC
December 2020

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases.

Int J Biol Sci 2021 1;17(1):32-49. Epub 2021 Jan 1.

Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.

βII spectrin, the most common isoform of non-erythrocyte spectrin, is a cytoskeleton protein present in all nucleated cells. Interestingly, βII spectrin is essential for the development of various organs such as nerve, epithelium, inner ear, liver and heart. The functions of βII spectrin include not only establishing and maintaining the cell structure but also regulating a variety of cellular functions, such as cell apoptosis, cell adhesion, cell spreading and cell cycle regulation. Notably, βII spectrin dysfunction is associated with embryonic lethality and the DNA damage response. More recently, the detection of altered βII spectrin expression in tumors indicated that βII spectrin might be involved in the development and progression of cancer. Its mutations and disorders could result in developmental disabilities and various diseases. The versatile roles of βII spectrin in disease have been examined in an increasing number of studies; nonetheless, the exact mechanisms of βII spectrin are still poorly understood. Thus, we summarize the structural features and biological roles of βII spectrin and discuss its molecular mechanisms and functions in development, homeostasis, regeneration and differentiation. This review highlight the potential effects of βII spectrin dysfunction in cancer and other diseases, outstanding questions for the future investigation of therapeutic targets. The investigation of the regulatory mechanism of βII spectrin signal inactivation and recovery may bring hope for future therapy of related diseases.
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http://dx.doi.org/10.7150/ijbs.52375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757025PMC
January 2021

The role of the microbiome in diabetes mellitus.

Diabetes Res Clin Pract 2021 Feb 24;172:108645. Epub 2020 Dec 24.

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

The microbiome is greatly significant for immune system development and homeostasis. Dysbiosis in gut microbial composition and function is linked to immune responses and the development of metabolic diseases, including diabetes mellitus (DM). However, skin microbiome changes in diabetic patients and their role in DM are poorly elucidated. In this review, we summarize recent findings about the association between the gut and skin microbiota and DM, highlighting their roles in the proinflammatory status of DM. Moreover, although there is evidence that the connection between the gut and skin causes the same activated innate immune response, additional studies are needed to explore the mechanism. These findings might inform future DM prevention, diagnosis and treatment.
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http://dx.doi.org/10.1016/j.diabres.2020.108645DOI Listing
February 2021

ISSD: Improved SSD for Insulator and Spacer Online Detection Based on UAV System.

Sensors (Basel) 2020 Dec 5;20(23). Epub 2020 Dec 5.

College of Electrical Engineering, Guangxi University, Nanning 530000, China.

In power inspection tasks, the insulator and spacer are important inspection objects. UAV (unmanned aerial vehicle) power inspection is becoming more and more popular. However, due to the limited computing resources carried by a UAV, a lighter model with small model size, high detection accuracy, and fast detection speed is needed to achieve online detection. In order to realize the online detection of power inspection objects, we propose an improved SSD (single shot multibox detector) insulator and spacer detection algorithm using the power inspection images collected by a UAV. In the proposed algorithm, the lightweight network MnasNet is used as the feature extraction network to generate feature maps. Then, two multiscale feature fusion methods are used to fuse multiple feature maps. Lastly, a power inspection object dataset containing insulators and spacers based on aerial images is built, and the performance of the proposed algorithm is tested on real aerial images and videos. Experimental results show that the proposed algorithm can efficiently detect insulators and spacers. Compared with existing algorithms, the proposed algorithm has the advantages of small model size and fast detection speed. The detection accuracy can achieve 93.8%. The detection time of a single image on TX2 (NVIDIA Jetson TX2) is 154 ms and the capture rate on TX2 is 8.27 fps, which allows realizing online detection.
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http://dx.doi.org/10.3390/s20236961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729514PMC
December 2020

Photoactivatable diazido Pt(IV) anticancer complex can bind to and oxidize all four nucleosides.

Dalton Trans 2020 Dec;49(47):17157-17163

Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials; School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P. R. China.

Photoactivatable diazidodihydroxido Pt(iv) complex trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1; py = pyridine) is a promising anticancer agent which can be activated by visible light to induce cancer cell death. DNA has been thought to be involved in the mechanism of action of this kind of Pt(iv) prodrug. However, the detailed photodecomposition pathways of complex 1 and its interaction modes with DNA are complex. Herein we report that upon light irradiation complex 1 can bind to all four nucleosides covalently with the reduced Pt(ii) species. Moreover, apart from the covalent coordination, various oxidation adducts of these four nucleosides induced by the reactive oxidative species (ROS) generated during the photoactivation of the complex 1 have also been identified, especially the induced oxidation of adenosine and cytidine which was firstly reported for this kind of photoactivatable Pt(iv) prodrug. Such dual-action may contribute to the highly potent photo-antiproliferativity of complex 1 towards cancer cells, which may account for the unique mechanism of action of the photoactivatable diazido Pt(iv) anticancer complexes.
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http://dx.doi.org/10.1039/d0dt03090bDOI Listing
December 2020

Hyperbranched molecules having multiple functional groups as effective corrosion inhibitors for Al alloys in aqueous NaCl.

J Colloid Interface Sci 2021 Mar 20;585:614-626. Epub 2020 Oct 20.

Chongqing Key Laboratory of Catalysis and New Environmental Materials, College of Environment and Resources, Chongqing Technology and Business University, Chongqing 400067, China.

Hyperbranched molecules are a kind of promising materials due to their unique structures. In this work, two hyperbranched molecules (GON and GOH) are used as effective inhibitors for Al alloys in NaCl solution. Their inhibitive performances are evaluated by electrochemical measurements and surface characterization. The results indicate that inhibition performances of GON and GOH are closely related to the concentrations, influenced by the combination of steric hindrance and bonding effects. At relatively low concentrations (0.03-0.10 mM), GON displays a more pronounced ability to inhibit corrosion than GOH, owing to more anchoring functional groups. Oppositely, GOH has good inhibition performance at higher concentrations (0.50-1.00 mM). The interaction between the Al electrode and GOH results in the formation of a more condenser protective film than GON at high concentrations. In addition, the adsorption mechanism of two hyperbranched molecules is revealed by theoretical calculations.
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http://dx.doi.org/10.1016/j.jcis.2020.10.041DOI Listing
March 2021

Protectin DX promotes epithelial injury repair and inhibits fibroproliferation partly via ALX/PI3K signalling pathway.

J Cell Mol Med 2020 12 24;24(23):14001-14012. Epub 2020 Oct 24.

Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, China.

Acute respiratory distress syndrome/acute lung injury (ARDS/ALI) is histologically characterized by extensive alveolar barrier disruption and excessive fibroproliferation responses. Protectin DX (PDX) displays anti-inflammatory and potent inflammation pro-resolving actions. We sought to investigate whether PDX attenuates LPS (lipopolysaccharide)-induced lung injury via modulating epithelial cell injury repair, apoptosis and fibroblasts activation. In vivo, PDX was administered intraperitoneally (IP) with 200 ng/per mouse after intratracheal injection of LPS, which remarkedly stimulated proliferation of type II alveolar epithelial cells (AT II cells), reduced the apoptosis of AT II cells, which attenuated lung injury induced by LPS. Moreover, primary type II alveolar cells were isolated and cultured to assess the effects of PDX on wound repair, apoptosis, proliferation and transdifferentiation in vitro. We also investigated the effects of PDX on primary rat lung fibroblast proliferation and myofibroblast differentiation. Our result suggests PDX promotes primary AT II cells wound closure by inducing the proliferation of AT II cells and reducing the apoptosis of AT II cells induced by LPS, and promotes AT II cells transdifferentiation. Furthermore, PDX inhibits transforming growth factor-β (TGF-β ) induced fibroproliferation, fibroblast collagen production and myofibroblast transformation. Furthermore, the effects of PDX on epithelial wound healing and proliferation, fibroblast proliferation and activation partly via the ALX/ PI3K signalling pathway. These data present identify a new mechanism of PDX which targets the airway epithelial cell and fibroproliferation are potential for treatment of ARDS/ALI.
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http://dx.doi.org/10.1111/jcmm.16011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754026PMC
December 2020

Diagnostic accuracy of donor-derived cell-free DNA in renal-allograft rejection: a meta-analysis.

Transplantation 2020 Sep 2. Epub 2020 Sep 2.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Donor-derived cell-free DNA (dd-cfDNA) is a potential noninvasive molecular marker of graft rejection after kidney transplant, whose diagnostic accuracy remains controversial.

Methods: We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of dd-cfDNA. Relevant literature was searched from online databases, and the data on the diagnostic accuracy of discriminating main rejection episodes (MRE) and antibody-mediated rejection (AMR) were merged, respectively.

Results: Nine studies were included in the meta-analysis, of which 6 were focused on the diagnostic accuracy of dd-cfDNA for MRE, whose pooled sensitivity, specificity, area under the receiver operating characteristics curve (AUC), diagnostic odds ratio(DOR), overall positive likelihood ratio (PLR), and negative likelihood ratio (NLR) with 95% confidence intervals were 0.70(0.57-0.81), 0.78(0.70-0.84), 0.81(0.77-0.84), 8.18(5.11-13.09), 3.15(2.47-4.02), 0.39(0.27-0.55), respectively. 5 tests were focused on discriminating AMR, whose pooled indicators were 0.84(0.75-0.90), 0.80(0.74-0.84), 0.89(0.86-0.91), 20.48(10.76-38.99), 4.13(3.21-5.33), 0.20(0.12-0.33), respectively.

Conclusions: Donor-derived cell-free DNA can be a helpful marker for the diagnosis of antibody-mediated rejection among those recipients suspected of renal dysfunction. Its diagnostic accuracy on the main rejection episodes remains uncertain, which requires further prospective, large-scale, multicenter, and common population research.
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http://dx.doi.org/10.1097/TP.0000000000003443DOI Listing
September 2020

Analysis of the Composition and Functions of the Microbiome in Diabetic Foot Osteomyelitis Based on 16S rRNA and Metagenome Sequencing Technology.

Diabetes 2020 11 14;69(11):2423-2439. Epub 2020 Aug 14.

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China

Metagenome sequencing has not been used in infected bone specimens. This prospective observational study explored the microbiome and its function in patients with diabetic foot osteomyelitis (DFO) and posttraumatic foot osteomyelitis (PFO) based on 16S rRNA sequencing and metagenome sequencing technologies. Spearman analysis was used to explore the correlation between dominant species and clinical indicators of patients with DFO. High-throughput sequencing showed that all the specimens were polymicrobial. The microbial diversity was significantly higher in the DFO group than in the PFO group. , , and were the most abundant microbes in the DFO group. The most abundant microbes in the PFO group were , , and , , and had positive correlation with the duration of diabetic foot infection (DFI_d). was positively correlated with the infection index, while was negatively correlated. The microbial functional genes were more abundant in the DFO group than in the PFO group. Metagenome sequencing is feasible for the analysis of the microbiome in infected bone specimens. Gram-negative bacteria and anaerobes are dominant in DFO.
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http://dx.doi.org/10.2337/db20-0503DOI Listing
November 2020

Sensory Brand Experience: Development and Validation in the Chinese Context.

Front Psychol 2020 21;11:1436. Epub 2020 Jul 21.

Research Center of City Development, Shanghai Urban Construction Vocational College, Shanghai, China.

Extant scales related to measuring the sensory aspect of a brand from the consumer's perspective are typically either too abstract or too concrete. Thus, this study aimed to create a scale with a medium degree of abstraction by which to measure sensory brand experience. This entailed a process of scale development and validation. In study 1, we conducted a qualitative study to explore possible dimensions and items using semi-structured interviews. Several dimensions and items were proposed by combining findings from a literature review and the consumer interviews. In study 2, we examined the items and preliminarily tested the validity of the scale. The results show that, according to our scale, most of the brands considered could be differentiated in terms of the sensory experience they generate. The scale is thus deemed to have potential as a useful tool by which to evaluate the sensory quality of brands. In study 3, we further examined the items, verified the dimensions, tested the reliability and validity of the scale, and formally presented a final version of the scale. This final version comprises three dimensions and 10 items. The three dimensions represent, respectively, three important factors that may influence consumers' perceptions and evaluations of the sensory quality of brands: the volume of sensory brand stimuli, the uniqueness of sensory brand stimuli, and the consistency between sensory brand stimuli and consumer. The scale's reliability and validity are found to be satisfactory. Future research can thus employ the scale to assess the sensory experience of various brands, and even to rank brands accordingly. While the present study in the Chinese context is expected to provide valuable insights into the brand experience and sensory branding literature, further research could be conducted to validate the scale in other geographical and cultural contexts.
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http://dx.doi.org/10.3389/fpsyg.2020.01436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385228PMC
July 2020

Risk factors associated with the severity of obstructive sleep apnea syndrome among adults.

Sci Rep 2020 08 11;10(1):13508. Epub 2020 Aug 11.

Department of Psychosomatics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.

Obstructive sleep apnea syndrome (OSAS) is a complete or partial airway obstruction that causes significant physiologic disturbance with various clinical impacts. The aim of the study was to determine the risk factors associated with the severity of OSAS. 303 patients with OSAS and 199 patients without OSAS enrolled in the sleep disorder center from 2017 to 2019 were included in the study. All patients completed physical examination, Epworth sleepiness scale, and polysomnography. By apnea-hypopnea index (AHI), patients were separated into four subsets: AHI < 5 as non-OSAS group, AHI ≧ 5 and < 15 as mild group, AHI ≧ 15 and < 30 as moderate group and AHI ≧ 30 as severe group. AVONA analyses, chi-square test, univariate and multivariate linear regression analyses were conducted to assess the correlation between specific factors and AHI. Our study demonstrated that patients with severe OSAS were associated with higher body mass index, higher systolic blood pressure awake in the morning, lengthened latent period of slow wave sleep, lower level of average oxygen saturation and minimum oxygen saturation (P < 0.05). Our findings provide evidence regarding several potentially useful factors for recognizing OSAS in adults, and physicians should promote the early recognition, diagnosis and intervention of OSAS.
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http://dx.doi.org/10.1038/s41598-020-70286-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7421897PMC
August 2020

32A9, a novel human antibody for designing an immunotoxin and CAR-T cells against glypican-3 in hepatocellular carcinoma.

J Transl Med 2020 08 3;18(1):295. Epub 2020 Aug 3.

Key Laboratory of Human Functional Genomics of Jiangsu Province, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, 211166, People's Republic of China.

Background: Treatment of hepatocellular carcinoma (HCC) using antibody-based targeted therapies, such as antibody conjugates and chimeric antigen receptor T (CAR-T) cell therapy, shows potent antitumor efficacy. Glypican-3 (GPC3) is an emerging HCC therapeutic target; therefore, antibodies against GPC3 would be useful tools for developing immunotherapies for HCC.

Methods: We isolated a novel human monoclonal antibody, 32A9, by phage display technology. We determined specificity, affinity, epitope and anti-tumor activity of 32A9, and developed 32A9-based immunotherapy technologies for evaluating the potency of HCC treatment in vitro or in vivo.

Results: 32A9 recognized human GPC3 with potent affinity and specificity. The epitope of 32A9 was located in the region of the GPC3 protein core close to the modification sites of the HS chain and outside of the Wnt-binding site of GPC3. The 32A9 antibody significantly inhibited HCC xenograft tumor growth in vivo. We then pursued two 32A9-based immunotherapeutic strategies by constructing an immunotoxin and CAR-T cells. The 32A9 immunotoxin exhibited specific cytotoxicity to GPC3-positive cancer cells, while 32A9 CAR-T cells efficiently eliminated GPC3-positive HCC cells in vitro and caused HCC xenograft tumor regressions in vivo.

Conclusions: Our study provides a rationale for 32A9 as a promising GPC3-specific antibody candidate for HCC immunotherapy.
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http://dx.doi.org/10.1186/s12967-020-02462-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398316PMC
August 2020

"Star" miR-34a and CXCR4 antagonist based nanoplex for binary cooperative migration treatment against metastatic breast cancer.

J Control Release 2020 10 29;326:615-627. Epub 2020 Jul 29.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Invasion and metastasis of tumor cells is one of the major obstacles in cancer therapy. The process of tumor metastasis and diffusion is coordinated by multiple pathways associated with chemokine signals and migration microenvironment. In our previous work, chemokine CXC receptor 4 (CXCR4) antagonists showed significant anti-metastatic effects by blocking the CXCR4/stromal cell-derived factor-1(SDF-1) axis in pancreatic cancer and breast cancer. Here, we proposed to achieve migration chain-treatment for metastatic tumors by introducing a cell adhesion molecules CD44 inhibitor (Star miR-34a) to deprive of cell migration capability on the basis of CXCR4 antagonism (cyclam monomer, CM). Dextrin modified 1.8 k PEI with CM-end was prepared to deliver therapeutic miR-34a (named DPC/miR-34a) for efficient anti-metastasis by downregulating adhesion protein CD44 and targeting the CXCR4/SDF-1 axis. Additionally, reduced expression of the anti-apoptotic protein Bcl2 caused by miR-34a could enhance the anti-tumor efficacy of DPC/miR-34a nanoplex administration. Compared with inhibition of the CXCR4/SDF-1 axis or CD44 expression, the multidimensional therapy (DPC/miR-34a) exhibited considerable suppression of cancer cell invasion as assessed by an in vitro cell invasion assay and in vivo anti-metastasis model. Moreover, DPC/miR-34a demonstrated a superior antitumor and anti-metastatic efficacy both in lung metastatic model and orthotopic MDA-MB-231 tumor models, thus providing an efficient approach for combating metastatic tumors.
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http://dx.doi.org/10.1016/j.jconrel.2020.07.029DOI Listing
October 2020

Ionic Liquid Gate-Induced Modifications of Step Edges at SrCoO Surfaces.

ACS Nano 2020 Jul 14;14(7):8562-8569. Epub 2020 Jul 14.

Max Planck Institute for Microstructure Physics, Halle (Saale) 06120, Germany.

Intense electric fields developed during gating at the interface between an ionic liquid and an oxide layer have been shown to lead to significant structural and electronic phase transitions in the entire oxide layer. An archetypical example is the reversible transformation between the brownmillerite SrCoO and the perovskite SrCoO engendered by ionic liquid gating. Here we show using atomic force microscopy studies with photothermal excitation detection, that allows for high quality measurements in the viscous environment of the ionic liquid that the edges of atomically smooth terraces at the surface of SrCoO films are significantly modified by ionic liquid gating but that the terraces themselves remain smooth. The edges develop ridges that we show, using complementary X-ray photoemission spectroscopy studies, result from the adsorption of hydroxyl groups. Our findings exhibit a way of electrically controlled surface modifications in emergent ionitronic applications.
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http://dx.doi.org/10.1021/acsnano.0c02880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467809PMC
July 2020

Regular use of proton pump inhibitor and risk of rheumatoid arthritis in women: a prospective cohort study.

Aliment Pharmacol Ther 2020 08 29;52(3):449-458. Epub 2020 Jun 29.

Shatin, Hong Kong.

Background: Proton pump inhibitors (PPIs) have a significant impact on the gut microbiome, which in turn, might increase the risk of rheumatoid arthritis (RA).

Aim: To evaluate regular use of PPIs and risk of RA.

Methods: This is a prospective analysis of the US nurses who reported PPI use data, and were free of RA from the Nurses' Health Study (NHS 2002-2014) and NHS II (2003-2015). The exposure was regular use of PPI in the past 2 years, which was repeatedly evaluated in biennial surveys. RA was confirmed by the 1987 or 2010 American College of Rheumatology criteria. We estimated the hazard ratios (HRs) and confidence interval (CIs) with time-dependent Cox regression adjusting for potential confounders.

Results: We documented 421 cases of RA over 1 753 879 person-years of follow-up. Regular PPI users had a 44% higher risk of RA as compared with non-regular users (adjusted HR = 1.44; 95%CI, 1.10-1.89). The risk of RA increased with the total duration of PPI use (P-trend = 0.008). Compared with non-regular users, the adjusted HRs were 1.22 (95%CI, 0.93-1.62) for women with >0 to 4 years' use and 1.73 (95% CI, 1.14 to 2.61) for >4 years' use.

Conclusions: Regular use of PPI was associated with increased risk of RA in women, with a higher risk observed in individuals with a longer duration of PPI use. Due to the observational study design, large prospective trials are still required to confirm our finding.
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http://dx.doi.org/10.1111/apt.15834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406413PMC
August 2020

Metabolic syndrome and risk of pancreatic cancer: A population-based prospective cohort study.

Int J Cancer 2020 12 29;147(12):3384-3393. Epub 2020 Jul 29.

Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.

Metabolic syndrome (MetS) and its components may link to pancreatic cancer risk; however, current epidemiological evidence is limited, and the potential mechanisms underlying the associations remain unclear. To investigate this, we carried out this prospective cohort study of 474 929 participants without a diagnosis of cancer based on UK Biobank dataset. MetS was defined according to the International Diabetes Federation criteria and pancreatic cancer was identified through linkage to UK cancer registries (median follow-up time: 6.6 years). We evaluated hazard ratio (HR) and 95% confidence interval (CI) with Cox proportional hazards regression, adjusting for demography and lifestyle factors. Restricted cubic spline was performed for each MetS component to investigate their possible nonlinear associations with risk of pancreatic cancer. During 3 112 566 person-years of follow-up, 565 cases of pancreatic cancer were identified. Individuals with MetS (HR = 1.31, 95% CI, 1.09-1.56), central obesity (HR = 1.24, 95% CI, 1.02-1.50) and hyperglycemia (HR = 1.60, 95% CI, 1.31-1.97) had increased risk of pancreatic cancer. Higher waist circumference (WC) and blood glucose were independently associated with pancreatic cancer, with no evidence against nonlinearity. Although elevated CRP (≥1.00 mg/dL) showed a positive association with the risk for pancreatic cancer, the effect was substantially increased only in participants with MetS and CRP ≥1.00 mg/dL. Our study demonstrated a positive association between MetS and increased risk of pancreatic cancer, with two of the MetS components, WC and blood glucose, showing independent associations in linear manner. Our study also suggested a potential joint effect of MetS and CRP in pancreas tumorigenesis.
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http://dx.doi.org/10.1002/ijc.33172DOI Listing
December 2020

Unpaired Electron-Induced Wide-Range Light Absorption within Zn (or Cu) MOFs Containing Electron-Withdrawing Ligands: A Theoretical and Experimental Study.

J Phys Chem A 2020 Jul 23;124(26):5314-5322. Epub 2020 Jun 23.

National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, Jiangsu Key Laboratory for Nano Technology, School of Physics, Nanjing University, Nanjing 210093, P. R. China.

In photocatalysis, it is of general interest to understand and design wide-range light-absorbing inorganic/organic hybrid materials with an excellent photo-induced intramolecular charge-transfer (ICT) effect. To verify the role of unpaired electrons in enhancing ICT within electron-withdrawing ligand-based metal-organic frameworks (MOFs), the molecular structure, density of states (DOS), and electronic structure of strong electron-deficient pyridine-diketopyrrolopyrrole ()-based Zn (or Cu) MOFs were calculated in Gaussian package to validate the unpaired electron ICT. The electron spin resonance technique has detected the unpaired electrons for the coordination systems containing Zn-O or Cu-O clusters and ligand on photoexcitation. The estimated band gaps from the DOS calculation for and are 1.4 and 2.4 eV, respectively, showing a good agreement with the experimental UV-vis optical spectra. The partial DOS, dipole moment, and frontier orbital analysis prove that the ICT should happen from Zn-O or Cu-O clusters to ligands. This research may contribute to a comprehensive understanding of electron-withdrawing ligand-induced ICT within MOFs and shed light on the design of light-absorbing MOFs with excellent ICT or conductivity.
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http://dx.doi.org/10.1021/acs.jpca.0c01577DOI Listing
July 2020

Protective function of exosomes from adipose tissue-derived mesenchymal stem cells in acute kidney injury through SIRT1 pathway.

Life Sci 2020 Aug 16;255:117719. Epub 2020 May 16.

Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China; Department of Internal Medicine and Diagnostics, Xuzhou Medical University, Xuzhou, China. Electronic address:

Aims: To investigate the protective function of exosomes from adipose tissue-derived mesenchymal stem cells (AMSCs) in sepsis-induced acute kidney injury (AKI) in mice and the possible underlying mechanism in order to provide a theoretical and experimental basis for using exosomes in clinical.

Main Methods: The AKI model was prepared through cecal ligation and puncture (CLP). Exosomes were injected via the tail vein of mice. Male C57/BL6 mice (18-22 g; 6-8 weeks old) were randomly grouped. Firstly, after mice were modeled, the variations of inflammatory cytokines and kidney functions at different time points (0, 6, 12, 24 and 48 h) were comprehended. Secondly, mice were divided into Sham, CLP and CLP + Exo, and the survival rates of each group were observed. Lastly, a time point (24 h) was selected for exploring the effect and mechanism of exosomes. The levels of inflammatory cytokines in serum were detected by ELISA, while the kidney was by immunohistochemistry. Kidney histopathological score were analyzed by hematoxylin-eosin (HE) staining. The protein levels of sirtuin 1 (SIRT1), inflammation-related and apoptosis-related were detected by western blot.

Key Findings: In CLP group, renal function gradually deteriorated, and the kidneys was in a state of inflammation, apoptosis and microcirculation disorders. However, SIRT1 was activated after intervention of exosomes in CLP mice, which reversed above changes. The mortality was reduced with treatment of exosomes in AKI mice.

Significance: In mice of sepsis-induce AKI, the intervention of AMSCs derived exosomes played a renal protective effect. The mechanism may be through SIRT1 signaling pathway.
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http://dx.doi.org/10.1016/j.lfs.2020.117719DOI Listing
August 2020

Association analysis between SNPs in LATS1 and LATS2 and non-cardia gastric cancer.

BMC Gastroenterol 2020 May 18;20(1):155. Epub 2020 May 18.

Inner Mongolia Institute of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, 30 Hudemulin Street, Baotou, 014030, Inner Mongolia, China.

Background: Many studies have found that large tumor suppressor kinase 1 (LATS1) and LATS2 play important roles in many diseases, but studies have been rare on the relationship between these genes and non-cardia gastric cancer (GC). We performed a case-control association study to investigate the associations between single nucleotide polymorphisms (SNPs) in LATS1 and LATS2 genes and Helicobacter pylori (H. pylori) infection as well as the risk of non-cardia GC.

Methods: First, H. pylori infection was determined by the serological test using enzyme-linked immunoassay. Then genotyping of SNPs was performed for 808 samples by the Taqman method. Finally, unconditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age and gender, for the association of each SNP with the infection of H. pylori, the risk of non-cardia gastric cancer, as well as the expression of LATS1 and LATS2 proteins in non-cardia GC tissues, using the codominant, dominant, recessive, overdominant, and log-additive inheritance models, respectively.

Results: The statistical results showed that LATS2 rs9552315 was associated with H. pylori infection, and the CC + CT genotype could reduce the risk of H. pylori infection (odds ratio [OR]: 0.549, 95% confidence interval [CI]: 0.339-0.881, P < 0.05) compared with the TT genotype in a dominant model. LATS1 rs9393175 was associated with the risk of non-cardia GC, and the AG genotype reduced the risk of non-cardia GC (OR: 0.702, 95% CI: 0.516-0.952, P < 0.05) compared with the GG + AA genotype in an overdominant model. LATS2 rs9509492 was associated with the risk of GC in an log-additive model. No associations were found between five SNPs and expression of LATS1 and LATS2 proteins in non-cardia GC tissue.

Conclusions: LATS2 rs9552315 CT genotype may be a protective factor against infection of H. pylori. LATS1 rs9393175 AG genotype and LATS2 rs9509492 GG genotype may be protective factors for non-cardia GC.
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http://dx.doi.org/10.1186/s12876-020-01250-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236108PMC
May 2020

Tolerance between non-resource stress and an invader determines competition intensity and importance in an invaded estuary.

Sci Total Environ 2020 Jul 25;724:138225. Epub 2020 Mar 25.

School of Environment, Beijing Normal University, State Key Joint Laboratory of Environmental Simulation and Pollution Control, Beijing 100875, China. Electronic address:

The competition-to-stress hypothesis suggests that some competitively disadvantaged species are excluded from higher inundation estuaries due to abiotic stress (high flooding level) and from lower inundation estuaries by competition. How abiotic and biotic stress interactions affect plant growth and whether competition intensity and importance are stable along environmental gradients is a controversial subject. We explored the influence of two factors, and we clarified that inundation stress and invasion competition are the main reasons leading to the traits exhibited by target plant Suaeda salsa and population presence changes. Our results indicated that when the flooding height exceeded 13.4 cm, the S. salsa mortality rate was 90%-100%. At the lower flooding heights (<13.4 cm), the S. salsa mortality rate when neighboring plants were present was 77.7%-100%, whereas, without neighbors it was 30.9%-83.7%. The invader Spartina alterniflora inhibited S. salsa plant height by 48%-77%, whereas the S. alterniflora inhibited S. salsa density by 11%-98% and reduced its biomass by 50.5%-90.1%. The changes in competition intensity and importance showed that the S. alterniflora had a distinct impact from the early germinant period to growing period (from May to July), finally stable no differences along the flooding height in the maturity period. At the same flooding level, the analysis of above and belowground competition by S. alterniflora showed that aboveground and belowground competition are the main causes of individual S. salsa inhibition. Our results confirm the competitive stress hypothesis, which is that competition shapes individual traits and population presence in the context of abiotic stress. This conclusion can guide the management and protection of native plants under biological invasion in a stressful environment.
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http://dx.doi.org/10.1016/j.scitotenv.2020.138225DOI Listing
July 2020

Lyophilization enabled disentanglement of polyethylenimine on rambutan-like silica nanoparticles for enhanced plasmid DNA delivery.

J Mater Chem B 2020 06 11;8(21):4593-4600. Epub 2020 May 11.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.

Polyethylenimine (PEI) functionalization onto nanoparticles is a widely used strategy for constructing particulate vectors for gene delivery. However, how to control the conformation of PEI chains and the resultant impact on gene transfection efficiency remains largely unexplored. Herein, we report that drying methods dramatically affect the conformation of PEI chains modified on the surface of silica nanoparticles and consequently the plasmid DNA transfection performance. Specifically, lyophilization renders less entangled PEI compared to commonly used vacuum drying as evidenced by an elevated glass transition temperature. The lyophilization induced disentangled conformation is likely associated with the solid-to-gas phase transition drying mechanism, which removes the bound crystal water content and thus reduces hydrogen bonding between amines. Moreover, we find that the stretched PEI chains on the surface of rambutan-like silica nanoparticles promote their binding capacity towards plasmid DNA molecules and thereby enhanced gene delivery and transfection efficiency. Our findings have provided new understanding about amine based polymers modified on nanoparticles, and have significant implications on the design of efficient particulate vectors for gene delivery.
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http://dx.doi.org/10.1039/d0tb00720jDOI Listing
June 2020

The Inhibition of P-Selectin Reduced Severe Acute Lung Injury in Immunocompromised Mice.

Oxid Med Cell Longev 2020 23;2020:8430465. Epub 2020 Apr 23.

Zhongnan Hospital of Wuhan University; Institute of Hepatobiliary Diseases of Wuhan University; Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan 430071, China.

In an immunocompetent host, excess infiltration of immune cells in the lung is a key factor in infection-induced severe acute lung injury. Kidney transplant patients are immunocompromised by the use of immunosuppressive drugs. Immune cell infiltration in the lung in a renal transplant recipient suffering from pulmonary infection is significantly less than that in an immunocompetent host; however, the extent of lung injury in renal transplant patients is more serious than that in immunocompetent hosts. Therefore, we explored the role of platelet activation in a Klebsiella pneumoniae-induced lung injury model with P-selectin gene knockout mice or wild-type mice. Our study suggested that the inhibition of platelets reduced severe acute lung injury and increased survival after acute lung infection in mice. In addition, P-selectin expression on the surface of platelets in mice increased after administration of immunosuppressive drugs, and the extent of lung injury induced by infection decreased in P-selectin gene knockout mice. In conclusion, p-selectin plays a key role in severe acute lung injury in immunocompromised mice by reducing platelet activation and inflammatory processes.
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http://dx.doi.org/10.1155/2020/8430465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196163PMC
February 2021