Publications by authors named "Qing Yao"

287 Publications

Generation of ordered protein assemblies using rigid three-body fusion.

Proc Natl Acad Sci U S A 2021 Jun;118(23)

Institute for Protein Design, University of Washington, Seattle, WA 98195;

Protein nanomaterial design is an emerging discipline with applications in medicine and beyond. A long-standing design approach uses genetic fusion to join protein homo-oligomer subunits via α-helical linkers to form more complex symmetric assemblies, but this method is hampered by linker flexibility and a dearth of geometric solutions. Here, we describe a general computational method for rigidly fusing homo-oligomer and spacer building blocks to generate user-defined architectures that generates far more geometric solutions than previous approaches. The fusion junctions are then optimized using Rosetta to minimize flexibility. We apply this method to design and test 92 dihedral symmetric protein assemblies using a set of designed homodimers and repeat protein building blocks. Experimental validation by native mass spectrometry, small-angle X-ray scattering, and negative-stain single-particle electron microscopy confirms the assembly states for 11 designs. Most of these assemblies are constructed from designed ankyrin repeat proteins (DARPins), held in place on one end by α-helical fusion and on the other by a designed homodimer interface, and we explored their use for cryogenic electron microscopy (cryo-EM) structure determination by incorporating DARPin variants selected to bind targets of interest. Although the target resolution was limited by preferred orientation effects and small scaffold size, we found that the dual anchoring strategy reduced the flexibility of the target-DARPIN complex with respect to the overall assembly, suggesting that multipoint anchoring of binding domains could contribute to cryo-EM structure determination of small proteins.
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http://dx.doi.org/10.1073/pnas.2015037118DOI Listing
June 2021

A Case of Phyllodes Tumor of the Breast with Mixed Liposarcoma: Case Report and Literature Review.

Onco Targets Ther 2021 6;14:3003-3011. Epub 2021 May 6.

Department of Pathology, Shihezi University School of Medicine and the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, People's Republic of China.

Phyllodes tumors (PTs) account for less than 1% of breast tumors, and malignant PTs account for even less. Here, we described an unusual case of malignant PT with mixed liposarcoma (myxoid liposarcoma [MLP] and pleomorphic liposarcoma [PLP]). A 52-year-old woman discovered a small lump in her left breast. Twenty years later, the lump suddenly grew within 1 month. Mammography showed space-occupying lesions of the left breast. Histologically, the tumor was characterized by hypercellular stroma covering the epithelium and protrusion of the myoepithelium into the cyst to form a lobulated structure; regions of loose mucus and hypercellular structures alternated. A region of peripheral benign fibroadenoma was also observed, and many stellate and spindle cells or signet ring-like cells were identified in loose areas. Some areas showed a characteristic thin branching vascular pattern. In the cell-rich area, adipocytes and odd megakaryocytes were observed. Atypical mitotic figures were observed in the cell-rich and mucus areas (16 mitoses/10 high-power fields [HPF] and 2 mitoses/10 HPF, respectively). In the immunohistochemical analysis, a small number of tumor cells were positive for AE1/3 and vimentin, whereas all cells were negative for cytokeratin 34βE12, E-cadherin, p63, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and S-100, ruling out the possibility of metaplastic carcinoma. Interestingly, cyclin-dependent kinase 4, mouse double minute 2 (MDM2), and p16 were strongly positive in both loose mucus and cell-rich areas. However, the fluorescence in situ hybridization test results showed that MDM2 was not amplified. Combined with morphological characteristics, these findings supported that the tumor was a mixed malignant PT with MLP and PLP. Our patient did not receive radiation therapy, and after 47 months of follow-up, no recurrence or metastasis occurred. This case report serves to expand the morphologic spectrum of mixed malignant PT with liposarcoma.
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http://dx.doi.org/10.2147/OTT.S298379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110257PMC
May 2021

Challenges in solving structures from radiation-damaged tomograms of protein nanocrystals assessed by simulation.

Acta Crystallogr D Struct Biol 2021 May 14;77(Pt 5):572-586. Epub 2021 Apr 14.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

Structure-determination methods are needed to resolve the atomic details that underlie protein function. X-ray crystallography has provided most of our knowledge of protein structure, but is constrained by the need for large, well ordered crystals and the loss of phase information. The rapidly developing methods of serial femtosecond crystallography, micro-electron diffraction and single-particle reconstruction circumvent the first of these limitations by enabling data collection from nanocrystals or purified proteins. However, the first two methods also suffer from the phase problem, while many proteins fall below the molecular-weight threshold required for single-particle reconstruction. Cryo-electron tomography of protein nanocrystals has the potential to overcome these obstacles of mainstream structure-determination methods. Here, a data-processing scheme is presented that combines routines from X-ray crystallography and new algorithms that have been developed to solve structures from tomograms of nanocrystals. This pipeline handles image-processing challenges specific to tomographic sampling of periodic specimens and is validated using simulated crystals. The tolerance of this workflow to the effects of radiation damage is also assessed. The simulations indicate a trade-off between a wider tilt range to facilitate merging data from multiple tomograms and a smaller tilt increment to improve phase accuracy. Since phase errors, but not merging errors, can be overcome with additional data sets, these results recommend distributing the dose over a wide angular range rather than using a finer sampling interval to solve the protein structure.
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http://dx.doi.org/10.1107/S2059798321002369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098477PMC
May 2021

Hyaluronic acid coated bilirubin nanoparticles attenuate ischemia reperfusion-induced acute kidney injury.

J Control Release 2021 Jun 27;334:275-289. Epub 2021 Apr 27.

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. Electronic address:

Acute kidney injury (AKI) is a common pathological process that is globally associated with a high morbidity and mortality rate. The underlying AKI mechanisms include over-produced reactive oxygen species (ROS), inflammatory cell infiltration, and high levels of inflammatory mediators. Bilirubin is an endogenous compound with antioxidant, anti-inflammatory and anti-apoptotic properties, and could, therefore, be a promising therapeutic candidate. Nanotechnology-mediated therapy has emerged as a novel drug delivery strategy for AKI treatment. In this study, we report a hyaluronic acid (HA) coated ε-polylysine-bilirubin conjugate (PLBR) nanoparticle (nHA/PLBR) that can selectively accumulate in injured kidneys and alleviate the oxidative/inflammatory-induced damage. The in vitro study revealed that nHA/PLBR has good stability, biocompatibility, and exhibited higher antioxidant as well as anti-apoptotic effects when compared to nPLBR or bilirubin. The in vivo study showed that nHA/PLBR could target and accumulate in the injured kidney, effectively relieve oxidative stress and inflammatory reactions, protect the structure and function of the mitochondria, and more importantly, inhibit the apoptosis of tubular cells in an ischemia/reperfusion-induced AKI rat model. Therefore, nHA/PLBR has the capacity to enhance specific biodistribution and delivery efficiency of bilirubin, thereby providing better treatment for AKI in the future.
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http://dx.doi.org/10.1016/j.jconrel.2021.04.033DOI Listing
June 2021

Phase-Controlled Synthesis of Pd-Se Nanocrystals for Phase-Dependent Oxygen Reduction Catalysis.

Nano Lett 2021 May 20;21(9):3805-3812. Epub 2021 Apr 20.

State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Searching for highly efficient oxygen reduction reaction (ORR) electrocatalysts for fuel cell technology, in which the crystal structure plays a powerful role in regulating the electrocatalysis, is urgent yet challenging. Herein, we have explored the active and stable Pd-Se alloy electrocatalysts with controlled phase toward alkaline ORR. The phase-controlled Pd-Se nanoparticles (NPs) show interesting phase-dependent electrocatalytic performance, in which the PdSe NPs/C exhibits much better ORR performance than its counterpart, PdSe NPs/C, and the commercial Pd/C and Pt/C. Based on the detailed analysis, Pd in PdSe possesses more Se atom coordination and a higher valence state, thus providing a stronger capacity for the absorption of oxygenated species. DFT further reveals more charge transfer from the PdSe surface to the *OOH intermediate, which is the reason for the activity enhancement.
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http://dx.doi.org/10.1021/acs.nanolett.1c00147DOI Listing
May 2021

The role of SYT-SSX fusion gene in tumorigenesis of synovial sarcoma.

Pathol Res Pract 2021 Jun 24;222:153416. Epub 2021 Mar 24.

Department of Pathology, Shihezi University School of Medicine & the First Affiliated Hospital to Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China; Department of Pathology, Central People's Hospital of Zhanjiang and Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, China. Electronic address:

Synovial sarcoma (SS) is an aggressive malignancy of an unknown tissue origin that is characterized by biphasic differentiation. A possible basis of the pathogenesis of SS is pathognomonic t(X;18) (p11.2; q11.2) translocation, leading to the formation and expression of the SYT-SSX fusion gene. More than a quarter of the patients die of SS metastasis within 5 years after the diagnosis, but the pathogenic factors are unknown. Therefore, there is an urgent need to explore the pathogenesis, invasion, metastasis, and clinical treatment options for SS, especially molecular-targeted drug therapy. Recent studies have shown that the SYT-SSX fusion gene associated with SS may be regulated by different signaling pathways, microRNAs, and other molecules, which may produce stem cell characteristics or promote epithelial-mesenchymal transition, resulting in SS invasion and metastasis. This review article aims to show the relationship between the SYT-SSX fusion gene and the related pathway molecules as well as other molecules involved from different perspectives, which may provide a deeper and clearer understanding of the SYT-SSX fusion gene function. Therefore, this review may provide a more innovative and broader perspective of the current research, treatment options, and prognosis assessment of SS.
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http://dx.doi.org/10.1016/j.prp.2021.153416DOI Listing
June 2021

Dual Targeting EGFR and STAT3 With Erlotinib and Alantolactone Co-Loaded PLGA Nanoparticles for Pancreatic Cancer Treatment.

Front Pharmacol 2021 19;12:625084. Epub 2021 Mar 19.

Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Pancreatic cancer (PC) is one of the most common malignancies and also a leading cause of cancer-related mortality worldwide. Many studies have shown that epidermal growth factor receptor (EGFR) is highly expressed in PC, which provides a potential target for PC treatment. However, EGFR inhibitors use alone was proven ineffective in clinical trials, due to the persistence of cellular feedback mechanisms which foster therapeutic resistance to single targeting of EGFR. Specifically, the signal transducer and activator of transcription 3 (STAT3) is over-activated when receiving an EGFR inhibitor and is believed to be highly involved in the failure and resistance of EGFR inhibitor treatment. Therein, we hypothesized that dual inhibition of EGFR and STAT3 strategy could address the STAT3 induced resistance during EGFR inhibitor treatment. To this end, we tried to develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles to co-load Alantolactone (ALA, a novel STAT3 inhibitor) and Erlotinib (ERL, an EGFR inhibitor) for pancreatic cancer to test our guess. The loading ratio of ALA and ERL was firstly optimized to achieve a combined cancer-killing effect. Then, the ALA- and ERL-co-loaded nanoparticles ([email protected]) were successfully prepared and characterized, and the related anticancer effects and cellular uptake of [email protected] were studied. We also further detailly explored the underlying mechanisms. The results suggested that [email protected] with uniform particle size and high drug load could induce significant pancreatic cancer cell apoptosis and display an ideal anticancer effect. Mechanism studies showed that [email protected] inhibited the phosphorylation of both EGFR and STAT3, indicating the dual suppression of these two signaling pathways. Additionally, [email protected] could also activate the ROS-p38 axis, which is not observed in the single drug treatments. Collectively, the [email protected] prepared in this study possess great potential for pancreatic cancer treatment by dual suppressing of EGFR and STAT3 pathways and activating ROS-responsive p38 MAPK pathway.
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http://dx.doi.org/10.3389/fphar.2021.625084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017486PMC
March 2021

The effects of heatwaves and cold spells on patients admitted with acute ischemic stroke.

Ann Transl Med 2021 Feb;9(4):309

Department of Neurology, The Second Hospital of Tianjin Medical University, Tianjin, China.

Background: This study aimed to explore the effects of heatwaves and cold spells on blood pressure, thrombus formation, and systemic inflammation at admission in patients with ischemic stroke.

Methods: Data of patients with ischemic stroke who were admitted to the Second Hospital of Tianjin Medical University between May 2014 and March 2019 were reviewed, along with meteorological data from the same time period. A total of 806 clinically confirmed patients with ischemic stroke (34-97 years old) were included in the final analysis. Heatwaves and cold spells were defined as ≥2 consecutive days with average temperature >95 percentile (May-August) and <5 percentile (November-March), respectively. Coagulation parameters, inflammation indices, blood pressure, and neurological impairment were evaluated within 24 hours of admission. General linear and logistic regression models were created to investigate the relationships of heatwaves and cold spells with the examination results of patients with ischemic stroke at admission.

Results: After adjustment for potential environmental confounders, heatwaves were positively associated with high systolic blood pressure (SBP) (β=8.693, P=0.019), diastolic blood pressure (DBP) (β=3.665, P=0.040), reduced thrombin time (TT) (β=-0.642, P=0.027), and activated partial thromboplastin time (APTT) (β=-1.572, P=0.027) in ischemic stroke patients at admission. Cold spells were positively associated with high SBP (β=5.277, P=0.028), DBP (β=4.672, P=0.012), fibrinogen (β=0.315, P=0.011), globulin (β=1.523, P=0.011), and reduced TT (β=-0.784, P<0.001) and APTT (β=-1.062, P=0.024). Cold spells were also associated with a higher risk of respiratory infection [odds ratio (OR) =2.677, P=0.001].

Conclusions: Exposure to heatwaves or cold spells was associated with blood pressure and coagulation at admission in patients with ischemic stroke. Cold spells also resulted in higher levels of inflammation. These findings suggest that changes in coagulation, blood pressure, and inflammation may be the potential biological mechanisms underlying the cerebrovascular effects of exposure to extreme temperatures.
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http://dx.doi.org/10.21037/atm-20-4256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944308PMC
February 2021

Analysis of Differentially Expressed Genes in Endothelial Cells Following Tumor Cell Adhesion, and the Role of PRKAA2 and miR-124-3p.

Front Cell Dev Biol 2021 19;9:604038. Epub 2021 Feb 19.

Department of Pharmacology, Health Science Center, School of Basic Medical Sciences, Peking University, Beijing, China.

Tumor cell adhesion to the endothelium is one pattern of tumor-endothelium interaction and a key step during tumor metastasis. Endothelium integrity is an important barrier to prevent tumor invasion and metastasis. Changes in endothelial cells (ECs) due to tumor cell adhesion provide important signaling mechanisms for the angiogenesis and metastasis of tumor cells. However, the changes happened in endothelial cells when tumor-endothelium interactions are still unclear. In this study, we used Affymetrix Gene Chip Human Transcriptome Array 2.0. and quantitative real-time PCR (qPCR) to clarify the detailed gene alteration in endothelial cells adhered by prostate tumor cells PC-3M. A total of 504 differentially expressed mRNAs and 444 lncRNAs were obtained through chip data analysis. Gene Ontology (GO) function analysis showed that differentially expressed genes (DEGs) mainly mediated gland development and DNA replication at the biological level; at the cell component level, they were mainly involved in the mitochondrial inner membrane; and at the molecular function level, DEGs were mainly enriched in ATPase activity and catalytic activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway analysis showed that the DEGs mainly regulated pathways in cancer, cell cycle, pyrimidine metabolism, and the mTOR signaling pathway. Then, we constructed a protein-protein interaction functional network and mRNA-lncRNA interaction network using Cytoscape v3.7.2. to identify core genes, mRNAs, and lncRNAs. The miRNAs targeted by the core mRNA PRKAA2 were predicted using databases (miRDB, RNA22, and Targetscan). The qPCR results showed that miR-124-3p, the predicted target miRNA of PRKAA2, was significantly downregulated in endothelial cells adhered by PC-3M. With a dual luciferase reporter assay, the binding of miR-124-3p with PRKAA2 3'UTR was confirmed. Additionally, by using the knockdown lentiviral vectors of miR-124-3p to downregulate the miR-124-3p expression level in endothelial cells, we found that the expression level of PRKAA2 increased accordingly. Taken together, the adhesion of tumor cells had a significant effect on mRNAs and lncRNAs in the endothelial cells, in which PRKAA2 is a notable changed molecule and miR-124-3p could regulate its expression and function in endothelial cells.
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http://dx.doi.org/10.3389/fcell.2021.604038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933219PMC
February 2021

Magnetic PLGA microspheres loaded with SPIONs promoted the reconstruction of bone defects through regulating the bone mesenchymal stem cells under an external magnetic field.

Mater Sci Eng C Mater Biol Appl 2021 Mar 21;122:111877. Epub 2021 Jan 21.

Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, China; Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China. Electronic address:

Superparamagnetic iron oxide nanoparticles (SPIONs) have been presented to regulate the migration and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under magnetic field (MF). However, the toxicity and short residence for the massively exposed SPIONs at bone defects compromises their practical application. Herein, SPIONs were encapsulated into PLGA microspheres to overcome these shortcomings. Three types of PLGA microspheres (PFe-I, PFe-II and PFe-III) were prepared by adjusting the feeding amount of SPIONs, in which the practical SPIONs loading amounts was 1.83%, 1.38% and 1.16%, respectively. The average diameter of the fabricated microspheres ranged from 160 μm to 200 μm, having the porous and rough surfaces displayed by SEM. Moreover, they displayed the magnetic property with a saturation magnetization of 0.16 emu/g. In vitro cell studies showed that most of BMSCs were adhered on the surface of PFe-II microspheres after 2 days of co-culture. Moreover, the osteoblasts differentiation of BMSCs was significantly promoted by PFe-II microspheres after 2 weeks of co-culture, as shown by detecting osteogenesis-related proteins expressions of ALP, COLI, OPN and OCN. Afterward, PFe-II microspheres were surgically implanted into the defect zone of rat femoral bone, followed by exposure to an external MF, to evaluate their bone repairing effect in vivo. At 6th week after treatment with PFe-II + MF, the bone mineral density (BMD, 263.97 ± 25.99 mg/cm), trabecular thickness (TB.TH, 0.58 ± 0.08 mm), and bone tissue volume/total tissue volume (BV/TV, 78.28 ± 5.01%) at the defect zone were markedly higher than that of the PFe-II microspheres alone (BMD, 194.34 ± 26.71 mg/cm; TB.TH, 0.41 ± 0.07 mm; BV/TV, 50.49 ± 6.41%). Moreover, the higher expressions of ALP, COLI, OPN and OCN in PFe-II + MF group were displayed in the repairing bone. Collectively, magnetic PLGA microspheres together with MF may be a promising strategy for repairing bone defects.
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http://dx.doi.org/10.1016/j.msec.2021.111877DOI Listing
March 2021

sp. nov., isolated from intestinal content of a Pacific white shrimp ().

Int J Syst Evol Microbiol 2019 Jun 23;71(3). Epub 2021 Feb 23.

Guangdong Microbial Culture Collection Center (GDMCC), Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510070, PR China.

The polyphasic taxonomic approach was used to characterize a novel bacteria strain, designated SG-8, which was isolated from intestinal content of a Pacific white shrimp (). Cells were Gram-stain-negative, aerobic, non-gliding rods. Growth occurred at 10-45 °C (optimum, 20-30 °C), pH 5.0-10.0 (optimum, 6.0-7.0) and in 0-6.0 % (w/v) NaCl (optimum, 0-4.0 %). The 16S rRNA gene sequence of strain SG-8 showed the highest sequence similarity to KMU-14 (98.6 %). On phylogenetic trees, strain SG-8 formed a stable cluster with KMU-14, SJ-36, 119BY6-57 and S2-C. The average nucleotide identity and digital DNA-DNA hybridization values between strain SG-8 and the four reference type strains listed above were 83.3, 82.3, 83.5, 83.3% and 22.8, 22.7, 22.7, 22.9 %, respectively. The major fatty acids (>5 %) were iso-C, summed feature 9 (iso-C9 and/or 10-methyl C), iso-C, summed feature 3 (C6 and/or C7), iso-C, iso-C 3OH and iso-C. Ubiquinone-8 (Q-8) was the only respiratory quinone. The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The DNA G+C content was 68.8 mol%. Based on the results of genomic, phylogenetic, phenotypic and chemotaxonomic analyses, strain SG-8 represents a novel species of the genus , for which the name sp. nov. is proposed. The type strain is SG-8 (=GDMCC 1.1817=KACC 21942).
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http://dx.doi.org/10.1099/ijsem.0.004593DOI Listing
June 2019

Gravity model in dockless bike-sharing systems within cities.

Phys Rev E 2021 Jan;103(1-1):012312

Center for Polymer Studies and Physics Department, Boston University, Boston, Massachusetts 02215, USA.

Due to previous technical challenges with the collection of data on riding behaviors, there have only been a few studies focusing on patterns and regularities of biking traffic, which are crucial to understand to help achieve a greener and more sustainable future urban development. Recently, with the booming of the sharing economy, and the development of the Internet of Things (IoT) and mobile payment technology, dockless bike-sharing systems that record information for every trip provide us with a unique opportunity to study the patterns of biking traffic within cities. We first reveal a spatial scaling relation between the cumulative volume of riding activities and the corresponding distance to the city center, and a power law distribution on the volume of biking flows between fine-grained locations in both Beijing and Shanghai. We validate the effectiveness of the general gravity model on predicting biking traffic at fine spatial resolutions, where population-related parameters are less than unity, indicating that smaller populations are relatively more important per capita in generating biking traffic. We then further study the impacts of spatial scale on the gravity model and reveal that the distance-related parameter grows in a similar way as population-related parameters when the spatial scale of the locations increases. In addition, the flow patterns of some special locations (sources and sinks) that cannot be fully explained by the gravity model are studied.
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http://dx.doi.org/10.1103/PhysRevE.103.012312DOI Listing
January 2021

Highly In-Plane Polarization-Sensitive Photodetection in CsPbBr Single Crystal.

J Phys Chem Lett 2021 Feb 16;12(7):1904-1910. Epub 2021 Feb 16.

College of Materials Science and Engineering, Shandong University of Science and Technology, Qingdao 266590, China.

The fully inorganic perovskite lead cesium bromide single crystal (CsPbBr SC) is considered as an excellent candidate semiconductor for photodetectors because of its superior humidity resistance, thermal stability, and light stability compared with organic-inorganic hybrid perovskites as well as its photoelectric properties such as large light absorption coefficient and ultralong carrier migration distance. In this Letter, we utilize the inverse temperature solubility of CsPbBr in ternary solvents to grow large-sized CsPbBr SCs. By the use of the (101) plane, CsPbBr SC-based photodetectors are fabricated, which exhibit excellent polarized light response characteristics. The photocurrent relies on the polarization angle in a sinusoidal fashion and shows strong anisotropic optoelectronic properties. The photodetection performance perpendicular to the axis is significantly higher than that parallel to the axis, and the dichroic ratio under 405 nm illumination at a bias voltage of 1 V reaches 2.65. The experimental results are consistent with the results of first-principles calculations.
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http://dx.doi.org/10.1021/acs.jpclett.1c00127DOI Listing
February 2021

Arbuscular mycorrhizal fungi improve uptake and control efficacy of carbosulfan on Spodoptera frugiperda in maize plants.

Pest Manag Sci 2021 Jun 25;77(6):2812-2819. Epub 2021 Feb 25.

Key Laboratory of Natural Pesticide & Chemical Biology, Ministry of Education, South China Agricultural University, Guangzhou, China.

Background: Inoculation of arbuscular mycorrhizal (AM) fungi in soil can promote the uptake of nutrients and xenobiotics by plants. In this study, the effects of arbuscular mycorrhizal fungi (including Glomus intraradices and Glomus mossea) on the growth of maize, the uptake of carbosulfan and the control efficacy on Spodoptera frugiperda were investigated through maize seed coating.

Results: Results from the pot experiment showed that carbofuran reduced the mycorrhizal colonization of AM fungi in the early stage of the experiment. The inhibiting effect disappeared in 21-49 DAP, whereas the mycorrhizal colonization rate under the G. intraradices treatment was maintained at ≈90%. Compared with noninoculated treatment, the fresh weights of roots in G. intraradices and G. mosseae treatments increased by 20-41% and 10-23%, respectively. Mycorrhizal treatment could significantly increase the transmission rates (root/soil and leaf/stem) and the carbosulfan accumulation in maize. During the harvest period, the control efficacy against S. frugiperda in mycorrhizal treatment was significantly higher than that in noninoculated treatments (P < 0.05) in both Guangzhou and Nanning.

Conclusions: Inoculation with AM could accelerate the degradation process of carbofuran in soil and the propagation of carbofuran from soil to plants. Glomus intraradices showed more pronounced effects than G. mosseae on both plant growth and carbosulfan content in plants and soil. The experimental results showed that inoculation of AM fungi increased the accumulation of carbofuran in plants, improved the effective utilization rate and enhanced the control efficacy against S. frugiperda. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6314DOI Listing
June 2021

Glucose-responsive hydrogel enhances the preventive effect of insulin and liraglutide on diabetic nephropathy of rats.

Acta Biomater 2021 03 11;122:111-132. Epub 2021 Jan 11.

Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China; Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, China. Electronic address:

Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus. The combination of insulin (Ins) with liraglutide (Lir) has a greater potential for preventing DN than monotherapy. However, the renal protective effect of the combined Ins/Lir therapy is largely compromised due to their short half-lives after subcutaneous injection. Herein, a glucose-responsive hydrogel was designed in situ forming the dynamic boronic esters bonds between phenylboronic acid-grafted γ-Polyglutamic acid (PBA-PGA) and konjac glucomannan (KGM). It was hypothesized that the KGM/PBA-PGA hydrogel as the delivery vehicle of Ins/Lir would enhance the combinational effect of the latter on preventing the DN progress. Scan electronic microscopy and rheological studies showed that KGM/PBA-PGA hydrogel displayed good glucose-responsive property. Besides, the glucose-sensitive release profile of either Ins or Lir from KGM/PBA-PGA hydrogel was uniformly displayed at hyperglycemic level. Furthermore, the preventive efficacy of KGM/PBA-PGA hydrogel incorporating insulin and liraglutide (Ins/Lir-H) on DN progress was evaluated on streptozotocin-induced rats with diabetic mellitus (DM). At 6 weeks after subcutaneous injection of Ins/Lir-H, not only the morphology of kidneys was obviously recovered as shown by ultrasonography, but also the renal hemodynamics was significantly improved. Meanwhile, the 24-h urinary protein and albumin/creatinine ratio were well modulated. Inflammation and fibrosis were also largely inhibited. Besides, the glomerular NPHS-2 was obviously elevated after treatment with Ins/Lir-H. The therapeutic mechanism of Ins/Lir-H was highly associated with the alleviation of oxidative stress and activation of autophagy. Conclusively, the better preventive effect of the combined Ins/Lir via KGM/PBA-PGA hydrogel on DN progress was demonstrated as compared with their mixed solution, suggesting KGM/PBA-PGA hydrogel might be a potential vehicle of Ins/Lir to combat the progression of DN.
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http://dx.doi.org/10.1016/j.actbio.2021.01.007DOI Listing
March 2021

Polylysine-bilirubin conjugates maintain functional islets and promote M2 macrophage polarization.

Acta Biomater 2021 03 31;122:172-185. Epub 2020 Dec 31.

Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. Electronic address:

Macrophage polarization is one of the main factors contributing to the proinflammatory milieu of transplanted islets. It causes significant islet loss. Bilirubin exhibits protective effects during the islet transplantation process, but the mode of delivering drugs along with the islet graft has not yet been developed. In addition, it remains unclear whether bilirubin or its derivatives can modulate macrophage polarization during islet transplantation. Therefore, this study aimed to develop an ε-polylysine-bilirubin conjugate (PLL-BR) to encapsulate the islets for protection and to explore its macrophage modulation activities. In in vitro studies, the PLL-BR was shown to tightly adhere to the islet surface. It also exhibited enhanced cytoprotective effects against oxidative and inflammatory conditions by promoting M2-type macrophage polarization. In in vivo studies, the PLL-BR-protected islets successfully prolonged the euglycemia period in diabetic mice and accelerated the blood glucose clearance rate by maintaining the insulin secretion function. Compared to the untreated islets, the PLL-BR-encapsulated islets induced anti-inflammatory responses that were characterized by elevated levels of M2 macrophage markers and local vascularization. In conclusion, PLL-BR can be used as a tool for reprograming macrophage polarization while providing a more efficient immune protection for transplanted islets. STATEMENT OF SIGNIFICANCE: Macrophage polarization is one main factor that caused significant loss of transplanted islets. Bilirubin possesses protective effects toward pancreatic islet, but how to deliver the drug along with the islet graft has not yet been harnessed. More importantly, whether bilirubin or its derivatives could modulate macrophage polarization during the host rejections has also not been answered. In this study, we developed an ε-polylysine-bilirubin conjugate (PLL-BR) to encapsulate the islets and explore its role in macrophage modulation activities. PLL-BR could attach to the surface of islets and exerted high oxidation resistance and anti-inflammatory effect. For the first time, we demonstrate that bilirubin and its derivatives effectively promoted the M2-type macrophage polarization, and optimize the immune microenvironment for islets survival and function.
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http://dx.doi.org/10.1016/j.actbio.2020.12.047DOI Listing
March 2021

Cell relay-delivery improves targeting and therapeutic efficacy in tumors.

Bioact Mater 2021 Jun 19;6(6):1528-1540. Epub 2020 Nov 19.

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, PR China.

Cell-mediated drug delivery system (CDDS) has shown great potential for cancer therapy. However, a single cell-mediated drug delivery mechanism has not generally been successful, particularly for systemic administration. To augment the antitumor therapy efficacy, herein, we propose a strategy of cell relay-delivery for the use of artificially damaging/aging erythrocytes to hitchhike on circulating monocytes/macrophages for intratumoral accumulation of anticancer drugs. This biomimetic relay-delivery strategy was derived from the manner in which circulating monocytes/macrophages in body specifically engulf damaged/senescent erythrocytes and actively transmigrate into the tumor bulk. The strategy elegantly combines the natural functions of both cells, which therefore provides a new perspective to challenge current obstacles in drug delivery. According to the strategy, we developed biotinylated erythrocyte-poly (lactic-co-glycolic acid) (PLGA) nanoparticle hybrid DDSs (bE-NPs) using avidin-biotin coupling. In such a system, biotinylated erythrocytes can mimic the natural property of damaged/senescent erythrocytes, while PLGA NPs are capable of encapsulating anticancer drugs and promoting sustained drug release. Anticancer drugs can effectively target tumor sites by two steps. First, by using biotinylated erythrocytes as the carrier, the drug-loaded PLGA NPs could be specifically phagocytized by monocytes/macrophages. Second, by taking advantage of the tumor-tropic property of monocytes/macrophages, the drug-loaded PLGA NPs could be efficiently transported into the tumor bulk. After encapsulating vincristine (VIN) as the model drug, bE-NPs exhibited the most favorable antitumor effects and by the cell relay-delivery effect. These results demonstrate that the cell relay-delivery provides a potential method for improving tumor treatment efficacy.
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http://dx.doi.org/10.1016/j.bioactmat.2020.11.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689215PMC
June 2021

Responses of Arbuscular Mycorrhizal Symbiosis to Abiotic Stress: A Lipid-Centric Perspective.

Front Plant Sci 2020 12;11:578919. Epub 2020 Nov 12.

College of Horticulture, Guangdong Province Key Laboratory of Microbial Signals and Disease Control, South China Agricultural University, Guangzhou, China.

Arbuscular mycorrhizal (AM) fungi are one of the most important soil microbial resources that help host plants cope with various abiotic stresses. Although a tremendous number of studies have revealed the responses of AM fungi to abiotic stress and their beneficial effects transferred to host plants, little work has focused on the role of lipid metabolism in AM fungi under abiotic stress conditions. AM fungi contain a large amount of lipids in their biomass, including phospholipids (PLs) in their hyphal membranes and neutral lipids (NLs) in their storage structures (e.g., vesicles and spores). Recently, lipid transfer from plants to AM fungi has been suggested to be indispensable for the establishment of AM symbiosis, and extraradical hyphae are capable of directly taking up lipids from the environment. This experimental evidence highlights the importance of lipids in AM symbiosis. Moreover, abiotic stress reduces lipid transfer to AM fungi and promotes arbuscule collapse as well as the hydrolysis and conversion of PLs to NLs in collapsed arbuscules. Overall, this knowledge encourages us to rethink the responses of AM symbiosis to abiotic stress from a lipid-centric perspective. The present review provides current and comprehensive knowledge on lipid metabolism in AM fungi, especially in response to various abiotic stresses. A regulatory role of abscisic acid (ABA), which is considered a "stress hormone," in lipid metabolism and in the resulting consequences is also proposed.
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http://dx.doi.org/10.3389/fpls.2020.578919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688922PMC
November 2020

Soil Organic Carbon Attenuates the Influence of Plants on Root-Associated Bacterial Community.

Front Microbiol 2020 9;11:594890. Epub 2020 Nov 9.

State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Microbial Culture Collection Center (GDMCC), Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China.

Plant-derived carbon (PDC) released by roots has a strong effect on root-associated bacterial community, which is critical for plant fitness in natural environments. However, the freshly exuded PDC can be diluted by the ancient soil-derived carbon (SDC) at a short distance from root apices. Thus, the rhizosphere C pools are normally dominated by SDC rather than PDC. Yet, how PDC and SDC interact to regulate root-associated bacterial community is largely unknown. In this study, a grass species and a legume species were planted in two contrasting matrixes, quartz sand and soil, to assess the role of PDC and SDC in regulating root-associated bacterial community, and to explore whether SDC affects the influence of PDC on bacterial community in soil. Our results indicated that the legume plant showed significantly positive priming effect on soil organic matter decomposition but the grass plant did not. PDC significantly shaped bacterial community in sand culture as indicated by PCR-DGGE and high-throughput sequencing of bacterial 16S rRNA gene. Intriguingly, we found that dissimilarity of bacterial communities associated with two plant species and the percentage of specific OTUs in quartz sand were significantly higher than those in soil. Moreover, several biomarkers enriched by plants in quartz sand turned to be general taxa in soil, which indicated that SDC attenuated the regulation of bacterial community by PDC. Taken together, these results suggest that SDC interacted with PDC and the root-associated microbial community, thus acted as soil buffering component of biological process contributing to soil resilience. The importance of PDC in structuring rhizosphere bacterial community needs to be reconsidered in the context of wider contribution of other C pool, such as SDC.
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http://dx.doi.org/10.3389/fmicb.2020.594890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680919PMC
November 2020

The role of sirt1 in the retinal ganglion cells cultured by high glucose.

Int Ophthalmol 2021 Mar 11;41(3):845-852. Epub 2020 Nov 11.

Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Ningxia Medical University, Yinchuan, Ningxia, China.

Objective: To observe the effect of sirt1 on retinal ganglion cells (RGC) with high glucose culture and to explore the role of sirt1 in the development of diabetic retinopathy. Method RGC was infected by sirt1 lentivirus overexpression vector pLV5-sirt1 and interference vector pLV3-si-sirt1. The normal control group and control virus vector group were set up at the same time. After 48 h of infection, the viability of RGC was detected by CCK8 kit, the apoptosis rate was detected by FCM analysis, and the protein expression of p53, FOXO3a, NF-κ B, caspase-3 was detected by Western blot.

Results: After RGC were infected with lentivirus, the cell viability of lentivirus overexpression vector pLV5-sirt1 was significantly higher than that of the high glucose group and the sirt1 overexpression control group, while the cell viability of interference vector pLV3-si-sirt1 was significantly lower than that of the high glucose group and the sirt1 interference control group (P < 0.05). At the same time, the apoptosis rate of RGC cells infected by lentivirus overexpression vector pLV5-sirt1 was lower than that of the high glucose group and the control virus vector group, while the apoptosis rate of the interference vector pLV3-si-sirt1 cells was significantly higher than that of the high glucose group and the control virus vector group (P < 0.05). The results of Western blotting showed that the expression of p53, FOXO3a, NF-κ B and caspase-3 in RGC cells decreased significantly after infection with pLV5-sirt1 compared with the high glucose group and the control virus vector group, while the expression of p53, FOXO3a, NF-κB and caspase-3 in RGC cells increased significantly after infection with pLV3-si-sirt1 (P < 0.05).

Conclusion: Sirt1 can inhibit the apoptosis of RGCs through regulating the expression of some apoptotic cytokinessome, and it can be used as a candidate gene for the biotherapy of retinal diseases.
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http://dx.doi.org/10.1007/s10792-020-01638-4DOI Listing
March 2021

[Transport Characteristics of Air Pollution in Tianjin Based on Weather Background].

Huan Jing Ke Xue 2020 Nov;41(11):4855-4863

Tianjin Meteorological Institute, Tianjin 300074, China.

Regional transport is an important factor when considering the prevention and control of air pollution. The aim of this study was to provide support for the joint prevention and control of air pollution in the Beijing-Tianjin-Hebei region. With a focus on an analysis of the relationship between regional transport and meteorological conditions based on the weather background, an atmospheric chemical model was developed to quantitatively estimate the impact of regional transport on Tianjin from October 2016 to September 2017. The results showed that the contribution percentage of regional transport in cities in plains in the Beijing-Tianjin-Hebei region was significantly higher than in cities in mountains. The local contribution of PM in the Tianjin area was 62.9% and the contribution of regional transport was 37.1%. This was mainly affected by transmissions of Chanzhou, Langfang, central and southern Hebei, Beijing, Tanshan, and Shandong. Regional transport was the most significant from April to June, the weakest from July to August, and the highest contributor to local emissions. Regional transport was closely related to weather situation, wind field, precipitation, and other meteorological conditions. Post-high pressure and pre-frontal low pressure were the two types of pollution weather with the highest proportion in regional transport, and the impact of air pollution transport under the southwest wind, westerly wind and south wind was the most apparent. Wind speed of 2-3 m·s was beneficial to the regional transport of PM, and precipitation above 5 mm will effectively reduce the regional transport of air pollutants. For different pollution types and heavy pollution stages, the contribution of regional transport was the most apparent in light pollution weather, being 20.5% higher than the average. The heavy pollution weather was controlled by static stable air mass, and because of the migration of high PM concentrations, pollution air mass in the surrounding area had a significant impact on the accumulation of pollution and transport in the region. The contribution ratio of PM transport in the heavy pollution period was more than the average and was approximately 10% and 15% higher. In the process of heavy pollution, the proportion of transport contribution in the initial accumulation stage and peak stage were higher than in other periods, and 14.5% and 19.5% higher than in the outbreak stage. The contribution of local emissions in the outbreak stage was more significant, being 9.9% higher than average.
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http://dx.doi.org/10.13227/j.hjkx.202004252DOI Listing
November 2020

Drug discovery and formulation development for acute pancreatitis.

Drug Deliv 2020 Dec;27(1):1562-1580

Municipal Key Laboratory of Paediatric Pharmacy, Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Acute pancreatitis is a sudden inflammation and only last for a short time, but might lead to a life-threatening emergency. Traditional drug therapy is an essential supportive method for acute pancreatitis treatment, yet, failed to achieve satisfactory therapeutic outcomes. To date, it is still challenging to develop therapeutic medicine to redress the intricate microenvironment promptly in the inflamed pancreas, and more importantly, avoid multi-organ failure. The understanding of the acute pancreatitis, including the causes, mechanism, and severity judgment, could help the scientists bring up more effective intervention and treatment strategies. New formulation approaches have been investigated to precisely deliver therapeutics to inflammatory lesions in the pancreas, and some even could directly attenuate the pancreatic damages. In this review, we will briefly introduce the involved pathogenesis and underlying mechanisms of acute pancreatitis, as well as the traditional Chinese medicine and the new drug option. Most of all, we will summarize the drug delivery strategies to reduce inflammation and potentially prevent the further development of pancreatitis, with an emphasis on the bifunctional nanoparticles that act as both drug delivery carriers and therapeutics.
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http://dx.doi.org/10.1080/10717544.2020.1840665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598990PMC
December 2020

Bioinspired biliverdin/silk fibroin hydrogel for antiglioma photothermal therapy and wound healing.

Theranostics 2020 23;10(25):11719-11736. Epub 2020 Sep 23.

Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Photothermal therapy employs the photoabsorbers to generate heat under the near-infrared (NIR) irradiation for thermal tumor ablation. However, NIR irradiation might damage the adjacent tissue due to the leakage of the photoabsorbers and the residual materials after treatment might hinder the local healing process. A bifunctional hydrogel that holds both photothermal property and potent pro-healing ability provides a viable option to resolve this issue. In this study, we developed a bioinspired green hydrogel (BVSF) with the integration of bioproduct biliverdin into natural derived silk fibroin matrix for antiglioma photothermal therapy and wound healing. The BVSF hydrogel possessed excellent and controllable photothermal activity under NIR irradiation and resulted in effective tumor ablation both in vitro and in vivo. Additionally, the BVSF hydrogel exerted anti-inflammatory effects both in vitro and in vivo, and stimulated angiogenesis and wound healing in a full-thickness defect rat model. Overall, this proof-of-concept study was aimed to determine the feasibility and reliability of using an all-natural green formulation for photothermal therapy and post-treatment care.
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http://dx.doi.org/10.7150/thno.47682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545989PMC
June 2021

"One-stop shop": safety and efficacy of combining atrial septal defect occlusion and left atrial appendage closure for patients with atrial septal defect and atrial fibrillation.

BMC Cardiovasc Disord 2020 10 12;20(1):444. Epub 2020 Oct 12.

Department of Cardiology, Southwest Hospital, Army Medical University, Chongqing, China.

Background: One-stop occlusion, which is defined as the combination of atrial septal defect [ASD] or patent foramen ovale [PFO] occlusion and left atrial appendage [LAA] closure, in patients with ASD/PFO and atrial fibrillation (AF) has not yet been investigated systematically. This study aimed to evaluate the safety and efficacy of one-stop occlusion in the treatment of adult patients with ASD/PFO and AF.

Methods: Inpatients with AF and ASD/PFO were recruited between August 2014 and April 2019. Preoperatively, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were conducted to identify the ASD/PFO size and margin, presence of thrombus in the LAA, and LAA orifice width and depth at 0°, 45°, 90°, and 135°. After confirmation of the indications of LAA closure (LAAC) and ASD/PFO occlusion, the procedures were performed simultaneously under general anesthesia. Oral anticoagulants were administered for 45-60 days, followed with regular evaluation of TTE and TEE.

Results: Forty-nine patients (age, 65.6 ± 9.6 years) were recruited in this study, including 24 patients with ASD and 25 patients with PFO. They were treated with LAAC and ASD/PFO occlusion successfully. The mean ASD size and mean diameter of the ASD occluders were 14.2 ± 7.7 and 25.4 ± 8.5 mm, respectively. The mean PFO size was 3.5 ± 0.4 mm. The mean maximal LAA orifice width and depth were 20.5 ± 3.4 and 28.3 ± 3.6 mm, respectively. All patients were implanted with a Watchman device (diameter, 27.1 ± 2.9 mm). Postoperatively, all patients took anticoagulants orally for 45-60 days, and their mean postoperative follow-up duration was 29.0 ± 12.1 months. Postoperative TEE showed that all had normal positioning of the LAA and ASD/PFO occluders. At 45-60 days after operation, TEE showed that the LAA and ASD/PFO occluder were in the normal position; however, two patients who took warfarin and novel oral anticoagulants, respectively, have developed occluder thrombosis. After adjusted anticoagulant therapy, TEE showed that the thrombus disappeared at 6 months after operation.

Conclusion: One-stop occlusion is safe and effective for the treatment of adult patients with ASD/PFO and AF. It is also feasible to administer warfarin or novel oral anticoagulants after operation.
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http://dx.doi.org/10.1186/s12872-020-01708-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552475PMC
October 2020

Transporter-Targeted Nano-Sized Vehicles for Enhanced and Site-Specific Drug Delivery.

Cancers (Basel) 2020 Oct 1;12(10). Epub 2020 Oct 1.

Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang 325027, China.

Nano-devices are recognized as increasingly attractive to deliver therapeutics to target cells. The specificity of this approach can be improved by modifying the surface of the delivery vehicles such that they are recognized by the target cells. In the past, cell-surface receptors were exploited for this purpose, but plasma membrane transporters also hold similar potential. Selective transporters are often highly expressed in biological barriers (e.g., intestinal barrier, blood-brain barrier, and blood-retinal barrier) in a site-specific manner, and play a key role in the vectorial transfer of nutrients. Similarly, selective transporters are also overexpressed in the plasma membrane of specific cell types under pathological states to meet the biological needs demanded by such conditions. Nano-drug delivery systems could be strategically modified to make them recognizable by these transporters to enhance the transfer of drugs across the biological barriers or to selectively expose specific cell types to therapeutic drugs. Here, we provide a comprehensive review and detailed evaluation of the recent advances in the field of transporter-targeted nano-drug delivery systems. We specifically focus on areas related to intestinal absorption, transfer across blood-brain barrier, tumor-cell selective targeting, ocular drug delivery, identification of the transporters appropriate for this purpose, and details of the rationale for the approach.
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http://dx.doi.org/10.3390/cancers12102837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599460PMC
October 2020

Both Soil Bacteria and Soil Chemical Property Affected the Micropredator Myxobacterial Community: Evidence from Natural Forest Soil and Greenhouse Rhizosphere Soil.

Microorganisms 2020 Sep 10;8(9). Epub 2020 Sep 10.

Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, State Key Laboratory of Applied Microbiology Southern China, Guangdong Microbial Culture Collection Center (GDMCC), Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China.

Myxobacteria are abundant micropredators in soil, and are social bacteria with multicellular behavior and producers of versatile secondary metabolites. The interaction between predator and prey populations is an important component in the soil microbial food web, and this is expected to shape the composition and dynamics of microbial communities. Here we hypothesize the regulation of bacterial abundance and community composition on soil myxobacterial community. Field investigation indicated that the relative abundance of Myxococcales in subtropical and tropical forest soil from South China was 1.49-4.74% of all the 16S rRNA gene sequences, and myxobacterial community composition differed between subtropical and tropical forest. The canonical correspondence analysis and variation partitioning analysis indicated that biotic factor (bacterial community composition) showed slightly stronger explanation for variation of myxobacteria than soil properties (soil pH and soil organic matter). Based on the rhizosphere bacterial network, the greenhouse mesocosm experiment showed that most of the myxobacterial links were with Gram-negative bacteria, except that some nodes from Haliangiacea and Polyangiaceae interacted with actinomycetes and actinomycetes-like Gram-positive bacteria. We inferred that myxobacteria preferential predation on specific bacterial taxa may explain the influence of bacteria on myxobacterial community. Further study confirming the biological process of myxobacterial predation in situ is necessary to advance the understanding of the ecological role of predation behavior in the microbial world.
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http://dx.doi.org/10.3390/microorganisms8091387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563646PMC
September 2020

Culture-dependent and -independent methods revealed an abundant myxobacterial community shaped by other bacteria and pH in Dinghushan acidic soils.

PLoS One 2020 14;15(9):e0238769. Epub 2020 Sep 14.

State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Microbial Culture Collection Center (GDMCC), Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China.

Myxobacteria are one of the most promising secondary metabolites producers. However, they are difficult to isolate and cultivate. To obtain more myxobacteria and know the effects of environmental factors on myxobacterial community, we characterized myxobacterial communities in Dinghushan acidic forest soils of pH 3.6-4.5 with culture-dependent and -independent techniques, and analyzed environmental factors shaping myxobacterial communities. A total of 21 myxobacteria were isolated using standard cultivation methods, including eleven isolates of Corallococcus, nine isolates of Myxococcus and one isolate of Archangium, and contained three potential novel species. In addition, a total of 67 unknown myxobacterial operational taxonomic units (OTUs) were obtained using high-throughput sequencing method. The abundance of Myxococcales account for 0.9-2.2% of bacterial communities, and Sorangium is the most abundant genus (60.1%) in Myxococcales. Correlation analysis demonstrated that bacterial diversity and soil pH are the key factors shaping myxobacterial community. These results revealed an abundant myxobacterial community which is shaped by other bacteria and pH in Dinghushan acidic forest soils.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238769PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489521PMC
November 2020

Therapeutic application and construction of bilirubin incorporated nanoparticles.

J Control Release 2020 12 1;328:407-424. Epub 2020 Sep 1.

Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. Electronic address:

Bilirubin is a yellow-colored metabolite of heme degradation (a bile pigment), once believed to be toxic, but recently recognized as a powerful endogenous antioxidant of physiologic importance. During the past two decades, several studies have demonstrated the potential of bilirubin in theranostic applications. Here this paper summarizes the current state of the field, providing a detailed review of the published literature on the theranostic applications of bilirubin-conjugated nanoparticles and the basis and mechanisms underlying their efficacy. This review covers the analytical description of the construction of the nanoparticulate bilirubin system, primary mechanisms of therapeutic action, drug delivery, and imaging potential. It also lays out the possible translational future of bilirubin-conjugated nanoparticles in therapy and diagnosis.
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http://dx.doi.org/10.1016/j.jconrel.2020.08.054DOI Listing
December 2020

Short-term effects of outdoor air pollution on acute ischaemic stroke occurrence: a case-crossover study in Tianjin, China.

Occup Environ Med 2020 12 27;77(12):862-867. Epub 2020 Aug 27.

Department of Neurology, The Second Hospital of Tianjin Medical University, Tianjin, China

Objective: Ambient air pollution is associated with ischaemic stroke incidence. However, most of the previous studies used stroke-related hospital admission rather than stroke onset itself. This study aimed to evaluate the relationship between ambient air pollutant exposures and acute ischaemic stroke based on the timing of symptom onset.

Methods: A time-stratified, case-crossover analysis was performed among 520 patients who had ischaemic stroke admitted to the Second Hospital of Tianjin Medical University (Tianjin, China) between 1 April 2018 and 31 March 2019 (365 days). Daily air pollutant concentrations of particulate matter with aerodynamic diameter 2.5 µm, particulate matter with aerodynamic diameter 10 µm (PM10), sulfur dioxide, nitrogen dioxide, carbon monoxide and ozone were obtained from fixed-site monitoring stations. We used conditional logistic regression to estimate OR and 95% CI corresponding to an increase in IQR of each air pollutant after adjusting for the effects of temperature and relative humidity.

Results: Overall, a higher risk of ischaemic stroke was found between April and September. During this period PM10 was associated with an increased risk of ischaemic stroke (1-day lag: OR=1.49, 95% CI 1.09 to 2.02; 3-day mean: OR=1.58, 95% CI 1.09 to 2.29) among patients between 34 and 70 years old. Positive associations were also observed between PM10 (1-day lag: OR=1.51, 95% CI 1.10 to 2.07; 3-day mean: OR=1.57, 95% CI 1.08 to 2.29), ozone (1-day lag: OR=1.83, 95% CI 1.16 to 2.87; 3-day mean: OR=1.90, 95% CI 1.06 to 3.42) and ischaemic stroke occurrence among those with hyperlipidaemia.

Conclusion: Our results suggest that air pollution is associated with a higher risk of ischaemic stroke in younger people or people with hyperlipidemia. These findings still need to be further investigated.
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http://dx.doi.org/10.1136/oemed-2019-106301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677458PMC
December 2020

Silk Fibroin-Modified Disulfiram/Zinc Oxide Nanocomposites for pH Triggered Release of Zn and Synergistic Antitumor Efficacy.

Mol Pharm 2020 10 8;17(10):3857-3869. Epub 2020 Sep 8.

Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 32500, Zhejiang, China.

Disulfiram (DSF) is an FDA-approved anti-alcoholic drug that has recently proven to be effective in cancer treatment. However, the short half-life in the bloodstream and the metal ion-dependent antitumor activity significantly limited the further application of DSF in the clinical field. To this end, we constructed a silk fibroin modified disulfiram/zinc oxide nanocomposites (SF/[email protected]) to solubilize and stabilize DSF, and, more importantly, achieve pH triggered Zn release and subsequent synergistic antitumor activity. The prepared SF/[email protected] nanocomposites were spherical and had a high drug loading. Triggered by the lysosomal pH, SF/[email protected] could induce the rapid release of Zn under the acidic conditions and caused nanoparticulate disassembly along with DSF release. In vitro experiments showed that cytotoxicity of DSF could be enhanced by the presence of Zn, and further amplified when encapsulated into SF/[email protected] nanocomposites. It was confirmed that the significantly amplified cytotoxicity of SF/[email protected] was resulted from pH-triggered Zn release, inhibited cell migration, and increased ROS production. In vivo study showed that SF/[email protected] nanocomposites significantly increased the tumor accumulation and prolonged the retention time. In vivo antitumor experiments in the xenograft model showed that SF/[email protected] exerted the highest tumor-inhibition rate among all the drug treatments. Therefore, this exquisite study established silk fibroin-modified disulfiram/zinc oxide nanocomposites, SF/[email protected], where ZnO not only acted as a delivery carrier but also served as a metal ion reservoir to achieve synergistic antitumor efficacy. The established DSF nanoformulation displayed excellent therapeutic potential in future cancer treatment.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00604DOI Listing
October 2020