Publications by authors named "Bowen Wang"

190 Publications

Unveiling the Mechanism for the Photochemistry and Photodegradation of Vanillin.

Photochem Photobiol 2021 Sep 27. Epub 2021 Sep 27.

Department of Chemistry and Biomolecular Sciences and Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, Ontario, Canada, K1N 6N5.

The photolysis of vanillin produces a short-lived triplet state where its lifetime is controlled by efficient self-quenching (k ~ 2 X 10 M s ) which also generates radicals. Free radical reactions, including vanillin dimer formation, are responsible for the degradation of vanillin and is accompanied by yellowing of the acetonitrile solutions. Laser flash photolysis studies reveal a triplet absorbing at 390 nm, readily quenched by naphthalenes, conjugated dienes and oxygen. Vanillin is also a good singlet oxygen sensitizer as revealed by its characteristic NIR emission at 1270 nm.
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http://dx.doi.org/10.1111/php.13520DOI Listing
September 2021

Quantitative analysis of morphological and functional features in Meibography for Meibomian Gland Dysfunction: Diagnosis and Grading.

EClinicalMedicine 2021 Oct 11;40:101132. Epub 2021 Sep 11.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, Guangdong, China.

Background: To explore the performance of quantitative morphological and functional analysis in meibography images by an automatic meibomian glands (MGs) analyser in diagnosis and grading Meibomian Gland Dysfunction (MGD).

Methods: A cross-sectional study collected 256 subjects with symptoms related to dry eye and 56 healthy volunteers who underwent complete ocular surface examination was conducted between January 1, 2019, and December 31, 2020. The 256 symptomatic subjects were classified into MGD group (n = 195) and symptomatic non-MGD group (n = 61). An automatic MGs analyser was used to obtained multi-parametric measurements in meibography images including the MGs area ratio (GA), MGs diameter deformation index (DI), MGs tortuosity index (TI), and MGs signal index (SI). Adjusted odds ratios (ORs) of the multi-parametric measurements of MGs for MGD, and the area under the receiver operating characteristic (AUC-ROC) curves of multi-parametric measurements for MGD diagnosing and grading were conducted.

Findings: When consider age, sex, ocular surface condition together, the estimated ORs for DI was 1.62 (95% CI, 1.29-2.56), low-level SI was 24.34 (95% CI, 2.73-217.3), TI was 0.76(95% CI, 0.54-0.90), and GA was 0.86 (95% CI, 0.74-0.92) for MGD. The combination of DI-TI-GA-SI showed an AUC = 0.82 ( < 0.001) for discriminating MGD from symptomatic subjects. The DI had a higher AUC in identifying early-stage MGD (grade 1-2), while TI and GA had higher AUCs in moderate and advanced stages (grade 3-5). Merging DI-TI-GA showed the highest AUCs in distinguish MGD severities.

Interpretation: The MGs area ratio, diameter deformation, tortuosity and signal intensity could be considered promising biomarkers for MGD diagnosis and objective grading.

Funding: This work was supported by the Key-Area Research and Development Program of Guangdong Province (No. 2019B010152001), the National Natural Science Foundation of China under Grant (81901788) and Guangzhou Science and Technology Program (202002030412).
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http://dx.doi.org/10.1016/j.eclinm.2021.101132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435692PMC
October 2021

Mechano-chemical regulation of bat wing bones for flight.

J Mech Behav Biomed Mater 2021 Sep 6;124:104809. Epub 2021 Sep 6.

Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA; Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA. Electronic address:

Distal phalanges in bat wings have been hypothesized to be cartilaginous to allow for flight. We provide new evidence on how bat wing development might facilitate flight though protein-based regulation of bone mineralization and lead to more deflection at phalanx than humerus. Between Pteropus poliocephalus and Pteropus hypomelanus, two large bat species, we detected 112 proteins including 11 associated with mineralization and analyzed their distribution between the wing bones. Here, in contrast to previous reports, we found no cartilage-specific proteins and demonstrate that distal phalanges in bat wings are in fact low density bone that contain collagen I (the main constituent of bone's organic matrix) and proteins associated with mineralization in bone such as osteomodulin, bone-specific protein osteocalcin. The functional relevance of these changes was explored by measuring changes in mineral (crystal sizes, packing and density), material (Young's modulus and hardness) and structural characteristics. Consistent with changes in proteins associated with mineralization, mineral crystal thickness and alignment decreased from humerus to phalanges, and the mineral platelets were less densely packed along the wing length. Crystal thickness was negatively correlated with proteins associated with inhibition of mineralization as well as with two types of small leucine-rich proteoglycans, indicating the mineral growth and maturity is down regulated by these proteins independent of mineral quantity. The Young's modulus decreased across the wing and was significantly correlated with bone mineral density. Thus, the results from two bat species, studied here, demonstrate progressive alterations in bone mineralization occur in concert with the changes in secretion of bone regulatory proteins along the wing length. This altered mineralization together with structural changes serve to lighten the limb bone and optimize biomechanical properties conducive to flight.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104809DOI Listing
September 2021

Evaluation and management of COVID-19-related severity in people with type 2 diabetes.

BMJ Open Diabetes Res Care 2021 09;9(1)

Center for Biotechnology and Interdisciplinary Studies, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA

Introduction: People with type 2 diabetes (T2D) have an increased rate of hospitalization and mortality related to COVID-19. To identify ahead of time those who are at risk of developing severe diseases and potentially in need of intensive care, we investigated the independent associations between longitudinal glycated hemoglobin (HbA1c), the impact of common medications (metformin, insulin, ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and corticosteroids) and COVID-19 severity in people with T2D.

Research Design And Methods: Retrospective cohort study was conducted using deidentified claims and electronic health record data from the OptumLabs Data Warehouse across the USA between January 2017 and November 2020, including 16 504 individuals with T2D and COVID-19. A univariate model and a multivariate model were applied to evaluate the association between 2 and 3-year HbA1c average, medication use between COVID-19 diagnosis and intensive care unit admission (if applicable), and risk of intensive care related to COVID-19.

Results: With covariates adjusted, the HR of longitudinal HbA1c for risk of intensive care was 1.12 (per 1% increase, p<0.001) and 1.48 (comparing group with poor (HbA1c ≥9%) and adequate glycemic control (HbA1c 6%-9%), p<0.001). The use of corticosteroids and the combined use of insulin and metformin were associated with significant reduction of intensive care risk, while ACEIs and ARBs were not associated with reduced risk of intensive care.

Conclusions: Two to three-year longitudinal glycemic level is independently associated with COVID-19-related severity in people with T2D. Here, we present a potential method to use HbA1c history, which presented a stronger association with COVID-19 severity than single-point HbA1c, to identify in advance those more at risk of intensive care due to COVID-19 in the T2D population. The combined use of metformin and insulin and the use of corticosteroids might be significant to prevent patients with T2D from becoming critically ill from COVID-19.
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http://dx.doi.org/10.1136/bmjdrc-2021-002299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424422PMC
September 2021

LncPSCA in the 8q24.3 risk locus drives gastric cancer through destabilizing DDX5.

EMBO Rep 2021 Sep 2:e52707. Epub 2021 Sep 2.

Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

Genome-wide association studies (GWAS) have identified multiple gastric cancer risk loci and several protein-coding susceptibility genes. However, the role of long-noncoding RNAs (lncRNAs) transcribed from these risk loci in gastric cancer development and progression remains to be explored. Here, we functionally characterize a lncRNA, lncPSCA, as a novel tumor suppressor whose expression is fine-regulated by a gastric cancer risk-associated genetic variant. The rs2978980 T > G change in an intronic enhancer of lncPSCA interrupts binding of transcription factor RORA, which down-regulates lncPSCA expression in an allele-specific manner. LncPSCA interacts with DDX5 and promotes DDX5 degradation through ubiquitination. Increased expression of lncPSCA results in low levels of DDX5, less RNA polymerase II (Pol II) binding with DDX5 in the nucleus, thus activating transcription of multiple p53 signaling genes by Pol II. These findings highlight the importance of functionally annotating lncRNAs in GWAS risk loci and the great potential of modulating lncRNAs as innovative cancer therapy.
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http://dx.doi.org/10.15252/embr.202152707DOI Listing
September 2021

Automatic creation of annotations for chest radiographs based on the positional information extracted from radiographic image reports.

Comput Methods Programs Biomed 2021 Sep 4;209:106331. Epub 2021 Aug 4.

Department of Medical Informatics, Osaka University Graduate School of Medicine, Japan. Electronic address:

Background And Objective: In this study, we tried to create a machine-learning method that detects disease lesions from chest X-ray (CXR) images using a data set annotated with extracted CXR reports information. We set the nodule as the target disease lesion. Manually annotating nodules is costly in terms of time. Therefore, we used the report information to automatically produce training data for the object detection task.

Methods: First, we use semantic segmentation model PSP-Net to recognize lung fields described in the CXR reports. Next, a classification model ResNeSt-50 is used to discriminate the nodule in segmented right and left field. It also can provide attention map by Grad-Cam. If the attention region corresponds to the location of the nodule in the CXR reports, an attention bounding box is generated. Finally, object detection model Faster-RCNN was performed using generated attention bounding box. The bounding boxes predicted by Faster-RCNN were filtered to satisfy the location extracted from CXR reports.

Results: For lung field segmentation, a mean intersection of union of 0.889 was achieved in our best model. 15,156 chest radiographs are used for classification. The area under the receiver operating characteristics curve was 0.843 and 0.852 for the left and right lung, respectively. The detection precision of the generated attention bounding box was 0.341 to 0.531 depending on the binary setting for attention map. Through object detection process, the detection precisions of the bounding boxes were improved to 0.567 to 0.800.

Conclusion: We successfully generated bounding boxes with nodule on CXR images based on the positional information of the diseases extracted from the CXR reports. Our method has the potential to provide bounding boxes for various lung lesions which can reduce the annotation burden for specialists.

Short Abstract: Machine learning for computer aided image diagnosis requires annotation of images, but manual annotation is time-consuming for medical doctor. In this study, we tried to create a machine-learning method that creates bounding boxes with disease lesions on chest X-ray (CXR) images using the positional information extracted from CXR reports. We set the nodule as the target lesion. First, we use PSP-Net to segment the lung field according to the CXR reports. Next, a classification model ResNeSt-50 was used to discriminate the nodule in segmented lung field. We also created an attention map using the Grad-Cam algorithm. If the area of attention matched the area annotated by the CXR report, the coordinate of the bounding box was considered as a possible nodule area. Finally, we used the attention information obtained from the nodule classification model and let the object detection model trained by all of the generated bounding boxes. Through object detection model, the precision of the bounding boxes to detect nodule is improved.
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http://dx.doi.org/10.1016/j.cmpb.2021.106331DOI Listing
September 2021

Biomimetic, ROS-detonable nanoclusters - A multimodal nanoplatform for anti-restenotic therapy.

J Control Release 2021 Aug 18;338:295-306. Epub 2021 Aug 18.

Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.. Electronic address:

The long-term success of endovascular intervention has long been overshadowed by vessel re-occlusion, also known as restenosis. Mainstream anti-restenotic devices, such as drug-eluting stent (DES) and drug-coated balloon (DCB), were recently shown with suboptimal performances and life-threatening complications, thereby underpinning the urgent need for alternative strategies with enhanced efficacy and safety profile. In our current study, we engineered a multimodal nanocluster formed by self-assembly of unimolecular nanoparticles and surface coated with platelet membrane, specifically tailored for precision drug delivery in endovascular applications. More specifically, it incorporates the combined merits of platelet membrane coating (lesion targetability and biocompatibility), reactive oxygen species (ROS)-detonable "cluster-bomb" chemistry (to trigger the large-to-small size transition at the target site, thereby achieving longer circulation time and higher tissue penetration), and sustained drug release. Using RVX-208 (an emerging anti-restenotic drug under clinical trials) as the model payload, we demonstrated the superior performances of our nanocluster over conventional poly(lactic-co-glycolic acid) (PLGA) nanoparticle. In cultured vascular smooth muscle cell (VSMC), the drug-loaded nanocluster induced effective inhibition of proliferation and protective gene expression (e.g., APOA-I) with a significantly reduced dosage of RVX-208 (1 μM). In a rat model of balloon angioplasty, intravenous injection of Cy5.5-tagged nanocluster led to greater lesion targetability, improved biodistribution, and deeper penetration into injured vessel walls featuring enriched ROS. Moreover, in contrast to either free drug solution or drug-loaded PLGA nanoparticle formulation, a single injection with the drug-loaded nanocluster (10 mg/kg of RVX-208) was sufficient to substantially mitigate restenosis. Additionally, this nanocluster also demonstrated biocompatibility according to in vitro cytotoxicity assay and in vivo histological and tissue qPCR analysis. Overall, our multimodal nanocluster offers improved targetability, tissue penetration, and ROS-responsive release over conventional nanoparticles, therefore making it a highly promising platform for development of next-generation endovascular therapies.
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http://dx.doi.org/10.1016/j.jconrel.2021.08.025DOI Listing
August 2021

Membrane-bound SCF and VCAM-1 synergistically regulate the morphology of hematopoietic stem cells.

J Cell Biol 2021 Oct 17;220(10). Epub 2021 Aug 17.

Department of Biomedical Engineering, University of Southern California, Los Angeles, CA.

Membrane-bound factors expressed by niche stromal cells constitute a unique class of localized cues and regulate the long-term functions of adult stem cells, yet little is known about the underlying mechanisms. Here, we used a supported lipid bilayer (SLB) to recapitulate the membrane-bound interactions between hematopoietic stem cells (HSCs) and niche stromal cells. HSCs cluster membrane-bound stem cell factor (mSCF) at the HSC-SLB interface. They further form a polarized morphology with aggregated mSCF under a large protrusion through a synergy with VCAM-1 on the bilayer, which drastically enhances HSC adhesion. These features are unique to mSCF and HSCs among the factors and hematopoietic populations we examined. The mSCF-VCAM-1 synergy and the polarized HSC morphology require PI3K signaling and cytoskeletal reorganization. The synergy also enhances nuclear retention of FOXO3a, a crucial factor for HSC maintenance, and minimizes its loss induced by soluble SCF. Our work thus reveals a unique role and signaling mechanism of membrane-bound factors in regulating stem cell morphology and function.
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http://dx.doi.org/10.1083/jcb.202010118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374872PMC
October 2021

miR-486 Promotes the Invasion and Cell Cycle Progression of Ovarian Cancer Cells by Targeting CADM1.

Anal Cell Pathol (Amst) 2021 5;2021:7407086. Epub 2021 Aug 5.

Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China.

Objective: To explore the role and possible underlying mechanism of miR-486 in ovarian cancer (OC) cells.

Methods: The expression of miR-486 and CADM1 was detected by qRT-PCR in OC tissues and adjacent nontumor tissues and OC cell lines. The dual-luciferase reporter gene system was used to determine the targeting relationship between miR-486 and CADM1. CCK-8, colony formation assay, Transwell, and flow cytometry were performed to detect cell proliferation, cell invasion, cell cycle progression, and the apoptotic cell death, respectively. Western blot was carried out to detect the expression of CADM1 protein and the proteins associated with cell cycle progression.

Results: miR-486 was significantly upregulated in OC tissues and cells, while CADM1 expression was significantly downregulated. Dual-luciferase reporter assays further confirmed that CADM1 was a target gene of miR-486. Interference with miR-486 could inhibit the proliferation and invasion and promoted the apoptosis of SKOV3 cells. Knocking down both miR-486 and CADM1 significantly increased the SKOV3 cell proliferation, invasion, and the number of cells transitioning from the G0/G1 phase into the S phase of cell cycle and reduced the cellular apoptosis. Western blot analysis revealed that the expression of cell cycle progression-related proteins (CyclinD1, CyclinE, and CDK6) was significantly reduced, and the p21 expression was increased when interfering with both miR-486 and CADM1 expression.

Conclusion: Our results suggested that miR-486 could act as a tumor promoter by targeting CADM1 and be a potential therapeutic target for the treatment of OC.
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http://dx.doi.org/10.1155/2021/7407086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360751PMC
August 2021

Low-Roughness-Surface Additive Manufacturing of Metal-Wire Feeding with Small Power.

Materials (Basel) 2021 Jul 30;14(15). Epub 2021 Jul 30.

School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

Aiming at handling the contradiction between power constraint of on-orbit manufacturing and the high energy input requirement of metal additive manufacturing (AM), this paper presents an AM process based on small-power metal fine wire feed, which produces thin-wall structures of height-to-width ratio up to 40 with core-forming power only about 50 W. In this process, thermal resistance was introduced to optimize the gradient parameters which greatly reduces the step effect of the typical AM process, succeeded in the surface roughness () less than 5 μm, comparable with that obtained by selective laser melting (SLM). After a 10 min electrolyte-plasma process, the roughness of the fabricated specimen was further reduced to 0.4 μm, without defects such as pores and cracks observed. The ultimate tensile strength of the specimens measured about 500 MPa, the relative density was 99.37, and the Vickers hardness was homogeneous. The results show that the proposed laser-Joule wire feed-direct metal deposition process (LJWF-DMD) is a very attractive solution for metal AM of high surface quality parts, particularly suitable for rapid prototyping for on-orbit AM in space.
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http://dx.doi.org/10.3390/ma14154265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348733PMC
July 2021

Interaction Regulation Between Ionomer Binder and Catalyst: Active Triple-Phase Boundary and High Performance Catalyst Layer for Anion Exchange Membrane Fuel Cells.

Adv Sci (Weinh) 2021 Aug 2:e2101744. Epub 2021 Aug 2.

College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China.

As one of the most crucial components, the catalyst layer (CL) plays a critical role in the performance of anion exchange membrane fuel cells (AEMFCs). However, the effect of the structural evolution of ionomer binder on the micromorphology and catalytic activity of CL is yet to be clarified. In this study, pyrrolidinum and quaternary ammonium cations are attached to the polyphenylene oxide (PPO) backbone through flexible spacer units (five, seven, or nine carbon atoms) with different terminal alkyl groups. The Van der Waals force and electrostatic repulsion between the ionomer binder and catalyst are regulated through the flexible spacer units and terminal alkyl groups to alleviate the agglomeration of catalyst particles and acquire a high catalytic activity. To evaluate the electrochemical stability of the cationic groups, the alkaline stability of the ionomer binder is tested under a constant voltage to simulate the true operational environment of the fuel cells. The results reveal that the degradation of the cation groups of ionomer binder is accelerated under a constant voltage condition. This phenomenon in neglect earlier, may serve as a useful reference for the synthesis and performance enhancement of ionomer binders.
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http://dx.doi.org/10.1002/advs.202101744DOI Listing
August 2021

Integrated Analysis of the Roles of RNA Binding Proteins and Their Prognostic Value in Clear Cell Renal Cell Carcinoma.

J Healthc Eng 2021 30;2021:5568411. Epub 2021 Jun 30.

Department of Urology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.

Methods: We downloaded the RNA sequencing data of ccRCC from the Cancer Genome Atlas (TCGA) database and identified differently expressed RBPs in different tissues. In this study, we used bioinformatics to analyze the expression and prognostic value of RBPs; then, we performed functional analysis and constructed a protein interaction network for them. We also screened out some RBPs related to the prognosis of ccRCC. Finally, based on the identified RBPs, we constructed a prognostic model that can predict patients' risk of illness and survival time. Also, the data in the HPA database were used for verification.

Results: In our experiment, we obtained 539 ccRCC samples and 72 normal controls. In the subsequent analysis, 87 upregulated RBPs and 38 downregulated RBPs were obtained. In addition, 9 genes related to the prognosis of patients were selected, namely, RPL36A, THOC6, RNASE2, NOVA2, TLR3, PPARGC1A, DARS, LARS2, and U2AF1L4. We further constructed a prognostic model based on these genes and plotted the ROC curve. This ROC curve performed well in judgement and evaluation. A nomogram that can judge the patient's life span is also made.

Conclusion: In conclusion, we have identified differentially expressed RBPs in ccRCC and carried out a series of in-depth research studies, the results of which may provide ideas for the diagnosis of ccRCC and the research of new targeted drugs.
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http://dx.doi.org/10.1155/2021/5568411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263288PMC
June 2021

Molecular characterization and functional analysis of multidrug resistance-associated genes of Pinewood nematode (Bursaphelenchus xylophilus) for nematicides.

Pestic Biochem Physiol 2021 Aug 12;177:104902. Epub 2021 Jun 12.

School of Forestry, Northeast Forestry University, Harbin 150040, China. Electronic address:

Bursaphelenchus xylophilus (Pinewood nematode, PWN) is the causative agent of pine wilt disease (PWD) which caused serious threat to pine forests in the world, especially in East Asia and Western Europe. At present, the control of PWD mainly rely on the massive use of pesticide despite the damage to human health and environmental safety. Developing novel drug targets is the optimized strategy for developing new method to control PWN. In this study, four multidrug resistance-associated protein (MRP) genes containing highly conserved MRP-associated domains were cloned from PWN. The expression patterns of the four Bx-mrps under three different nematicides treatments were studied by quantitative reverse transcription PCR (qRT-PCR) and the function of the four genes in multidrug resistance were also validated by RNA interference (RNAi). Results showed that the expression of Bx-mrp1, Bx-mrp2, Bx-mrp3, and Bx-mrp4 were significantly increased when exposed to different nematicides, wherein, Bx-mrp4 exposed by 4.0 mg/mL of matrine own the highest expression level. The mortality rates of Bx-mrps silenced nematodes revealed significant increase(P < 0.05)under matrine, avermectin, and emamectin benzoate exposure. Specially, Bx-mrp4 exposed with 4.0 mg/mL matrine for 24 h own the highest mortality increase by 18.34%. After RNAi of Bx-mrps, feeding ability of the nematodes were also significantly decreased. These results demonstrate that Bx-mrps were linked to the detoxification process and feeding behavior of PWN. Silencing of Bx-mrps can lead to increased sensitivity of PWN to nematicides and decrease its feeding ability. Bx-mrps are potential new PWN control targets in the future.
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http://dx.doi.org/10.1016/j.pestbp.2021.104902DOI Listing
August 2021

Designing the next generation of proton-exchange membrane fuel cells.

Nature 2021 Jul 14;595(7867):361-369. Epub 2021 Jul 14.

State Key Laboratory of Engines, Tianjin University, Tianjin, China.

With the rapid growth and development of proton-exchange membrane fuel cell (PEMFC) technology, there has been increasing demand for clean and sustainable global energy applications. Of the many device-level and infrastructure challenges that need to be overcome before wide commercialization can be realized, one of the most critical ones is increasing the PEMFC power density, and ambitious goals have been proposed globally. For example, the short- and long-term power density goals of Japan's New Energy and Industrial Technology Development Organization are 6 kilowatts per litre by 2030 and 9 kilowatts per litre by 2040, respectively. To this end, here we propose technical development directions for next-generation high-power-density PEMFCs. We present the latest ideas for improvements in the membrane electrode assembly and its components with regard to water and thermal management and materials. These concepts are expected to be implemented in next-generation PEMFCs to achieve high power density.
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http://dx.doi.org/10.1038/s41586-021-03482-7DOI Listing
July 2021

Risk-Aware Identification of Highly Suspected COVID-19 Cases in Social IoT: A Joint Graph Theory and Reinforcement Learning Approach.

IEEE Access 2020 19;8:115655-115661. Epub 2020 Jun 19.

School of Electronics and Computer ScienceUniversity of SouthamptonSouthamptonSO17 1BJU.K.

The recent outbreak of the coronavirus disease 2019 (COVID-19) has rapidly become a pandemic, which calls for prompt action in identifying suspected cases at an early stage through risk prediction. To suppress its further spread, we exploit the social relationships between mobile devices in the Social Internet of Things (SIoT) to help control its propagation by allocating the limited protective resources to the influential so-called high-degree individuals to stem the tide of precipitated spreading. By exploiting the so-called differential contact intensity and the infectious rate in susceptible-exposed-infected-removed (SEIR) epidemic model, the resultant optimization problem can be transformed into the minimum weight vertex cover (MWVC) problem of graph theory. To solve this problem in a high-dynamic random network topology, we propose an adaptive scheme by relying on the graph embedding technique during the state representation and reinforcement learning in the training phase. By relying on a pair of real-life datasets, the results demonstrate that our scheme can beneficially reduce the epidemiological reproduction rate of the infection. This technique has the potential of assisting in the early identification of COVID-19 cases.
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http://dx.doi.org/10.1109/ACCESS.2020.3003750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043494PMC
June 2020

Complementary Photo-Synapses Based on Light-Stimulated Porphyrin-Coated Silicon Nanowires Field-Effect Transistors (LPSNFET).

Small 2021 07 29;17(30):e2101434. Epub 2021 Jun 29.

Key Laboratory of Microelectronic Devices and Circuits (MOE), Institute of Microelectronics, Peking University, Beijing, 100871, China.

Neuromorphic computing has emerged as the high-energy-efficiency and intelligent solution for processing sensory data. As a potential alternative to neuromorphic computing, photo-excited synaptic systems can integrate the functions of optoelectronic sensing and synaptic computing to realize the low-power and high-performance visual perception. However, one major challenge in high-efficient photo-excited synaptic system is to realize the complementarily enhanced and inhibited synaptic behaviors with small hardware cost as possible. Another challenge is to fabricate the photo-synapse devices with complementary metal oxide semiconductor (CMOS)-compatible process to achieve high enough integration density for practical application. Here, a CMOS-compatible Light-stimulated Porphyrin-coated Silicon Nanowire Field Effect Transistor (LPSNFET) technology is proposed and developed to form the complementary photo-synapses with only two CMOS-like transistors. LPSNFET exhibits fivefold improvement in photo-sensitivity compared to the bare silicon nanowire (SiNW) devices, and can still show obvious responses when incident illumination power is as low as 0.1 mW cm . Moreover, it enables tunable dynamic synaptic plasticity and versatile synaptic functions. Especially, the complementarily enhanced and inhibited behaviors can be realized by modulating SiNW/porphyrin interface via simply changing the MOS type of LPSNFET, which acts like the photonic counterpart of CMOS technology to provide the basic brick for building complex neuromorphic circuits efficiently and economically. Finally, the CMOS process compatibility of LPSNFET provides potential application in future large scale in-sensor computing.
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http://dx.doi.org/10.1002/smll.202101434DOI Listing
July 2021

Psychosocial Characteristics, Perceived Neighborhood Environment, and Physical Activity Among Chinese Adolescents.

J Phys Act Health 2021 Jun 29:1-6. Epub 2021 Jun 29.

This study examined the independent associations between psychosocial factors, perceived neighborhood characteristics, and physical activity (PA) in Chinese adolescents. A cross-sectional study using a convenience sample was conducted in fall 2019 at a high school in Wuhan, China. Sociodemographic data, body weight, height, psychosocial factors, perceptions of neighborhood environment, and PA were collected using questionnaires. Hierarchical linear regression analyses were performed in 4 steps, where step 1 included demographic covariates, step 2 added psychosocial factors into the model, step 3 added perceived neighborhood environmental factors, and step 4 added interaction terms between significant psychosocial and environmental factors. A total of 4027 adolescents were included in analysis. The results of the third model indicated that friends' support (b = 4.58), friends' norms (b = 7.16), barriers to PA (b = -10.19), autonomous motivation (b = 4.75), self-efficacy (b = 8.86), the presence of shops/stores nearby (b = 5.79), and the availability of PA resources (b = 6.02) were significant predictors (P < .05) of moderate to vigorous PA. None of the interaction terms were significant in the fourth model. Our results suggest that interventions targeting the PA of Chinese adolescents should take into account the attitudes toward PA, perceived barriers to PA, controlled motivation, perceptions of neighborhood PA resource availability, and perceived neighborhood safety to maximize effectiveness.
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http://dx.doi.org/10.1123/jpah.2020-0397DOI Listing
June 2021

Modeling the emissions of rural vehicles based on real-world driving cycles.

Sci Total Environ 2021 Nov 16;793:148380. Epub 2021 Jun 16.

State Environmental Protection Key Laboratory of Vehicle Emission Control and Simulation, Chinese Research Academy of Environmental Sciences, Beijing 100012, China; Vehicle Emission Control Center of Ministry of Ecology and Environment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.

Characterized by a high frequency of use, harsh working environments, poor maintenance, and low levels of emission controls, rural vehicles (RVs) are becoming an important source of air pollution. Our study used a portable emission measurement system (PEMS) to test the real-world emissions of 35 RVs on provincial, rural, and farm roads. The results show that high emission rates of carbon monoxide (CO) and hydrocarbons (HC) mainly occurred when accelerating at low speeds. However, high levels of nitrogen oxides (NO) were emitted during high-speed acceleration. The particulate number (PN) of emissions was higher when the RVs were accelerating. According to the overall test results, the vehicle specific power (VSP) on the provincial road mostly ranged within (0, 3], accounting for 68.80% of the total. The VSP on rural and farm roads was concentrated within (0, 2] kW·ton, accounting for 67.09% and 76.64% of the total, respectively. We defined 14 bins based on the distribution of the VSP values and calculated the average emission rate of each bin. By comparing the average emission rate among the bins, we found that within Bins 1-7 (VSP < 0 kW·ton), CO, HC, and NO emissions slowly increased as the VSP increased. In Bins 8-13 (VSP ≥ 0 kW·ton), the average emission rates of four pollutants increased as the VSP increased. However, all pollutants decreased in Bin 14 (VSP ≥ 6 kW·ton). We built a microscopic emission model according to the VSP distribution characteristics of RVs on different road types. We compared the measured and simulated emission factors and found that our emission model can greatly simulate the HC, NOx and PN emission factors of RVs.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148380DOI Listing
November 2021

An adventitial painting modality of local drug delivery to abate intimal hyperplasia.

Biomaterials 2021 08 10;275:120968. Epub 2021 Jun 10.

Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22903, USA. Electronic address:

A major medical problem is the persistent lack of approved therapeutic methods to prevent postoperative intimal hyperplasia (IH) which leads to high-rate failure of open vascular reconstructions such as bypass grafting. Hydrogel has been widely used in preclinical trials for perivascular drug administration to mitigate postoperative IH. However, bulky hydrogel is potentially pro-inflammatory, posing a significant hurdle to clinical translation. Here we developed a new modality of directly "painting" drug-loaded unimolecular micelles (UM) to the adventitia thus obviating the need for a hydrogel. To render tissue adhesion, we generated amine-reactive unimolecular micelles with N-hydroxysuccinimide ester (UM-NHS) terminal groups to form stable amide bonds with the adventitia. To test periadventitial application, we either soaked balloon-injured rat carotid arteries in crosslinked UM-NHS (Mode-1) or non-crosslinked UM-NHS (Mode-2), or painted the vessel surface with non-crosslinked UM-NHS (Mode-3). The UM-NHS were loaded with or without a model drug (rapamycin) known to be IH inhibitory. We found that Mode-1 produced a marked IH-mitigating drug effect but also caused severe tissue damage. Mode-2 resulted in lower tissue toxicity yet less drug effect on IH. However, the painting method, Mode-3, demonstrated a pronounced therapeutic effect (75% inhibition of IH) without obvious toxicity. In summary, we present a simple painting modality of periadventitial local drug delivery using tissue-adhesive UM. Given the robust IH-abating efficacy and low tissue toxicity, this prototype merits further development towards an effective anti-stenosis therapy suitable for open vascular reconstructions.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325643PMC
August 2021

A High-Efficiency Wavelength-Tunable Monolayer LED with Hybrid Continuous-Pulsed Injection.

Adv Mater 2021 Jul 6;33(29):e2101375. Epub 2021 Jun 6.

Research School of Electrical, Energy and Materials Engineering, College of Engineering and Computer Science, the Australian National University, Canberra, ACT, 2601, Australia.

High-efficiency and wavelength-tunable light-emitting diode (LED) devices will play an important role in future advanced optoelectronic systems. Traditional semiconductor LED devices typically have a fixed emission wavelength that is determined by the energy of the emission states. Here, a novel high-efficiency and wavelength-tunable monolayer WS LED device, which operates in the hybrid mode of continuous-pulsed injection, is developed. This hybrid injection enables highly enhanced emission efficiency (>20 times) and effective size of emission area (>5 times) at room temperature. The emission wavelength of the WS monolayer LED device can be tuned over more than 40 nm by driving AC voltages, from exciton emission to trion emission, and further to defect emission. The quantum efficiency of defect electroluminescence (EL) emission is measured to be more than 24.5 times larger than that from free exciton and trion EL emission. The separate carrier injection in the LED also demonstrates advantages in allowing defect species to be visualized and distinguished in real space. Those defects are assigned to be negatively charged defects. The results open a new route to develop high-performance and wavelength-tunable LED devices for future advanced optoelectronic applications.
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http://dx.doi.org/10.1002/adma.202101375DOI Listing
July 2021

Preventing alloimmune rejection using circular RNA FSCN1-silenced dendritic cells in heart transplantation.

J Heart Lung Transplant 2021 Jul 8;40(7):584-594. Epub 2021 Apr 8.

Department of Pathology and Laboratory Medicine, Western University, London, Ontario Canada; Department of Surgery, Western University, London, Ontario Canada; Lawson Health Research Institute, London, Ontario Canada; Department of Oncology, Western University, London, Ontario Canada. Electronic address:

Background: While heart transplantation is used as a standard treatment for heart failure, transplant rejection continues to pose a challenge. Recent evidence has shown that circular RNA (circRNA) is a new type of gene regulator in cell development. Our aim was to demonstrate that treatment with tolerogenic dendritic cells (Tol-DCs) generated by circular RNA FSCN1 (circFSCN1) silencing could prevent alloimmune rejection and prolong heart graft survival in heart transplantation.

Methods: Bone marrow-derived DCs were transfected with circFSCN1 siRNA in vitro. The circFSCN1 level was measured by qRT-PCR. DC maturation was determined by flow cytometry. Mixed lymphocyte reactions (MLRs) were conducted to assess the function of DCs to activate T cells and to generate regulatory T cells (Tregs). In situ RNA hybridization and fluorescent microscopy were performed to detect the distribution of circFSCN1 in DCs. A heterotopic allogeneic murine heart transplantation was conducted where recipients were pre-treated with donor derived circFSCN1-silenced Tol-DCs. Heartbeat was monitored to assess immune rejection.

Results: Exonic circFSCN1 was highly expressed in the cytoplasm of mature DCs. Knockdown of circFSCN1 using siRNA arrested DCs at an immature state, impaired DC's ability to activate T cells and enhanced Treg generation. Treatment with circFSCN1-silenced Tol-DCs prevented alloimmune rejection, prolonged allograft survival, reduced fibrosis, and induced Tregs in vivo.

Conclusions: Knockdown of circFSCN1 induces Tol-DCs and treatment with these Tol-DCs prevents alloimmune rejection and prolongs allograft survival. This is a promising therapeutic target to combat transplant rejection in heart transplantation and increases our understanding of circRNA in the immune system.
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http://dx.doi.org/10.1016/j.healun.2021.03.025DOI Listing
July 2021

Oncogenic SNORD12B activates the AKT-mTOR-4EBP1 signaling in esophageal squamous cell carcinoma via nucleus partitioning of PP-1α.

Oncogene 2021 May 4;40(21):3734-3747. Epub 2021 May 4.

Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.

Esophageal cancer is a complex malignancy and the sixth leading cause of cancer death worldwide. In Eastern Asia including China, about 90% of all incident cases have esophageal squamous cell carcinoma (ESCC). Mounting evidence elucidates that aberrant expression of various non-coding RNAs (ncRNAs) contributes to ESCC progression, but it remains unclear how small nucleolar RNAs (snoRNAs) are involved in ESCC development. We systemically screened clinically relevant snoRNAs in ESCC via integrative analyses of The Cancer Genome Atlas (TCGA) data and validation in ESCC tissues. We found that snoRNA SNORD12B was one of the most evidently upregulated snoRNAs in ESCC specimens and its high expression was significantly associated with poor prognosis of patients. SNORD12B profoundly promoted proliferation, migration, invasion, and metastasis of ESCC cells in vitro and in vivo, indicating its oncogene nature. In particular, SNORD12B could interact with PP-1α, one of the three catalytic subunits of serine/threonine protein phosphatase 1, which is a major phosphatase that directly dephosphorylates AKT to suppress its activation. Interestingly, high levels of SNORD12B in ESCC cells could break interactions between 14-3-3ζ and PP-1α, abolish the retention of PP-1α in the cytosol by 14-3-3ζ and relocate PP-1α from the cytosol to the nucleus. This led to sequestered PP-1α in the nucleus, enhanced phosphorylation of AKT in the cytosol, activated AKT-mTOR-4EBP1 signaling, and, thus, ESCC progression. These insights would improve our understanding of how snoRNAs contribute to tumorigenesis and highlight the potential of snoRNAs as future therapeutic targets against cancers.
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http://dx.doi.org/10.1038/s41388-021-01809-2DOI Listing
May 2021

High Sensitivity Humidity Detection Based on Functional GO/MWCNTs Hybrid Nano-Materials Coated Titled Fiber Bragg Grating.

Nanomaterials (Basel) 2021 Apr 27;11(5). Epub 2021 Apr 27.

School of Physics, Dalian University of Technology, Dalian 116024, China.

A high performance humidity sensor using tilted fiber Bragg grating (TFBG) and functional graphene oxide (GO)/multi-walled carbon nanotubes (MWCNTs) hybrid nano-materials was proposed. The humidity-sensitive material with three-dimensional (3D) structure was synthesized by the MWCNTs and GOs. Comparing with traditional two dimensional (2D) GOs film, water molecules could be absorbed effectively due to the larger ripples and more holes in GO/MWCNTs layers. The water molecule will fill the entire space in the 3D structure instead of air, which further enhances the absorption efficiency of the hybrid nanomaterial. TFBG as a compact and robust surrounding complex dielectric constant sensing platform was utilized. The mode coupling coefficient or the amplitude of TFBG cladding mode will vary sharply with the imaginary part of permittivity of the hybrid nanomaterial, realizing the high performance RH sensing. In the experiments, we successfully demonstrated that this 3D structural nanomaterial composed by the MWCNTs and GOs has significant advantages for expanding the range of humidity detection (range from 30% to 90%) and enhancing the detection sensitivity (0.377 dB/% RH is twice more than humidity sensor with 2D GO film). The TFBG-based RH sensor also exhibits good repeatability and stability. Our proposed humidity sensor has potential application in environmental and healthy monitoring fields.
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http://dx.doi.org/10.3390/nano11051134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145005PMC
April 2021

Midday Nap Duration and Hypertension among Middle-Aged and Older Chinese Adults: A Nationwide Retrospective Cohort Study.

Int J Environ Res Public Health 2021 04 1;18(7). Epub 2021 Apr 1.

Department of Health Management, School of Health Sciences, Wuhan University, Wuhan 430071, China.

The goal of this study was to investigate the associations of midday nap duration and change in midday nap duration with hypertension in a retrospective cohort using a nationwide representative sample of middle-aged and older Chinese adults. Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) database during 2011-2015. Information on midday nap duration was collected via a self-reported questionnaire and blood pressure was objectively measured. Hazard ratios (HR) with 95% confidence interval (CI) were estimated using Cox proportional hazards regression models to quantify the associations. A sample of 5729 Chinese adults (≥45 years old) were included in the longitudinal analysis. Relative to non-nappers, participants who napping for ≥90 min/day was associated with significantly larger HR for hypertension at four-year follow-up (HR = 1.18, 95% CI = 1.01-1.40, = 0.048). Compared with people who napped ≥90 min/day both at baseline (2011) and follow-up (2013), hypertension risk at four-year follow-up declined in individuals whose midday nap durations decreased in the 2-year study period from ≥ 90 min/day to 1-59 min/day (HR = 0.59, 95% CI = 0.36-0.97, = 0.037) and 60-89 min/day (HR = 0.68, 95% CI = 0.47-0.99, = 0.044). Among middle-aged and older Chinese adults, relative to non-nappers, people who had longer midday nap duration (≥90 min/day) were associated with significantly larger HR for hypertension and decreased napping duration may confer benefit for hypertension prevention.
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http://dx.doi.org/10.3390/ijerph18073680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037516PMC
April 2021

Optimization of protein hydrolysis conditions and antioxidant activity of tetrapeptide Asp-Arg-Glu-Leu by elevating the Nrf2/Keap1-p38/PI3K-MafK signaling pathway.

Food Funct 2021 Jun;12(11):4808-4824

Beijing Laboratory of Food Quality and Safety, Beijing Technology and Business University, Beijing 100048, China.

Tetrapeptide Asp-Arg-Glu-Leu (DREL) was isolated from Jiuzao protein hydrolysates (JPHs) by alkaline proteinase (AP) and exhibited antioxidant activity in the HepG2 cell model in the previous study. In this study, the hydrolysis method of Jiuzao protein (JP) was further optimized by using different proteinases under different conditions (i.e., temperature, time, ratio between proteinase and substrate, and pH). Considering the limitation of in vitro assays, the AAPH-induced oxidative stress Sprague-Dawley (SD) rat model was selected to measure the antioxidant capacity of DREL in vivo. Pepsin exhibited the highest hydrolysis degree under the optimum conditions after single factor analysis (SFA) among seven proteinases. The total yield of DREL in Jiuzao was 158.24 mg kg-1Jiuzao under the pepsin's optimum hydrolysis conditions determined by response surface methodology analysis (RSMA). In addition, DREL could activate the Nrf2/Keap1-p38/PI3K-MafK signaling pathway and downstream antioxidant enzymes to improve the antioxidant ability in vivo. DREL also preliminarily exhibited anti-inflammatory activity by inhibiting the secretion of inflammatory cytokines and the mediator through the activation of Nrf2. Of note, the addition of DREL in baijiu brought an inconspicuous change in the taste after sensory evaluation. This study finds out the better proteinase used for JP hydrolysis and verifies the antioxidant capacity of DREL in vivo, which provides a potential approach to apply functional components from Jiuzao for by-product utilization. Meanwhile the antioxidant function of baijiu or other foods can be increased through adding these functional peptides without affecting the original flavor and taste in the future.
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http://dx.doi.org/10.1039/d0fo02852eDOI Listing
June 2021

A Role for Polo-Like Kinase 4 in Vascular Fibroblast Cell-Type Transition.

JACC Basic Transl Sci 2021 Mar 22;6(3):257-283. Epub 2021 Mar 22.

Department of Surgery, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.

Polo-like kinase 4 (PLK4) is canonically known for its cytoplasmic function in centriole duplication. Here we show a noncanonical PLK4 function of regulating the transcription factor SRF's nuclear activity and associated myofibroblast-like cell-type transition. In this context, we have further found that PLK4's phosphorylation and transcription are respectively regulated by PDGF receptor and epigenetic factor BRD4. Furthermore, in vivo experiments suggest PLK4 inhibition as a potential approach to mitigating vascular fibrosis.
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http://dx.doi.org/10.1016/j.jacbts.2020.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987547PMC
March 2021

A hierarchical and collaborative BRD4/CEBPD partnership governs vascular smooth muscle cell inflammation.

Mol Ther Methods Clin Dev 2021 Jun 27;21:54-66. Epub 2021 Feb 27.

Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.

Bromodomain protein BRD4 reads histone acetylation (H3K27ac), an epigenomic mark of transcription enhancers. CCAAT enhancer binding protein delta (CEBPD) is a transcription factor typically studied in metabolism. While both are potent effectors and potential therapeutic targets, their relationship was previously unknown. Here we investigated their interplay in vascular smooth muscle cell (SMC) inflammation. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) revealed H3K27ac/BRD4 enrichment at in injured rat carotid arteries. While genomic deletion of BRD4-associated enhancer in SMCs decreased transcripts, BRD4 gene silencing also diminished mRNA and protein, indicative of a BRD4 control over CEBPD expression. Bromodomain-1, but not bromodomain-2, accounted for this BRD4 function. Moreover, endogenous BRD4 protein co-immunoprecipitated with CEBPD, and both proteins co-immunoprecipitated the promoter and enhancer DNA fragments. These co-immunoprecipitations (coIPs) were all abolished by the BRD4-bromodomain blocker JQ1, suggesting a BRD4/CEBPD /promoter/enhancer complex. While BRD4 and CEBPD were both upregulated upon tumor necrosis factor alpha (TNF-α) stimulation of SMC inflammation (increased interleukin [IL]-1b, IL-6, and MCP-1), they mediated this stimulation via preferentially elevated expression of platelet-derived growth factor receptor alpha (PDGFRα, versus PDGFRβ), as indicated by loss- and gain-of-function experiments. Taken together, our study unravels a hierarchical yet collaborative BRD4/CEBPD relationship, a previously unrecognized mechanism that prompts SMC inflammation and may underlie other pathophysiological processes as well.
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http://dx.doi.org/10.1016/j.omtm.2021.02.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966960PMC
June 2021

Highly Enhanced Light-Matter Interaction in MXene Quantum Dots-Monolayer WS Heterostructure.

Small 2021 Mar 23;17(11):e2006309. Epub 2021 Feb 23.

Research School of Electrical, Energy and Materials Engineering, College of Engineering and Computer Science, The Australian National University, Canberra, ACT, 2601, Australia.

Since the Ti C was discovered in 2011, the family of MXenes has attracted much attention. MXenes offer great potential in the tuning of many fundamental properties by the synthesis of new structures. The synthesis methods of MXene mainly require steps including immersing a MAX phase in hydrofluoric acid (HF) and processing at high temperatures. However, the HF may be hard to acquire in many countries and processing at high temperatures may cause risk issues. In this article, a simple and cost-effective synthesis of Ti C T quantum dots (QDs) via chemical solution method that follows the long-time magnetic stirring process-initiated etching of Al atoms from commercial Ti AlC powder at room temperature is introduced. With WS monolayer sitting over the MXenes QD arrays, a higher level of photoluminescence (PL) enhancement is found in the heterostructure with increasing laser power at room temperature and a few novel quasi-particles species in the heterostructure at -190 °C. The observations show that the possible plasmonic behavior initiated by QD arrays and the suspension state of WS may coplay the roles to trigger multiple quasi-particles species. This study can be an important benchmark for the extensive understanding of quasi-particles species, and their dynamics.
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http://dx.doi.org/10.1002/smll.202006309DOI Listing
March 2021

Hydrogen peroxide-responsive platelet membrane-coated nanoparticles for thrombus therapy.

Biomater Sci 2021 Apr 22;9(7):2696-2708. Epub 2021 Feb 22.

Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.

Occlusion of blood vessels caused by thrombi is the major pathogenesis of various catastrophic cardiovascular diseases. Thrombi can be prevented or treated by antithrombotic drugs. However, free antithrombotic drugs often have relatively low therapeutic efficacy due to a number of limitations such as short half-life, unexpected bleeding complications, low thrombus targeting capability, and negligible hydrogen peroxide (HO)-scavenging ability. Inspired by the abundance of HO and the active thrombus-targeting property of platelets, a HO-responsive platelet membrane-cloaked argatroban-loaded polymeric nanoparticle (PNP) was developed for thrombus therapy. Poly(vanillyl alcohol-co-oxalate) (PVAX), a HO-degradable polymer, was synthesized to form an argatroban-loaded nanocore, which was further coated with platelet membrane. The PNP can effectively target the blood clots due to the thrombus-homing property of the cloaked platelet membrane, and subsequently exert combined HO-scavenging effect via the HO-degradable nanocarrier polymer and antithrombotic effect via argatroban, the released payload. The PNP effectively scavenged HO and protected cells from HO-induced cellular injury in RAW 264.7 cells and HUVECs. The PNP rapidly targeted the thrombosed vessels and remarkably suppressed thrombus formation, and the levels of HO and inflammatory cytokines in the ferric chloride-induced carotid arterial thrombosis mouse model. Safety assessment indicated good biocompatibility of the PNP. Taken together, the biomimetic PNP offers multiple functionalities including thrombus-targeting, antioxidation, and HO-stimulated antithrombotic action, thereby making it a promising therapeutic nanomedicine for thrombosis diseases.
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http://dx.doi.org/10.1039/d0bm02125cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056337PMC
April 2021

Melatonin ameliorates oxidative stress-mediated injuries through induction of HO-1 and restores autophagic flux in dry eye.

Exp Eye Res 2021 04 12;205:108491. Epub 2021 Feb 12.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address:

This study aimed to investigate the protective effect of melatonin on the corneal epithelium in dry eye disease(DED) and explore its underlying mechanism. Human corneal epithelial(HCE) cells was exposure to t-butylhydroperoxide(tBH), C57BL/6 mice were injected of subcutaneous scopolamine to imitate DED. Melatonin was used both in vivo and in vitro. Cell viability was detected by Cell Counting Kit-8 assay and Lactate Dehydrogenase Leakage. The change of cellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and apoptosis was analyzed by flow cytometry. Western blot assays and immunofluorescence were carried out to measure protein changes. mRNA expression was investigated by RNA sequencing (RNA-Seq) and quantitative real-time PCR. The change of autophagic flux were observed through mCherry-GFP-LC3 transfection and electron microscopy(TEM). Clinical parameters of corneal epithelium defects, conjunctival goblet cells, tear volume, and level of ocular surface inflammation was recorded. Melatonin was able to reduce excessive ROS production and maintain mitochondrial function. TEM assay found melatonin rescued impaired autophagic flux under tBH. Moreover, melatonin significantly preserved cell viability, abolished LDH release, and decreased apoptosis. RNA-Seq indicated that melatonin greatly activating hemeoxygenase-1 (HO-1) expression. Interestingly, HO-1 ablation largely attenuated its protective effects. Besides, in dry eye mouse model, intraperitoneal injection of melatonin showed greatly improved clinical parameters, inhibited activated NLRP3 inflammation cascade, and increased density of goblet cells and tear volume. Thus, melatonin protects corneal epithelial cells from oxidative damage, maintain normal level of autophagy, and reduce inflammation via trigging HO-1 expression in DED.
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http://dx.doi.org/10.1016/j.exer.2021.108491DOI Listing
April 2021
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