Publications by authors named "Tianlu Wang"

38 Publications

SP1-induced lncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) aggravates glioma progression via the miR-515-5p/Superoxide dismutase 2 (SOD2) axis.

Bioengineered 2021 Dec;12(1):2299-2310

Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University.

Glioma is a common life-threatening tumor with high malignancy and high invasiveness. LncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) was confirmed to be implicated in numerous tumors, while its biological function and mechanism have not been thoroughly understood in glioma. The gene expression was measured by RT-qPCR. Cell proliferation, cell cycle, and cell apoptosis of glioma cells were validated by CCK-8, colony formation, flow cytometry and TUNEL assays. The effect of ZFPM2-AS1 on tumor growth was verified by assay. The exploration on ZFPM2-AS1-mediated mechanism was carried out via ChIP, luciferase reporter, and RIP assays. In the present study, ZFPM2-AS1 was demonstrated as a highly-expressed lncRNA in glioma tissues and cells. ZFPM2-AS1 silencing suppressed cell proliferation and cell cycle, but facilitated cell apoptosis. In addition, the inhibitive effect of silenced ZFPM2-AS1 was also observed in tumor growth. Furthermore, we found that SP1 interacted with ZFPM2-AS1 promoter to transcriptionally activate ZFPM2-AS1 expression. Moreover, ZFPM2-AS1 was identified as a competing endogenous RNA (ceRNA) for miR-515-5p to target SOD2. Rescue assays verified that SOD2 overexpression partially abolished the suppressive impact of ZFPM2-AS1 silencing on glioma cell growth. In conclusion, this study corroborated the regulatory mechanism of SP1/ZFPM2-AS1/miR-515-5p/SOD2 axis in glioma, indicating that targeting ZFPM2-AS1 might be an effective way to treat glioma.
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http://dx.doi.org/10.1080/21655979.2021.1934241DOI Listing
December 2021

Effect of body stiffness distribution on larval fish-like efficient undulatory swimming.

Sci Adv 2021 May 5;7(19). Epub 2021 May 5.

Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany.

Energy-efficient propulsion is a critical design target for robotic swimmers. Although previous studies have pointed out the importance of nonuniform body bending stiffness distribution () in improving the undulatory swimming efficiency of adult fish-like robots in the inertial flow regime, whether such an elastic mechanism is beneficial in the intermediate flow regime remains elusive. Hence, we develop a class of untethered soft milliswimmers consisting of a magnetic composite head and a passive elastic body with different These robots realize larval zebrafish-like undulatory swimming at the same scale. Investigations reveal that uniform and high swimming frequency (60 to 100 Hz) are favorable to improve their efficiency. A shape memory polymer-based milliswimmer with tunable on the fly confirms such findings. Such acquired knowledge can guide the design of energy-efficient leading edge-driven soft undulatory milliswimmers for future environmental and biomedical applications in the same flow regime.
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http://dx.doi.org/10.1126/sciadv.abf7364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099186PMC
May 2021

Titanium implant alters the effect of zoledronic acid on the behaviour of endothelial cells.

Oral Dis 2021 Apr 28. Epub 2021 Apr 28.

Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, China.

Objectives: To evaluate the effect of zoledronic acid (ZA) on human umbilical vein endothelial cells (HUVECs) attached to different surfaces.

Materials And Methods: A total of three groups were evaluated in this study: sandblasting and acid etching (SLA) + HUVECs; mechanically polished (MP) + HUVECs; and plastic cell culture plates + HUVECs. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, surface roughness and water contact angle were tested for titanium surface characterisation. ZA was added at different concentrations (0, 1, 10, 50 and 100 μM). Cell adhesion, proliferation, viability, apoptosis and gene expression were evaluated.

Results: Mechanically polished and SLA surfaces showed negative effects on cell adhesion and proliferation and promoted cell apoptosis with 100 μM ZA (p < .05). The highest expression of intercellular adhesion molecule-1 (ICAM-1) and angiopoietin-1 was found on SLA surfaces (p < .01). The lowest expression of platelet-endothelial cell adhesion molecule-1 and ICAM-1 was found on MP surfaces (p < .05). A significant decrease in von Willebrand factor was detected on MP and SLA surfaces (p < .001).

Conclusions: Zoledronic acid has an anti-angiogenic effect on HUVECs attached to titanium implants, while the SLA surface might stimulate HUVECs to express angiogenic and adhesive factor genes despite ZA treatment.
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http://dx.doi.org/10.1111/odi.13890DOI Listing
April 2021

Ultrasound-Guided Wireless Tubular Robotic Anchoring System.

IEEE Robot Autom Lett 2020 Jul 19;5(3):4859-4866. Epub 2020 Jun 19.

Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany, with the Department of Information Technology and Electrical Engineering, ETH Zurich, 8092 Zurich, Switzerland, and also with the School of Engineering and School of Medicine, Koc University, Istanbul 34450, Turkey.

Untethered miniature robots have significant poten-tial and promise in diverse minimally invasive medical applications inside the human body. For drug delivery and physical contra-ception applications inside tubular structures, it is desirable to have a miniature anchoring robot with self-locking mechanism at a target tubular region. Moreover, the behavior of this robot should be tracked and feedback-controlled by a medical imaging-based system. While such a system is unavailable, we report a reversible untethered anchoring robot design based on remote magnetic actuation. The current robot prototype's dimension is 7.5 mm in diameter, 17.8 mm in length, and made of soft polyurethane elastomer, photopolymer, and two tiny permanent magnets. Its relaxation and anchoring states can be maintained in a stable manner without supplying any control and actuation input. To control the robot's locomotion, we implement a two-dimensional (2D) ultrasound imaging-based tracking and control system, which automatically sweeps locally and updates the robot's position. With such a system, we demonstrate that the robot can be controlled to follow a pre-defined 1D path with the maximal position error of 0.53 ± 0.05 mm inside a tubular phantom, where the reversible anchoring could be achieved under the monitoring of ultrasound imaging.
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http://dx.doi.org/10.1109/LRA.2020.3003868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610639PMC
July 2020

Micro/nano-textured hierarchical titanium topography promotes exosome biogenesis and secretion to improve osseointegration.

J Nanobiotechnology 2021 Mar 19;19(1):78. Epub 2021 Mar 19.

Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, No.56 of LingYuanXiLu, Guangzhou, 510055, Guangdong, People's Republic of China.

Background: Micro/nano-textured hierarchical titanium topography is more bioactive and biomimetic than smooth, micro-textured or nano-textured titanium topographies. Bone marrow mesenchymal stem cells (BMSCs) and exosomes derived from BMSCs play important roles in the osseointegration of titanium implants, but the effects and mechanisms of titanium topography on BMSCs-derived exosome secretion are still unclear. This study determined whether the secretion behavior of exosomes derived from BMSCs is differently affected by different titanium topographies both in vitro and in vivo.

Results: We found that both micro/nanonet-textured hierarchical titanium topography and micro/nanotube-textured hierarchical titanium topography showed favorable roughness and hydrophilicity. These two micro/nano-textured hierarchical titanium topographies enhanced the spreading areas of BMSCs on the titanium surface with stronger promotion of BMSCs proliferation in vitro. Compared to micro-textured titanium topography, micro/nano-textured hierarchical titanium topography significantly enhanced osseointegration in vivo and promoted BMSCs to synthesize and transport exosomes and then release these exosomes into the extracellular environment both in vitro and in vivo. Moreover, micro/nanonet-textured hierarchical titanium topography promoted exosome secretion by upregulating RAB27B and SMPD3 gene expression and micro/nanotube-textured hierarchical titanium topography promoted exosome secretion due to the strongest enhancement in cell proliferation.

Conclusions: These findings provide evidence that micro/nano-textured hierarchical titanium topography promotes exosome biogenesis and extracellular secretion for enhanced osseointegration. Our findings also highlight that the optimized titanium topography can increase exosome secretion from BMSCs, which may promote osseointegration of titanium implants.
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http://dx.doi.org/10.1186/s12951-021-00826-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980346PMC
March 2021

Encouraging Digital Technology in Neuropsychology: The Theory of Visual Attention on Tablet Devices.

Arch Clin Neuropsychol 2021 Feb 24. Epub 2021 Feb 24.

Department of Brain and Cognition, KU Leuven, Leuven, Belgium.

Objective: Visual attention helps us to selectively process relevant information and is crucial in our everyday interactions with the environment. Not surprisingly, it is one of the cognitive domains that is most frequently affected by acquired brain injury. Reliable assessment of attention deficits is pivotal to neuropsychological examination and helps to optimize individual rehabilitation plans. Compared with conventional pen-and-paper tests, computerized tasks borrowed from the field of experimental psychology bring many benefits, but lab-based experimental setups cannot be easily incorporated in clinical practice. Light-weight and portable mobile tablet devices may facilitate the translation of computerized tasks to clinical settings. One such task is based on the Theory of Visual Attention (TVA), a mathematical model of visual attention. TVA-based paradigms have been widely used to investigate several aspects of visual attention in both fundamental and clinical research, and include measures for general processing capacity as well as stimulus-specific attentional parameters.

Methods: This article discusses the benefits of TVA-based assessments compared with frequently used neuropsychological tests of visual attention, and examines the reliability of a tablet-based TVA-based assessment in 59 neurologically healthy participants.

Results: Pearson's correlations indicate that the tablet-based TVA assessment and the conventional lab-based TVA assessment have a comparable parallel-form (range: .67-.93), test-retest (range: .61-.78), and internal reliability (range: .56-.97).

Conclusion: Our results suggest that tablet-based TVA assessment may be a promising tool to acquire clinical measures of visual attention at low cost at the bedside of the patient.
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http://dx.doi.org/10.1093/arclin/acab007DOI Listing
February 2021

Caffeine-Operated Synthetic Modules for Chemogenetic Control of Protein Activities by Life Style.

Adv Sci (Weinh) 2021 Feb 13;8(3):2002148. Epub 2020 Dec 13.

Center for Translational Cancer Research Institute of Biosciences and Technology Texas A&M University Houston TX 77030 USA.

A genetically encoded caffeine-operated synthetic module (COSMO) is introduced herein as a robust chemically induced dimerization (CID) system. COSMO enables chemogenetic manipulation of biological processes by caffeine and its metabolites, as well as caffeinated beverages, including coffee, tea, soda, and energy drinks. This CID tool, evolved from an anti-caffeine nanobody via cell-based high-throughput screening, permits caffeine-inducible gating of calcium channels, tumor killing via necroptosis, growth factors-independent activation of tyrosine receptor kinase signaling, and enhancement of nanobody-mediated antigen recognition for the severe acute respiratory distress coronavirus 2 (SARS-CoV-2) spike protein. Further rationalized engineering of COSMO leads to 34-217-fold enhancement in caffeine sensitivity (EC = 16.9 nanomolar), which makes it among the most potent CID systems like the FK506 binding protein (FKBP)-FKBP rapamycin binding domain (FRB)-rapamycin complex. Furthermore, bivalent COSMO (biCOMSO) connected with a long linker favors intramolecular dimerization and acts as a versatile precision switch when inserted in host proteins to achieve tailored function. Given the modularity and high transferability of COMSO and biCOSMO, these chemical biology tools are anticipated to greatly accelerate the development of therapeutic cells and biologics that can be switched on and off by caffeinated beverages commonly consumed in the daily life.
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http://dx.doi.org/10.1002/advs.202002148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856909PMC
February 2021

Modulating the interhemispheric activity balance in the intraparietal sulcus using real-time fMRI neurofeedback: Development and proof-of-concept.

Neuroimage Clin 2020 27;28:102513. Epub 2020 Nov 27.

Brain and Cognition, KU Leuven, Leuven, Belgium; Leuven Brain Institute, KU Leuven, Leuven, Belgium. Electronic address:

The intraparietal sulcus (IPS) plays a key role in the distribution of attention across the visual field. In stroke patients, an imbalance between left and right IPS activity has been related to a spatial bias in visual attention characteristic of hemispatial neglect. In this study, we describe the development and implementation of a real-time functional magnetic resonance imaging neurofeedback protocol to noninvasively and volitionally control the interhemispheric IPS activity balance in neurologically healthy participants. Six participants performed three neurofeedback training sessions across three weeks. Half of them trained to voluntarily increase brain activity in left relative to right IPS, while the other half trained to regulate the IPS activity balance in the opposite direction. Before and after the training, we estimated the distribution of attention across the visual field using a whole and partial report task. Over the course of the training, two of the three participants in the left-IPS group increased the activity in the left relative to the right IPS, while the participants in the right-IPS group were not able to regulate the interhemispheric IPS activity balance. We found no evidence for a decrease in resting-state functional connectivity between left and right IPS, and the spatial distribution of attention did not change over the course of the experiment. This study indicates the possibility to voluntarily modulate the interhemispheric IPS activity balance. Further research is warranted to examine the effectiveness of this technique in the rehabilitation of post-stroke hemispatial neglect.
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http://dx.doi.org/10.1016/j.nicl.2020.102513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941162PMC
November 2020

Surface modification of titanium manufactured through selective laser melting inhibited osteoclast differentiation through mitogen-activated protein kinase signaling pathway.

J Biomater Appl 2020 08 27;35(2):169-181. Epub 2020 Apr 27.

Department of Oral Implantology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, PR China.

Selective laser melting used in manufacturing custom-made titanium implants becomes more popular. In view of the important role played by osteoclasts in peri-implant bone resorption and osseointegration, we modified selective laser melting-manufactured titanium surfaces using sandblasting/alkali-heating and sandblasting/acid-etching, and investigated their effect on osteoclast differentiation as well as their underlying mechanisms. The properties of the surfaces, including elements, roughness, wettability and topography, were analyzed. We evaluated the proliferation and morphology of primary mouse bone marrow-derived monocytes, as well as induced osteoclasts derived from bone marrow-derived monocytes, on samples. Then, osteoclast differentiation was determined by the tartrate-resistant acid phosphatase activity assay, calcitonin receptors immunofluorescence staining and the expression of osteoclast-related genes. The results showed that sandblasting/alkali-heating established nanonet structure with the lowest water contact angle, and both sandblasting/alkali-heating and sandblasting/acid-etching significantly decreased surface roughness and heterogeneity compared with selective laser melting. Surface modifications of selective laser melting-produced titanium altered bone marrow-derived monocyte morphology and suppressed bone marrow-derived monocyte proliferation and osteoclastogenesis in vitro (sandblasting/alkali-heating>sandblasting/acid-etching>selective laser melting). These surface modifications reduced the activation of extracellular signal-regulated kinase and c-Jun N-terminal kinases compared to native-selective laser melting. Sandblasting/alkali-heating additionally blocked tumor necrosis factor receptor-associated factor 6 recruitment. The results suggested that sandblasting/alkali-heating and sandblasting/acid-etching modifications on selective laser melting titanium could inhibit osteoclast differentiation through suppressing extracellular signal-regulated kinase and c-Jun N-terminal kinase phosphorylation in mitogen-activated protein kinase signaling pathway and provide a promising technique which might reduce peri-implant bone resorption for optimizing native-selective laser melting implants.
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http://dx.doi.org/10.1177/0885328220920457DOI Listing
August 2020

LncRNA LINC00963 Promotes Tumorigenesis and Radioresistance in Breast Cancer by Sponging miR-324-3p and Inducing ACK1 Expression.

Mol Ther Nucleic Acids 2019 Dec 22;18:871-881. Epub 2019 Oct 22.

Department of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China.

Upregulation of long non-coding RNA LINC00963 has been observed in several cancer types. In this study, we analyzed the clinical and biological significance of LINC00963 in breast cancer. The key microRNA (miR) mediating the action of LINC00963 was identified. We show that LINC00963 upregulation is correlated with aggressive parameters of breast cancer. Silencing of LINC00963 suppresses the proliferation and tumorigenesis of breast cancer cells, whereas LINC00963 overexpression exerts an opposite effect. Knockdown of LINC00963 enhances DNA damage and oxidative stress and sensitizes breast cancer cells to radiation. Mechanistically, LINC00963 antagonizes the repressive activity of miR-324-3p on ACK1 expression. Clinically, there is a negative correlation between miR-324-3p and LINC00963 expression in breast cancer tissues. Overexpression of LINC00963 or ACK1 rescues the inhibitory effects of miR-324-3p on breast cancer cell proliferation and radiosensitivity. In addition, knockdown of ACK1 attenuates LINC00963-dependent breast cancer growth and tumorigenesis. Taken together, LINC00963 promotes tumorigenesis and radioresistance in breast cancer through interplay with miR-324-3p and derepression of ACK1. LINC00963 may represent a potential target for the treatment of breast cancer.
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http://dx.doi.org/10.1016/j.omtn.2019.09.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881674PMC
December 2019

MicroRNA-125a-5p modulates radioresistance in LTEP-a2 non-small cell lung cancer cells by targeting SIRT7.

Cancer Biomark 2020 ;27(1):39-49

Background: Micro(mi)RNAs are a series of 20-24 nt non-coding small-molecule single-stranded RNAs that are believed to be closely related to tumor occurrence, development and other biological processes. MicroRNA-125a modulates radiochemotherapy sensitivity. However, the mechanism by which miRNA-125a regulates radiation resistance by lung cancer cells is yet to be elucidated.

Objective: The present study was designed to explore the biological role of miR-125a in regulating radioresistance in non-small cell lung carcinoma (NSCLC).

Methods And Results: The expression of miR-125a was assessed by quantitative real-time PCR in the human lung cancer cell lines, A549 and LTEP-a2. Notably, we found that miRNA-125a-5p regulated lung cancer radiosensitivity. We found that miRNA-125a-5p was more highly expressed in LTEP-a2 cells, which showed radiosensitivity compared to A549 cells with lower expression of miRNA-125a-5p. In addition, we up-regulated or down-regulated miR-125a-5p expression using an miR-125a-5p mimic or inhibitor, respectively, to reverse radioresistance. Flow cytometry revealed that the mimic increased the apoptotic rate as well as the expression of the apoptosis-related protein, cleaved poly ADP-ribose polymerase (PARP). Gene detection by luciferase reporter showed that sirtuin (SIRT)7 is a direct target of miR-125a-5p. Inhibiting SIRT7 using a small interfering RNA (siSIRT) abrogated resistance to radiation. In addition, the overexpression of SIRT7 decreased radiation-induced cell apoptosis.

Conclusion: Our results indicated that the miR-125a level varies in NSCLC cell lines with different radiosensitivities. We demonstrated that miR-125a-5p upregulated SIRT7 and further upregulated apoptosis in lung cancer cells to increase their radiosensitivity. Our findings provide new directions for improving radiosensitivity in malignant lung tumors.
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http://dx.doi.org/10.3233/CBM-190381DOI Listing
June 2020

MicroRNA-524 inhibits the progress of glioma via the direct targeting of NCF2.

Am J Transl Res 2019 15;11(3):1605-1615. Epub 2019 Mar 15.

Department of Neurosurgery, Sir Run Run Hospital, Nanjing Medical University Nanjing, Jiangsu Province, China.

In recent years, a large amount of research has reported that microRNA (miRNA) dysregulation is closely related to glioma progression. miR-524, a member of the miRNA family, has been confirmed to be involved in many human diseases, including glioma. However, the role and molecular mechanism of miR-524 in glioma have not been clarified. In our study, we showed that miR-524 expression was significantly decreased in glioma and was associated with glioma recurrence. Next, we performed a series of assays and confirmed that the upregulation of miR-524 suppressed glucose uptake, proliferation, migration and invasion in glioma cell lines. Then, through bioinformatics software and a dual luciferase assay, we demonstrated that NCF2 was a target gene of miR-524. In addition, we found that NCF2 reintroduction restored the inhibitor effect of miR-524 on glioma progression. These results elucidate the mechanism of miR-524 in glioma development and provide a potential therapeutic strategy for glioma patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456563PMC
March 2019

Identification of YTH Domain-Containing Proteins as the Readers for N1-Methyladenosine in RNA.

Anal Chem 2018 06 25;90(11):6380-6384. Epub 2018 May 25.

N1-methyladenosine (mA) is an important post-transcriptional modification in RNA; however, the exact biological role of mA remains to be determined. By employing a quantitative proteomics method, we identified multiple putative protein readers of mA in RNA, including several YTH domain family proteins. We showed that YTHDF1-3 and YTHDC1, but not YTHDC2, could bind directly to mA in RNA. We also found that Trp in YTHDF2, a conserved residue in the hydrophobic pocket of the YTH domain that is necessary for its binding to N-methyladenosine (mA), is required for its recognition of mA. An analysis of previously published data revealed transcriptome-wide colocalization of YTH domain-containing proteins and mA sites in HeLa cells, suggesting that YTH domain-containing proteins can bind to mA in cells. Together, our results uncovered YTH domain-containing proteins as readers for mA in RNA and provided new insight into the functions of mA in RNA biology.
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http://dx.doi.org/10.1021/acs.analchem.8b01703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157021PMC
June 2018

TVA-Based Assessment of Visual Attention Using Line-Drawings of Fruits and Vegetables.

Front Psychol 2018 27;9:207. Epub 2018 Feb 27.

Department of Brain and Cognition, KU Leuven, Leuven, Belgium.

Visuospatial attention and short-term memory allow us to prioritize, select, and briefly maintain part of the visual information that reaches our senses. These cognitive abilities are quantitatively accounted for by Bundesen's theory of visual attention (TVA; Bundesen, 1990). Previous studies have suggested that TVA-based assessments are sensitive to inter-individual differences in spatial bias, visual short-term memory capacity, top-down control, and processing speed in healthy volunteers as well as in patients with various neurological and psychiatric conditions. However, most neuropsychological assessments of attention and executive functions, including TVA-based assessment, make use of alphanumeric stimuli and/or are performed verbally, which can pose difficulties for individuals who have troubles processing letters or numbers. Here we examined the reliability of TVA-based assessments when stimuli are used that are not alphanumeric, but instead based on line-drawings of fruits and vegetables. We compared five TVA parameters quantifying the aforementioned cognitive abilities, obtained by modeling accuracy data on a whole/partial report paradigm using conventional alphabet stimuli versus the food stimuli. Significant correlations were found for all TVA parameters, indicating a high parallel-form reliability. Split-half correlations assessing internal reliability, and correlations between predicted and observed data assessing goodness-of-fit were both significant. Our results provide an indication that line-drawings of fruits and vegetables can be used for a reliable assessment of attention and short-term memory.
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http://dx.doi.org/10.3389/fpsyg.2018.00207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835087PMC
February 2018

Precise Antibody-Independent m6A Identification via 4SedTTP-Involved and FTO-Assisted Strategy at Single-Nucleotide Resolution.

J Am Chem Soc 2018 05 5;140(18):5886-5889. Epub 2018 Mar 5.

College of Chemistry and Molecular Sciences , Wuhan University , Wuhan , Hubei 430072 , China.

Innovative detection techniques to achieve precise m6A distribution within mammalian transcriptome can advance our understanding of its biological functions. We specifically introduced the atom-specific replacement of oxygen with progressively larger atoms (sulfur and selenium) at 4-position of deoxythymidine triphosphate to weaken its ability to base pair with m6A, while maintaining A-T* base pair virtually the same as the natural one. 4SedTTP turned out to be an outstanding candidate that endowed m6A with a specific signature of RT truncation, thereby making this "RT-silent" modification detectable with the assistance of m6A demethylase FTO through next-generation sequencing. This antibody-independent, 4SedTTP-involved and FTO-assisted strategy is applicable in m6A identification, even for two closely gathered m6A sites, within an unknown region at single-nucleotide resolution.
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http://dx.doi.org/10.1021/jacs.7b13633DOI Listing
May 2018

Deficiency of α Calcitonin-gene-related peptide impairs peri-implant angiogenesis and osseointegration via suppressive vasodilative activity.

Biochem Biophys Res Commun 2018 03 5;498(1):139-145. Epub 2018 Feb 5.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address:

Blood supply is essential for the bone healing process to obtain successful osseointegration. α Calcitonin gene-related peptide (αCGRP) is osteoanabolic and is the most potent microvascular vasodilator currently known with validated angiogenic effect in vitro. We previously demonstrated that lentiviral αCGRP overexpression vector system could express the gene effectively to enhance titanium implant osseointegration. In this study, we investigated the effect of αCGRP on peri-implant angiogenesis during healing process in vivo. Based on investigation of blood vessel alteration in the peri-implant region of wild-type mice, we found a reduced angiogenesis alongside a decline in bone-implant contact percentage and bone mass in αCGRP mice. Overexpression of αCGRP could partly rescue the impairment. Alterations were also detected in three-dimensional vascular structural parameters and expression of bone and vessel related genes. The results showed αCGRP increased vascular volume fraction and mean vessel size, as well as spatially relocated vessels approximate to the region of bone formation. And angiogenic and osteogenic genes were significantly upregulated in the transfection and αCGRP group. These results suggested that αCGRP played a synergic role in angiogenesis and osseointegration, partly as a consequence of its vasodilative activity.
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http://dx.doi.org/10.1016/j.bbrc.2018.02.027DOI Listing
March 2018

The potential of real-time fMRI neurofeedback for stroke rehabilitation: A systematic review.

Cortex 2018 10 18;107:148-165. Epub 2017 Sep 18.

Department of Brain & Cognition, University of Leuven, Leuven, Belgium; Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom. Electronic address:

Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback aids the modulation of neural functions by training self-regulation of brain activity through operant conditioning. This technique has been applied to treat several neurodevelopmental and neuropsychiatric disorders, but its effectiveness for stroke rehabilitation has not been examined yet. Here, we systematically review the effectiveness of rt-fMRI neurofeedback training in modulating motor and cognitive processes that are often impaired after stroke. Based on predefined search criteria, we selected and examined 33 rt-fMRI neurofeedback studies, including 651 healthy individuals and 15 stroke patients in total. The results of our systematic review suggest that rt-fMRI neurofeedback training can lead to a learned modulation of brain signals, with associated changes at both the neural and the behavioural level. However, more research is needed to establish how its use can be optimized in the context of stroke rehabilitation.
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http://dx.doi.org/10.1016/j.cortex.2017.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182108PMC
October 2018

Geniposide Attenuates Post-Ischaemic Neurovascular Damage via GluN2A/AKT/ ERK-Dependent Mechanism.

Cell Physiol Biochem 2017 22;43(2):705-716. Epub 2017 Sep 22.

Department of Neurosurgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.

Background/aims: Calcium-permeable ionotropic NMDAR-mediated hyperactivity is regarded as the critical factor in modulating the development of ischaemic stroke. Recently, there has been increasing interest in preventing post-stroke neuronal death by focusing on intervening in the function of subpopulations of NMDARs and their downstream signalling. Geniposide, an iridoid glycoside, has been found to have cytoprotective functions in various conditions. However, it is still unclear whether and how geniposide affects neuronal insult under experimental stroke.

Methods: We demonstrate that dose-dependent geniposide significantly decreased the infarct volume in tMCAO models.

Results: A medium level of geniposide improved anti-apoptotic functions and inhibited BBB leakage/haemorrhage via elevating GluN2A-containing NMDAR expression in tMCAO rats. Importantly, these effects could be eliminated by co-treatment of geniposide with the GluN2A antagonist NVP but not the GluN2B inhibitor ifenprodil. Moreover, geniposide's protection was due to the enhancement of GluN2A-dependent survival signals, including pAKT, pERK and PSD-95.

Conclusion: The results suggest that geniposide protects neurons against post-ischaemic neurovascular injury through the activation of GluN2A/AKT/ERK pathways. As a very promising natural agent, geniposide may be a future therapeutic for stroke patients.
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http://dx.doi.org/10.1159/000480657DOI Listing
October 2017

Strategies for reducing the fertilizer application rate in the ridge and furrow rainfall harvesting system in semiarid regions.

Sci Rep 2017 06 1;7(1):2644. Epub 2017 Jun 1.

College of Agronomy, Northwest A&F University, Yangling, Shaanxi, 712100, China.

The ridge and furrow rainwater harvesting (RFRH) system is a promising water-saving planting technique for dryland farming, but we lack a full understanding of the effects of different fertilizer rates (N:P) on plant nutrient uptake and nutrient use efficiency (NuUE) in foxtail millet using this planting method, as well as the available nutrient residues in the soil. We conducted field studies (Loess Plateau, China) comparing RFRH planting (R) and traditional flat planting (T) at four different fertilizer rates to determine suitable fertilizer application rates for R during 2013-2015. Compared with T, R improved the soil moisture and the utilization of rainwater and fertilizer, thereby enhancing the grain yield, water use efficiency (WUE), grain nutrient uptake, and NUE in a dry year, but with no improvements in a rainy year. The grain yield and WUE exhibited parabolic increasing trends as the fertilizer application rate increased over three years, but no significant increase was found when the fertilizer rate exceeded 189:96 kg N:P ha under R, which significantly reduced the NuUE and might waste nutrients. Therefore, we recommend R combined with 189:96 kg N:P ha as a promising planting strategy for foxtail millet in semiarid areas.
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http://dx.doi.org/10.1038/s41598-017-02731-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454006PMC
June 2017

Selective detection of N6-methyladenine in DNA metal ion-mediated replication and rolling circle amplification.

Chem Sci 2017 Jan 10;8(1):200-205. Epub 2016 Aug 10.

College of Chemistry and Molecular Sciences , Key Laboratory of Biomedical Polymers of Ministry of Education , The Institute for Advanced Studies , Wuhan University , Wuhan , Hubei 430072 , P. R. China . Email: ; ; Tel: +86-27-68756663.

N6-methyladenine (6mA) is reported as a potential epigenetic marker in eukaryotic genomes. However, accurate identification of the location of 6mA in DNA remains a challenging task. Here, we show that Ag can selectively stabilize the A-C mismatch and efficiently promote primer extension. In contrast, the complex of 6mA-Ag-C is instable and therefore cannot be recognized by DNA polymerases, resulting in the termination of primer extension. Based on this finding, we successfully identified and quantified 6mA at the single-base level through the analysis of gel bands of extended primers and fluorescence measurements combined with rolling circle amplification. The high selectivity and sensitivity of this strategy may provide a new platform for the efficient analysis of 6mA in DNA in the future.
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http://dx.doi.org/10.1039/c6sc02271eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308289PMC
January 2017

Beta-adrenergic signaling affect osteoclastogenesis via osteocytic MLO-Y4 cells' RANKL production.

Biochem Biophys Res Commun 2017 07 5;488(4):634-640. Epub 2016 Nov 5.

Dental Implant Center, West China Hospital of Stomatology, Sichuan University, Chengdu, China; State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address:

The sympathetic nervous system play a pivotal role in bone remodeling through β-adrenoceptor (β-AR). However, it is not well documented whether the β-adrenoceptor pathway has the potential to influence osteocytes. In this study, cell viability, the expression of β-AR subtypes, enzymes of catecholamine synthesis or degradation, bone-related gene and protein in osteocytic MLO-Y4 cells were investigated by β-adrenergic stimulation. Isoproterenol (ISO) promoted RANKL to OPG expression in osteocytes, as well as osteoclasts formation in osteocytes-RAW264.7 cell co-cultures but not RAW264.7 cell monoculture. The ISO-stimulated effect was enhanced in β1-AR antagonist pretreatment, but was rescued by blocking β2-AR. The results indicate that β1-and β2-AR play reciprocal roles on MLO-Y4 cells in the regulation of osteoclastogenesis, and osteocyte β-adrenergic signaling might be a new valuable therapy for bone disease.
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http://dx.doi.org/10.1016/j.bbrc.2016.11.011DOI Listing
July 2017

GlyT1 Inhibitor NFPS Exerts Neuroprotection via GlyR Alpha1 Subunit in the Rat Model of Transient Focal Cerebral Ischaemia and Reperfusion.

Cell Physiol Biochem 2016 9;38(5):1952-62. Epub 2016 May 9.

Background/aims: Glycine is a strychnine-sensitive inhibitory neurotransmitter in the central nervous system (CNS), especially in the spinal cord, brainstem, and retina. The objective of the present study was to investigate the potential neuroprotective effects of GlyT1 inhibitor N [3-(4'-fluorophenyl)-3-(4'-phenylphenoxy) propyl] sarcosine (NFPS) in the rat model of experimental stroke.

Methods: In vivo ischaemia was induced by transient middle cerebral artery occlusion (tMCAO). The methods of Western Blotting, Nissl Staining and Morris water maze methods were applied to analyze the anti-ischaemia mechanism.

Results: The results showed that high dose of NFPS (H-NFPS) significantly reduced infarct volume, neuronal injury and the expression of cleaved caspase-3, enhanced Bcl-2/Bax, and improved spatial learning deficits which were administered three hours after transient middle cerebral artery occlusion (tMCAO) induction in rats, while, low dose of NFPS (L-NFPS) exacerbated the injury of ischaemia. These findings suggested that low and high dose of NFPS produced opposite effects. Importantly, it was demonstrated that H-NFPS-dependent neuronal protection was inverted by salicylate (Sal), a specific GlyR x0251;1 antagonist. Such effects could probably be attributed to the enhanced glycine level in both synaptic and extrasynaptic clefts and the subsequently altered extrasynaptic GlyRs and their subtypes.

Conclusions: These data imply that GlyT1 inhibitor NFPS may be a novel target for clinical treatment of transient focal cerebral ischaemia and reperfusion which are associated with altered GlyR alpha 1 subunits.
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http://dx.doi.org/10.1159/000445556DOI Listing
February 2017

Detecting 5-methylcytosine using an enzyme-free DNA strand exchange reaction without pretreatment under physiological conditions.

Chem Commun (Camb) 2016 May 3;52(41):6833-6. Epub 2016 May 3.

College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University Wuhan, Hubei, 430072, P. R. China.

We present here a novel and efficient method for 5mC detection using a DNA strand exchange reaction (SER) strategy. This enzyme-free method needs no pre-treatment of target DNAs and can be adapted to most of the target duplexes under physiological conditions. The high sequence selectivity of this method can distinguish 5mC from normal cytosine in an accurate manner.
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http://dx.doi.org/10.1039/c6cc03138bDOI Listing
May 2016

Highly Selective Detection of 5-Methylcytosine in Genomic DNA Based on Asymmetric PCR and Specific DNA Damaging Reagents.

Anal Chem 2016 Mar 22;88(6):3348-53. Epub 2016 Feb 22.

College of Chemistry and Molecular Sciences, Institute of Advanced Studies, Wuhan University , Wuhan, Hubei 430072, P. R. China.

DNA methylation is a significant epigenetic modification of the genome that is involved in regulating many cellular processes. An increasing number of human diseases have been discovered to be associated with aberrant DNA methylation, and aberrant DNA methylation has been deemed to be a potential biomarker for diseases such as cancers. A safe, nontoxic, and sensitive method for accurate detection of 5-methylcytosine in genomic DNA is extremely useful for early diagnosis and therapy of cancers. In this paper, we established a novel system to detect 5-methylcytosine, which is based on bisulfite treatment, asymmetric PCR, and specific DNA damaging reagents. Our method could be used for identifying the loci of 5mC in genomic DNA and detecting the DNA methylation levels in tissues as well.
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http://dx.doi.org/10.1021/acs.analchem.5b04939DOI Listing
March 2016

In-Situ Onlay Grafting Combined with Titanium Mesh for Three-Dimensional Reconstruction of the Anterior Maxillary Ridge.

Int J Periodontics Restorative Dent 2016 Jan-Feb;36(1):95-101

Reconstruction of anterior maxillary ridge defects involving both horizontal and vertical dimensions has always been a challenge. This case report proposes a novel approach to reconstruct labial bony walls with onlay bone blocks harvested in situ held by titanium mesh covered with concentrated growth factor. Favorable outcomes were shown because of better space maintenance and nutrition supply.
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http://dx.doi.org/10.11607/prd.2306DOI Listing
May 2017

Fluorescein Derivatives as Bifunctional Molecules for the Simultaneous Inhibiting and Labeling of FTO Protein.

J Am Chem Soc 2015 Nov 20;137(43):13736-9. Epub 2015 Oct 20.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.

The FTO protein is unequivocally reported to play a critical role in human obesity and in the regulation of cellular levels of m(6)A modification, which makes FTO a significant and worthy subject of study. Here, we identified that fluorescein derivatives can selectively inhibit FTO demethylation, and the mechanisms behind these activities were elucidated after we determined the X-ray crystal structures of FTO/fluorescein and FTO/5-aminofluorescein. Furthermore, these inhibitors can also be applied to the direct labeling and enrichment of FTO protein combined with photoaffinity labeling assay.
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http://dx.doi.org/10.1021/jacs.5b06690DOI Listing
November 2015

Effect of lentiviral vector overexpression α-calcitonin gene-related peptide on titanium implant osseointegration in α-CGRP-deficient mice.

Bone 2017 01 8;94:135-140. Epub 2015 Aug 8.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address:

α-Calcitonin gene-related peptide (α-CGRP) plays a significant pathophysiological role in bone development, metabolism and remodeling around dental implants. However, the half-life of α-CGRP in plasma is only 10min, which affects its long-time application and an alternative approach should be developed to deliver α-CGRP over long periods of time. The aim of this study is to investigate whether a lentiviral α-CGRP overexpression vector system can express this target-gene longer at peri-implant sites, thus enhancing osseointegration. Animals were divided to the following groups: α-CGRP, α-CGRP with lentivirus transfection and α-CGRP mice. IVIS Spectrum imaging observations identified the successful transfection of α-CGRP around experimental implants inserted in the femurs at 5days after injection. Histomorphometrical analysis indicated an increase of bone-implant contact (BIC) at 1-month healing in the transfection group. Moreover, real-time RT-PCR and western blot results of bone-related markers Runx2, Osterix, and BSP levels elevated in lentivirus-transfected mice at 21days, compared to the untreated α-CGRP mice. There was no significant difference between the transfection group and α-CGRP group. Further α-CGRP protein detection confirmed the persistent expression of this transgene at 21days post-operatively. These results suggest that this lentiviral vector system expresses α-CGRP in an effective, appropriate and sustained manner, which might have a potential application in enhancing titanium implant osseointegration.
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http://dx.doi.org/10.1016/j.bone.2015.08.009DOI Listing
January 2017

Preparation and preliminary in vitro evaluation of a bFGF-releasing heparin-conjugated poly(ε-caprolactone) membrane for guided bone regeneration.

J Biomater Sci Polym Ed 2015 12;26(10):600-16. Epub 2015 Jun 12.

a State Key Laboratory of Oral Diseases , Sichuan University , Chengdu 610041 , P.R. China.

In an effort to improve guided bone regeneration (GBR), we successfully fabricated a novel basic fibroblast growth factor (bFGF)-releasing heparin-conjugated poly(ε-caprolactone) membrane (hep-PCL/bFGF). This material has a porous microstructure with smooth and rough pore walls before and after heparinization, respectively. Our FTIR analyses indicated that chemical bonds were formed between PCL and heparin with a new amide C=O band at 1660 cm(-1) and a band at 3400 cm(-1) that can be attributed to -OH stretching in cross-linked heparin. We showed that bFGF was released from hep-PCL/bFGF in a continuous pattern, which remained for 3 weeks. We evaluated MG63 cell proliferation and biocompatibility of GBR membrane by a CCK-8 assay and a live/dead assay. The CCK-8 results revealed that the hep-PCL/bFGF group had superiority compared to other groups. Furthermore, cell morphology of hep-PCL membrane exhibited larger projected areas than those of PCL surfaces based on scanning electron microscopy analysis and immunofluorescent staining of cell cytoskeleton and vinculin expression. Our alkaline phosphatase activity assay also confirmed better performance of the hep-PCL/bFGF group. These results suggested that this novel hep-PCL/bFGF membrane is suitable for osteoblast-like cells to attach, proliferate, and differentiate. Therefore, the hep-PCL/bFGF membrane has potential to be a biodegradable membrane for GBR and warrants further investigation.
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http://dx.doi.org/10.1080/09205063.2015.1049044DOI Listing
March 2016

-Hydroperoxymethyladenosine: a new intermediate of chemical oxidation of -methyladenosine mediated by bicarbonate-activated hydrogen peroxide.

Chem Sci 2015 May 11;6(5):3013-3017. Epub 2015 Mar 11.

College of Chemistry and Molecular Sciences , Institute of Advanced Studies , Wuhan University , Wuhan , Hubei 430072 , P. R. China . Email: ; ; Tel: +86-27-68756663.

-Methyladenosine (mA) represents a relatively abundant modification in eukaryotic RNA. Because mA has similar properties to adenosine and a low reactivity, limited research has been focused on this nucleoside. In this study, we revealed an important intermediate in the oxidation of mA through the bicarbonate-activated peroxide system. Over the course of oxidation, we found a new mechanism in which -hydroxymethyladenosine (hmA), -formyladenosine (fA) and -hydroperoxymethyladenosine (oxmA) were intermediate products, and adenosine was the final product. In this study, oxmA was isolated using HPLC and characterized by mass spectrometry, NMR and diphenyl-1-pyrenylphosphine (DPPP) fluorescence detection. This study provides a new modified nucleoside and demonstrates oxidative demethylation of mA by reactive oxygen species at the nucleobase level and in RNA strands.
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http://dx.doi.org/10.1039/c5sc00484eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657413PMC
May 2015