Publications by authors named "Longqiang Zhang"

5 Publications

  • Page 1 of 1

Revisiting bone morphogenetic protein-2 knuckle epitope and redesigning the epitope-derived peptides.

J Pept Sci 2021 Jun 22;27(6):e3309. Epub 2021 Feb 22.

Department of Orthopedics, Yidu Central Hospital Affiliated to Weifang Medical University, Weifang, China.

The bone morphogenetic protein-2 (BMP2) plays a crucial role in bone formation, growth and regeneration, which adopts a conformational wrist epitope and a linear knuckle epitope to interact with its type-I (BRI) and type-II (BRII) receptors, respectively. In this study, we systematically examine the BRII-recognition site of BMP2 at structural, energetic and dynamic levels and accurately locate hotspots of the recognition at BMP2-BRII complex interface. It is revealed that the traditional knuckle epitope (BMP2 residue range 73-92) do fully match the identified hotspots; the BMP2-recognition site includes the C-terminal region of traditional knuckle epitope as well as its flanked β-strands. In addition, the protein context of full-length BMP2 is also responsible for the recognition by addressing conformational constraint on the native epitope segment. Therefore, we herein redefine the knuckle epitope to BMP2 residue range 84-102, which has a similar sequence length but is slid along the protein sequence by ~10 residues as compared to traditional knuckle epitope. The redefined one is also a linear epitope that is natively a double-stranded β-sheet with two asymmetric arms as compared to the natively single β-strand of the traditional version, although their sequences are partially overlapped to each other. It is revealed that the redefined epitope-derived peptide LN exhibits an improved affinity by >3-fold relative to the traditional epitope-derived peptide KL . Even so, the LN peptide still cannot fully represent the BMP2 recognition event by BRII that has been reported to have a nanomolar affinity. We further introduce a disulfide bond across the two arms of double-stranded β-sheet to constrain the free LN peptide conformation, which mimics the conformational constraint addressed by protein context. Consequently, several cyclic peptides are redesigned, in which the LN (cyc89-101) is determined to exhibit a sub-micromolar affinity; this value is ~5-fold higher than its linear counterpart. Structural analysis also reveals that the cyclic peptide can interact with BRII in a similar binding mode with the redefined knuckle epitope region in full-length BMP2 protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/psc.3309DOI Listing
June 2021

Downregulated Long Non-Coding RNA MSC-AS1 Inhibits Osteosarcoma Progression and Increases Sensitivity to Cisplatin by Binding to MicroRNA-142.

Med Sci Monit 2020 Mar 10;26:e921594. Epub 2020 Mar 10.

Health Management Center, Weifang People's Hospital, Weifang, Shandong, China (mainland).

BACKGROUND Osteosarcoma (OS) is the most prevalent malignant primary bone tumor, resulting from severe transformation of primitive mesenchymal cells, which induces osteogenesis. Long non-coding RNA (lncRNA) MSC-AS1 triggers osteogenic differentiation by sponging microRNA (miR)-140-5p. The present study assessed the mechanism of lncRNA MSC-AS1 in OS biological features and sensitivity to cisplatin (DDP) by binding to miR-142. MATERIAL AND METHODS Firstly, lncRNA MSC-AS1 expression in OS tissues and cells was analyzed. OS cells were transfected with silenced MSC-AS1 to determine its role in OS biological behaviors, and we also assessed the effect of MSC-AS1 on OS sensitivity to DDP. Then, website prediction and dual-luciferase reporter gene assay were utilized for verification of the binding site between MSC-AS1 and miR-142. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were performed to determine the effect of MSC-AS1 on expression of miR-142, cyclin-dependent kinase 6 (CDK6), and the PI3K/AKT signaling pathway. Xenograft transplantation was also applied to confirm the in vitro experiments. RESULTS Overexpressed MSC-AS1 was associated with poor prognosis of OS patients. OS cell proliferation, invasion, and migration were reduced after silencing MSC-AS1, while cell apoptosis was enhanced. Moreover, silencing MSC-AS1 made OS cells more sensitive to DDP. Interestingly, MSC-AS1 knockdown induced miR-142 expression and reduced CDK6 levels, thereby decreasing the protein expression of p-PI3K/t-PI3K and p-AKT/t-AKT. Silencing MSC-AS1 repressed OS progression in vivo. CONCLUSIONS Our study demonstrated that silencing MSC-AS1 inhibited OS biological behaviors by enhancing miR-142 to decrease CDK6 and inactivating the PI3K/AKT axis. Our results may provide new insights for OS treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.921594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081928PMC
March 2020

Direct Observation of Landau Level Resonance and Mass Generation in Dirac Semimetal CdAs Thin Films.

Nano Lett 2017 04 2;17(4):2211-2219. Epub 2017 Mar 2.

State Key Laboratory of Surface Physics and Department of Physics, Fudan University , Shanghai 200433, China.

Three-dimensional topological Dirac semimetals have hitherto stimulated unprecedented research interests as a new class of quantum materials. Breaking certain types of symmetries has been proposed to enable the manipulation of Dirac fermions, and that was soon realized by external modulations such as magnetic fields. However, an intrinsic manipulation of Dirac states, which is more efficient and desirable, remains a significant challenge. Here, we report a systematic study of quasi-particle dynamics and band evolution in CdAs thin films with controlled chromium (Cr) doping by both magneto-infrared spectroscopy and electrical transport. We observe the √B relation of inter-Landau-level resonance in CdAs, an important signature of ultrarelativistic massless state inaccessible in previous optical experiments. A crossover from quantum to quasi-classical behavior makes it possible to directly probe the mass of Dirac fermions. Importantly, Cr doping allows for a Dirac mass acquisition and topological phase transition enabling a desired dynamic control of Dirac fermions. Corroborating with the density-functional theory calculations, we show that the mass generation can be explained by the explicit C rotation symmetry breaking and the resultant Dirac gap engineering through Cr substitution for Cd atoms. The manipulation of the system symmetry and Dirac mass in CdAs thin films provides a tuning knob to explore the exotic states stemming from the parent phase of Dirac semimetals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.nanolett.6b04778DOI Listing
April 2017

Preventive effect of zoledronic acid on aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole.

Onco Targets Ther 2016 5;9:6029-6036. Epub 2016 Oct 5.

Department of Orthopedics, Yidu Central Hospital of Weifang, Weifang, Shandong, People's Republic of China.

Background: This study aims to compare the efficacy and safety between zoledronic acid combined with calcium and calcium alone to prevent aromatase inhibitor-associated bone loss for postmenopausal breast cancer patients receiving adjuvant letrozole.

Methods: One hundred twenty patients were randomly divided into two groups, A and B. Patients in group A (n=60) received modified radical mastectomy or breast-conserving surgery + four cycles of AC followed by T regimen (optional) + radiotherapy (optional) + letrozole 2.5 mg daily + calcium 500 mg twice daily + vitamin D 400 international units daily +4 mg of zoledronic acid every 6 months, while patients in group B (n=60) were not given zoledronic acid and the rest of the treatments of group B were the same as group A. All the patients were followed up for 1 year. The primary endpoint was the intrapatient percentage change in lumbar spine (LS) bone mineral density (BMD) from baseline to month 12. Secondary endpoints included the percentage change in total hip (TH) and femoral neck (FN) BMD, the incidence of osteoporosis, the incidence of a clinically meaningful 5% decline in BMD at 1 year, change of serum N-telopeptide of type 1 collagen (NTX) and bone-specific alkaline phosphatase (BSAP) concentrations.

Results: Patients in group A had a statistically significant higher average change and average percent change in LS, FN, and TH than group B. Group A had a statistically significant lower incidence of a clinically meaningful loss of bone density at the LS, FN, or TH than Group B. The incidence of osteoporosis in group A was significantly lower than group B. The decreases in NTX and BSAP concentrations from baseline to month 12 in patients of group A were significant; in contrast, patients in group B were found to have increases in NTX and BSAP concentrations from baseline. The most common adverse reactions in patients are flu-like symptoms (38%), bone pain (28%), and joint pain (20%).

Conclusion: AI-associated bone loss can be prevented by concurrent zoledronic acid for postmenopausal breast cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S115058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063560PMC
October 2016

Gate-tunable negative longitudinal magnetoresistance in the predicted type-II Weyl semimetal WTe.

Nat Commun 2016 10 11;7:13142. Epub 2016 Oct 11.

National Laboratory of Solid State Microstructures, School of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China.

The progress in exploiting new electronic materials has been a major driving force in solid-state physics. As a new state of matter, a Weyl semimetal (WSM), in particular a type-II WSM, hosts Weyl fermions as emergent quasiparticles and may harbour novel electrical transport properties. Nevertheless, such a type-II WSM material has not been experimentally observed. In this work, by performing systematic magneto-transport studies on thin films of a predicted material candidate WTe, we observe notable negative longitudinal magnetoresistance, which can be attributed to the chiral anomaly in WSM. This phenomenon also exhibits strong planar orientation dependence with the absence along the tungsten chains, consistent with the distinctive feature of a type-II WSM. By applying a gate voltage, we demonstrate that the Fermi energy can be in-situ tuned through the Weyl points via the electric field effect. Our results may open opportunities for implementing new electronic applications, such as field-effect chiral devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncomms13142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062597PMC
October 2016
-->