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1.
RNA Biol ; 18(12): 2531-2545, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34110975

RESUMO

Methylation is a common post-transcriptional modification of tRNAs, particularly in the anticodon loop region. The cytosine 38 (C38) in tRNAs, such as tRNAAsp-GUC, tRNAGly-GCC, tRNAVal-AAC, and tRNAGlu-CUC, can be methylated by human DNMT2/TRDMT1 and some homologs found in bacteria, plants, and animals. However, the substrate properties and recognition mechanism of DNMT2/TRDMT1 remain to be explored. Here, taking into consideration common features of the four known substrate tRNAs, we investigated methylation activities of DNMT2/TRDMT1 on the tRNAGly-GCC truncation and point mutants, and conformational changes of mutants. The results demonstrated that human DNMT2/TRDMT1 preferred substrate tRNAGly-GCC in vitro. L-shaped conformation of classical tRNA could be favourable for DNMT2/TRDMT1 activity. The complete sequence and structure of tRNA were dispensable for DNMT2/TRDMT1 activity, whereas T-arm was indispensable to this activity. G19, U20, and A21 in D-loop were identified as the important bases for DNMT2/TRDMT1 activity, while G53, C56, A58, and C61 in T-loop were found as the critical bases. The conserved CUXXCAC sequence in the anticodon loop was confirmed to be the most critical determinant, and it could stabilize C38-flipping to promote C38 methylation. Based on these tRNA properties, new substrates, tRNAVal-CAC and tRNAGln-CUG, were discovered in vitro. Moreover, a single nucleotide substitute, U32C, could convert non-substrate tRNAAla-AGC into a substrate for DNMT2/TRDMT1. Altogether, our findings imply that DNMT2/TRDMT1 relies on a delicate network involving both the primary sequence and tertiary structure of tRNA for substrate recognition.

2.
Environ Res ; 206: 112628, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34973193

RESUMO

The surface plasmon resonance (SPR) effect of noble nanometals can be utilized to effectively improve the catalytic performance of semiconductor photocatalysts. In this work, a novel composite photocatalyst of BiOBr microspheres simultaneously decorated by Ag and Bi dual nanoparticles (NPs) has been successfully synthesized by the hydrothermal method plus one-step reduction method. And the morphology, structure, chemical composition and photoelectrical properties of this composite photocatalyst (Ag/Bi-BiOBr) were further characterized. Due to the SPR effect of Ag and Bi dual NPs, Ag/Bi-BiOBr showed the high light absorption with narrow band gap, as well as fast charge separation via metal-semiconductor heterojunction so as to realize an efficient degradation of ibuprofen (IBP) under simulated solar irradiation. Through the further optimization of the loading amounts of Ag and Bi dual NPs, the excellent photocatalytic activity in the Ag/Bi-BiOBr has been achieved that 92.3% of IBP was removed within 60 min, which is among the best results reported so far for IBP degradation via photocatalysis.

3.
ACS Omega ; 5(1): 726-734, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31956823

RESUMO

A combination of platinum drugs with immunotherapy has shown promising anticancer effects, especially in the drug resistance cancer model. Herein, a new type of immunochemotherapeutic was designed by tethering the toll-like receptor 7 (TLR7) agonist on the axial position of oxaliplatin-based platinum(IV) prodrug. The prodrug simultaneously induced immunogenic cell death of 4T1 cancer cells to initiate an immune response and activate dendritic cells (DCs) to secrete proinflammatory cytokines including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-12, to further enhance the adaptive immunity. The prodrug exhibited better in vivo anticancer effects than oxaliplatin in the 4T1 allograft mouse model, a later stage breast cancer model, which showed poor response to traditional chemotherapy. Mechanism studies revealed that enhanced activation of cytotoxic T cells within tumor contribute to the high in vivo anticancer efficiency of the prodrug. Moreover, the prodrug displayed much lower cytotoxicity to DCs compared with oxaliplatin, indicating its safety to normal cells. These results highlight the potential of the conjugation of TLR7 agonist with oxaliplatin-based Pt(IV) prodrug as an effective anticancer agent to overcome the toxic side effects and drug resistance of traditional platinum chemotherapy.

4.
Proc Inst Mech Eng H ; 231(6): 525-533, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28639517

RESUMO

The aim of this study was to design a hemi-pelvic prosthesis for a patient affected by pelvic sarcoma. To investigate the biomechanical functionality of the pelvis reconstructed with designed custom-made prosthesis, a patient-specific finite element model of whole pelvis with primary ligaments inclusive was constructed based on the computed tomography images of the patient. Then, a finite element analysis was performed to calculate and compare the stress distribution between the normal and implanted pelvis models when undergoing three different static conditions-both-leg standing, single-leg standing for the healthy and the affected one. No significant differences were observed in the stresses between the normal and reconstructed pelvis for both-leg standing, but 20%-40% larger stresses were predicted for the peak stress of the single-leg standing (affected side). Moreover, two- to threefold of peak stresses were predicted within the prostheses compared to that of the normal pelvis especially for single-leg standing case, however, still below the allowable fatigue limitation. The study on the load transmission functionality of prosthesis indicated that it is crucial to carry out finite element analysis for functional evaluation of the designed customized prostheses before three-dimensional printing manufacturing, allowing better understanding of the possible peak stresses within the bone as well as the implants for safety precaution. The finite element model can be equally applicable to other bone tumor model for biomechanical studying.


Assuntos
Neoplasias Ósseas/terapia , Análise de Elementos Finitos , Ossos Pélvicos , Desenho de Prótese/métodos , Fenômenos Biomecânicos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/fisiopatologia , Humanos , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/fisiopatologia , Impressão Tridimensional , Tomografia Computadorizada por Raios X
5.
Int Immunol ; 29(3): 109-120, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28338936

RESUMO

Hepatitis B virus (HBV) is a virus whose replication cycle cannot be completely reproduced using cultured cell lines. Here, we report an engineered cell line capable of supporting the complete HBV life cycle. We generated HepG2 cells over-expressing the HBV entry receptor human NTCP (sodium taurocholate cotransporting polypeptide), and defective in RIG-I (retinoic acid-inducible gene-I)-like receptor signaling, by knocking down the IPS-1 (IFNß-promoter stimulator-1) adaptor molecule. The resultant NtG20.i7 cells were susceptible to HBV, and its replication was detectable at 14 days post-infection and persisted for at least 35 days with a gradual increase of HBV core expression. The cells produced infectious HBV in the culture supernatant, and the addition of preS1 peptide myr47-WT, which blocks HBV entry, impaired the persistence of the infection. These findings suggest that the persistence of the infection was maintained by continuous release of infectious HBV virions and their re-infection. This system is useful for expanding our basic understanding of the HBV replication cycle and for screening of anti-HBV chemicals.


Assuntos
Vírus da Hepatite B/crescimento & desenvolvimento , Hepatócitos/citologia , Hepatócitos/virologia , Replicação Viral , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteína DEAD-box 58/genética , Células Hep G2 , Vírus da Hepatite B/genética , Humanos , Transportadores de Ânions Orgânicos Dependentes de Sódio/genética , Receptores Imunológicos , Transdução de Sinais/genética , Simportadores/genética
6.
Artigo em Chinês | MEDLINE | ID: mdl-30129736

RESUMO

Objective: To determine the prevalence and subtypes of Blastocystis in pet dogs in Anhui and Zhejiang Provinces. Methods: Pet dog fecal samples were collected from veterinary clinics in Baohe District of Hefei City, Xuanzhou District of Xuancheng City, Fengyang County and Mingguang City of Chuzhou City, Longzihu District of Bengbu City, Si County of Suzhou City in Anhui Province, as well as in Yuhang District of Hangzhou City in Zhejiang Province from April to December, 2013. Blastocystis was detected by microscopic examination as well as nested PCR and single-step PCR based on small subunit ribosomal DNA sequences. The PCR products were sequenced, and Blastocystis subtypes were assigned. Results: A total of 315 pet dog fecal samples were collected. The incidence of Blastocystis infection determined by microscopic examination, nested PCR and single-step PCR was 1.3%(4/315), 1.9%(6/315) and 1.9%(6/315), respectively. In addition, the two PCR methods both revealed Blastocystis infection only in Chuzhou City(3.4%, 1/29) and Hefei City(5.6%, 4/72). The pet dogs in Chuzhou City carried ST1 and ST2 subtypes while those in Hefei carried only ST1. There was no significant difference in infection rate between adult and young dogs and between male and female dogs. Conclusion: Blastocystis infection exists in pet dogs in Chuzhou City and Hefei City.


Assuntos
Infecções por Blastocystis/veterinária , Blastocystis , Animais , Sequência de Bases , Doenças do Cão , Cães , Fezes , Feminino , Masculino , Reação em Cadeia da Polimerase , Prevalência
7.
J Craniomaxillofac Surg ; 43(7): 1296-302, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26174791

RESUMO

Customized mandible implants are used as the most effective surgical option for the reconstruction of the mandible after resection, and have become more prevalent, especially with the development of reverse engineering and rapid prototyping (RP). The fixing plate is the most important and complicated part; however, improper structures of the fixing plate often cost unnecessary workloads during surgery and might lead to fracture failure eventually. The fillet radius, cross-section, and countersinks distribution of the fixing plate are the three most significant factors to affect the strength of the implant. The fillet radius on the plate-body transition determines the amount of grinding bone and can also affect the strength of the fixing plate. In addition, both the different cross-sections of the fixing plate and the different distributions of the countersinks can influence the strength and anti-bending capacity of the fixing plate. Various structures of the fixing plate have been designed, and theoretical calculations and finite element analysis on its strength have been conducted in this study, and results presented an optimized design of the structure of the fixing plate. Moreover, for validation purposes, several clinical applications were successfully implemented with the optimized structure.


Assuntos
Placas Ósseas , Análise de Elementos Finitos , Mandíbula/cirurgia , Desenho de Prótese/métodos , Humanos
8.
Artigo em Chinês | MEDLINE | ID: mdl-24844005

RESUMO

OBJECTIVE: To summarize the latest research development of the application of digital design and three-dimensional (3-D) printing technique on individualized medical treatment. METHODS: Recent research data and clinical literature about the application of digital design and 3-D printing technique on individualized medical treatment in Xi'an Jiaotong University and its cooperation unit were summarized, reviewed, and analyzed. RESULTS: Digital design and 3-D printing technique can design and manufacture individualized implant based on the patient's specific disease conditions. And the implant can satisfy the needs of specific shape and function of the patient, reducing dependence on the level of experience required for the doctor. So 3-D printing technique get more and more recognition of the surgeon on the individualized repair of human tissue. Xi'an Jiaotong University is the first unit to develop the commercial 3-D printer and conduct depth research on the design and manufacture of individualized medical implant. And complete technological processes and quality standards of product have been developed. CONCLUSION: The individualized medical implant manufactured by 3-D printing technique can not only achieve personalized match but also meet the functional requirements and aesthetic requirements of patients. In addition, the individualized medical implant has the advantages of accurate positioning, stable connection, and high strength. So 3-D printing technique has broad prospects in the manufacture and application of individualized implant.


Assuntos
Desenho Assistido por Computador , Imageamento Tridimensional/métodos , Medicina de Precisão/métodos , Impressão/métodos , Próteses e Implantes , Materiais Biocompatíveis/química , Substitutos Ósseos/química , Osso e Ossos/cirurgia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Desenho de Prótese/métodos , Estudos Retrospectivos , Cirurgia Assistida por Computador , Resistência à Tração
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