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1.
Cell Mol Biol (Noisy-le-grand) ; 63(3): 36-39, 2017 Mar 31.
Article in English | MEDLINE | ID: mdl-28466821

ABSTRACT

Some studies assessed the association between lncRNA taurine-upregulated gene 1 (TUG1) and the survival in cancer. However, the results were inconclusive.  Therefore, we performed a meta-analysis to determine this association. We used the following electronic databases to search for eligible literature: PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Wanfang. We used ORs and 95% CIs to measure the association between TUG1 and the survival of cancer. There was no significant association between TUG1 and OS of cancer (HR=1.26, 95% CI=0.97-1.64). In the subgroup analysis by cancer type, significant association could be find in osteosarcoma (HR=1.72, 95% CI=1.27-2.32) and digestive system's tumors (HR=1.66, 95% CI=1.04-2.66). In conclusion, this meta-analysis study indicated that TUG1 might associate with the OS of osteosarcoma and digestive system's tumors.


Subject(s)
Neoplasms/genetics , RNA, Long Noncoding/genetics , Humans , Prognosis , Publication Bias , Survival Analysis
2.
Cell Mol Biol (Noisy-le-grand) ; 62(13): 62-64, 2016 Nov 30.
Article in English | MEDLINE | ID: mdl-28040068

ABSTRACT

Some studies investigated the association between ADD1 rs4963 polymorphism and hypertension risk. However, the results remained inconclusive. Thus, we performed a meta-analysis. Published reports were searched in PubMed and Google Scholar. The strength of association was assessed by calculating odds ratios (OR) and 95% confidence interval (CI). Twelve studies with 5097 cases and 5937 controls were conducted in this study. Individuals with ADD1 rs4963 polymorphism showed an increased hypertension risk (OR = 1.21; 95%CI, 1.11-1.33; P < 0.0001). Subgroup analyses were performed according to country and age. The results showed that Chinese with ADD1 rs4963 polymorphism showed an increased hypertension risk (OR = 1.28; 95%CI, 1.09-1.51; P = 0.003). However, subjects in Japan and India did not have increased hypertension risk. In the subgroup analysis by age, older subjects, but not younger subjects, with ADD1 rs4963 polymorphism showed an increased hypertension risk (OR = 1.19; 95%CI, 1.07-1.32; P = 0.001). In conclusion, this meta-analysis suggested that ADD1 rs4963 polymorphism might be associated with increased hypertension risk.


Subject(s)
Asian People/genetics , Calmodulin-Binding Proteins/genetics , Hypertension/genetics , Age Factors , Databases, Factual , Genetic Predisposition to Disease , Genotype , Humans , Hypertension/pathology , Odds Ratio , Polymorphism, Single Nucleotide
3.
Phys Chem Chem Phys ; 18(38): 26602-26608, 2016 Sep 29.
Article in English | MEDLINE | ID: mdl-27711699

ABSTRACT

The development of novel materials with excellent performance depends not only on the constituents but also on their remarkable micro/nanostructures. In this work, manganese oxide (Mn3O4) hausmannite structures with a uniform three-dimensional (3D) flower-like hierarchical architecture have been successfully synthesized by a novel chemical route using surfactants as structure-directing agents. Microstructure analysis indicates that the obtained 3D flower-like Mn3O4 superstructure consists of a large number of two-dimensional (2D) Mn3O4 nanosheets, which is different from the reported 3D Mn3O4 hierarchical structures based on zero-dimensional nanoparticles or one-dimensional nanowires and nanorods. This 3D Mn3O4 hierarchical architecture provides us with another type of manganese oxide with different superstructural characteristics, which may have potential practical applications in the catalytic degradation of organic pollutants. The catalytic performance of this hierarchical Mn3O4 superstructure, which was prepared by three different types of structure-directing agents, including cetyltrimethylammonium bromide (CTAB), poly(vinylpyrrolidone) (PVP), and poly(ethylene oxide)-poly(propylene oxide) (P123), was evaluated for the catalytic degradation of organic pollutants, e.g. methylene blue. Interestingly, the hierarchical Mn3O4 superstructure prepared using CTAB as a template showed efficient catalytic degradation. The formation processes and possible growth mechanism of this novel 3D Mn3O4 hierarchical superstructure assembled by 2D Mn3O4 nanosheets are discussed in detail.

4.
Curr Oncol ; 22(2): 133-43, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25908912

ABSTRACT

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy has been shown to prevent vte; however, unique clinical circumstances in patients with cancer can often complicate the decisions surrounding the administration of prophylactic anticoagulation. No national Canadian guidelines on the prevention of cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin can be used prophylactically in cancer patients at high risk of developing vte. Direct oral anticoagulants are not recommended for vte prophylaxis at this time. Specific clinical scenarios, including renal insufficiency, thrombocytopenia, liver disease, and obesity can warrant modifications in the administration of prophylactic anticoagulant therapy. There is no evidence to support the monitoring of anti-factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, factor Xa levels could be checked at baseline and periodically in patients with renal insufficiency. The use of anticoagulation therapy to prolong survival in cancer patients without the presence of risk factors for vte is not recommended.

5.
Curr Oncol ; 22(2): 144-55, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25908913

ABSTRACT

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy is used to treat vte; however, patients with cancer have unique clinical circumstances that can often make decisions surrounding the administration of therapeutic anticoagulation complicated. No national Canadian guidelines on the management of established cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin is the treatment of choice for cancer patients with established vte. Direct oral anticoagulants are not recommended for the treatment of vte at this time. Specific clinical scenarios, including the presence of an indwelling venous catheter, renal insufficiency, and thrombocytopenia, warrant modifications in the therapeutic administration of anticoagulation therapy. Patients with recurrent vte should receive extended (>3 months) anticoagulant therapy. Incidental vte should generally be treated in the same manner as symptomatic vte. There is no evidence to support the monitoring of anti-factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, levels of anti-factor Xa could be checked at baseline and periodically thereafter in patients with renal insufficiency. Follow-up and education about the signs and symptoms of vte are important components of ongoing patient care.

6.
Cell Microbiol ; 15(1): 82-97, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22985085

ABSTRACT

Enterohaemorrhagic Escherichia coli (EHEC) causes life-threatening infections in humans as a consequence of the production of Shiga-like toxins. Lack of a good animal model system currently hinders in vivo study of EHEC virulence by systematic genetic methods. Here we applied the genetically tractable animal, Caenorhabditis elegans, as a surrogate host to study the virulence of EHEC as well as the host immunity to this human pathogen. Our results show that E. coli O157:H7, a serotype of EHEC, infects and kills C. elegans. Bacterial colonization and induction of the characteristic attaching and effacing (A/E) lesions in the intact intestinal epithelium of C. elegans by E. coli O157:H7 were concomitantly demonstrated in vivo. Genetic analysis indicated that the Shiga-like toxin 1 (Stx1) of E. coli O157:H7 is a virulence factor in C. elegans and is required for full toxicity. Moreover, the C. elegans p38 mitogen-activated protein kinase (MAPK) pathway, an evolutionarily conserved innate immune and stress response signalling pathway, is activated in the regulation of host susceptibility to EHEC infection in a Stx1-dependent manner. Our results validate the EHEC-C. elegans interaction as suitable for future comprehensive genetic screens for both novel bacterial and host factors involved in the pathogenesis of EHEC infection.


Subject(s)
Caenorhabditis elegans/enzymology , Caenorhabditis elegans/microbiology , Escherichia coli O157/pathogenicity , Host-Pathogen Interactions , Shiga Toxin 1/metabolism , Virulence Factors/metabolism , p38 Mitogen-Activated Protein Kinases/biosynthesis , Animals , Caenorhabditis elegans/immunology , Escherichia coli Infections , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Models, Animal , Survival Analysis
7.
J Nanosci Nanotechnol ; 14(2): 1318-37, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24749428

ABSTRACT

Germanium materials are a class of unique semiconductor materials with widespread technological applications because of their valuable semiconducting, electrical, optical, and thermoelectric power properties in the fields of macro/mesoscopic materials and micro/nanodevices. In this review, we describe the efforts toward understanding the microstructures and various properties of the fractal germanium micro/nanoclusters induced by gold prepared by high vacuum thermal evaporation techniques, highlighting contributions from our laboratory. First, we present the integer and non-integer dimensional germanium micro/nanoclusters such as nanoparticles, nanorings, and nanofractals induced by gold and annealing. In particular, the nonlinear electrical behavior of a gold/germanium bilayer film with the interesting nanofractal is discussed in detail. In addition, the third-order optical nonlinearities of the fractal germanium nanocrystals embedded in gold matrix will be summarized by using the sensitive and reliable Z-scan techniques aimed to determine the nonlinear absorption coefficient and nonlinear refractive index. Finally, we emphasize the thermoelectric power properties of the gold/germanium bilayer films. The thermoelectric power measurement is considered to be a more effective method than the conductivity for investigating superlocalization in a percolating system. This research may provide a novel insight to modulate their competent performance and promote rational design of micro/nanodevices. Once mastered, germanium thin films with a variety of fascinating micro/nanoclusters will offer vast and unforeseen opportunities in the semiconductor industry as well as in other fields of science and technology.


Subject(s)
Crystallization/methods , Germanium/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Electric Conductivity , Fractals , Macromolecular Substances/chemistry , Microspheres , Molecular Conformation , Particle Size , Refractometry , Surface Properties
8.
J Nanosci Nanotechnol ; 14(2): 1693-709, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24749450

ABSTRACT

Transition metal oxides belong to a class of versatile materials that are vitally important for developing new materials with functionality and smartness. Research on manganese oxides has been a key topic among studies on transition metal oxides. This is due to their potential applications in diverse areas, including rechargeable lithium ion batteries, catalysis, molecular adsorption, gas sensors, energy storage, and magnetics. In this review, we will elucidate in detail various characterization strategies, including temperature-dependent growth, micro/nanostructures, Raman, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and electron spin resonance, for Mn2O3 nanocrystals, highlighting contributions from our laboratory. This review article mainly focuses on the wide-ranging research effort on the development of preparation methodologies and the assessment of various characterization strategies in Mn2O3 nanomaterials. The main purpose is to provide the readers a comprehensive understanding of the research progress of manganese oxides. This is an interdisciplinary work that integrates the areas of physics, chemistry, materials science, and nanotechnology.


Subject(s)
Manganese Compounds/chemical synthesis , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Oxides/chemical synthesis , Crystallization/methods , Electric Conductivity , Materials Testing , Molecular Conformation , Particle Size , Surface Properties , Temperature
9.
Clin Otolaryngol ; 39(1): 32-8, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24373232

ABSTRACT

OBJECTIVES: This study aimed to compare the differences in vocal quality between Mandarin-speaking children with cochlear implants and normal-hearing peers and to understand which cochlear implant usage parameters may predict unfavourable voice outcomes. DESIGN: A cross-sectional, case-controlled study. SETTING: A tertiary medical centre. PARTICIPANTS: Thirty-five pre-lingually deaf children (age = 10.3 ± 1.6 years; 17 boys and 18 girls) who had used cochlear implants for >2 years and 35 age- and gender-matched controls with normal hearing. MAIN OUTCOME MEASURES: Through sustained phonation of /a/ and reading of the Hare and Tortoise passage, the subjects' voice quality was analysed with aerodynamics and acoustics. A six-point scale was used for auditory-perceptual evaluation. A Pediatric Voice-Related Quality of Life Survey was filled out by the caregivers. RESULTS: The implanted subjects had significantly lower mean airflow rate (P = 0.006), higher phonation threshold pressure (P < 0.001), higher fundamental frequency variations (P < 0.001) and peak-amplitude variations (P < 0.001), wider fundamental frequency range (P = 0.043), wider speaking intensity range (P = 0.015) and greater perceptual severity level of monotone (P < 0.001), resonance (P < 0.001), loudness (P < 0.001) and strain (P = 0.006) than their normal-hearing peers. Duration of postoperative rehabilitation was an independent predictor of unfavourable mean speaking fundamental frequency (odds ratio = 8.56, P = 0.008). CONCLUSION: Inadequate postoperative rehabilitation may hinder the normalisation of Mandarin-speaking implantees' voice quality. A multidimensional analysis may precisely evaluate the voice of paediatric implantees; however, the generalisability of these findings requires different forms of validation, including data from other languages and other institutions.


Subject(s)
Cochlear Implants , Voice Quality , Acoustics , Case-Control Studies , Child , Cross-Sectional Studies , Female , Humans , Male , Phonation , Quality of Life
10.
Curr Oncol ; 21(3): e504-14, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24940110

ABSTRACT

Venous thromboembolism (vte) is a serious, life-threatening complication of cancer. Anticoagulation therapy such as low molecular weight heparin (lmwh) has been shown to treat and prevent vte. Cancer therapy is often complex and ongoing, making the management of vte less straightforward in patients with cancer. There are no published Canadian guidelines available to suggest appropriate strategies for the management of vte in patients with solid tumours. We therefore aimed to develop a clear, evidence-based guideline on this topic. A systematic review of clinical trials and meta-analyses published between 2002 and 2013 in PubMed was conducted. Reference lists were hand-searched for additional publications. The National Guidelines Clearinghouse was searched for relevant guidelines. Recommendations were developed based on the best available evidence. In patients with solid tumours, lmwh is recommended for those with established vte and for those without established vte but with a high risk for developing vte. Options for lmwh include dalteparin, enoxaparin, and tinzaparin. No one agent can be recommended over another, but in the setting of renal insufficiency, tinzaparin is preferred. Unfractionated heparin can be used under select circumstances only (that is, when rapid clearance of the anticoagulant is desired). The most common adverse event is bleeding, but major events are rare, and with appropriate follow-up care, bleeding can be monitored and appropriately managed.

11.
Langmuir ; 29(12): 4111-8, 2013 Mar 26.
Article in English | MEDLINE | ID: mdl-23451867

ABSTRACT

Nanocomposites have significant potential in the development of advanced materials for numerous applications. Tin dioxide (SnO2) is a functional material with wide-ranging prospects because of its high electronic mobility and wide band gap. Graphene as the basic plane of graphite is a single atomic layer two-dimensional sp(2) hybridized carbon material. Both have excellent physical and chemical properties. Here, SnO2 quantum dots/graphene composites have been successfully fabricated by a facile ultrasonic method. The experimental investigations indicated that the graphene was exfoliated and decorated with SnO2 quantum dots, which was dispersed uniformly on both sides of the graphene. The size distribution of SnO2 quantum dots was estimated to be ranging from 4 to 6 nm and their average size was calculated to be about 4.8 ± 0.2 nm. This facile ultrasonic route demonstrated that the loading of SnO2 quantum dots was an effective way to prevent graphene nanosheets from being restacked during the reduction. During the calcination process, the graphene nanosheets distributed between SnO2 nanoparticles have also prevented the agglomeration of SnO2 nanoparticles, which were beneficial to the formation of SnO2 quantum dots.

14.
Inorg Chem ; 51(15): 8473-8, 2012 Aug 06.
Article in English | MEDLINE | ID: mdl-22803828

ABSTRACT

Results on Al-induced crystallization of amorphous Ge (a-Ge) deposited by vacuum thermal evaporation techniques under thermal annealing in N(2) atmosphere are presented in detail. The a-Ge crystallization and fractal Ge pattern formation on the free surface of annealed Al/Ge bilayer films deposited on single-crystal Si (100) substrates were investigated by using scanning electron microscopy (SEM), X-ray diffraction (XRD), atomic force microscopy (AFM), energy dispersive X-ray spectrometry (EDS), and Raman spectra. It is found that the temperature field effects play an extremely crucial role in a-Ge crystallization and fractal Ge formation process. The open branched structure of fractal Ge clusters in Al/Ge bilayer films was effectively prepared by Al-induced crystallization when they were annealed at 400 °C for 60 min. These films with fractal Ge clusters exhibit charming noninteger dimensional nanostructures, which differ from those of conventional integer dimensional materials such as one-dimensional nanowires/nanorods, nanotubes, nanobelts/nanoribbons, two-dimensional heterojunctions, thin films, and zero-dimensional nanoparticles. The SEM image shows that a big Al grain was found located near the center of a fractal Ge cluster after the films were annealed at 400 and 500 °C for 60 min. This suggests that the grain boundaries of polycrystalline Al films are the initial nucleation sites of a-Ge. It also validates the preferred nucleation theory of a-Ge at triple-point grain boundaries of polycrystalline Al at the interface. This discovery may be explained by the metal-induced nucleation (MIN) mechanism.

15.
J Nanosci Nanotechnol ; 12(1): 26-59, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22523945

ABSTRACT

Metal/semiconductor thin films are a class of unique materials that are widespread technological applications, particularly in the field of microelectronic devices. Assessment strategies of fractal and tures are of fundamental importance in the development of nano/microdevices. This review presents the preparation methodologies and nano/microstructural evaluation of metal/semiconductor thin films including Au/Ge bilayer films and Pd-Ge alloy thin films, which show in the form of fractals and nanocrystals. Firstly, the extended version of Au/Ge thin films for the fractal crystallization of amorphous Ge and the formation of nanocrystals developed with improved micro- and nanostructured features are described in Section 2. Secondly, the nano/microstructural characteristics of Pd/Ge alloy thin films during annealing have been investigated in detail and described in Section 3. Finally, we will draw the conclusions from the present work as shown in Section 4. It is expected that the preparation methodologies developed and the knowledge of nano/microstructural evolution gained in metal/semiconductor thin films, including Au/Ge bilayer films and Pd-Ge alloy thin films, will provide an important fundamental basis underpinning further interdisciplinary research in these fields such as physics, chemistry, materials science, and nanoscience and nanotechnology, leading to promising exciting opportunities for future technological applications involving these thin films.


Subject(s)
Crystallization/methods , Membranes, Artificial , Metals/chemistry , Nanostructures/chemistry , Nanostructures/ultrastructure , Semiconductors , Particle Size , Surface Properties
16.
Inorg Chem ; 50(14): 6756-61, 2011 Jul 18.
Article in English | MEDLINE | ID: mdl-21679001

ABSTRACT

Metal/semiconductor thin films are a class of unique materials that have widespread technological applications, particularly in the field of microelectronic devices. New strategies of fractal assessment for Pd/Ge bilayer films formed at various annealing temperatures are of fundamental importance in the development of micro/nanodevices. Herein, Pd/Ge bilayer films with interesting fractal nanoclusters were successfully prepared by evaporation techniques. Temperature-dependent properties of resistance and fractal dimensions in Pd/Ge bilayer films with self-similar Ge fractal nanoclusters were investigated in detail. Experimental results indicated that the fractal crystallization behavior and film resistance in Pd/Ge bilayer films are influenced significantly by annealing temperatures and fractal dimensions. The measurements of film resistance confirmed that there is an evident relationship between the film resistance and the fractal dimension. These phenomena were reasonably explained by the random tunneling junction network mechanism.

18.
J Endocrinol Invest ; 34(8): e235-9, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21270512

ABSTRACT

Mutations in the DAX1 gene result in X-linked congenital adrenal hypoplasia (AHC). Affected boys usually present with primary adrenal failure in early infancy or childhood and hypogonadotropic hypogonadism (HH) at puberty. This paper describes the clinical, hormonal, radiological, and genetic characteristics of 2 Chinese patients with X-linked AHC. Primary adrenal insufficiency occurred in the 2 patients during their childhood and HH was recognized at puberty. Genomic DNA was extracted from their peripheral blood leukocytes and coding sequence abnormalities of the DAX1 gene were assessed by PCR and direct sequencing analysis. Genetic analysis of the DAX1 gene revealed 2 novel mutations c.572-575 dupGGGC, p.Thr193Gly,fs,205X and c.773- 774 dupCC, p.Ser259Pro,fs,264X in exon 1, causing frameshifts and yeilding premature stop codons at 205 and 264, respectively. This study identifies 2 novel mutations in the DAX1 gene which can further expand the mutation database and benefit patients in the diagnosis and treatment of AHC.


Subject(s)
Adrenal Hyperplasia, Congenital/genetics , Asian People/genetics , DAX-1 Orphan Nuclear Receptor/genetics , Genetic Diseases, X-Linked/genetics , Mutation , Adrenal Hyperplasia, Congenital/pathology , Adrenal Hyperplasia, Congenital/physiopathology , Adrenal Insufficiency , Adult , Base Sequence , Child , DNA Mutational Analysis , Female , Genetic Diseases, X-Linked/pathology , Genetic Diseases, X-Linked/physiopathology , Genetic Testing , Humans , Hypoadrenocorticism, Familial , Hypogonadism/congenital , Hypogonadism/genetics , Male , Molecular Sequence Data , Pedigree
19.
J Nanosci Nanotechnol ; 11(12): 10659-63, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22408968

ABSTRACT

Nanocrystalline SnO2 thin films were prepared by pulsed laser deposition techniques on clean glass substrates, and the films were then annealed for 30 min from 50 to 550 degrees C with a step of 50 degrees C, respectively. The investigation of X-ray diffraction confirmed that the various SnO2 thin films were consisted of nanoparticles with average grain size in the range of 23.7-28.9 nm. Root-mean-square surface roughness of the as-prepared SnO2 thin film was measured to be 25.6 nm which decreases to 16.2 nm with thermal annealing. Electrical resistivity and refractive index were measured as a function of annealing temperature, and found to lie between 1.24 to 1.45 momega-cm, and 1.502 to 1.349, respectively. The results indicate that nearly opposite actions to root-mean-square surface roughness and electrical resistivity make a unique performance with thermal annealing temperature. The post annealing shows greater tendency to affect the structural and electrical properties of SnO2 thin films which composed of nanoparticles.

20.
J Nanosci Nanotechnol ; 11(11): 9709-13, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22413277

ABSTRACT

A modified technique was developed by electron beam irradiation to prepare tin dioxide (SnO2) nanocrystals using the sol-gel method. SnO2 nanoparticles were radiated under a 1,400 KGy dose. The morphology and microstructure of the SnO2 nanocrystals were investigated by X-ray diffraction, high-resolution transmission electron microscopy (HRTEM), and Raman spectroscopy. The results indicate that the irradiated SnO2 nanoparticles have better crystallinity than unirradiated SnO2 nanoparticles, and the resulting nanocrystals have a tetragonal rutile crystalline structure. The HRTEM image proves that the average grain size is about 4 nm, and the clear lattice fringes indicate the improvement of SnO2 nanocrystals after irradiation. The Raman spectrum shows that there are new peaks at 535 cm(-1) and 691 cm(-1). The optical properties of SnO2 nanoparticles were characterized by ultraviolet-visible (UV-vis) and photoluminescence spectrophotometers. The band gap energy of the irradiated SnO2 was 3.29 eV smaller than that of the unirradiated SnO2 due to size effects and some defects of SnO2 nanocrystals. This work provides a novel approach for the improvement of SnO2 nanocrystals. The optical properties of the irradiated SnO2 nanomaterials are also expected to improve.

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