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1.
Kaohsiung J Med Sci ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34213074

RESUMO

To explore the role of suppressor of cytokine signaling-3 (SOCS-3) in mesangial proliferative glomerulonephritis (MsPGN). SOCS-3 expression in kidney tissues from MsPGN patients was detected using immunohistochemistry. Double immunofluorescence staining was performed to investigate the localization of SOCS-3 with α-SMA in glomeruli. Heminephrectomized wild-type (WT) and SOCS-3-/- (KO) mice were injected with Habu-snake venom (HSV) to establish MsPGN models, and renal function were compared. Simultaneously, immunofluorescence, periodic acid-Schiff staining, Picrosirius red staining, as well as immunohistochemistry for PCNA, MAC-2 and type IV collagen in glomeruli were performed. In addition, primary mouse renal mesangial cells and SV40 MES-13 cells were transfected with SOCS-3 siRNA or SOCS-3 lentiviral activation particles, followed by EdU assay, flow cytometry, quantitative reverse transcription-polymerase chain reaction, and Western blotting. Mesangial SOCS-3 expression was enhanced in glomeruli of MsPGN patients, and SOCS-3 was well co-localized with activated α-SMA. After HSV injection, WT and KO mice presented with the increases in the serum creatinine, urea nitrogen, and urinary protein, especially in KO mice. Besides, SOCS-3-/- alleviated the hyperplasia of glomerular MCs in MsPGN mice, with the reductions in PCNA, MAC-2, and collagen deposition. Furthermore, SOCS-3 inhibition reduced the cell proportion at S phase to suppress cell proliferation, with the downregulations of Cyclin A, Cyclin D1, PCNA, and Ki-67. SOCS-3 knockout can alleviate the hyperplasia of glomerular MCs in MsPGN mice via affecting the cell cycle and proliferation of MCs, thus being a potential therapeutic target for MsPGN.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34213812

RESUMO

A Co-catalyzed enantioselective desymmetric [2+2+2] cycloaddition for synthesis of pyridines with all-carbon quaternary carbon centers has been developed. The regio- and enantioselectivities are controlled by the inherent nature of terminal alkynes and the substituents on the bisoxazolinephosphine ligands. Pyridines with 5-substitutents could be obtained with above 20 : 1 regioselectivity and up to 94% ee when terminal alkyl, alkenyl or silyl alkynes and DTBM/phenyl-based NPN* ligand L6 are used. The applying of terminal aryl alkynes and phenyl/benzyl-based ligand L4 leads to formation of pyridines with reversed 6-substitutents in up to 99% ee .

3.
Artigo em Inglês | MEDLINE | ID: mdl-34302379

RESUMO

OBJECTIVES: Little is known about children's oral health disparities and their changes in developing countries. This study aimed to measure rural-urban and maternal education-related disparities in dental visits and untreated caries among Chinese children, and to describe their changes between 2005 and 2015. METHODS: The 12-year-old children's oral health data were from the 3rd (2005) and 4th (2015) oral health surveys in Beijing, China. Rural-urban disparities and maternal education-related disparities in dental visits and untreated caries were measured. The slope index of inequality (SII) and a relative index of inequality (RII) were applied to reflect the absolute and relative disparities respectively. These were estimated using a generalized linear regression model. RESULTS: Data were analysed from 388 children in 2005 and 1926 children in 2015. The proportion of 12-year-old schoolchildren who visited the dentist was 24.0% in 2005 and 36.0% in 2015. Untreated caries prevalence in 2005 and 2015 was 20.9% and 16.2% respectively. Rural-urban disparities in dental visits narrowed between 2005 and 2015 (SII: -10.75 to -3.30, RII: 0.55 to 0.87), and maternal education-related disparities in dental visits also decreased during this decade (SII: -18.52 to -8.49, RII: 0.38 to 0.65). These changes were statistically significant. For disparities in untreated caries, only maternal education-related disparities in untreated caries in 2015 were found. The SII and RII were 6.39% (95% CI: 1.65, 11.13) and 1.57 (95% CI: 1.13, 2.20) respectively. The change in disparities in untreated caries was not statistically significant for rural-urban disparities (P = .319) or maternal education-related disparities (P = .501). CONCLUSIONS: These findings indicate that in Beijing, China, disparities in children's dental visits narrowed between 2005 and 2015. However, maternal education-related disparities in dental visits and in untreated caries were still apparent, suggesting that policies to improve children's oral healthcare utilization equality should target the children with less-educated mothers.

5.
Int J Mol Sci ; 22(14)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34299064

RESUMO

The effective cryopreservation of mesenchymal stem cells (MSCs) is indispensable to the operation of basic research and clinical transplantation. The prevalent protocols for MSC cryopreservation utilize dimethyl sulfoxide (DMSO), which is easily permeable and able to protect MSCs from cryo-injuries, as a primary cryoprotectant (CPA). However, its intrinsic toxicity and adverse effects on cell function remain the bottleneck of MSC cryopreservation. In this work, we cryopreserved human umbilical cord mesenchymal stem cells (UCMSCs) using zwitterionic betaine combined with electroporation without any addition of DMSO. Betaine was characterized by excellent compatibility and cryoprotective properties to depress the freezing point of pure water and balance the cellular osmotic stress. Electroporation was introduced to achieve intracellular delivery of betaine, intending to further provide comprehensive cryoprotection on UCMSCs. Compared with DMSO cryopreservation, UCMSCs recovered from the protocol we developed maintained the normal viability and functions and reduced the level of reactive oxygen species (ROS) that are harmful to cell metabolism. Moreover, the in vivo distribution of thawed UCMSCs was consistent with that of fresh cells monitored by a bioluminescence imaging (BLI) system. This work opens a new window of opportunity for DMSO-free MSC cryopreservation using zwitterionic compounds like betaine combined with electroporation.

6.
J Asian Nat Prod Res ; : 1-6, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34308707

RESUMO

A new aurone glycoside named licoagroaurone 6-O-α-ʟ-arabinopyranoside (1), together with six known compounds (2-7), was isolated from EtOAc-soluble extract of the aerial parts of Saussurea involucrata. Their structures were elucidated on the basis of spectroscopic methods. All compounds were evaluated for their inhibitory activities against α-glucosidase in vitro. Among them, compounds 1 and 6 showed significant inhibitory activities on α-glucosidase with the IC50 values of 47.1 and 57.7 µM, respectively.

7.
Bioengineered ; 12(1): 4361-4373, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34308747

RESUMO

Gastric cancer (GC) is one of the most common malignancies worldwide. Despite rapid advances in systemic therapy, GC remains the third leading cause of cancer-related deaths. We aimed to identify a novel prognostic signature associated with FAT2 mutations in GC. We analyzed the expression levels of FAT2-mutant and FAT2-wildtype GC samples obtained from The Cancer Genome Atlas (TCGA). The Kaplan-Meier survival curve showed that patients with FAT2 mutations showed better prognosis than those without the mutation. Sixteen long non-coding RNAs (lncRNAs) and 62 messenger RNAs (mRNAs) associated with FAT2 mutations were correlated with the prognosis of GC. We then constructed a 4-mRNA signature and a 5-lncRNA signature for GC. Finally, we identified the most relevant RP11-21 C4.1/SVEP1 gene pair as a prognostic signature of GC that exhibited superior predictive performance in comparison with the 4-mRNA or 5-lncRNA signature by weighted gene correlation network analysis (WGCNA) and Cox proportional hazards regression analysis. In this study, we constructed a prognostic signature of GC by integrative genomics analysis, which also provided insights into the molecular mechanisms linked to FAT2 mutations in GC.

8.
Endokrynol Pol ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34292572

RESUMO

OBJECTIVES: The clinical data of 23 cases of congenital hyperinsulinemia (CHI) treated by pancreatectomy were retrospectively analyzed, and the therapeutic effect and prognosis of pancreatectomy in the treatment of CHI were discussed. METHODS: A total of 23 Chinese children with CHI who had undergone pancreatectomy between February 2002 and March 2020 were selected as the study objects. The clinical data, the results of the 18Fluoro-L-3-4 dihydroxyphenylalanine positron emission tomography/computerized tomography (18F-DOPA PET/CT) scanning, and the diagnosis, treatment, and follow-up were analyzed retrospectively. RESULTS: Among the 23 cases, 14 patients were diagnosed with focal-type CHI via a 18F-DOPA PET/CT scan prior to the operation, with the lesions removed via partial pancreatectomy. After the operation, ten patients (71%) had normal blood glucose levels, while frequent feeding was required in four patients (29%) to control the hypoglycemia. Three cases were diagnosed as diffuse-type CHI via preoperative scanning, two of which were treated by subtotal pancreatectomy, with one returning to normal blood glucose levels, while a subcutaneous injection of octreotide was required in the other to prevent hypoglycemia. The other case was treated by near-total pancreatectomy, and the blood glucose level was normal following the operation. The remaining six cases were not diagnosed via the pancreatic scanning prior to the operation due to the limitation of certain conditions. Here, pancreatectomy was performed directly due to severe hypoglycemia. CONCLUSIONS: 18F-DOPA PET/CT scanning was a reliable method for determining the histological type and localizing the lesion before the operation. Partial pancreatectomy for focal-type CHI had a high cure rate. In the children with diffuse-type CHI, the surgical methods were more complex and the therapeutic effect and the prognosis were also different.

9.
BMC Plant Biol ; 21(1): 319, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217205

RESUMO

BACKGROUND: PTI1 (Pto-interacting 1) protein kinase belongs to the receptor-like cytoplasmic kinase (RLCK) group of receptor-like protein kinases (RLK), but lack extracellular and transmembrane domains. PTI1 was first identified in tomato (Solanum lycopersicum) and named SlPTI1, which has been reported to interact with bacterial effector Pto, a serine/threonine protein kinase involved in plant resistance to bacterial disease. Briefly, the host PTI1 specifically recognizes and interacts with the bacterial effector AvrPto, which triggers hypersensitive cell death to inhibit the pathogen growth in the local infection site. Previous studies have demonstrated that PTI1 is associated with oxidative stress and hypersensitivity. RESULTS: We identified 12 putative PTI1 genes from the genome of foxtail millet (Setaria italica) in this study. Gene replication analysis indicated that both segmental replication events played an important role in the expansion of PTI1 gene family in foxtail millet. The PTI1 family members of model plants, i.e. S. italica, Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa), maize (Zea mays), S. lycopersicum, and soybean (Glycine max), were classified into six major categories according to the phylogenetic analysis, among which the PTI1 family members in foxtail millet showed higher degree of homology with those of rice and maize. The analysis of a complete set of SiPTI1 genes/proteins including classification, chromosomal location, orthologous relationships and duplication. The tissue expression characteristics revealed that SiPTI1 genes are mainly expressed in stems and leaves. Experimental qRT-PCR results demonstrated that 12 SiPTI1 genes were induced by multiple stresses. Subcellular localization visualized that all of foxtail millet SiPTI1s were localized to the plasma membrane. Additionally, heterologous expression of SiPTI1-5 in yeast and E. coli enhanced their tolerance to salt stress. CONCLUSIONS: Our results contribute to a more comprehensive understanding of the roles of PTI1 protein kinases and will be useful in prioritizing particular PTI1 for future functional validation studies in foxtail millet.


Assuntos
Genoma de Planta , Família Multigênica , Proteínas de Plantas/genética , Salinidade , Setaria (Planta)/genética , Setaria (Planta)/fisiologia , Cromossomos de Plantas/genética , Escherichia coli/metabolismo , Duplicação Gênica/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Anotação de Sequência Molecular , Motivos de Nucleotídeos/genética , Filogenia , Proteínas de Plantas/metabolismo , Saccharomyces cerevisiae/metabolismo , Estresse Fisiológico/genética , Sintenia/genética
10.
Mol Nutr Food Res ; : e2100070, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34223710

RESUMO

SCOPE: Obesity is a major public health and economic problem of global significance. Here, we investigate the role of diosmetin, a natural flavonoid presents mainly in citrus fruits, in the regulation of obesity and metabolic dysfunctions in mice. METHODS AND RESULTS: Eight-week-old male C57BL/6 mice fed a high-fat diet (HFD) or 5-week-old male ob/ob mice fed a normal diet are treated with diosmetin (50 mg kg-1 daily) or vehicle for 8 weeks. Diosmetin treatment decreases body weight and fat mass, improves glucose tolerance and insulin resistance in obese mice. These metabolic benefits are mainly attributed to increase energy expenditure via enhancing thermogenesis in brown adipose tissue (BAT) and browning of white adipose tissue (WAT). Mechanistically, diosmetin acts as an agonist for estrogen receptors (ERs), and subsequently elevates adipose expressions of ERs in mice and in cultured adipocytes. When ERs are blocked by their antagonist fulvestrant in mice, diosmetin loses its beneficial effects, suggesting that ERs are indispensable for the metabolic benefits of diosmetin. CONCLUSION: The results indicate that diosmetin may be a potential anti-obesity nutritional supplement and could be explored for low ERs-related obesity populations.

11.
Sci Total Environ ; 795: 148768, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34247082

RESUMO

The recent discovery of complete ammonia oxidizers (comammox), which convert ammonia to nitrate in a single organism, revolutionized the conventional understanding that two types of nitrifying microorganisms have to be involved in the nitrification process for more than 100 years. However, how different types of nitrifiers in response to salinity change remains largely unclear. This study not only investigated nitrifier community (including ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), comammox and nitrite-oxidizing Nitrospira) in the Nanliu estuary to find the ecological relationship between salinity and functional communities and also studied the physiology of a typical comammox Nitrospira inopinata in response to a salinity gradient. Based on sequences retrieved with four sets of functional gene primes, comammox Nitrospira was in general, mainly composed of clade A, with a clear separation of clade A1 subgroup in all samples and clade A2 subgroup in low salinity ones. As expected, group I.1b and group I.1a AOA dominated the AOA community in low- and high-salinity samples, respectively. Nitrosomonas-AOB were detected in all samples while Nitrosospira-AOB were mainly found in relatively high-salinity samples. Regarding general Nitrospira, lineages II and IV were the major groups in most of the samples, while lineage I Nitrospira was only detected in low-salinity samples. Furthermore, the comammox pure culture of N. inopinata showed an optimal salinity at 0.5‰ and ceased to grow at 12.8‰ for ammonia oxidation, but remained active for nitrite oxidation. These results show new evidence regarding niche specificity of different nitrifying microorganisms modulated mainly by salinity, and also a clear response by comammox N. inopinata to a wide range of simulated salinity levels.

12.
Ann Palliat Med ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34263612

RESUMO

Leptomeningeal metastasis (LM) is a disastrous complication in lung cancer. LM patients with oncogene-addicted non-small cell lung cancer (NSCLC) have a relatively better prognosis than those with the wild-type counterpart; however, overall post-LM survival is short. Additionally, the high heterogenicity of the LM entity creates a treatment challenge, and to date, no standard strategy has been established. This article describes a female lung adenocarcinoma patient with a resistant epidermal growth factor receptor (EGFR) exon20ins mutation who developed LM only 11 months after radical surgery IIIA (pT1bN2). Intrathecal chemotherapy (ITC), whole-brain radiotherapy (WBRT) with a simultaneous integrated boost (SIB) followed by Osimertinib was initiated. The cerebrospinal fluid (CSF) cytology turned negative. The first remission lasted 6 months, then bone metastases occurred, and the LM progressed. An Ommaya reservoir was implanted. ITC with pemetrexed and anlotinib was administered. A CSF next-generation sequencing (NGS) examination revealed EGFR exon20ins (p. A767_V769 dup 1.5%), which was different from that of the primary tumor (p. V769_D770 ins ASV 17.48%). The CSF cytology then turned negative again; however, the patient succumbed to the disease in December 2020. The patient's post-LM overall survival (OS) time was 13.5 months. This case is novel and of great value. Clinicians should pay special attention to populations at high risk of developing LM. Early detection followed by active intervention, including ITC, RT, and systemic treatment, will result in a better prognosis. The NGS of CSF is fundamental to understanding the genetic profiles of LM and providing effective and precise treatment.

13.
Org Lett ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34286988

RESUMO

In this paper, we designed and synthesized a new type of cyclic carbonates, allenylethylene carbonates (AECs). With AECs as reactive precursors, we developed palladium-catalyzed (3+3) annulation of AECs with nitrile oxides. Various AECs worked well in this reaction under mild reaction conditions. A variety of 5,6-dihydro-1,4,2-dioxazine derivatives with allenyl quaternary stereocenters can be accessed in a facile manner in high yields (≤98%).

14.
J Prosthet Dent ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34294417

RESUMO

Standardized radiographs produced by using the paralleling technique play an important role in monitoring prosthetic misfit and marginal bone levels around endosseous implants. Under clinical conditions, parallel adjustment of the film with respect to the implant requires the use of positioning devices. This article describes the fabrication of a custom computer-aided design and computer-aided manufacturing (CAD-CAM) device suitable for implants adjacent to natural teeth.

15.
Chem Commun (Camb) ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34296236

RESUMO

In this paper, an asymmetric allylic alkylation of easily available azomethine ylides with Morita-Baylis-Hillman (MBH) carbonates through a copper (i)/Lewis base cooperative catalysis strategy has been realized. The co-catalyzed asymmetric allylic alkylation provided the corresponding amino acid derivatives in up to 90% yields with up to 99% ee as well as good to excellent regioselectivity.

16.
Food Funct ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34296713

RESUMO

The present study aimed to investigate the relationship between the n-3 index, serum metabolites and breast cancer risk. A total of 104 newly diagnosed breast cancer patients and 70 healthy controls were recruited. The erythrocyte phospholipid fatty acid composition was determined by gas-liquid chromatography, and the n-3 index was calculated with the percentage of eicosapentaenoic acid plus docosahexaenoic acid in total fatty acids. Serum metabolomic profiles were analyzed by UHPLC-Q-Exactive Orbitrap/MS. The results showed that the erythrocyte phospholipid n-3 index was significantly lower in breast cancer patients than in healthy controls, and it was inversely associated with breast cancer risk (OR = 0.60; 95% CI: 0.36-0.84). Metabolomics analyses showed that serum 16α-hydroxy dehydroepiandrosterone (DHEA) 3-sulfate, lysophatidylethanolamines (LPE) 22:0/0:0 and hexanoylcarnitine were significantly higher, while thromboxane B3, prostaglandin E3 (PGE3) and 18ß-glycyrrhetinic acid were significantly lower in breast cancer patients than those in healthy controls. In addition, serum 16α-hydroxy DHEA 3-sulfate was inversely correlated with the n-3 index (r = -0.412, p = 0.036). In conclusion, our findings suggest that the lack of n-3 PUFAs might be a potential risk factor for breast cancer, and the serum metabolite 16α-hydroxy DHEA 3-sulfate may play an important role in linking n-3 PUFA deficiency and breast disease etiology.

17.
Nano Lett ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34291936

RESUMO

We highlight a new metal-molecule charge transfer process by tuning the Fermi energy of plasmonic silver nanoparticles (AgNPs) in situ. The strong adsorption of halide ions upshifts the Fermi level of AgNPs by up to ∼0.3 eV in the order Cl- < Br- < I-, favoring the spontaneous charge transfer to aligned molecular acceptor orbitals until charge neutrality across the interface is achieved. By carefully quantifying, experimentally and theoretically, the Fermi level upshift, we show for the first time that this effect is comparable in energy to different plasmonic effects such as the plasmoelectric effect or hot-carriers production. Moreover, by monitoring in situ the adsorption dynamic of halide ions in different AgNP-molecule systems, we show for the first time that the catalytic role of halide ions in plasmonic nanostructures depends on the surface affinity of halide ions compared to that of the target molecule.

18.
Cancer Res ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301759

RESUMO

Castration-resistant prostate cancer (CRPC) is a lethal stage of disease in which androgen receptor (AR) signaling is persistent despite androgen deprivation therapy (ADT). Most studies have focused on investigating cell-autonomous alterations in CRPC, while the contributions of the tumor microenvironment are less well understood. Here we sought to determine the role of tumor-associated macrophages in CRPC, based upon their role in cancer progression and therapeutic resistance. In a syngeneic model that reflected the mutational landscape of CRPC, macrophage depletion resulted in a reduced transcriptional signature for steroid and bile acid synthesis, indicating potential perturbation of cholesterol metabolism. As cholesterol is the precursor of the five major types of steroid hormones, we hypothesized that macrophages were regulating androgen biosynthesis within the prostate tumor microenvironment. Macrophage depletion reduced androgen levels within prostate tumors and restricted androgen receptor (AR) nuclear localization in vitro and in vivo. Macrophages were also cholesterol-rich and were able to transfer cholesterol to tumor cells in vitro. AR nuclear translocation was inhibited by activation of Liver X Receptor (LXR)-ß, the master regulator of cholesterol homeostasis. Consistent with these data, macrophage depletion extended survival during ADT and the presence of macrophages correlated with therapeutic resistance in patient-derived explants. Taken together, these findings support the therapeutic targeting of macrophages in CRPC.

19.
J Mol Neurosci ; 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34218423

RESUMO

Progressive myoclonic epilepsy is a group of neurodegenerative diseases with complex clinical and genetic heterogeneity, which is associated with spontaneous or action-induced myoclonus and progressive neurodegeneration. Since 2020, 4 families with progressive myoclonic epilepsy-11 [OMIM#618876] have been reported with a very limited spectrum of SEMA6B pathogenic variants. In our study, whole-exome sequencing was used in a proband from a nonconsanguineous Chinese family presenting with growth retardation and recurrent atonic seizures. A deletion mutation (c.1960_1978del, p.Leu654Argfs*25) in the last exon of SEMA6B was detected, which is a de novo variant and pathogenic. The new genetic evidence we reported here strengthened the gene-disease relationship, and the gene curation level between SEMA6B and progressive myoclonic epilepsy-11 became "strong" following the ClinGen SOP. Therefore, the results of this study broaden the mutation spectrum of SEMA6B in different ethnic groups and strengthen the gene-disease relationship between SEMA6B and progressive myoclonic epilepsy-11.

20.
Math Biosci Eng ; 18(4): 3887-3906, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34198416

RESUMO

In this paper, an asymmetric image encryption algorithm based on DNA coding and hyperchaotic system is designed. Unlike other image encryption schemes, for example, sharing of same private keys between sender and receiver, and fixed rules with simple operation, three stages are studied as follows to deal with these problems. Firstly, to eliminate the possible risk of key transmission and management, the initial values of the hyperchaotic system are generated for ahead by the RSA (Rivest-Shamir-Adleman) algorithm and the plain image, in which the sum of odd rows, even rows, odd columns, and even columns are computed respectively to extra the plain message from the plain image as input of RSA algorithm. Then, a mathematical map is established to transform all of them into initial values of the hyperchaotic system. Secondly, the pixel level permutation is performed to confuse the image according to the chaotic sequences generated. Finally, to solve the problem of fixed rules with simple operations in current DNA based image encryption algorithms, dynamical DNA encryption is designed to diffuse the permuted image. The process of DNA encryption includes DNA coding, DNA operation and DNA decoding. In particular, DNA rules are selected according to chaotic sequences dynamically, rather than fixed rules with simple operation. Theoretical analysis and numerical simulations show that the proposed algorithm is secure and reliable for image encryption.

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