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Precise manipulation of cancer cell death by harnessing reactive oxygen species (ROS) is a promising strategy to defeat malignant tumors. However, it is quite difficult to produce active ROS with spatial precision and regulate their biological outcomes. We succeed here in selectively generating short-lived and lipid-reactive hydroxyl radicals (â¢OH) adjacent to cancer cell membranes, successively eliciting lipid peroxidation and ferroptosis. DiFc-K-pY, a phosphorylated self-assembling precursor that consists of two branched Fc moieties and interacts specifically with epidermal growth factor receptor, can in situ produce membrane-bound nanofibers and enrich ferrocene moieties on cancer cell membranes in response to alkaline phosphatase. Within the acidic tumor microenvironment, DiFc-K-pY nanofibers efficiently convert tumoral H2O2 to active â¢OH around the target cell membranes via Fenton-like reactions, leading to lipid peroxidation and ferroptosis with good cellular selectivity. Our strategy successfully prevents tumor progression with acceptable biocompatibility through intratumoral administration.
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Nanofibras , Neoplasias , Humanos , Espécies Reativas de Oxigênio/metabolismo , Metalocenos , Peróxido de Hidrogênio/metabolismo , Morte Celular , Neoplasias/terapia , Oxirredução , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Two-dimensional (2D) layered palladium dichalcogenides PdX2 (X = S and Se) have attracted increasing interest due to their tunable electronic structure and abundant physicochemical properties. Recently, as the sister material of PdX2, PdSSe has received increasing attention and shows great promise for technological applications and fundamental research. In the present study, we focus on the layer-dependent geometry, electronic structure, and optical properties of PdSSe using first-principles calculations. The lattice shrinkage effect present in the 2D structure is suppressed with increasing number of layers. Attributed to the strong interlayer coupling interactions, the band gap decreases from 2.30 to 0.83 eV with increased thickness. Particularly, the dispersion of the band edges on the high symmetry path changes considerably from the monolayer to bilayer PdSSe, resulting in shifts of the conduction band minimum and valence band maximum. The multilayer PdSSe shows band convergence feature with multi-valley for the conduction band, which are maintained with reduced effective mass. Furthermore, the increasing number of layers drives a wider absorption range in the visible light region, and the light absorption capability increases from â¼10% to â¼30%. Meanwhile, the band edge positions of the multilayer PdSSe are more appropriate for photocatalytic water splitting. Our theoretical study reveals the enhanced valley convergence, conductivity and optical absorption performance of the few-layer PdSSe, which suggests its promising application in thermoelectric conversion, solar harvesting and photocatalysis.
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Due to their unique structure, abundant properties and potential applications, low-dimensional materials with covalently bonded building blocks through van der Waals (vdW) interactions have sparked widespread interest. Recently, the bulk phase NbS4 consisting of one-dimensional (1D) chains has been synthesized successfully, adding a new member to the group V metallic polychalcogenide family. In the present study, based on density functional theory calculations, we obtained a better understanding of the stability, mechanical properties, electronic structures, transport properties and optical performances of the bulk phase NbS4. Furthermore, the possibility of exfoliating 1D single-chain nanowires from the bulk phase was uncovered. Both bulk phase and 1D nanowires show dynamic, thermal, and mechanical stabilities. The bulk phase possesses an indirect band gap of 1.39 eV with high anisotropic carrier mobilities of 471.814 cm2 s-1 v-1 for electrons (along the b axis direction) and 546.92 cm2 s-1 v-1 for holes (along the a axis direction). The single-chain nanowire exhibits remarkable flexibility and can resist 24% tensile strain along the chain direction. The decreased dimension from the bulk phase to the individual 1D chain not only makes the band gap increase to 1.81 eV but also results in an indirect-to-direct band gap transition, indicating a strong quantum confinement effect. The 1D single-chain nanowire also shows high carrier mobilities of 111.91 cm2 s-1 v-1 for electrons and 316.63 cm2 s-1 v-1 for holes along the chain direction. In addition, both bulk phase and 1D nanowire display excellent visible light absorption performance along the chain direction and the absorption coefficients reach the order of 106 and 105 cm-1. These promising properties render quasi 1D NbS4 as candidate materials for nanoscale applications in high-performance optoelectronic and nanoelectronic devices. The predicted unconventional properties of NbS4 not only provide a meaningful complement to the fascinating quasi 1D material family, but also will attract extensive interest from a wide audience to explore unanticipated properties and design new nanoscale devices based on NbS4.
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In order to verify the technology of the membrane diffractive imaging system for Chinese next generation geo-stationary earth orbit (GEO) satellite, a series of ground experiments have been carried out using a membrane optical camera with 80 mm aperture (Φ80) lens. The inherent chromatic aberration due to diffractive imaging appears in the obtained data. To address the issue, an effective color restoration algorithm framework by matching, tailoring, and non-linearly stretching the image histograms is proposed in this letter. Experimental results show the proposed approach has good performances in color restoration of the diffractive optical images than previous methods. The effectiveness and robustness of the algorithm are also quantitatively assessed using various color deviation indexes. The results indicate that the chromatic aberration of diffractive images can be effectively removed by about 85%. Also, the proposed method presents reasonable computational efficiency.
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Enhancers regulate multiple genes via higher-order chromatin structures, and they further affect cancer progression. Epigenetic changes in cancer cells activate several cancer-specific enhancers that are silenced in normal cells. These cancer-specific enhancers are potential therapeutic targets of cancer. However, the functions and regulation networks of colorectal-cancer-specific enhancers are still unknown. In this study, we profile colorectal-cancer-specific enhancers and reveal their regulation network through the analysis of HiChIP data that were derived from a colorectal cancer cell line and Hi-C and RNA-seq data that were derived from tissue samples by in silico analysis and in vitro experiments. Enhancer-promoter loops in colorectal cancer cells containing colorectal-cancer-specific enhancers are involved in more than 50% of the topological associated domains (TADs) changed in colorectal cancer cells compared to normal colon cells. In addition, colorectal-cancer-specific enhancers interact with 152 genes that are significantly and highly expressed in colorectal cancer cells. These colorectal-cancer-specific enhancer target genes include ITGB4, RECQL4, MSLN, and GDF15. We propose that the regulation network of colorectal-cancer-specific enhancers plays an important role in the progression of colorectal cancer.
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Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Elementos Facilitadores Genéticos , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Regiões Promotoras Genéticas , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Neoplasias Colorretais/genética , Progressão da Doença , Humanos , Mesotelina , Células Tumorais CultivadasRESUMO
The Davydov splitting of dye aggregates represents unique molecular excitons. In this paper, we report the formation of Davydov split aggregates of 3,3'-diethylthiacarbocyanine iodide (DiSC2 (3)) and 3,3'-diethylthiadicarbocyanine iodide (DiSC2 (5)) templated by the helical nanotubes of lithocholic acid (LCA). The templated Davydiv split aggregates show a strong J-band and a weak H-band in the adsorption spectra. As the LCA helical nanotubes transform into a straight shape, the relative intensities of the J-band and the H-band of the templated Davydov split aggregates become roughly equal. The twisted angle change of the transition moment of DiSC2 (3) and DiSC2 (5) molecules in the templated Davydov split aggregates in response to the helical-to-straight shape transformation of LCA nanotubes is estimated. The templated Dvaydov split aggregates with well-defined shapes and molecular excitons are of interest for artificial light-harvesting and optoelectronic devices.
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INTRODUCTION: Previous studies found that vitamin D receptor (VDR) TaqI, BsmI, FokI and ApaI gene polymorphisms are associated with several inflammatory diseases. However, the relationship between VDR gene polymorphisms and chronic spontaneous urticaria (CSU) is not clear. AIM: The purpose of our study was to explore the relationship between the polymorphism of VDR and the incidence of chronic spontaneous urticaria in the Chinese Han population. Meanwhile, the vitamin D levels in patients with chronic spontaneous urticaria were also detected and the effects of VDR gene polymorphism on vitamin D levels were detected. MATERIAL AND METHODS: The genotypes of four VDR polymorphisms (TaqI, BsmI, ApaI, and FokI) were studied using allele-specific PCR analysis in 90 CSU patients and 90 healthy controls. RESULTS: Compared to the control group, the mutant allele (C) of FokI were more common in patients with CSU (57.2% vs. 45%, p = 0.020, odds ratio (OR) = 0.612, 95% confidence interval (CI): 0.403-0.928). We found that serum vitamin D levels were significantly lower in CSU patients than in healthy controls (p = 0.023). However, the effect of VDR gene polymorphism on vitamin D levels was not found in patients of CSU. CONCLUSIONS: We first reported the effect of VDR gene FokI (rs2228570) polymorphism on the incidence of chronic spontaneous urticaria in the Chinese Han population.
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Lymphomatoid papulosis (LyP) belongs to the group of cutaneous CD30+ lymphoproliferative disorders. Pseudocarcinomatous hyperplasia has rarely been reported in patients with LyP. In this report, we describe a case of LyP presenting as pseudocarcinomatous hyperplasia. The patient was a 7-year-old girl who presented with a recurrent papulonodular eruption on her face and trunk for 2 months. Histopathologic examination revealed an irregular growth of hyperkeratotic epidermis into the whole dermal layer with marked nests of squamous cells in the background of diffuse atypical lymphoid cells, eosinophils and neutrophils. The large atypical cells were positive for CD30 and CD3, but negative for CD4, CD5, CD8, CD20 and CD56. A TCR-γ clone was identified by polymerase chain reaction (PCR). The correct diagnosis in cases of LyP with overlying pseudocarcinomatous epithelial hyperplasia can be very difficult both clinically and histopathologically. Clinical and histopathologic characteristics should be integrated to avoid an erroneous diagnosis of squamous cell carcinoma or keratoacanthoma.
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Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Papulose Linfomatoide/metabolismo , Papulose Linfomatoide/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Antígenos CD/metabolismo , Criança , Feminino , Humanos , Hiperplasia , Leucócitos/metabolismo , Leucócitos/patologiaRESUMO
The propagation of linear and nonlinear edge modes in bounded photonic honeycomb lattices formed by an array of rapidly varying helical waveguides is studied. These edge modes are found to exhibit strong transmission (reflection) around sharp corners when the dispersion relation is topologically nontrivial (trivial). An asymptotic theory is developed that establishes the presence (absence) of typical edge states, including, in particular, armchair and zigzag edge states in the topologically nontrivial (trivial) case. In the presence of topological protection, nonlinear edge solitons can persist over very long distances.
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BACKGROUND: Acute myocardial infarction (AMI) is the leading cause of death for patients with cardiovascular disease (CVD). Although researchers have made substantial efforts to elucidate its pathogenesis, the molecular mechanisms underlying AMI remain unknown. The aim of this study was to use proteomics to identify differentially expressed proteins (DEPs) and the possible biological functions and metabolic pathways related to coronary blood microparticles (MPs) in patients with AMI and stable coronary artery disease (SCAD); this study will allow for the identification of individuals at risk of acute thrombosis. METHODS: The study was performed on 5 AMI patients and 5 SCAD patients. DEPs were identified, and Gene Ontology (GO) enrichment and KEGG pathway enrichment analyzes were performed to determine the relative abundance and biological function of the significant DEPs that were identified in the present study. RESULTS: The current analysis identified 198 DEPs in the coronary blood of AMI patients and SCAD patients, including 85 proteins that were significantly upregulated and 113 proteins that were significantly downregulated. GO enrichment analysis demonstrated that GDP binding and GTP binding were enriched in molecular function. Similarly, KEGG pathway enrichment analysis revealed that the identified proteins were involved in pantothenate and coenzyme A biosynthesis, starch and sucrose metabolism, and the AMPK signalling pathway. CONCLUSIONS: The proteome of coronary MPs differs between patients with AMI and patients with SCAD. In summary, the GO terms and KEGG pathways enriched by the DEPs may reflect the possible molecular mechanisms underlying the pathogenesis of acute thrombosis in patients with AMI.
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Doença da Artéria Coronariana , Infarto do Miocárdio , Humanos , Proteômica , Infarto do Miocárdio/genética , Doença da Artéria Coronariana/diagnóstico , CoraçãoRESUMO
Ischemic postconditioning has been described in both heart and brain. The first aim of this study was to evaluate the effects of Sevoflurane postconditioning (SP) on brain biochemical parameters, Bcl-2, Bax, c-Fos and Caspase-3 protein levels and Bcl-2, Bax, TNF-α and Caspase-3 mRNA expression in the middle cerebral artery occlusion model. Results showed that SP markedly decreased cerebral oxidative injury and improved immunity activity. In addition, SP significantly enhanced cerebral Bcl-2, c-Fos and decreased Bax, Caspase-3 proteins positive expression. Reverse transcription polymerase chain reaction analysis showed that SP markedly enhanced Bcl-2, and decreased Bax, TNF-α and Caspase-3 mRNA expression. Our results confirm that SP can play the protective action against cerebral ischemia reperfusion-induced brain injury by regulating cerebral antioxidant enzymes activities, Bcl-2, Bax, c-Fos and Caspase-3 protein positive expression levels and Bcl-2, Bax, TNF-α and Caspase-3 mRNA expression.
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Encéfalo/metabolismo , Encéfalo/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/patologia , Pós-Condicionamento Isquêmico , Éteres Metílicos/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Caspase 3/genética , Caspase 3/metabolismo , Catalase/metabolismo , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/enzimologia , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Sevoflurano , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Background: Acute Myocardial Infarction (AMI) is a kind of cardiovascular disease with high mortality and incidence. Extracellular vesicles (EVs) and microRNA-126 (miR-126) are known to play important role in the development and prognosis of several cardiovascular diseases. Therefore, this study aimed to investigate the changes in Extracellular vesicle (EV)-associated miR-126 levels in the coronary blood of patients with AMI to explore the relationship between miR-126 levels and AMI. Materials and methods: We analyzed EV-associated miR-126 in the coronary blood of patients with AMI and stable coronary artery disease (SCAD) using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: We tested the coronary blood of 20 patients with AMI and 20 with SCAD. The mean age of the patients was 58.8 ± 10.3 years and 32 (80%) were men. We observed that the EV-associated miR-126 levels were lower in patients with AMI [median = 0.13; interquartile range (IQR): 0.08-0.22] than in patients with SCAD (median = 0.37; IQR: 0.26-0.48) (P < 0.001). In addition, the levels of miR-126 were negatively associated with the Thrombolysis in Myocardial Infarction (TIMI) score (r = -0.66, P = 0.001). Conclusion: Reduction of EV-associated miR-126 levels in the coronary blood of patients with AMI may be involved in acute coronary thrombosis events.
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Dopamine (DA) is an important neurotransmitter, which is essential for transmitting signals in neuronal communications. The deficiency of DA release from neurons is implicated in neurological disorders. There has been great interest in developing new optical probes for monitoring the release behavior of DA from neurons. H-aggregates of organic dyes represent an ordered supramolecular structure with delocalized excitons. In this paper, we use the self-assembly of 3,3'-diethylthiadicarbocyanine iodide (DiSC2(5)) in ammonia solution to develop crystalline H-aggregate nanoparticles, in which DiSC2(5) molecules show long-range π-π stacking. The crystalline H-aggregate nanoparticles are stable in cell culture medium and can serve as an efficient photo-induced electron transfer (PET) probe for the detection of DA with the concentration as low as 0.1 nM in cell culture medium. Furthermore, the crystalline H-aggregate nanoparticle-based PET probe is used to detect the release behavior of DA from the M17 human neuroblastoma cells. We find that the DA release from the cells is enhanced by nicotine stimulations. Our results highlight the potential of crystalline H-aggregate nanoparticle-based PET probes for diagnosing nervous system diseases and verifying therapies.
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Ditiazanina , Nanopartículas , Neuroblastoma , Amônia , Corantes , Dopamina/farmacologia , Humanos , Iodetos , Neuroblastoma/diagnóstico por imagem , Neurotransmissores , NicotinaRESUMO
BACKGROUND: The nitrogenous compound deposited from the atmosphere to the soil is complex, but most field experiments mimic nitrogen deposition with the acid NH4NO3 alone. Thus, whether the acid and non-acid nitrogenous compounds have similar effects on biodiversity and ecosystem functions remains understudied. We mimicked nitrogen deposition with acidic NH4NO3 and (NH4)2SO4, and non-acidic urea, slow-released urea and NH4HCO3 in a temperate steppe, and quantified soil microbial taxonomic and functional gene composition with amplicon sequencing and shotgun metagenomics, respectively. RESULTS: While NH4NO3 and (NH4)2SO4 significantly altered the soil microbial taxonomic and functional composition as well as their carbon decomposition potential, the other three compounds had smaller effects. CONCLUSION: Our results suggested that previous nitrogen deposition experiments mimicked with NH4NO3 or (NH4)2SO4 alone may have overestimated the effect on biodiversity and ecosystem functions in the Eurasian steppe and similar ecosystems affected by mainly nonacidic nitrogen deposition.
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Contact lenses are ideally suited for sustained ocular drug delivery to bypass the issues associated with eye drop therapy. However, drugs such as bimatoprost loaded by the conventional soaking method show poor drug uptake, high burst release, and altered critical lens properties. In this study, the effect of gold nanoparticles (GNPs) on bimatoprost loading/uptake from the soaking solution and its release kinetics from the lens was investigated. In one method, GNP solutions of varying strength were loaded into the bimatoprost soaking solution (mM-SS batches), and in another method, the GNPs were included in the contact lens matrix during casting (mM-GN-L batches). The GNPs were spherical with average size of 21.1 nm and -20.1 mV zeta potential. The swelling, oxygen permeability, and optical transmittance of the lens were improved compared to those of the lens drug-loaded by the conventional soaking method (SM-L). The mM-GN-L batches showed significant improvement in drug uptake from the soaking solution compared to the SM-L and mM-SS batches. The in vitro studies showed relatively low burst and sustained bimatoprost release up to 72 h compared to 24 h with the SM-L batch. The ability to sustain drug release improved proportionally with an increase in the amount of GNPs in the lens. The presence of GNPs lowered protein adherence. The GNP-laden lenses were deemed safe in ocular irritation and histopathology reports (rabbit model). Further, they showed higher drug retention in the rabbit tear fluid compared to the SM-L lens. In conclusion, the presence of GNPs in contact lenses increased drug uptake from the soaking solution, and improved the in vitro and in vivo release kinetics without affecting the critical properties of the contact lenses for therapeutic application.
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Lentes de Contato , Nanopartículas Metálicas , Animais , Bimatoprost , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Ouro , CoelhosRESUMO
Ferulic acid (FA), an active component extracted from Chinese medicine, shows excellent anti-inflammatory properties and favorable safety in various animal models. However, the application of FA as an anti-inflammatory drug is hindered by its instability and short half-life in vivo . In this paper, we synthesize PEGylated diphenylalanine nanoparticles by using glutaraldehyde (GTA) as a cross-linker of diphenylalanine NH2 -Phe-Phe-COOH and poly(ethylene glycol) methyl ether amine (PEG5k -NH2). The PEGylated Phe-Phe nanoparticles are used to deliver FA for the treatment of Rheumatoid arthritis (RA). We find that the FA-loaded PEGylated Phe-Phe nanoparticles are biocompatible and inhibit the production of reactive oxygen species (ROS) from cells effectively. After being intravenously administrated in vivo , the FA-loaded PEGylated Phe-Phe nanoparticles show prolonged circulation time and accumulate in arthritic joints. More importantly, we show that the pre-arthritis treatment with the FA-loaded PEGylated Phe-Phe nanoparticles can significantly block the progression of RA.
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Ácido Fólico , Nanopartículas , Animais , Ácidos Cumáricos , Sistemas de Liberação de Medicamentos , PolietilenoglicóisRESUMO
OBJECTIVE: To investigate the clinical effect of vancomycin bone cement in the treatment of diabetic foot ulcer (DFU) ruptured Wagner gradeâ ¡-â £. METHODS: From March 2019 to April 2021, 32 patients with Wagner gradeâ ¡-â £ diabetic foot were divided into vacuum sealing drainage (VSD) group and bone cement group according to different treatment methods. There were 16 cases in VSD group, 8 males and 8 females;the age ranged from 66 to 81 (70.50±7.20) years, and the course of disease ranged from 8 to 40 (27.56±8.55) months;Wagner gradeâ ¡in 2 cases, grade â ¢in 7 cases and grade â £in 7 cases;debridement and VSD were used. There were 16 cases in the bone cement group, 9 males and 7 females;the age ranged from 63 to 79 (69.56±7.29) years, and the course of disease ranged from 11 to 39(22.75±11.43) months;Wagner gradeâ ¡ in 2 cases, grade â ¢in 5 cases and grade â £ in 9 cases;vancomycin loaded bone cement was used for treatment. The types of bacteria, negative time of bacterial culture, skin healing time, hospital stay, operation times and complications were observed and compared between two groups. RESULTS: All patients were followed up for 3 to 6 (4.00±1.07) months. The bacterial negative time, skin healing time and hospital stay in bone cement group were significantly lower than those in VSD group (P<0.05). The median number of operations in both groups was 2, and there was no significant difference (P>0.05). According to the analysis of pathogens in two groups, there were 13 cases of G+ patients, 14 cases of G- patients and 5 cases of mixed bacteria. The number of G+, G- and mixed bacteria in bone cement group was 6, 7 and 3 cases respectively, and the number of G+, G- and mixed bacteria in VSD group was 7, 7 and 2 cases respectively. The wounds of 32 patientsin two groups healed completely without complications. CONCLUSION: Vancomycin loaded bone cement is effective in the treatment of Wagner grade â ¡-â £ diabetic foot ulceration wounds. It can reduce the length of hospital stay, shorten the healing time of skin and kill pathogens as soon as possible. It is one of the effective methods to treat Wagner gradeâ ¡-â £diabetic foot ulceration.
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Diabetes Mellitus , Pé Diabético , Cimentos Ósseos/uso terapêutico , Criança , Pré-Escolar , Pé Diabético/tratamento farmacológico , Feminino , Humanos , Masculino , Resultado do Tratamento , Vancomicina , CicatrizaçãoRESUMO
Genotype imputation is a fundamental step in genomic data analysis, where missing variant genotypes are predicted using the existing genotypes of nearby "tag" variants. Although researchers can outsource genotype imputation, privacy concerns may prohibit genetic data sharing with an untrusted imputation service. Here, we developed secure genotype imputation using efficient homomorphic encryption (HE) techniques. In HE-based methods, the genotype data are secure while it is in transit, at rest, and in analysis. It can only be decrypted by the owner. We compared secure imputation with three state-of-the-art non-secure methods and found that HE-based methods provide genetic data security with comparable accuracy for common variants. HE-based methods have time and memory requirements that are comparable or lower than those for the non-secure methods. Our results provide evidence that HE-based methods can practically perform resource-intensive computations for high-throughput genetic data analysis. The source code is freely available for download at https://github.com/K-miran/secure-imputation.