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2.
Heliyon ; 10(12): e33179, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-39021908

RESUMEN

Background: Corona Virus Disease 2019(COVID-19)is a global pandemic novel coronavirus infection disease caused by Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Although rapid, large-scale testing plays an important role in patient management and slowing the spread of the disease. However, there has been no good and widely used drug treatment for infection and transmission of SARS-CoV-2. Key findings: Therefore, this review updates the body of knowledge on viral structure, infection routes, detection methods, and clinical treatment, with the aim of responding to the large-section caused by SARS-CoV-2. This paper focuses on the structure of SARS-CoV-2 viral protease, RNA polymerase, serine protease and main proteinase-like protease as well as targeted antiviral drugs. Conclusion: In vitro or clinical trials have been carried out to provide deeper thinking for the pathogenesis, clinical diagnosis, vaccine development and treatment of SARS-CoV-2.

3.
iScience ; 27(6): 110071, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38868199

RESUMEN

Piezoelectric atomization is becoming mainstream in the field of inhalation therapy due to its significant advantages. With the rapid development of high-viscosity gene therapy drugs, the demand for piezoelectric atomization devices is increasing. However, conventional piezoelectric atomizers with a single-dimensional energy supply are unable to provide the energy required to atomize high-viscosity liquids. To address this problem, our team has designed a flow tube internal cavitation atomizer (FTICA). This study focuses on dissecting the atomization mechanism of FTICA. In contrast to the widely supported capillary wave hypothesis, our study provides evidence in favor of the cavitation hypothesis, proving that cavitation is the key to atomizing high-viscosity liquids with FTICA. In order to prove that the cavitation is the key to atomizing in the structure of FTICA, the performance of atomization is experimented after changing the cavitation conditions by heating and stirring of the liquids.

4.
Fungal Genet Biol ; 173: 103910, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38897560

RESUMEN

The homologous recombination strategy has a long history of editing Saccharomyces cerevisiae target genes. The application of CRISPR/Cas9 strategy to editing target genes in S. cerevisiae has also received a lot of attention in recent years. All findings seem to indicate that editing relevant target genes in S. cerevisiae is an extremely easy event. In this study, we systematically analyzed the advantages and disadvantages of homologous recombination (HR) strategy, CRISPR/Cas9 strategy, and CRISPR/Cas9 combined homology-mediated repair (CRISPR/Case9-HDR) strategy in knocking out BY4742 ade2. Our data showed that when the ade2 was knocked out by HR strategy, a large number of clones appeared to be off-target, and 10 %-80 % of the so-called knockout clones obtained were heteroclones. When the CRISPR/Cas9 strategy was applied, 60% of clones were off-target and the rest were all heteroclones. Interestingly, most of the cells were edited successfully, but at least 60 % of the clones were heteroclones, when the CRISPR/Cas9-HDR strategy was employed. Our results clearly showed that the emergence of heteroclone seems inevitable regardless of the strategies used for editing BY4742 ade2. Given the characteristics of BY4742 defective in ade2 showing red on the YPD plate, we attempted to build an efficient yeast gene editing strategy, in which the CRISPR/Cas9 combines homology-mediated repair template carrying an ade2 expression cassette, BY4742(ade2Δ0) as the start strain. We used this strategy to successfully achieve 100 % knockout efficiency of trp1, indicating that technical challenges of how to easily screen out pure knockout clones without color phenotype have been solved. Our data showed in this study not only establishes an efficient yeast gene knockout strategy with dual auxotrophy coupled red labeling but also provides new ideas and references for the knockout of target genes in the monokaryotic mycelium of macrofungi.

5.
Dalton Trans ; 53(7): 3377-3385, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38264854

RESUMEN

Phosphates, whose obvious disadvantage is the relatively small birefringence, can be overcome by the introduction of post-transition metal cations containing stereochemically active lone-pair electrons. In this paper, two new compounds were successfully explored in the A-Sb-P-O system, i.e. Cs2Sb3O(PO4)3 (CsSbPO) and (NH4)2Sb4O2(H2O)(PO4)2[PO3(OH)]2 (NH4SbPOH). Transmission spectra show that CsSbPO has a surprising transmission range with a UV cutoff edge of 213 nm. First-principles calculations show that both compounds have a wide band gap (5.02 eV for CsSbPO and 5.30 eV for NH4SbPOH) and enlarged birefringence (Δn = 0.034@1064 nm for CsSbPO and Δn = 0.045@1064 nm for NH4SbPOH). The results of real-space atom-cutting investigations show that the distorted [SbOx] polyhedra originating from the asymmetric lone pair electrons give the main contribution to the total birefringence and overcome the disadvantage of small birefringence of phosphates but maintain wide transition windows.

7.
Nanomaterials (Basel) ; 13(23)2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38063734

RESUMEN

Oxyhalides, containing oxygen and halogen atoms and combining the advantages of oxides and halides in geometry and optical response, have great potential in optical materials. In this study, the electronic structures and the optical properties of the Pb3O2X2 (X = Cl, Br, I) compounds have been investigated using the first principles method. The results show that these compounds have birefringence at 0.076, 0.078, and 0.059 @ 1064 nm, respectively. And, the asymmetric stereochemical active lone pair electrons were found around lead atoms, which were confirmed by the projected density of states, the electronic localization functions, and the crystal orbitals. The contribution of atoms and polyhedra to birefringence was further evaluated using the Born effective charge. The results show that halogen atoms give negative contribution, and lead-oxygen polyhedra give positive contribution. The spin-orbit coupling effect is also investigated, and the downshift of the conduction band and variation in the valence band are found after relevant spin-orbit coupling (SOC), which leads to a reduction in the band gap and birefringence.

8.
Dalton Trans ; 52(45): 16920-16926, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37927065

RESUMEN

Two new selenites, K2Zn3Se4O12 (compound 1) and K4Zn3V4Se2O19 (compound 2), have been successfully synthesized by solid-state reactions in vacuum tubes. Compound 1 consists of a three-dimensional (3D) framework with [SeO3] triangular pyramids and [ZnO4] tetrahedra in the monoclinic space group P21/c (No. 14). Compound 1's cut-off edge is below 344 nm, based on its UV-Vis-NIR diffuse reflectance studies, and theoretical calculations indicate a birefringence of around 0.043 at 1064 nm. The two-dimensional layer of compound 2, in contrast, is made up of [SeO3] triangular pyramids, [ZnO4] tetrahedra, and [V4O13] tetrahedra. It crystallizes in the monoclinic space group C2/c (No. 15). Its UV-Vis-NIR diffuse reflectance studies demonstrate that the compound's cut-off edge is lower than 330 nm.

9.
Sensors (Basel) ; 23(11)2023 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-37299809

RESUMEN

The intelligent fault diagnosis of main circulation pumps is crucial for ensuring their safe and stable operation. However, limited research has been conducted on this topic, and applying existing fault diagnosis methods designed for other equipment may not yield optimal results when directly used for main circulation pump fault diagnosis. To address this issue, we propose a novel ensemble fault diagnosis model for the main circulation pumps of converter valves in voltage source converter-based high voltage direct current transmission (VSG-HVDC) systems. The proposed model employs a set of base learners already able to achieve satisfying fault diagnosis performance and a weighting model based on deep reinforcement learning that synthesizes the outputs of these base learners and assigns different weights to obtain the final fault diagnosis results. The experimental results demonstrate that the proposed model outperforms alternative approaches, achieving an accuracy of 95.00% and an F1 score of 90.48%. Compared to the widely used long and short-term memory artificial neural network (LSTM), the proposed model exhibits improvements of 4.06% in accuracy and 7.85% in F1 score. Furthermore, it surpasses the latest existing ensemble model based on the improved sparrow algorithm, with enhancements of 1.56% in accuracy and 2.91% in F1 score. This work presents a data-driven tool with high accuracy for the fault diagnosis of main circulation pumps, which plays a critical role in maintaining the operational stability of VSG-HVDC systems and satisfying the unmanned requirements of offshore flexible platform cooling systems.


Asunto(s)
Algoritmos , Electricidad , Inteligencia , Memoria a Corto Plazo , Redes Neurales de la Computación
10.
Small ; 19(34): e2301828, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37093169

RESUMEN

Enhanced second-harmonic generation (SHG) responses are reported in monolayer transition metal dichalcogenides (e.g., MX2 , M: Mo, W; X: S, Se) due to the broken symmetries. The 3R-like stacked MX2 spiral structures possessing the similar broken inversion symmetry should present dramatically enhanced SHG responses, thus providing great flexibility in designing miniaturized on-chip nonlinear optical devices. To achieve this, the first direct synthesis of twisted 3R-stacked chiral molybdenum diselenide (MoSe2 ) spiral structures with specific screw dislocations (SD) arms is reported, via designing a water-assisted chemical vapor transport (CVT) approach. The study also clarifies the formation mechanism of the MoSe2 spiral structures, by precisely regulating the precursor supply accompanying with multiscale characterizations. Significantly, an up to three orders of magnitude enhancement of the SHG responses in twisted 3R stacked MoSe2 spirals is demonstrated, which is proposed to arise from the synergistic effects of broken inversion symmetry, strong light-matter interaction, and band nesting effects. Briefly, the work provides an efficient synthetic route for achieving the 3R-stacked TMDCs spirals, which can serve as perfect platforms for promoting their applications in on-chip nonlinear optical devices.

11.
J Exp Bot ; 74(8): 2740-2753, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-36807675

RESUMEN

The root-associated microbiomes play important roles in plant growth. However, it is largely unknown how wheat variety evolutionary relatedness shapes each subcommunity in the root microbiome and, in turn, how these microbes affect wheat yield and quality. Here we studied the prokaryotic communities associated with the rhizosphere and root endosphere in 95 wheat varieties at regreening and heading stages. The results indicated that the less diverse but abundant core prokaryotic taxa occurred among all varieties. Among these core taxa, we identified 49 and 108 heritable amplicon sequence variants, whose variations in relative abundances across the root endosphere and rhizosphere samples were significantly affected by wheat variety. The significant correlations between phylogenetic distance of wheat varieties and prokaryotic community dissimilarity were only observed in non-core and abundant subcommunities in the endosphere samples. Again, wheat yield was only significantly associated with root endosphere microbiota at the heading stage. Additionally, wheat yield could be predicted using the total abundance of 94 prokaryotic taxa as an indicator. Our results demonstrated that the prokaryotic communities in the root endosphere had higher correlations with wheat yield and quality than those in the rhizosphere; thus, managing root endosphere microbiota, especially core taxa, through agronomic practices and crop breeding, is important for promoting wheat yield and quality.


Asunto(s)
Microbiología del Suelo , Triticum , Triticum/genética , Filogenia , Raíces de Plantas/genética , Fitomejoramiento , Rizosfera
12.
Sensors (Basel) ; 24(1)2023 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-38202984

RESUMEN

Piezoelectric pumps play an important role in modern medical technology. To improve the flow rate of valveless piezoelectric pumps with flow tube structures and promote the miniaturization and integration of their designs, a cardioid flow tube valveless piezoelectric pump (CFTVPP) is proposed in this study. The symmetric dual-bend tube design of CFTVPP holds great potential in applications such as fluid mixing and heat dissipation systems. The structure and working principle of the CFTVPP are analyzed, and flow resistance and velocity equations are established. Furthermore, the flow characteristics of the cardioid flow tube (CFT) are investigated through computational fluid dynamics, and the output performance of valveless piezoelectric pumps with different bend radii is studied. Experimental results demonstrate that CFTVPP exhibits the pumping effect, with a maximum vibration amplitude of 182.5 µm (at 22 Hz, 100 V) and a maximum output flow rate of 5.69 mL/min (at 25 Hz, 100 V). The results indicate that a smaller bend radius of the converging bend leads to a higher output flow rate, while the performance of valveless piezoelectric pumps with different diverging bends shows insignificant differences. The CFTVPP offers advantages such as a high output flow rate, low cost, small size for easy integration, and ease of manufacturing.

13.
Appl Bionics Biomech ; 2022: 7729959, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36523568

RESUMEN

Purpose: To investigate the relative position of femur fixed screws using intramedullary systems for intertrochanteric fractures and to improve the accurate measurement method of the tip-to-apex distance (TAD) while providing a theoretical basis for the clinical treatment of such fractures. Methods: In the anteroposterior (AP) radiographs of the hip joint, the femoral neck axis through the femoral head geometry point was designated as the X-axis, while the line perpendicular to the X-axis passing through the femoral head geometry point was designated as the Y-axis. In the lateral radiographs of the hip joint, the line perpendicular to the X-axis passing through the femoral head geometry point was identified as the Z-axis. The head of the nail tip's location projected on the three axes was described as A AP, B in the AP radiographs; and A LAT, C in the lateral radiograph. The TAD was described as X AP and X LAT. The radius of the femoral head was D. All distance units were expressed in mm. Results: When the lateral projection angle was standardized, the A AP was equal to the A LAT, while the X AP 2=B 2+(D - A AP)2 and X LAT 2=C 2+(D - A LAT)2. When the lateral projection angle was not standardized, the value of C had no significant change; however, the (D - A LAT) value changed. Conclusions: The measurement value did not match the actual values of TAD when the lateral projection angle was not standardized, possibly leading to a misinterpretation during clinical work. The X LAT should be amended using the formula X LAT 2=C 2+(D - A AP)2.

14.
Sci Total Environ ; 842: 156952, 2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-35752240

RESUMEN

The effect of long-term water and integrated fertilization on prokaryotic microorganisms and their regulation for crop nutrient uptake remains unknown. Therefore, the impact of soil water and integrated fertilization after eight years on prokaryotic microbial communities in different compartments of root zone and their association with wheat nitrogen (N) absorption and yield were investigated. The results showed that compared with fertilization treatments (F), water regimes (W) more drastically modulated the prokaryotic microbial community structure and diversity in bulk soil, rhizosphere and endosphere. The increase of irrigation improved the prokaryotic diversity in the rhizosphere and endosphere while decreased the diversity in the bulk soil. Application of organic fertilizers significantly improved soil organic matter (SOM) and nutrient contents, increased rhizosphere and endophytic prokaryotic microbial diversity, and elevated the relative abundance of aerobic ammonia oxidation and nitrification-related functional microorganisms in rhizosphere and endosphere. Increasing irrigation elevated the relative abundance of functional microorganisms related to aerobic ammonia oxidation and nitrification in the rhizosphere and endosphere. Soil water content (SWC) and NH4+-N as well as NO3--N were key predictors of prokaryotic microbial community composition under W and F treatments, respectively. Appropriate application of irrigation and organic fertilizers increased the relative abundance of some beneficial bacteria such as Flavobacterium. Water and fertilization treatments regulated the prokaryotic microbial communities of bulk soil, rhizosphere and endosphere by altering SWC and SOM, and provided evidence for the modulation of prokaryotic microorganisms to promote nitrogen uptake and wheat yield under long-term irrigation and fertilization. Conclusively, the addition of organic manure (50 %) with inorganic fertilizers (50 %) and reduced amount of irrigation (pre-sowing and jointing-period irrigation) decreased the application amount of chemical fertilizers and water, while increased SOM and nutrient content, improved prokaryotic diversity, and changed prokaryotic microbial community structure in the wheat root zone, resulting in enhanced nutrient uptake and wheat yield.


Asunto(s)
Fertilizantes , Microbiota , Fertilización , Fertilizantes/análisis , Nitrógeno , Suelo/química , Microbiología del Suelo , Triticum , Agua
15.
Materials (Basel) ; 14(21)2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34772001

RESUMEN

A few-layer graphene (FLG) composite material was synthesized using a rich reservoir and low-cost coal under the microwave-assisted catalytic graphitization process. X-ray diffraction, Raman spectroscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy were used to evaluate the properties of the FLG sample. A well-developed microstructure and higher graphitization degree were achieved under microwave heating at 1300 °C using the S5% dual (Fe-Ni) catalyst for 20 min. In addition, the synthesized FLG sample encompassed the Raman spectrum 2D band at 2700 cm-1, which showed the existence of a few-layer graphene structure. The high-resolution TEM (transmission electron microscopy) image investigation of the S5% Fe-Ni sample confirmed that the fabricated FLG material consisted of two to seven graphitic layers, promoting the fast lithium-ion diffusion into the inner surface. The S5% Fe-Ni composite material delivered a high reversible capacity of 287.91 mAhg-1 at 0.1 C with a higher Coulombic efficiency of 99.9%. In contrast, the single catalyst of S10% Fe contained a reversible capacity of 260.13 mAhg-1 at 0.1 C with 97.96% Coulombic efficiency. Furthermore, the dual catalyst-loaded FLG sample demonstrated a high capacity-up to 95% of the initial reversible capacity retention-after 100 cycles. This study revealed the potential feasibility of producing FLG materials from bituminous coal used in a broad range as anode materials for lithium-ion batteries (LIBs).

16.
Phys Rev Lett ; 126(25): 251102, 2021 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-34241495

RESUMEN

We perform the three-dimensional lattice simulation of the magnetic field and gravitational wave productions from bubble collisions during the first-order electroweak phase transition. Except for the gravitational wave, the power-law spectrum of the magnetic field strength is numerically calculated for the first time, which is of a broken power-law spectrum: B_{ξ}∝f^{0.91} for the low-frequency region of ff_{⋆} in the thin-wall limit, with the peak frequency being f_{⋆}∼5 Hz at the phase transition temperature 100 GeV. When the hydrodynamics is taken into account, the generated magnetic field strength can reach B_{ξ}∼10^{-7} G at a correlation length ξ∼10^{-7} pc, which may seed the large scale magnetic fields. Our study shows that the measurements of cosmic magnetic field strength and gravitational waves are complementary to probe new physics admitting electroweak phase transition.

17.
Front Bioeng Biotechnol ; 8: 603083, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33282854

RESUMEN

A novel electrochemical biosensing method for protein kinase (PKA) activity was demonstrated by using a reduced graphene oxide-polydopamine-silver nanoparticle-Ti4+ (rGO-PDA-AgNPs-Ti4+) nanocomposite. The obtained nanocomposite possessed an integral capability for phosphopeptide recognition and signal readout. The polydopamine modified reduced graphene oxide (rGO-PDA) was firstly prepared based on a self-polymerization method of dopamine. The silver ions were adsorbed onto polydopamine (PDA) layer and directly reduced into silver nanoparticles (AgNPs), which was used for electrochemical signal reporting. Then, the Ti4+ cations were attached onto the PDA layer for phosphopeptide recognition according to the strong coordination ability of PDA with Ti4+ and phosphate group. The prepared rGO-PDA-AgNPs-Ti4+ nanocomposites were characterized with different methods. The developed rGO-PDA-AgNPs-Ti4+ nanocomposites were then employed for electrochemical analysis of PKA-catalyzed kemptide phosphorylation. The sensitive detection toward PKA activity was realized with an experimental detection limit of about 0.01 U/mL. It may be also extended for the inhibitor evaluation. Thus, it provided a facile and sensitive means for electrochemical analysis of PKA activity and inhibitor screening.

18.
Anal Chem ; 92(14): 9764-9771, 2020 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-32527089

RESUMEN

Herein, a new exonuclease III (Exo III)-powered self-propelled DNA machine was developed for the cascade multilevel signal amplification of nucleic acid and nucleic acid-related analytes. It could be easily and homogeneously operated with the use of an integral DNA hybrid probe as the recognition, amplification, and signaling element, and the Exo III cleavage as a driving force. The DNA hybrid probe was obtained by annealing two hairpin-like DNAs. The target recognition with the 3'-protruding domain of the DNA hybrid probe triggered Exo III cleavage, accompanied by target recycling and alternate generation of a large amount of target substitute and analogy. Simultaneously, the cascade bidirectional Exo III cleavage toward the DNA hybrid probe by the generated target substitute and analogy contributed for the exponential signal amplification toward target recognition event. It could be also extended for the application in protein detection with the thrombin as a protein example by introducing an additional hairpin-like aptamer switch. The proposed Exo III-powered self-propelled DNA amplification strategy showed a linear detection range for target DNA from 0.5 fM to 1 pM and for thrombin from 5 fM to 10 pM. The low detection limit toward target DNA and thrombin could reach about 0.1 fM and 5 fM, respectively, which were superior to most of reported methods. It also exhibited an excellent selectivity toward target detection. Therefore, the developed sensing system exhibits a new, simple and powerful means for amplified detection of nucleic acid and nucleic acid-related analytes, and may hold great potentials in bioanalysis, disease diagnosis and biomedicine.


Asunto(s)
Sondas de ADN , Exodesoxirribonucleasas/metabolismo , Técnicas de Amplificación de Ácido Nucleico/métodos , Ácidos Nucleicos/química , Proteínas/química , Técnicas Biosensibles/métodos , ADN/química , Exodesoxirribonucleasas/genética , Límite de Detección
19.
Artículo en Inglés | MEDLINE | ID: mdl-32082399

RESUMEN

Oroxylin A, a flavonoid, is naturally produced in many medicinal plants. Our previous study identified it as a phytoestrogen. Based on this, the present study investigated its vasoconstriction reducing effects and whether the action was mediated by the estrogen receptor (ER) signal pathway. Long-term in vitro treatment with oroxylin A reduced Ach-induced vasorelaxation and NE-mediated or KCl-mediated contractile responses in rat aortic rings. These effects were interfered by an ER inhibitor ICI 182,780. Rat cardiac microvascular endothelial cells (CMECs) and aortic vascular smooth muscle cells (VSMCs) were used to study the possible underlying mechanisms. Oroxylin A activated the ER signal pathway. In CMECs, it increased NO production and eNOS protein expression. In VSMCs, it promoted NO production and iNOS protein expression. These effects were also inhibited by ICI 182,780. Besides, oroxylin A stimulated ERα and ERß protein expression in CMECs and VSMCs. All these findings suggest that the ER signal pathway takes part in the vasoconstriction reducing effects of oroxylin A.

20.
J Biomed Mater Res A ; 108(5): 1086-1098, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31943702

RESUMEN

Bacterial cellulose (BC) membranes display special properties and structures, thus attracting much attention in application in the biomedical areas, for example, as implants for bone or cartilage tissue engineering, as substitutes for skin repairing, and as supports for controlled drug delivery. However, native BC lacks the activity to inhibit bacteria growth on its surface, which limits its applications in biomedical fields. There have been reports on chemical modification of BC membranes to endow them with antimicrobial properties needed for some special biomedical applications. In the present study, aminoalkyl-grafted BC membranes were prepared by alkoxysilane polycondensation using 3-aminopropyltriethoxysilane (APTES). The characterization for morphology and chemical composition showed that BC membranes were successfully grafted with aminoalkylsilane groups through covalent bonding. The surface morphology and roughness of the membranes changed after chemical grafting. Furthermore, after grafting with APTES, the membranes got less hydrophilic than native BC. The aminoalkyl-grafted BC membranes showed strong antibacterial properties against Staphylococcus aureus and Escherichia coli and moreover, they were nontoxic to normal human dermal fibroblasts. These results indicate that aminoalkyl-grafted BC membranes are potential to be used for biomedical applications.


Asunto(s)
Antibacterianos/química , Materiales Biocompatibles/química , Celulosa/análogos & derivados , Membranas Artificiales , Antibacterianos/farmacología , Materiales Biocompatibles/farmacología , Celulosa/farmacología , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/prevención & control , Humanos , Propilaminas/química , Propilaminas/farmacología , Silanos/química , Silanos/farmacología , Infecciones Estafilocócicas/prevención & control , Staphylococcus aureus/efectos de los fármacos
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