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1.
Nanoscale Adv ; 6(12): 3188-3198, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38868816

RESUMEN

The synthesis of drug-loaded PLGA nanoparticles through nanoprecipitation in solvent/antisolvent mixtures is well reported but lacks clarity in explaining drug loading mechanisms and the prediction of efficiency of drug entrapment. Various methods using physical parameters such as log P and solid-state drug-polymer solubility aim to predict the intensity of drug-polymer interactions but lack precision. In particular, the zero-enthalpy method for drug/polymer solubility may be intrinsically inaccurate, as we demonstrate. Conventional measurement of loading capacity (LC), expressed in weight ratios, can be misleading for comparing different drugs and we stress the importance of using molar units. This research aims to provide new insights and critically evaluate the established methodologies for drug loading of PLGA nanoparticles. The study employs four model drugs with varying solubilities in solvent/antisolvent mixtures, log P values, and solid-state solubility in PLGA: ketoprofen (KPN), indomethacin (IND), sorafenib (SFN), and clofazimine (CFZ). This study highlights that drug loading efficiency is primarily influenced by the drug's solubilities within the solvent system. We emphasise that both kinetic and thermodynamic factors play a role in the behaviour of the system by considering the changes in drug solubility during mixing. The study introduces a pseudo-constant K* to characterise drug-polymer interactions, with CFZ and SFN showing the highest K* values. Interestingly, while IND and KPN have lower K* values, they achieve higher loading capacities due to their greater solubilities, indicating the key role of solubility in determining LC.

2.
Org Lett ; 26(12): 2489-2494, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38498918

RESUMEN

Site-selective modification of complex peptides and the functionalization of their C-H bonds hold great promise for expanding their use in therapeutics and biomedical research. Herein, we leverage the power of late-stage chemoenzymatic catalysis using an indole prenyltransferase (IPT) enzyme and alkyl diphosphates to specifically modify the indole ring of tryptophan in clinically relevant peptides. Furthermore, the installed handle enables bioorthogonal click chemistry through an inverse electron-demand Diels-Alder (IEDDA) reaction with a biotin-conjugated tetrazine probe.


Asunto(s)
Compuestos Heterocíclicos , Triptófano , Péptidos , Reacción de Cicloadición , Indoles
3.
Poult Sci ; 103(2): 103358, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38176363

RESUMEN

Investigating the impact of early egg production selection (the first 90 d of laying) on egg production features, cumulative selection response (CSR), and the mRNA expression of gonadotropins (FSHß and LHß), and their receptors (FSHR and LHR), in Japanese quails was the goal. The selection experiment involved 1293 females in all, 257 from the base group and 1036 from the 4 selected generations. Age and body weight at sexual maturity (ASM, BWSM), weight of the first egg (WFE), days to the first 10 eggs (DF10E), egg mass for the first 10 eggs (EMF10E), egg weight (EW), egg number at the first 90 d of laying (EN90D), and egg mass at the first 90 d of laying (EM90D) were all recorded. Most egg production traits had heritability estimates that were low to moderate and ranged from 0.17 to 0.33., where the highest estimates were reported for EN90D (0.33) and BWSM (0.32). With the exception of EN90D, low to moderate positive genetic correlations were observed between ASM and other egg production traits (0.17-0.44). The fourth generation showed significantly (P < 0.05) lower ASM and DF10E but higher BWSM, WFE, EN90D, EM10E, and EM90D when compared with the base generation. CSR were significant (P < 0.05) for ASM (-6.67 d), BWSM (27.13 g), WFE (0.93 g), DF10E (-1.25 d), EN90D (7.24 egg), EM10E (10.57 g), and EM90D (140.0 g). FSHß, LHß, FSHR, and LHR gene mRNA expression was considerably (P < 0.05) greater in the fourth generation compared to the base generation. In conclusion, selection programs depending on the efficiency of egg production (EN90D) could improve the genetic gain of egg production traits and upregulate the mRNA expression of FSHß, LHß, FSHR, and LHR genes in selected quails (fourth generation). These findings might help to enhance breeding plans and create commercial lines of high egg production Japanese quails.


Asunto(s)
Coturnix , Hormona Folículo Estimulante de Subunidad beta , Femenino , Animales , Hormona Folículo Estimulante de Subunidad beta/genética , Coturnix/fisiología , Hormona Luteinizante de Subunidad beta/genética , Pollos/genética , Óvulo/metabolismo , ARN Mensajero/metabolismo
4.
Environ Sci Pollut Res Int ; 30(48): 105840-105855, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37721673

RESUMEN

A new fractional non-Fourier (Cattaneo) photovoltaic (PV) model is presented to enhance the thermal performance of a PV system combined with a heat spreader (HS). The fractional Cattaneo model is shown to be effective in examining transient processes across the entirety of a PV system, in contrast to the conventional Fourier model's inability to predict system performance. Consequently, a comparison is conducted between the classical Fourier model with the fractional Fourier and fractional Cattaneo models for the PV system. The impact of using an aluminum heat spreader, with rectangular and trapezoidal shapes, has been developed under hot and cold climate conditions. The findings show that adding a trapezoidal heat spreader reduced the cell temperature by 20 K in summer and 12 K in winter. The reduction in the PV temperature led to an enhancement in daily average power by approximately 28% and 37% in hot and cold weather, respectively. Moreover, economic, exergoeconomic, and enviroeconomic assessment is introduced. The outcomes revealed that the electrical production costs of the rectangular and trapezoidal HS systems are 0.272 and 0.214 $/kWh, respectively, while about 0.286 $/kWh for the conventional PV panel. Based on the environmental study, the estimated CO2 reduction for PV, PV with rectangular HS, and PV with trapezoidal spreader is 0.5504, 0.7704, and 0.8012 tons, respectively. Finally, real experimental data are used to validate the fractional Cattaneo model. The results demonstrate that there is a great fitting with the measured data, with errors in PV power and exergy efficiency of just 0.628% and 3.84%, respectively, whereas their corresponding values for the classical model are 5.72 and 13.13%.


Asunto(s)
Aluminio , Calor , Temperatura , Clima Frío , Frío
5.
Anim Biotechnol ; 34(9): 5028-5036, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37409468

RESUMEN

The objectives of the current study were to identify polymorphism in the prolactin receptor (PRLR) gene among three Egyptian goat breeds (Zaraibi, Damascus, and Barki) and to investigate the association between PRLR genotype, parity, season of kidding, and litter size factors with milk yield and reproductive traits of Zaraibi goats. One hundred and ninety blood samples were collected for DNA extraction, with 110 from Zaraibi, 40 from Barki, and 40 from Damascus breeds. Three genotypes, CC, CT and TT, for the prolactin receptor gene were identified in the 190 DNA samples using restriction fragment length polymorphism and were confirmed by direct sequencing technique. Milk yield during suckling and lactation periods in addition to age at first conception, gestation length, and litter size were determined in 110 Zaraibi goats. The Zaraibi goats recorded the highest heterozygosity (0.495) and the effective number of alleles (1.972). The g.62130C > T SNP showed a significant association (p < 0.01) with suckling, lactation, and total milk yield of Zaraibi goats with the highest values recorded at the third parity. Age at the first conception and gestation length traits were significantly influenced by the kidding season (p < 0.05) with younger age in autumn and shorter length in spring seasons. Milk yield during the suckling period was significantly (p < 0.01) higher in the case of triplets' litter size. The current study showed that litter size and parity played an important role in the amount of Zaraibi goats' milk yield. The g.62130C > T SNP of the PRLR gene may be a useful marker for assisted selection programs to improve goat milk yield during suckling and lactation periods with the heterozygous genotype CT recording the highest values.


Asunto(s)
Prolactina , Receptores de Prolactina , Embarazo , Femenino , Animales , Receptores de Prolactina/genética , Alelos , Prolactina/genética , Cabras/genética , Egipto , Leche , ADN
6.
ChemCatChem ; 15(11)2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37366495

RESUMEN

Indole is a significant structural moiety and functionalization of the C-H bond in indole-containing molecules expands their chemical space, and modifies their properties and/or activities. Indole prenyltransferases (IPTs) catalyze the direct regiospecific installation of prenyl, C5 carbon units, on indole-derived compounds. IPTs have shown relaxed substrate flexibility enabling them to be used as tools for indole functionalization. However, the mechanism by which certain IPTs target a specific carbon position is not fully understood. Herein, we use structure-guided site-directed mutagenesis, in vitro enzymatic reactions, kinetics and structural-elucidation of analogs to verify the key catalytic residues that control the regiospecificity of all characterized regiospecific C6 IPTs. Our results also demonstrate that substitution of PriB_His312 to Tyr leads to the synthesis of analogs prenylated at different positions than C6. This work contributes to understanding of how certain IPTs can access a challenging position in indole-derived compounds.

7.
Chembiochem ; 24(17): e202300372, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37338668

RESUMEN

The late-stage functionalization of peptides and proteins holds significant promise for drug discovery and facilitates bioorthogonal chemistry. This selective functionalization leads to innovative advances in in vitro and in vivo biological research. However, it is a challenging endeavor to selectively target a certain amino acid or position in the presence of other residues containing reactive groups. Biocatalysis has emerged as a powerful tool for selective, efficient, and economical modifications of molecules. Enzymes that have the ability to modify multiple complex substrates or selectively install nonnative handles have wide applications. Herein, we highlight enzymes with broad substrate tolerance that have been demonstrated to modify a specific amino acid residue in simple or complex peptides and/or proteins at late-stage. The different substrates accepted by these enzymes are mentioned together with the reported downstream bioorthogonal reactions that have benefited from the enzymatic selective modifications.


Asunto(s)
Péptidos , Proteínas , Catálisis , Proteínas/química , Péptidos/química , Aminoácidos/química , Biocatálisis
8.
Anim Biotechnol ; : 1-8, 2022 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-36409677

RESUMEN

This study was conducted to genetically and environmentally characterize prolificacy (litter size and weight at birth; LSB and LWB and litter size and weight at weaning; LSW and LWW, respectively), milk yield at the 7th (MY7), 15th (MY15), 30th (MY30), 60th (MY60), 90th (MY90) day of lactation and monthly milk yield (MMY) and milk composition traits in Egyptian Zaraibi goats. A total of 443 and 421 records produced by 121 Zaraibi lactating goats were used to assess prolificacy and milk production traits, respectively. The milk composition traits were measured using 371 milk samples obtained at random from 53 goats. The fourth parity showed the highest values for LWB, LWW, and MMY (3.62, 18.15, and 28.99 kg, respectively). Milk composition traits revealed an inverse tendency, decreasing until the second month and then increasing until the seventh month. The heritability estimates ranged from 0.07 to 0.13, from 0.04 to 0.39, and from 0.07 to 0.33 for prolificacy, milk yield, and milk composition traits, respectively. Negatively high genetic correlations between MMY and all milk composition traits were found. MMY had the highest estimate of heritability (0.39 ± 0.07), this means that the genetic improvement of this trait could be achieved through direct selection.

9.
Front Vet Sci ; 9: 918440, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35836502

RESUMEN

In the last 40 years, low pathogenic avian influenza virus (LPAIV) subtype H9N2 has been endemic in most Middle Eastern countries and of course Egypt which is one of the biggest poultry producers in the middle east region. The major losses with the H9N2 virus infections come from complicated infections in commercial broiler chickens, especially E. coli infection. In this work, 2,36,345 Arbor acres broiler chickens from the same breeder flock were placed equally in four pens, where two pens were vaccinated against LPAIV of subtype H9N2 virus, and the other two pens served as non-vaccinated controls. All were placed on the same farm under the same management conditions. A total of twenty birds from each pen were moved to biosafety level-3 chicken isolators (BSL-3) on days 21 and 28 of life and challenged with LPAIV-H9N2 or E. coli. Seroconversion for H9N2 was evaluated before and after the challenge. The recorded results revealed a significant decrease in clinical manifestations and virus shedding in terms of titers of shedding virus and number of shedders in vaccinated compared to non-vaccinated chickens. In groups early infected with LPAIV-H9N2 virus either vaccinated or not vaccinated, there was no significant difference in clinical sickness or mortalities in both groups, but in late infection groups with H9N2 alone, non-vaccinated infected group showed significantly higher clinical sickness in comparison with infected vaccinated group but also without mortality. In groups co-infected with E. coli (I/M) and H9N2, it showed 100% mortalities either in vaccinated or non-vaccinated H9N2 groups and thus reflect the high pathogenicity of used E. coli isolates, whereas in groups co-infected with E. coli (per os to mimic the natural route of infection) and LPAIV-H9N2, mortality rates were significantly higher in non-vaccinated groups than those vaccinated with H9N2 vaccine (15 vs. 5%). In conclusion, the use of the LPAIV H9N2 vaccine has significantly impacted the health status, amount of virus shed, and mortality of challenged commercial broilers, as it can minimize the losses and risks after co-infection with E. coli (orally) and LPAIV-H9N2 virus under similar natural route of infection in commercial broilers.

10.
Appl Opt ; 61(11): 3165-3173, 2022 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-35471294

RESUMEN

An ultrafast, compact, zero-biased, and complementary metal-oxide semiconductor-compatible graphene photodetector (PD) based on a silicon-on-insulator hybrid plasmonic waveguide (HPWG) is proposed. Lumerical MODE solver is employed to investigate the modal characteristics of TM-polarized modes in the HPWG composing the PD. It is shown that the input light can be completely coupled into the photonic-like and plasmonic-like fundamental TM modes at the PD section. These two modes are exploited together in the photodetection process to enhance the PD performance. A rigorous analysis is performed in order to extract the optoelectronic characteristics of the single-layer graphene (SLG) used in the proposed structure. Lumerical 3D-FDTD solver is then employed to quantify the light interaction of the two aforementioned optical modes with the SLG. With a proper design at a wavelength of 1550 nm, the PD voltage responsivity reaches 2.8 V/W, and the photocurrent responsivity is obtained as 18.5 mA/W, while the corresponding absorption length is kept below 8µm and the noise equivalent power is limited to 3.7pW/Hz. Moreover, as the PD operates under zero bias, its photoresponse is predominated by the photothermoelectric mechanism, exhibiting a bandwidth that exceeds 180 GHz while avoiding the dark current.

11.
Chemistry ; 28(20): e202104614, 2022 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-35178791

RESUMEN

The late-stage functionalization of indole- and tryptophan-containing compounds with reactive moieties facilitates downstream diversification and leads to changes in their biological properties. Here, the synthesis of two hydroxy-bearing allyl pyrophosphates is described. A chemoenzymatic method is demonstrated which uses a promiscuous indole prenyltransferase enzyme to install a dual reactive hydroxy-bearing allyl moiety directly on the indole ring of tryptophan-containing peptides. This is the first report of late-stage indole modifications with this reactive group.


Asunto(s)
Dimetilaliltranstransferasa , Triptófano , Indoles/química , Péptidos/química , Triptófano/química
12.
Korean J Anesthesiol ; 75(3): 276-282, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35016497

RESUMEN

BACKGROUND: The thoracic retrolaminar block (TRLB) is a relatively new regional analgesia technique that can be used as an alternative to the thoracic paravertebral block. This study aimed to evaluate the postoperative analgesia effects of ultrasound-guided TRLB in children undergoing open cardiac surgery via median sternotomy incision. METHODS: Sixty-six patients aged 2-8 years were recruited. In the TRLB group, 0.25% bupivacaine 0.4 ml/kg was injected into the retrolaminar space on both sides at the level of the T4 lamina. Patients in the control group were injected with 0.9% saline. The primary outcome measure was fentanyl consumption in the first 24 h post-extubation. The secondary outcome measures were the total intraoperative fentanyl consumption, postoperative modified objective pain score (MOPS), and time to extubation. RESULTS: The total intraoperative fentanyl requirements and fentanyl consumption in the first 24 h post-extubation were significantly lower (P < 0.001) in the TRLB group (9.3 ± 1.2; 6.9 ± 2.1 µg/kg, respectively) than in the control group (12.5 ± 1.4; 16.6 ± 2.8, respectively). The median (Q1, Q3) time to extubation was significantly shorter (P < 0.001) in the TRLB group (2 [1, 3] h) than in the control group (6 [4.5, 6] h). The MOPS was significantly lower (P < 0.05) in the TRLB group than in the control group at 0, 2, 4, 8, 12 and 16 h post-extubation. CONCLUSIONS: Bilateral ultrasound-guided TRLB is effective in providing postoperative analgesia in children undergoing open cardiac surgery via median sternotomy incision.


Asunto(s)
Analgesia , Procedimientos Quirúrgicos Cardíacos , Analgesia/métodos , Niño , Preescolar , Método Doble Ciego , Fentanilo , Humanos , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Estudios Prospectivos , Ultrasonografía Intervencional/métodos
13.
Cureus ; 14(12): e32859, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36694527

RESUMEN

Background In this study, we aimed to compare the performance of the National Emergency Laparotomy Audit (NELA) and Portsmouth Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (P-POSSUM) mortality risk scores in predicting 30-day and 90-day mortality in patients undergoing emergency laparotomy. Methodology A retrospective cohort study was conducted to compare the predictive performance of preoperative NELA, postoperative NELA, and P-POSSUM predicted mortality scores in patients undergoing emergency laparotomy between 2014 and 2021. The outcomes of interest included the observed 30-day and 90-day mortality. The discrimination of the mortality tools was assessed and compared by determining the area under the curve (AUC) for each tool using the receiver operating characteristic curve analysis. Results A total of 681 patients were included. The observed risk of 30-day and 90-day mortality was 10.4% (71/681) and 14.2% (97/681), respectively. Regarding 30-day mortality, the AUC was 0.791 (0.727-0.855) for the preoperative NELA score, 0.784 (0.721-0.848) for the preoperative P-POSSUM score, and 0.761 (0.699-0.824) for the postoperative NELA score. Regarding 90-day mortality, the AUC was 0.765 (0.708-0.821) for the preoperative NELA score, 0.749 (0.692-0.807) for the preoperative P-POSSUM score, and 0.745 (0.691-0.800) for the postoperative NELA score. The observed/expected ratio for 30-day and 90-day mortality was 3.25 and 4.43 for preoperative NELA, 2.81 and 3.84 for preoperative P-POSSUM, and 2.17 and 2.96 for postoperative NELA, respectively. Pairwise comparisons showed no statistically significant difference in discrimination among the three models. Conclusions Preoperative NELA, postoperative NELA, and P-POSSUM scores underestimated the risk of 30-day and 90-day mortality in patients undergoing emergency laparotomy. No significant difference in predictive performance was found among the three models.

14.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-926573

RESUMEN

Background@#The thoracic retrolaminar block (TRLB) is a relatively new regional analgesia technique that can be used as an alternative to the thoracic paravertebral block. This study aimed to evaluate the postoperative analgesia effects of ultrasound-guided TRLB in children undergoing open cardiac surgery via median sternotomy incision. @*Methods@#Sixty-six patients aged 2–8 years were recruited. In the TRLB group, 0.25% bupivacaine 0.4 ml/kg was injected into the retrolaminar space on both sides at the level of the T4 lamina. Patients in the control group were injected with 0.9% saline. The primary outcome measure was fentanyl consumption in the first 24 h post-extubation. The secondary outcome measures were the total intraoperative fentanyl consumption, postoperative modified objective pain score (MOPS), and time to extubation. @*Results@#The total intraoperative fentanyl requirements and fentanyl consumption in the first 24 h post-extubation were significantly lower (P < 0.001) in the TRLB group (9.3 ± 1.2; 6.9 ± 2.1 μg/kg, respectively) than in the control group (12.5 ± 1.4; 16.6 ± 2.8, respectively). The median (Q1, Q3) time to extubation was significantly shorter (P < 0.001) in the TRLB group (2 [1, 3] h) than in the control group (6 [4.5, 6] h). The MOPS was significantly lower (P < 0.05) in the TRLB group than in the control group at 0, 2, 4, 8, 12 and 16 h post-extubation. @*Conclusions@#Bilateral ultrasound-guided TRLB is effective in providing postoperative analgesia in children undergoing open cardiac surgery via median sternotomy incision.

15.
J Cardiothorac Vasc Anesth ; 36(3): 677-683, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34148802

RESUMEN

OBJECTIVE: The objective of the present study was to compare ultrasound-guided long-axis (LAX) and short-axis (SAX) femoral artery catheterization in neonates and infants undergoing cardiac surgery. DESIGN: A single-center, prospective, randomized, single-blinded, controlled study. SETTING: This study was conducted in the operating room and intensive care unit of the division of cardiac surgery, Mansoura University Children's Hospital, Egypt. PARTICIPANTS: Ninety neonates and infants undergoing elective cardiac surgery were enrolled in this study and randomly allocated to ultrasound-guided LAX and SAX groups. INTERVENTIONS: Ultrasound-guided femoral artery catheterization was done using either LAX (in-plane) or SAX (out-of-plane) technique. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the rate of a successful first puncture. The secondary outcome measures were the rates of mechanical complications, failure rate, time to a successful first, second, and third puncture, total time of catheterization, and imaging time. The first puncture success rate was significantly higher (p = 0.048) in the LAX group (34 of 41, 82.9%) than in the SAX group (25 of 41, 60.9%). The mean time to a successful first puncture was significantly shorter (p < 0.001) in the LAX group (153.1 ± 30.1 seconds) than in the SAX group (227.2 ± 48.8 seconds). The total catheterization time was significantly shorter in the LAX group than in the SAX group. There was no significant difference in the rate of complication. CONCLUSION: With a single experienced operator performing the ultrasound-guided femoral artery cannulation, the LAX technique resulted in a higher first puncture success rate and shorter time to cannulation than the SAX technique.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Cateterismo Venoso Central , Cateterismo Periférico , Cateterismo Venoso Central/métodos , Cateterismo Periférico/métodos , Niño , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/cirugía , Humanos , Lactante , Recién Nacido , Estudios Prospectivos , Ultrasonografía Intervencional/métodos
16.
Animals (Basel) ; 11(11)2021 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-34827838

RESUMEN

The objectives of this study were to achieve phenotypic characterization of three domestic Egyptian goose populations collected from three different geographical zones (Kafr El-Sheikh, Fayoum and Luxor) and to perform genetic characterization of these three populations based on mtDNA D-loop and 12 microsatellite markers. The body measurements of 402 domestic mature geese belonging to these three governorates showed that the lengths of the head, culmen and tarsus and the live body weight varied significantly among the three studied Egyptian goose populations. After alignment of a 710-base-pair segment of the goose mtDNA control region, there was a single haplotype in the three Egyptian goose populations, indicating the same maternal origins. The genotyping of the 12 microsatellite markers showed low diversity indices, including average observed (NA) and effective (NE) number of alleles and observed (HO) and expected heterozygosity (HE) (3.333, 1.760, 0.277 and 0.352, respectively), and a high inbreeding coefficient (FIS = 0.203) across the three Egyptian goose populations. The high inbreeding and low genetic and morphological differentiation of Egyptian geese could be corrected by establishing a large base population through capturing small populations with the highest genetic variation. The findings of the current study can therefore serve as an initial guide to design further investigations for developing conservation programs of Egyptian geese genetic resources.

17.
PLoS One ; 16(11): e0260232, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34797851

RESUMEN

Smartphone usage is nearly ubiquitous worldwide, and Android provides the leading open-source operating system, retaining the most significant market share and active user population of all open-source operating systems. Hence, malicious actors target the Android operating system to capitalize on this consumer reliance and vulnerabilities present in the system. Hackers often use confidential user data to exploit users for advertising, extortion, and theft. Notably, most Android malware detection tools depend on conventional machine-learning algorithms; hence, they lose the benefits of metaheuristic optimization. Here, we introduce a novel detection system based on optimizing the random vector functional link (RVFL) using the artificial Jellyfish Search (JS) optimizer following dimensional reduction of Android application features. JS is used to determine the optimal configurations of RVFL to improve classification performance. RVFL+JS minimizes the runtime of the execution of the optimized models with the best performance metrics, based on a dataset consisting of 11,598 multi-class applications and 471 static and dynamic features.


Asunto(s)
Procedimientos de Cirugía Plástica/instrumentación , Procedimientos de Cirugía Plástica/métodos , Teléfono Inteligente/instrumentación , Algoritmos , Benchmarking/métodos , Aprendizaje Automático , Programas Informáticos
18.
ACS Chem Biol ; 16(12): 2816-2824, 2021 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-34763417

RESUMEN

We report the identification of the ter gene cluster responsible for the formation of the p-terphenyl derivatives terfestatins B and C and echoside B from the Appalachian Streptomyces strain RM-5-8. We characterize the function of TerB/C, catalysts that work together as a dual enzyme system in the biosynthesis of natural terphenyls. TerB acts as a reductase and TerC as a dehydratase to enable the conversion of polyporic acid to a terphenyl triol intermediate. X-ray crystallography of the apo and substrate-bound forms for both enzymes provides additional mechanistic insights. Validation of the TerC structural model via mutagenesis highlights a critical role of arginine 143 and aspartate 173 in catalysis. Cumulatively, this work highlights a set of enzymes acting in harmony to control and direct reactive intermediates and advances fundamental understanding of the previously unresolved early steps in terphenyl biosynthesis.


Asunto(s)
Hidroliasas/metabolismo , Oxidorreductasas/metabolismo , Compuestos de Terfenilo/química , Secuencia de Aminoácidos , Arginina/química , Ácido Aspártico/química , Vías Biosintéticas , Catálisis , Cristalografía por Rayos X , Escherichia coli/metabolismo , Modelos Moleculares , Unión Proteica , Streptomyces/metabolismo , Relación Estructura-Actividad
19.
Mater Sci Eng C Mater Biol Appl ; 127: 112243, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34225883

RESUMEN

An effective delivery vehicle of genetic materials to their target site is the key to a successful gene therapy. In many cases, nanoparticles are used as the vehicle of choice and the efficiency of the delivery relies heavily on the physicochemical properties of the nanoparticles. Microfluidics, although being a low throughput method, has been increasingly researched for the preparation of nanoparticles. A range of superior properties were claimed in the literature for microfluidic-prepared platforms, but no evidence on direct comparison of the properties of the nanoparticles prepared by microfluidics and conventional high throughput method exists, leaving the industry with little guidance on how to select effective large-scale nanoparticle manufacturing method. This study used plasmid DNA-loaded PLGA-Eudragit nanoparticles as the model system to critically compare the nanoparticles prepared by conventional and microfluidics-assisted nanoprecipitation. The PLGA-Eudragit nanoparticles prepared by microfluidics were found to be statistically significantly larger than the ones prepared by conventional nanoprecipitation. PLGA-Eudragit nanoparticle prepared conventionally showed higher DNA loading efficiency. Although the DNA-loaded nanoparticles prepared by both methods did not induce significant cytotoxicity, the transfection efficiency was found to be higher for the ones prepared conventionally which has good potential for plasmid delivery. This study for the first time provides a direct comparison of the DNA-loaded nanoparticles prepared by microfluidic and conventional methods. The findings bring new insights into critical evaluation of the selection of manufacturing methods of nanoparticles for future gene therapy.


Asunto(s)
Microfluídica , Nanopartículas , ADN , Tamaño de la Partícula , Polímeros , Transfección
20.
J Clin Anesth ; 71: 110231, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33735670

RESUMEN

STUDY OBJECTIVE: Pulmonary arterial hypertension is commonly seen in children with left to right intracardiac shunts and affects the outcomes of cardiac surgery. Our study aimed to compare the efficacy of inhaled levosimendan (LS) versus intravenous LS in reducing elevated pulmonary artery pressure (PAP) in children scheduled for cardiac surgery. DESIGN: Non-inferiority, prospective, randomized, blinded, controlled study. SETTING: Operative room and intensive care unit (ICU), institutional children's hospital of Mansoura Faculty of Medicine, Egypt. PATIENTS: 50 patients of either sex, aged 1 to 5 years undergoing surgical repair of intracardiac left to right shunt complicated by pulmonary hypertension were recruited for the study. INTERVENTIONS: In the intravenous LS group, patients received intravenous infusion of LS a rate of 0.1 µg/kg/min and in the inhaled LS group, LS (36 µg/kg/6 h) was delivered by nebulization. MEASUREMENTS: The primary endpoint was systolic PAP, while the secondary endpoints were the heart rate, mean arterial blood pressure, dose of norepinephrine, time to extubation and ICU length of stay. MAIN RESULTS: Both intravenous and inhaled routes of LS similarly reduced the high systolic PAP over all time points of measurement and intravenous LS was associated with higher heart rate, lower arterial pressure and the need for a higher dose of norepinephrine than the inhaled LS. CONCLUSION: Inhalation of LS is non-inferior to intravenous LS in reducing high PAP in children who underwent on-pump cardiac surgery and it is associated with less tachycardia and hypotension with reduced need for vasoactive drugs.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Hipertensión Pulmonar , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Puente Cardiopulmonar , Niño , Egipto , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Infusiones Intravenosas , Estudios Prospectivos , Simendán/efectos adversos
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