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1.
ScientificWorldJournal ; 2023: 1954632, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37138904

RESUMO

The aim of the current research was to evaluate the effects of members of purple nonsulfur bacteria (PNSB), Rhodopseudomonas palustris strains of VNW02, TLS06, VNW64, and VNS89, mixed with spent rice straw (SRS) from mushroom cultivation as a carrier on promoting sesame growth and yield, and ameliorating the alluvial soil (AS) fertility in dykes. A 4 × 3 factorial experiment consisting of different levels of the solid PNSB biofertilizer mixture at 0, 3, 4, and 5 t·ha-1 (0, 1.81 × 108, 2.24 × 108, and 2.68 × 108 cells pot-1, respectively), and nitrogen (N) and phosphorus (P) inorganic fertilizer rates (100, 75, and 50 kg·N·ha-1; 60, 45, and 30 kg P2O5·ha-1, respectively) was performed in pots with the sesame variety of ADB1 in the dyked AS. The solid PNSB biofertilizer mixture at at least 3 t·ha-1 significantly enhanced the sesame seed yield by providing higher macronutrients for plants by increasing available N and soluble P concentrations in the soil. The solid PNSB biofertilizer mixture in addition to 75% of the recommended N and P fertilizers produced an equivalent yield in comparison to the utilized 100% of N and P inorganic fertilizers. The solid PNSB biofertilizer mixture in the SRS from the mushroom production reduced at least 25% of N and P chemical fertilizers for gaining the maximal seed yield and enriched soil characteristics for the sustainable black sesame cultivation in the dyked AS.


Assuntos
Agaricales , Oryza , Sesamum , Solo , Fertilizantes , Agricultura , Nitrogênio
2.
Phytopathology ; 112(2): 414-421, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34080915

RESUMO

Until recently, genotypes of Phytophthora infestans were regionally distributed in Europe, with populations in western Europe being dominated by clonal lineages and those in northern Europe being genetically diverse because of frequent sexual reproduction. However, since 2013 a new clonal lineage (EU_41_A2) has successfully established itself and expanded in the sexually recombining P. infestans populations of northern Europe. The objective of this study was to study phenotypic traits of the new clonal lineage of P. infestans, which may explain its successful establishment and expansion within sexually recombining populations. Fungicide sensitivity, aggressiveness, and virulence profiles of isolates of EU_41_A2 were analyzed and compared with those of the local sexual populations from Denmark, Norway, and Estonia. None of the phenotypic data obtained from the isolates collected from Denmark, Estonia, and Norway independently explained the invasive success of EU_41_A2 within sexual Nordic populations. Therefore, we hypothesize that the expansion of this new genotype could result from a combination of fitness traits and more favorable environmental conditions that have emerged in response to climate change.


Assuntos
Phytophthora infestans , Solanum tuberosum , Genótipo , Fenótipo , Phytophthora infestans/genética , Doenças das Plantas
3.
Exp Appl Acarol ; 88(3-4): 243-262, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36326982

RESUMO

In this study, we investigated if a steam treatment program used to produce disease-free strawberry transplants has the potential to also eliminate strawberry mite (Phytonemus pallidus) and two-spotted spider mite (Tetranychus urticae). Crowns of strawberry plants collected in a commercial field, containing young, folded leaves with all life stages of P. pallidus, and strawberry leaf discs on water agar with T. urticae with non-diapausing adult females and eggs from a laboratory rearing, were exposed to warm aerated steam in a steam cabinet in a series of four experimental runs over 2 years. The steam treatments constituted of a 1-h pre-treatment with 37 °C steam followed by a 1-h recovery period at 21-25 °C, and then a main steam treatment at 44 °C for either 2, 4 (both P. pallidus and T. urticae) or 6 h (the more heat tolerant T. urticae only). After steaming, the plant material with P. pallidus or T. urticae were incubated at 21-25 °C until survival was assessed after 1-6 days, depending on the mite species and life-stage. Non-steamed plant material with mites was used as controls. The 4-h treatment killed all P. pallidus eggs, larvae and adults, and the 2-h treatment killed all individuals in all three stages except for one egg in one of the runs. There were no or minor effects of the steam treatments on T. urticae adult and egg survival. Based on these results, the tested steam treatments may be used to eliminate the strawberry mite but not the two-spotted spider mite from strawberry planting material.


Assuntos
Fragaria , Tetranychidae , Animais , Vapor
4.
Drug Dev Ind Pharm ; 47(1): 22-35, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33185140

RESUMO

The aim of this study was the evaluation of the influence of bile salts and fatty acids, important components of intestinal fluids, on physical characteristics of self-emulsifying drug delivery systems (SEDDS) such as size, polydispersity (PDI), zeta potential (Zp), turbidity (T%), cloud point temperature (CPT) and drug release. At this purpose, nonionic (ni-SEDDS) and cationic (c-SEDDS) were emulsified in aqueous media containing increasing concentrations of bile salts (BS) and decanoate (Dec). Zp of ni-SEDDS and c-SEDDS became highly negative at 15 mM BS and Dec. Size of ni-SEDDS decreased of 112 nm and of 76 nm at 15 mM BS and Dec, respectively. Size of c-SEDDS decreased of 53 nm at 15 mM BS, but it was not affected by 15 mM Dec. PDI and T% of ni- and c-SEDDS were lowered as well. CPT of ni-SEDDS increased from 70 °C to 97 °C and 84 °C at 15 mM BS and Dec. CPT of c-SEDDS decreased from above 100 °C to 80 °C and to 85 °C at 1.5 mM BS and at 5 mM Dec, respectively. Generally, BS had a more pronounced effect on SEDDS Zp, size, PDI, T %, and CPT than Dec. The release of the model drug quinine was accelerated by BS and Dec. As BS and fatty acids affect the physical characteristics and drug release behavior of SEDDS, their impact should be addressed during the development process.


Assuntos
Ácidos e Sais Biliares , Sistemas de Liberação de Medicamentos , Ácidos Graxos/química , Liberação Controlada de Fármacos , Emulsões , Solubilidade
5.
Mol Carcinog ; 59(2): 193-201, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31782573

RESUMO

Gartanin, a 4-prenylated xanthone, has been identified from the purple mangosteen fruit as a potent growth inhibitor of various cancer cell lines, including prostate cancer. However, much of Gartanin's anticancer mechanism remains unknown. We have discovered that Gartanin docked onto the regulatory subunit of the precursor cell-expressed developmentally downregulated 8 (NEDD8)-activating enzyme (NAE) complex and next to the NEDD8 binding complex, which leads to inhibit NEDD8 conjugations to both Cullin1 and Ubc12 in prostate cancer cell lines and Ubc12 NEDDylation in an in vitro assay. The S phase kinase-associated protein (Skp2) and F-box and WD-repeat domain-containing 2 (FBXW2), the NEDD8 family members of E3 ubiqutin ligases, were also downregulated and upregulated by Gartainin, respectively. Knock-down of NEDD8 expression by short harpin (Sh) RNAs blocked or attenuated these effects of Gartainin. Finally, Gartanin demonstrated its ability to inhibit growth of prostate cancer lines via autophagy initiation. Our data support that Gartanin is a naturally occurring NEDDylation inhibitor and deserves further investigation for prostate cancer prevention and treatment.


Assuntos
Autofagia/efeitos dos fármacos , Proteínas F-Box/metabolismo , Proteína NEDD8/antagonistas & inibidores , Neoplasias da Próstata/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Xantonas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Proteínas F-Box/genética , Humanos , Masculino , Proteína NEDD8/metabolismo , Células PC-3 , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Interferência de RNA
6.
Sensors (Basel) ; 20(24)2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33333880

RESUMO

A thermal protection system (TPS) is designed and fabricated to protect a hypersonic vehicle from extreme conditions. Good condition of the TPS panels is necessary for the next flight mission. A loose bolted joint is a crucial defect in a metallic TPS panel. This study introduces an experimental method to investigate the dynamic characteristics and state of health of a metallic TPS panel through an operational modal analysis (OMA). Experimental investigations were implemented under free-free supports to account for a healthy state, the insulation effect, and fastener failures. The dynamic deformations resulted from an impulse force were measured using a non-contact three-dimensional point tracking (3DPT) method. Using changes in natural frequencies, the damping ratio, and operational deflection shapes (ODSs) due to the TPS failure, we were able to detect loose bolted joints. Moreover, we also developed an in-house program based on a modal assurance criterion (MAC) to detect the state of damage of test structures. In a damage state, such as a loose bolted joint, the stiffness of the TPS panel was reduced, which resulted in changes in the natural frequency and the damping ratio. The calculated MAC values were less than one, which pointed out possible damage in the test TPS panels. Our results also demonstrated that a combination of the 3DPT-based OMA method and the MAC achieved good robustness and sufficient accuracy in damage identification for complex aerospace structures such as TPS structures.

7.
Hum Mutat ; 40(10): 1664-1675, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31180159

RESUMO

Large scale human genome projects have created tremendous human genome databases for some well-studied populations. Vietnam has about 95 million people (the 14th largest country by population in the world) of which more than 86% are Kinh people. To date, genetic studies for Vietnamese people mostly rely on genetic information from other populations. Building a Vietnamese human genetic variation database is a must for properly interpreting Vietnamese genetic variants. To this end, we sequenced 105 whole genomes and 200 whole exomes of 305 unrelated Kinh Vietnamese (KHV) people. We also included 101 other previously published KHV genomes to build a Vietnamese human genetic variation database of 406 KHV people. The KHV database contains 24.81 million variants (22.47 million single nucleotide polymorphisms (SNPs) and 2.34 million indels) of which 0.71 million variants are novel. It includes more than 99.3% of variants with a frequency of >1% in the KHV population. Noticeably, the KHV database revealed 107 variants reported in the human genome mutation database as pathological mutations with a frequency above 1% in the KHV population. The KHV database (available at https://genomes.vn) would be beneficial for genetic studies and medical applications not only for the Vietnamese population but also for other closely related populations.


Assuntos
Povo Asiático/genética , Bases de Dados Genéticas , Variação Genética , Genoma Humano , Biologia Computacional/métodos , Genética Populacional , Humanos , Anotação de Sequência Molecular , Filogenia , Filogeografia , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes , Análise de Sequência de DNA , Vietnã , Sequenciamento do Exoma , Sequenciamento Completo do Genoma
8.
BMC Evol Biol ; 17(1): 136, 2017 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-28606055

RESUMO

BACKGROUND: Amino acid substitution models play an essential role in inferring phylogenies from mitochondrial protein data. However, only few empirical models have been estimated from restricted mitochondrial protein data of a hundred species. The existing models are unlikely to represent appropriately the amino acid substitutions from hundred thousands metazoan mitochondrial protein sequences. RESULTS: We selected 125,935 mitochondrial protein sequences from 34,448 species in the metazoan kingdom to estimate new amino acid substitution models targeting metazoa, vertebrates and invertebrate groups. The new models help to find significantly better likelihood phylogenies in comparison with the existing models. We noted remarkable distances from phylogenies with the existing models to the maximum likelihood phylogenies that indicate a considerable number of incorrect bipartitions in phylogenies with the existing models. Finally, we used the new models and mitochondrial protein data to certify that Testudines, Aves, and Crocodylia form one separated clade within amniotes. CONCLUSIONS: We introduced new mitochondrial amino acid substitution models for metazoan mitochondrial proteins. The new models outperform the existing models in inferring phylogenies from metazoan mitochondrial protein data. We strongly recommend researchers to use the new models in analysing metazoan mitochondrial protein data.


Assuntos
Invertebrados/genética , Modelos Genéticos , Filogenia , Vertebrados/genética , Substituição de Aminoácidos , Animais , Evolução Molecular , Humanos , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Homologia de Sequência de Aminoácidos
9.
BMC Bioinformatics ; 17: 22, 2016 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-26740458

RESUMO

BACKGROUND: Taxonomic assignment is a crucial step in a metagenomic project which aims to identify the origin of sequences in an environmental sample. Among the existing methods, since composition-based algorithms are not sufficient for classifying short reads, recent algorithms use only the feature of similarity, or similarity-based combined features. However, those algorithms suffer from the computational expense because the task of similarity search is very time-consuming. Besides, the lack of similarity information between reads and reference sequences due to the length of short reads reduces significantly the classification quality. RESULTS: This paper presents a novel taxonomic assignment algorithm, called SeMeta, which is based on semi-supervised learning to produce a fast and highly accurate classification of short-length reads with sufficient mutual overlap. The proposed algorithm firstly separates reads into clusters using their composition feature. It then labels the clusters with the support of an efficient filtering technique on results of the similarity search between their reads and reference databases. Furthermore, instead of performing the similarity search for all reads in the clusters, SeMeta only does for reads in their subgroups by utilizing the information of sequence overlapping. The experimental results demonstrate that SeMeta outperforms two other similarity-based algorithms on different aspects. CONCLUSIONS: By using a semi-supervised method as well as taking the advantages of various features, the proposed algorithm is able not only to achieve high classification quality, but also to reduce much computational cost. The source codes of the algorithm can be downloaded at http://it.hcmute.edu.vn/bioinfo/metapro/SeMeta.html.


Assuntos
Algoritmos , Metagenômica/métodos , Composição de Bases , Análise por Conglomerados , Bases de Dados Factuais , Humanos , Modelos Moleculares , Família Multigênica , Reprodutibilidade dos Testes
10.
Biol Lett ; 12(7)2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27405382

RESUMO

We studied the evolution of developmental plasticity in populations of Drosophila melanogaster that evolved at either constant or fluctuating temperatures. Consistent with theory, genotypes that evolved at a constant 16°C or 25°C performed best when raised and tested at that temperature. Genotypes that evolved at fluctuating temperatures performed well at either temperature, but only when raised and tested at the same temperature. Our results confirm evolutionary patterns predicted by theory, including a loss of plasticity and a benefit of specialization in constant environments.


Assuntos
Evolução Biológica , Drosophila melanogaster/genética , Voo Animal/fisiologia , Adaptação Fisiológica/genética , Animais , Drosophila melanogaster/fisiologia , Feminino , Masculino , Temperatura
12.
BMC Bioinformatics ; 15: 341, 2014 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-25344302

RESUMO

BACKGROUND: Amino acid replacement rate matrices are a crucial component of many protein analysis systems such as sequence similarity search, sequence alignment, and phylogenetic inference. Ideally, the rate matrix reflects the mutational behavior of the actual data under study; however, estimating amino acid replacement rate matrices requires large protein alignments and is computationally expensive and complex. As a compromise, sub-optimal pre-calculated generic matrices are typically used for protein-based phylogeny. Sequence availability has now grown to a point where problem-specific rate matrices can often be calculated if the computational cost can be controlled. RESULTS: The most time consuming step in estimating rate matrices by maximum likelihood is building maximum likelihood phylogenetic trees from protein alignments. We propose a new procedure, called FastMG, to overcome this obstacle. The key innovation is the alignment-splitting algorithm that splits alignments with many sequences into non-overlapping sub-alignments prior to estimating amino acid replacement rates. Experiments with different large data sets showed that the FastMG procedure was an order of magnitude faster than without splitting. Importantly, there was no apparent loss in matrix quality if an appropriate splitting procedure is used. CONCLUSIONS: FastMG is a simple, fast and accurate procedure to estimate amino acid replacement rate matrices from large data sets. It enables researchers to study the evolutionary relationships for specific groups of proteins or taxa with optimized, data-specific amino acid replacement rate matrices. The programs, data sets, and the new mammalian mitochondrial protein rate matrix are available at http://fastmg.codeplex.com.


Assuntos
Algoritmos , Substituição de Aminoácidos , Evolução Molecular , Funções Verossimilhança , Animais , Filogenia , Probabilidade , Proteínas/química , Proteínas/genética
15.
Plast Reconstr Surg Glob Open ; 12(7): e5941, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38957724

RESUMO

Background: Rhinoplasty in patients with previous unilateral cleft lip repair is a surgical challenge due to complex nasal deformities, including a horizontally positioned nasal wing, wide cleft side nostrils, nasal base defects, and a short and deviated nasal columella. To comprehensively address these complexities, we exclusively utilized autologous costal cartilage in rhinoplasty procedures, using various surgical techniques. Methods: This study presents a comprehensive case series of 39 patients who had previously undergone unilateral cleft lip surgery but still had nasal deformities. Rhinoplasty using autologous costal cartilage was performed at Cho Ray Hospital, Vietnam. Costal cartilage was partially crushed and then finely cut to shape the dorsal area and raise the nasal base on the cleft side. Partially crushed cartilage was also used to shape shield grafts, cap grafts, and alar batten grafts, whereas sliced cartilage was utilized for septal extension grafts. Evaluation was based on improvements in anthropometric indicators, patient satisfaction using Rhinoplasty Outcome Evaluation (ROE) scale and FACE-Q scores. Results: The average age of patients was 25.13 years. All postoperative anthropometric indicators showed significant improvements. Postsurgery, the total ROE score was three times higher than before surgery (P < 0.001), and the total FACE-Q score was 2.26 times higher (P < 0.001). No significant intraoperative or postoperative complications were observed. Conclusions: This procedure effectively addresses complex nasal deformities in patients with prior unilateral cleft lip repair, emphasizing the value of autologous costal cartilage in rhinoplasty for such individuals.

16.
J Biomed Opt ; 29(5): 052918, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38282917

RESUMO

Significance: Preterm birth is defined as a birth before 37 weeks of gestation and is one of the leading contributors to infant mortality rates globally. Premature birth can lead to life-long developmental impairment for the child. Unfortunately, there is a significant lack of tools to diagnose preterm birth risk, which limits patient care and the development of new therapies. Aim: To develop a speculum-free, portable preterm imaging system (PPRIM) for cervical imaging; testing of the PPRIM system to resolve polarization properties of birefringent samples; and testing of the PPRIM under an IRB on healthy, non-pregnant volunteers for visualization and polarization analysis of cervical images. Approach: The PPRIM can perform 4×3 Mueller-matrix imaging to characterize the remodeling of the uterine cervix during pregnancy. The PPRIM is built with a polarized imaging probe and a flexible insertable sheath made with a compatible flexible rubber-like material to maximize comfort and ease of use. Results: The PPRIM device is developed to meet specific design specifications as a speculum-free, portable, and comfortable imaging system with polarized imaging capabilities. This system comprises a main imaging component and a flexible silicone inserter. The inserter is designed to maximize comfort and usability for the patient. The PPRIM shows high-resolution imaging capabilities at the 20 mm working distance and 25 mm circular field of view. The PPRIM demonstrates the ability to resolve birefringent sample orientation and full field capture of a healthy, non-pregnant cervix. Conclusion: The development of the PPRIM aims to improve access to the standard of care for women's reproductive health using polarized Mueller-matrix imaging of the cervix and reduce infant and maternal mortality rates and better quality of life.


Assuntos
Nascimento Prematuro , Gravidez , Lactente , Criança , Recém-Nascido , Feminino , Humanos , Qualidade de Vida , Colo do Útero/diagnóstico por imagem
17.
PeerJ ; 12: e16943, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38770100

RESUMO

The aim of the current study was to assess the potency of the exopolymeric substances (EPS)-secreting purple non-sulfur bacteria (PNSB) on rice plants on acidic salt-affected soil under greenhouse conditions. A two-factor experiment was conducted following a completely randomized block design. The first factor was the salinity of the irrigation, and the other factor was the application of the EPS producing PNSB (Luteovulum sphaeroides EPS18, EPS37, and EPS54), with four replicates. The result illustrated that irrigation of salt water at 3-4‰ resulted in an increase in the Na+ accumulation in soil, resulting in a lower rice grain yield by 12.9-22.2% in comparison with the 0‰ salinity case. Supplying the mixture of L. sphaeroides EPS18, EPS37, and EPS54 increased pH by 0.13, NH4+ by 2.30 mg NH4+ kg-1, and available P by 8.80 mg P kg-1, and decreased Na+ by 0.348 meq Na+ 100 g-1, resulting in improvements in N, P, and K uptake and reductions in Na uptake, in comparison with the treatment without bacteria. Thus, the treatments supplied with the mixture of L. sphaeroides EPS18, EPS37, and EPS54 resulted in greater yield by 27.7% than the control treatment.


Assuntos
Oryza , Microbiologia do Solo , Solo , Oryza/microbiologia , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Solo/química , Salinidade , Estresse Salino , Proteobactérias/metabolismo , Concentração de Íons de Hidrogênio , Sódio/metabolismo , Sódio/farmacologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-38411893

RESUMO

Due to its versatility in formulation and manufacturing, self-emulsifying drug delivery systems (SEDDS) can be used to design parenteral formulations. Therefore, it is necessary to understand the effects of excipients on the behavior of SEDDS formulations upon parenteral administration, particularly their interactions with blood plasma and cell membranes. In this study, we prepared three neutrally charged SEDDS formulations composed of medium-chain triglycerides as the oil phase, polyoxyl-35 castor oil (EL35) and polyethylene glycol (15)-hydroxystearate (HS15) as the nonionic surfactants, medium-chain mono- and diglycerides as the co-surfactant, and propylene glycol as the co-solvent. The cationic surfactant, didodecyldimethylammonium bromide (DDA), and the anionic surfactant, sodium deoxycholate (DEO), were added to the neutral SEDDS preconcentrates to obtain cationic and anionic SEDDS, respectively. SEDDS were incubated with human blood plasma and recovered by size exclusion chromatography. Data showed that SEDDS emulsion droplets can bind plasma protein to different extents depending on their surface charge and surfactant used. At pH 7.4, the least protein binding was observed with anionic SEDDS. Positive charges increased protein binding. SEDDS stabilized by HS15 can adsorb more plasma protein and induce more plasma membrane disruption activity than SEDDS stabilized by EL35. These effects were more pronounced with the HS15 + DDA combination. The addition of DDA and DEO to SEDDS increased plasma membrane disruption (PMD) activities, and DDA (1% w/w) was more active than DEO (2% w/w). PMD activities of SEDDS were concentration-dependent and vanished at appropriate dilution ratios.

19.
PLoS One ; 19(3): e0290936, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451970

RESUMO

Autism spectrum disorder (ASD) is a developmental disorder with a prevalence of around 1% children worldwide and characterized by patient behaviour (communication, social interaction, and personal development). Data on the efficacy of diagnostic tests using copy number variations (CNVs) in candidate genes in ASD is currently around 10% but it is overrepresented by patients of Caucasian background. We report here that the diagnostic success of de novo candidate CNVs in Vietnamese ASD patients is around 6%. We recruited one hundred trios (both parents and a child) where the child was clinically diagnosed with ASD while the parents were not affected. We performed genetic screening to exclude RETT syndrome and Fragile X syndrome and performed genome-wide DNA microarray (aCGH) on all probands and their parents to analyse for de novo CNVs. We detected 1708 non-redundant CNVs in 100 patients and 118 (7%) of them were de novo. Using the filter for known CNVs from the Simons Foundation Autism Research Initiative (SFARI) database, we identified six CNVs (one gain and five loss CNVs) in six patients (3 males and 3 females). Notably, 3 of our patients had a deletion involving the SHANK3 gene-which is the highest compared to previous reports. This is the first report of candidate CNVs in ASD patients from Vietnam and provides the framework for building a CNV based test as the first tier screening for clinical management.


Assuntos
Transtorno do Espectro Autista , Masculino , Criança , Feminino , Humanos , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/genética , Variações do Número de Cópias de DNA/genética , Vietnã/epidemiologia , Análise de Sequência com Séries de Oligonucleotídeos , Genômica , DNA
20.
ACS Appl Bio Mater ; 7(6): 3877-3889, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38832760

RESUMO

Adjuvants and immunomodulators that effectively drive a Th17-skewed immune response are not part of the standard vaccine toolkit. Vaccine adjuvants and delivery technologies that can induce Th17 or Th1/17 immunity and protection against bacterial pathogens, such as tuberculosis (TB), are urgently needed. Th17-polarized immune response can be induced using agonists that bind and activate C-type lectin receptors (CLRs) such as macrophage inducible C-type lectin (Mincle). A simple but effective strategy was developed for codelivering Mincle agonists with the recombinant Mycobacterium tuberculosis fusion antigen, M72, using tunable silica nanoparticles (SNP). Anionic bare SNP, hydrophobic phenyl-functionalized SNP (P-SNP), and cationic amine-functionalized SNP (A-SNP) of different sizes were coated with three synthetic Mincle agonists, UM-1024, UM-1052, and UM-1098, and evaluated for adjuvant activity in vitro and in vivo. The antigen and adjuvant were coadsorbed onto SNP via electrostatic and hydrophobic interactions, facilitating multivalent display and delivery to antigen presenting cells. The cationic A-SNP showed the highest coloading efficiency for the antigen and adjuvant. In addition, the UM-1098-adsorbed A-SNP formulation demonstrated slow-release kinetics in vitro, excellent stability over 12 months of storage, and strong IL-6 induction from human peripheral blood mononuclear cells. Co-adsorption of UM-1098 and M72 on A-SNP significantly improved antigen-specific humoral and Th17-polarized immune responses in vivo in BALB/c mice relative to the controls. Taken together, A-SNP is a promising platform for codelivery and proper presentation of adjuvants and antigens and provides the basis for their further development as a vaccine delivery platform for immunization against TB or other diseases for which Th17 immunity contributes to protection.


Assuntos
Antígenos de Bactérias , Lectinas Tipo C , Nanopartículas , Dióxido de Silício , Células Th17 , Lectinas Tipo C/metabolismo , Lectinas Tipo C/imunologia , Lectinas Tipo C/agonistas , Nanopartículas/química , Células Th17/imunologia , Animais , Dióxido de Silício/química , Camundongos , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/química , Mycobacterium tuberculosis/imunologia , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Tamanho da Partícula , Teste de Materiais , Humanos , Feminino , Proteínas de Membrana/imunologia , Proteínas de Membrana/agonistas
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