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1.
Brain Behav Immun ; 119: 394-407, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38608743

RESUMEN

Chronic infection with Toxoplasma gondii (T. gondii) emerges as a risk factor for neurodegenerative diseases in animals and humans. However, the underlying mechanisms are largely unknown. We aimed to investigate whether gut microbiota and its metabolites play a role in T. gondii-induced cognitive deficits. We found that T. gondii infection induced cognitive deficits in mice, which was characterized by synaptic ultrastructure impairment and neuroinflammation in the hippocampus. Moreover, the infection led to gut microbiota dysbiosis, barrier integrity impairment, and inflammation in the colon. Interestingly, broad-spectrum antibiotic ablation of gut microbiota attenuated the adverse effects of the parasitic infection on the cognitive function in mice; cognitive deficits and hippocampal pathological changes were transferred from the infected mice to control mice by fecal microbiota transplantation. In addition, the abundance of butyrate-producing bacteria and the production of serum butyrate were decreased in infected mice. Interestingly, dietary supplementation of butyrate ameliorated T. gondii-induced cognitive impairment in mice. Notably, compared to the healthy controls, decreased butyrate production was observed in the serum of human subjects with high levels of anti-T. gondii IgG. Overall, this study demonstrates that gut microbiota is a key regulator of T. gondii-induced cognitive impairment.


Asunto(s)
Disfunción Cognitiva , Disbiosis , Microbioma Gastrointestinal , Hipocampo , Toxoplasma , Toxoplasmosis , Animales , Ratones , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/etiología , Disfunción Cognitiva/microbiología , Toxoplasmosis/metabolismo , Toxoplasmosis/complicaciones , Disbiosis/metabolismo , Humanos , Masculino , Hipocampo/metabolismo , Ratones Endogámicos C57BL , Trasplante de Microbiota Fecal/métodos , Butiratos/metabolismo , Femenino , Cognición/fisiología
2.
Artículo en Inglés | MEDLINE | ID: mdl-38457327

RESUMEN

We present a general, fast, and practical solution for interpolating novel views of diverse real-world scenes given a sparse set of nearby views. Existing generic novel view synthesis methods rely on time-consuming scene geometry pre-computation or redundant sampling of the entire space for neural volumetric rendering, limiting the overall efficiency. Instead, we incorporate learned MVS priors into the neural volume rendering pipeline while improving the rendering efficiency by reducing sampling points under the guidance of depth probability distributions. Specifically, fewer but important points are sampled under the guidance of depth probability distributions extracted from the learned MVS architecture. Based on the learned probability-guided sampling, we develop a sophisticated neural volume rendering module that effectively integrates source view information with the learned scene structures. We further propose confidence-aware refinement to improve the rendering results in uncertain, occluded, and unreferenced regions. Moreover, we build a four-view camera system for holographic display and provide a real-time version of our framework for free-viewpoint experience, where novel view images of a spatial resolution of 512×512 can be rendered at around 20 fps on a single GTX 3090 GPU. Experiments show that our method achieves 15 to 40 times faster rendering compared to state-of-the-art baselines, with strong generalization capacity and comparable high-quality novel view synthesis performance.

3.
Microb Pathog ; 186: 106484, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38052278

RESUMEN

Sexual reproduction plays a crucial role in the transmission and life cycle of toxoplasmosis. The merozoites are the only developmental stage capable of differentiation into male and female gametes, thereby initiating sexual reproduction to form oocysts that are excreted into the environment. Hence, our study aimed to perform proteomic analyses of T. gondii Pru strain merozoites, a pre-sexual developmental stage in cat IECs, and tachyzoites, an asexual developmental stage, using the tandem mass tag (TMT) method in order to identify the differentially expressed proteins (DEPs) of merozoites. Proteins functions were subjected to cluster analysis, and DEPs were validated through the qPCR method. The results showed that a total of 106 proteins were identified, out of which 85 proteins had quantitative data. Among these, 15 proteins were differentially expressed within merozoites, with four exhibiting up-regulation and being closely associated with the material and energy metabolism as well as the cell division of T. gondii. Two novel DEPs, namely S8GHL5 and A0A125YP41, were identified, and their homologous family members have been demonstrated to play regulatory roles in oocyte maturation and spermatogenesis in other species. Therefore, they may potentially exhibit regulatory functions during the differentiation of micro- and macro-gametophytes at the initiation stage of sexual reproduction in T. gondii. In conclusion, our results showed that the metabolic and divisional activities in the merozoites surpass those in the tachyzoites, thereby providing structural, material, and energetic support for gametophytes development. The discovery of two novel DEPs associated with sexual reproduction represents a significant advancement in understanding Toxoplasma sexual reproduction initiation and oocyst formation.


Asunto(s)
Parásitos , Toxoplasma , Animales , Masculino , Femenino , Toxoplasma/genética , Toxoplasma/química , Merozoítos/química , Merozoítos/metabolismo , Proteómica/métodos , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Oocistos , Reproducción , Factores de Transcripción/metabolismo
4.
PLoS Negl Trop Dis ; 17(9): e0011102, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37721957

RESUMEN

Toxoplasma gondii (T. gondii) is an opportunistic parasite that can infect the central nervous system (CNS), causing severe toxoplasmosis and behavioral cognitive impairment. Mortality is high in immunocompromised individuals with toxoplasmosis, most commonly due to reactivation of infection in the CNS. There are still no effective vaccines and drugs for the prevention and treatment of toxoplasmosis. There are five developmental stages for T. gondii to complete life cycle, of which the tachyzoite and bradyzoite stages are the key to the acute and chronic infection. In this study, to better understanding of how T. gondii interacts with the host CNS at different stages of infection, we constructed acute and chronic infection models of T. gondii in astrocytes, and used label-free proteomics to detect the proteome changes before and after infection, respectively. A total of 4676 proteins were identified, among which 163 differentially expressed proteins (fold change ≥ 1.5 or ≤ 0.67 and p-value ≤ 0.05) including 109 up-regulated proteins and 54 down-regulated proteins in C8-TA vs C8 group, and 719 differentially expressed proteins including 495 up-regulated proteins and 224 down-regulated proteins in C8-BR vs C8-TA group. After T. gondii tachyzoites infected astrocytes, differentially expressed proteins were enriched in immune-related biological processes to promote the formation of bradyzoites and maintain the balance of T. gondii, CNS and brain. After T. gondii bradyzoites infected astrocytes, the differentially expressed proteins up-regulated the host's glucose metabolism, and some up-regulated proteins were strongly associated with neurodegenerative diseases. These findings not only provide new insights into the psychiatric pathogenesis of T. gondii, but also provide potential targets for the treatment of acute and chronic Toxoplasmosis.

5.
J Cell Mol Med ; 27(20): 3107-3116, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37537752

RESUMEN

Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive disease manifested with recurrent infections of respiratory tract and infertility. DNAAF3 is identified as a novel gene associated with PCD and different mutations in DNAAF3 results in different clinical features of PCD patients, such as situs inversus, sinusitis and bronchiectasis. However, the sperm phenotypic characteristics of PCD males are generally poorly investigated. Our reproductive medicine centre received a case of PCD patient with infertility, who presented with sinusitis, recurrent infections of the lower airway and severe asthenozoospermia; However, no situs inversus was found in the patient. A novel homozygous mutation in DNAAF3(c.551T>A; p.V184E) was identified in the PCD patient by whole-exome sequencing. Subsequent Sanger sequencing further confirmed that the DNAAF3 had a homozygous missense variant in the fifth exon. Transmission electron microscopy and immunostaining analysis of the sperms from the patient showed a complete absence of outer dynein arms and partial absence of inner dynein arms, which resulted in the reduction in sperm motility. However, this infertility was overcome by intracytoplasmic sperm injections, as his wife achieved successful pregnancy. These findings showed that the PCD-associated pathogenic mutation within DNAAF3 also causes severe asthenozoospermia and male infertility ultimately due to sperm flagella axoneme defect in humans. Our study not only contributes to understand the sperm phenotypic characteristics of patients with DNAAF3 mutations but also expands the spectrum of DNAAF3 mutations and may contribute to the genetic diagnosis and therapy for infertile patient with PCD.

6.
Parasitol Res ; 122(7): 1695-1699, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37199766

RESUMEN

Due to the increasing number of returnees from malaria endemic areas, imported malaria has become a public health challenge in China. To better understand the characteristics of imported Plasmodium species and adjust appropriate strategies for malaria prevention and control in Eastern China, we conducted molecular detection and species identification on 1282 imported malaria cases in Shandong Province between 2012 and 2018. The findings showed that P. falciparum was predominant, particularly in cases imported from Africa. P. vivax was the dominant species imported from Asian countries. Additionally, imported P. ovale and P. malariae emerged in the province. Further surveillance and control of imported malaria among returnees from Africa and Southeast Asia is needed to be strengthened in Eastern China.


Asunto(s)
Malaria Falciparum , Malaria Vivax , Malaria , Plasmodium , Humanos , Malaria/diagnóstico , Malaria/epidemiología , Malaria/prevención & control , Plasmodium/genética , África , China/epidemiología
7.
Drug Discov Ther ; 17(1): 37-44, 2023 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-36843076

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious threat to global development. Rapid and accurate diagnosis is critical for containing the pandemic and treating patients in time. As the gold standard for SARS-CoV-2 diagnosis, the qualitative reverse transcription-PCR (RT-qPCR) test has long been criticized for its long detection time. In this study, we optimized the primers and probes targeting SARS-CoV-2 ORF1ab and N gene designed by the Chinese Center for Disease Control and Preventions (CDC) to increase their Tm values to meet the optimal elongation temperature of Taq DNA polymerase, thus greatly shortened the elongation time. The higher elongation temperature in turn narrowed the temperature range of the reaction and saved more time. In addition, by shortening the distance between the fluorophore at the 5' end and the quencher in the middle we got a probe with higher signal-to-noise ratio. Finally, by using all these measures and optimized RT-qPCR program we successfully reduced the time (nucleic acid extraction step is not included) for nucleic acid test from 74 min to 26 min.


Asunto(s)
COVID-19 , Ácidos Nucleicos , Humanos , SARS-CoV-2 , COVID-19/diagnóstico , Prueba de COVID-19 , ARN Viral/genética , Sensibilidad y Especificidad , Reacción en Cadena en Tiempo Real de la Polimerasa
8.
ERJ Open Res ; 8(4)2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36267898

RESUMEN

Background: Respiratory oscillometry is a promising complement to the traditional pulmonary function tests for its simplicity. The usefulness of oscillometry in adult clinical practice has not been clarified. This study aimed to analyse the characteristics and diagnostic performance of oscillometry in respiratory diseases, and explore the cut-offs of oscillometric parameters for severity grading. Methods: In this multicentre registry of impulse oscillometry (IOS), IOS and spirometric data of healthy individuals and patients with respiratory diseases were collected and analysed. Linear mixed model analysis was performed to explore the effects of disease and forced expiratory volume in 1 s (FEV1) on oscillometric parameters. Results: The study included 567 healthy subjects, 781 asthmatic patients, 688 patients with chronic obstructive pulmonary disease (COPD), 109 patients with bronchiectasis, 40 patients with upper airway obstruction (UAO) and 274 patients with interstitial lung disease (ILD) in the analysis. Compared at the same FEV1 level, asthma, COPD, bronchiectasis, UAO and ILD displayed different oscillometric characteristics. The z-score of resistance at 5 Hz (R 5) was the best variable to identify respiratory diseases with a sensitivity of 62.4-66.7% and a specificity of 81.5-90.3%. With reference to the severity grading cut-offs of FEV1, R 5 z-scores of 2.5 and 4 were defined as the cut-off values of moderately and severely increased R 5. Conclusion: Respiratory oscillometry is more appropriate to be a tool of evaluating, rather than of diagnosing, respiratory diseases. A severity grading system of oscillometric parameters was developed to help the interpretation of oscillometry in clinical practice.

9.
Korean J Parasitol ; 60(4): 241-246, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36041485

RESUMEN

Felids are the unique definitive host of Toxoplasma gondii. The intestine of felid is the only site for initiating Toxoplasma gondii sexual reproduction. T. gondii excretes millions of infectious oocysts from the intestine, which are the primary source of infection. There are many difficulties in developing vaccines and drugs to control oocyst excretion due to the lack of an appropriate experimental model. Here, we established an in vitro feline intestinal epithelial cell (IEC) infection system and an efficient animal model of T. gondii Chinese 1 genotype, Wh6 strain (TgCtwh6). The Kunming mice brain tissues containing TgCtwh6 cysts were harvested 42-day post-infection. The bradyzoites were co-cultured with cat IECs in vitro at a ratio of 1:10. Five 3-month-old domestic cats were orally inoculated with 600 cysts each. The oocysts were detected by daily observation of cat feces by microscopy and polymerase chain reaction. We found that the parasite adhered and invaded cat IECs in vitro, transformed into tachyzoites, and then divided to form rose-like structures. These parasites eventually destroyed host cells, escaped, and finished the asexual reproduction process. Schizonts associated with sexual reproduction have not been observed during development in vitro cultured cells. However, schizonts were detected in all infected cat intestinal epithelial cells, and oocysts were presented in all cat feces. Our study provides a feasible cell model and an efficient infection system for the following studies of T. gondii sexual reproduction, and also lays a foundation to develop drugs and vaccines for blocking excretion and transmission of oocysts.


Asunto(s)
Enfermedades de los Gatos , Toxoplasma , Toxoplasmosis Animal , Animales , Gatos , China , Células Epiteliales , Heces/parasitología , Genotipo , Intestinos , Ratones , Oocistos , Toxoplasmosis Animal/parasitología
10.
Microorganisms ; 10(6)2022 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-35744722

RESUMEN

Green tides caused by Ulva prolifera occur annually in the Yellow Sea, potentially influencing the marine microorganisms. Here, we focused on the variations in marine bacterial and archaeal communities during an U. prolifera green tide in coastal Qingdao areas with Illumina high-throughput sequencing analysis. Our results revealed that the diversity and structure of bacterial and archaeal communities, as well as the organization and structure of microbial co-occurrence networks, varied during the green tide. The decline phase may be favorable to the bacterial and archaeal diversity and richness. The bacterial community, as well as the archaeal community, showed clear variations between the outbreak and decline phases. A simpler and less connected microbial co-occurrence network was observed during the outbreak phase compared with the decline phase. Flavobacteriales and Rhodobacterales separately dominated the bacterial community during the outbreak and decline phase, and Marine Group II (MGII) dominated the archaeal community during the green tide. Combined with microbial co-occurrence network analysis, Flavobacteriales, Rhodobacterales and MGII may be important organisms during the green tide. Temperature, chlorophyll a content and salinity may have an important impact on the variations in bacterial and archaeal communities during the green tide.

11.
Front Cell Infect Microbiol ; 12: 803502, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35237531

RESUMEN

Toxoplasma gondii is known to have a complex life cycle and infect almost all kinds of warm-blooded animals around the world. The brain of the host could be persistently infected by cerebral cysts, and a variety of psychiatric disorders such as schizophrenia and suicide have been reported to be related with latent toxoplasmosis. The infected animals showed fear reduction and a tendency to be preyed upon. However, the mechanism of this "parasites manipulation" effects have not been elucidated. Here, we reviewed the recent infection prevalence of toxoplasmosis and the evidence of mental and behavioral disorders induced by T. gondii and discussed the related physiological basis including dopamine dysregulation and gamma-aminobutyric acid (GABA) pathway and the controversial opinion of the necessity for cerebral cysts existence. Based on the recent advances, we speculated that the neuroendocrine programs and neurotransmitter imbalance may play a key role in this process. Simultaneously, studies in the evaluation of the expression pattern of related genes, long noncoding RNAs (lncRNAs), and mRNAs of the host provides a new point for understanding the mechanism of neurotransmitter dysfunction induced by parasite manipulation. Therefore, we summarized the animal models, T. gondii strains, and behavioral tests used in the related epigenetic studies and the responsible epigenetic processes; pinpointed opportunities and challenges in future research including the causality evidence of human psychiatric disorders, the statistical analysis for rodent-infected host to be more vulnerable preyed upon; and identified responsible genes and drug targets through epigenetics.


Asunto(s)
Epigénesis Genética , Trastornos Mentales , Toxoplasma , Toxoplasmosis , Animales , Humanos , Trastornos Mentales/genética , Trastornos Mentales/parasitología , ARN Mensajero/genética , Toxoplasma/genética , Toxoplasmosis/psicología , Toxoplasmosis Animal/psicología
12.
Parasitol Res ; 121(1): 461-464, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34750654

RESUMEN

Malaria is one of the most important parasitic diseases that causes a serious public health problem. The genetic diversity of malaria parasites may affect malaria transmission and malaria control strategies. In China, imported malaria was significantly increased in recent years, among which numerous migrant workers were infected with Plasmodium falciparum from Africa. However, little was known about genetic diversity of these populations in China. In this study, we evaluated genetic polymorphism and allele frequencies of msp1, msp2, and glurp genes in P. falciparum among Chinese migrant workers returnee from Africa between 2013 and 2017. Of the 381 P. falciparum isolates, 89.0% for msp1 gene, 71.7% for msp2 gene, and 78.0% for glurp gene were successfully genotyped. In msp1, 29 different alleles were observed, among which the K1 allelic family (71.7%) was predominant. In msp2, 21 different alleles were detected, of which the 3D7 allelic family (91.2%) was more frequent than FC27 allelic family (72.5%). For glurp, 12 individual alleles were detected in the samples. Taken together, the findings showed a high genetic diversity of these isolates, which provided the baseline data for African P. falciparum population imported to China.


Asunto(s)
Malaria Falciparum , Migrantes , África , Alelos , Antígenos de Protozoos , China , Variación Genética , Genotipo , Humanos , Plasmodium falciparum/genética , Proteínas Protozoarias/genética
13.
Artículo en Chino | MEDLINE | ID: mdl-34672464

RESUMEN

Objective: Pulmonary function testing (PFT) and electrocardiograph (ECG) are the vital components of the cardiopulmonary exercise test (CPET). This study is to investigate clinical characteristics of abnormal PFT as pulmonary ventilation dysfunction, small airway dysfunction and gas exchange (diffusion) dysfunction. Methods: Across-sectional study was conducted The 76 698 outpatient subjects who received health examination from December 2016 to February 2019 in Henan Provincial People's Hospital were recruited. The results of the ECG, PFT were compared among different sex and age sub-groups. Then the severity of their impaired PFT were analyzed. Results: Among 76 698 subjects, 39 237 subjects were male and 37 461 subjects were female. There were total 71.04% patients with abnormal ECG. There were total 28 273 (36.86%) patients with abnormal pulmonary ventilation function. The 17 570 patients (44.78%) (17 570/39 237) were male, 10 703 patients (28.57%) (10 703/37 461) were female, both the number and percentage of abnormal pulmonary ventilation function in male was significantly more than these in female (P<0.01). The percentage detectable rates of male were significant higher than that of female in all the different age sub-groups: 20~29, 30~39, 40~49, 50~59, 60~69 and ≥70 year (P<0.01). The total detectable abnormal rate of small airway dysfunction were 43 160 and 56.26% (43 160/76 698). The 57.73% (22 661/39 237) in male was significantly higher than 54.72% (20 499/37 461) in female (x2=74.87, P<0.01). The detectable abnormal rate of small airway dysfunction in male were lower than female in 30~39 year and 40~49year sub-groups (P<0.05), but were significantly higher in 20~29, 50~59, 60~69, and ≥70 yr sub-groups (P<0.05). Abnormal gas exchange (diffusion) dysfunction were detected in 28.54% (12 940/45 107) subjects. They were 7 433 (30.55%) in male,and 5 507 (26.50%)in female with significant gender difference (P<0.05). The abnormal diffusion detectable rate in 30~39 year sub-group was significant higher in female than in male (P<0.05), and were slightly higher without significant difference in 20~29 and 40~49 year sub-groups (P>0.05), but were significant lower in female than male in 50~59, 60~69 and ≥70 year sub-groups (P<0.05). Conclusion: The abnormal detectable rates in ECG, pulmonary ventilation dysfunction, gas exchange dysfunction and small airway dysfunction were higher in male than female, and higher in elder ≥70 year subgroup than all other younger age subgroups.


Asunto(s)
Prueba de Esfuerzo , Pulmón , Anciano , Femenino , Humanos , Masculino , Examen Físico , Ventilación Pulmonar , Pruebas de Función Respiratoria
14.
Exp Cell Res ; 400(1): 112507, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33545131

RESUMEN

Macrophage mediated inflammation and foam cell formation play crucial roles in the development of atherosclerosis. MiR-375 is a small noncoding RNA that significantly implicated in multiple tumor regulation and has been emerged as a novel biomarker for type 2 diabetes. However, the exact role of miR-375 on macrophage activation remains unknown. In the present study, we observed that miR-375 expression showed an up-regulated expression in atherosclerotic aortas, as well as in bone marrow derived macrophages (BMDMs) and mouse peritoneal macrophages (MPMs) isolated from ApoE deficiency mice and was gradually increased followed the Ox-LDL treated time. Functionally, miR-375 inhibition significantly decreased foam cell formation accompanied by up-regulated genes expression involved in cholesterol efflux but reduced genes expression implicated in cholesterol influx. Moreover, miR-375 silencing increased resolving M2 macrophage but reduced pro-inflammatory M1 macrophage markers expression. Such above effects can be reversed by miR-375 overexpression. Mechanistically, we noticed that miR-375 knockdown promoted KLF4 expression which was required for the ameliorated effect of miR-375 silencing on macrophage activation. Importantly, the consistent results in mRNA expression of M1 and M2 markers were observed in vivo, and miR-375-/-ApoE-/- mice significant decreased atherosclerotic lesions in the whole aorta and aortic sinus. Taken together, these evidences suggested that miR-375 knockdown attenuated macrophage activation partially through activation of KLF4-dependent mechanism.


Asunto(s)
Aterosclerosis/prevención & control , Inflamación/prevención & control , Factores de Transcripción de Tipo Kruppel/antagonistas & inhibidores , Activación de Macrófagos , MicroARNs/antagonistas & inhibidores , Animales , Aterosclerosis/etiología , Aterosclerosis/metabolismo , Aterosclerosis/patología , Femenino , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología , Factor 4 Similar a Kruppel , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Noqueados para ApoE , MicroARNs/genética , Transducción de Señal
15.
J Org Chem ; 85(14): 9367-9374, 2020 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-32578986

RESUMEN

The dearomatizing spirocyclization of phenolic biarylic ketones using PhI(OCOCF3)2 as oxidant is presented. The reaction affords various cyclohexadienones through C-C bond cleavage under mild conditions. Mechanistic investigations reveal that an exocyclic enol ether acts as the key intermediate in the transformation.

16.
Parasit Vectors ; 12(1): 98, 2019 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-30867024

RESUMEN

BACKGROUND: Rhoptry protein 18 (ROP18) is a key virulence factor of Toxoplasma gondii. The host's immune responses mediated by immune-related GTPases (IRGs) could be blocked by ROP18's kinase activity. ROP18 also interacts with various substrates, such as activating transcription factor 6 beta (ATF6ß) and affects multiple physiological functions within host cells, thereby inducing intense virulence. In this study, competitive inhibitors targeted to ROP18 were subjected to virtual screening based on the principle of structure-based drug design (SBDD). METHODS: The preparation of the ROP18 structure was conducted using the "Structure Prepare" function of Molecular Operating Environment (MOE) software. The ATP-binding pocket was selected as the starting point for virtual screening. Construction of the pharmacophore model used Extended Hückel Theory (EHT) half-quantitative measurement and construction, as well as the characteristics of Type I kinase inhibitors. The pharmacophore model of ROP18 was imported into the Specs database for small molecule similarity screening using EHT pharmacophore measurement. Hit compounds were selected using the functions of London dG and generalized-born volume integral/weighted surface area (GBVI/WSA) scoring. The top 100 hits were analyzed by molecular docking and structure activity relationships (SAR) analysis. RESULTS: The final pharmacophore comprised three typical characteristics: three hydrogen bond acceptors/donors, two ring aromatic features occupying the hydrophobic core, and one cation group feature targeted to the terminus of ATP. A total of 1314 hit compounds analogous to ROP18 pharmacophore were passed through the Specs. After two rounds of docking, 25 out of 100 hits were identified as belonging to two main scaffold types: phthalimide ring structure, thiazole ring and styrene structure. Additionally, the screen also identified 13 inhibitors with distinct scaffold types. The docking models and SAR analysis demonstrated that these hits could engage in multiple hydrogen bonds, salt bridges halogen bonds, and hydrophobic interactions with ROP18, and para-position halo substituents on the benzene ring may enhance their affinity scoring. CONCLUSIONS: A pharmacophore against the ROP18 ATP-binding pocket was successfully constructed, and 25 representative inhibitors from 15 scaffold clusters were screened using the Specs database. Our results provide useful scaffold types for the chemical inhibition of ROP18 or alternative conformations to develop new anti-toxoplasmosis drug leads.


Asunto(s)
Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas/química , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Toxoplasma/enzimología , Diseño de Fármacos , Proteínas Serina-Treonina Quinasas/química , Proteínas Serina-Treonina Quinasas/genética , Proteínas Protozoarias , Programas Informáticos , Relación Estructura-Actividad , Toxoplasma/genética , Toxoplasma/patogenicidad , Virulencia , Factores de Virulencia
17.
Artículo en Inglés | MEDLINE | ID: mdl-30803964

RESUMEN

We evaluated markers of sulfadoxine-pyrimethamine (SP) resistance in Plasmodium falciparum among 254 returned migrant workers in China from Africa from 2013 to 2016. High prevalences of pfdhfr (97.2%) and pfdhps (96.5%) mutations were observed. The partially resistant genotype was homogeneously distributed in Africa with a modestly high prevalence (48%), whereas the super resistant genotype was only found in West Africa with a very low frequency (1.2%). The findings provided baseline data about the molecular markers of SP resistance.


Asunto(s)
Plasmodium falciparum/metabolismo , Proteínas Protozoarias/metabolismo , África , China , Genotipo , Humanos , Malaria/parasitología , Mutación/genética , Plasmodium falciparum/genética , Proteínas Protozoarias/genética
18.
RSC Adv ; 9(16): 9106-9112, 2019 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35517694

RESUMEN

To solve the contradiction of diffusion and selectivity, we reported a novel finger-citron-residue-based mesoporous carbon (FMC) as a support to prepare a novel adsorbent PTA@FMC (PTA represents phosphotungstic acid) for rubidium ion capture. This new adsorbent was characterized by X-ray diffraction, thermogravimetric analysis, scanning electron microscopy, Fourier transform infrared spectroscopy, and N2 adsorption, and the results showed that the PTA was immobilized in the FMC structure. Based on the results of batch tests, we demonstrated that PTA@FMC is the most distinctive adsorbent with a superior uptake capacity compared with some of those previously reported in the literatures. The adsorption tests in the presence of interfering ions (Na+, K+ and Cs+) showed that the more the added amount of the different types of interfering ions, the more severe is the degree by which the adsorption of Rb+ is weakened. In addition, the Rb+ sorption selectivity was moderately influenced by the co-ion effect in the presence of any ions (K+, Na+ and Cs+) due to PTA doping. In a word, due to its relatively facile preparation process and good uptake capacity, PTA@FMC might be a promising adsorption material for Rb+.

20.
Curr Microbiol ; 75(12): 1619-1625, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30218176

RESUMEN

We used the double-agar layer method to isolate a novel Marinobacter marina bacteriophage, B23, from the surface water sample of the Bohai sea of China. There is some work to better understand the phage. The result of transmission electron microscopy revealed that B23 belongs to the family Siphoviridae with a head of 80 nm in diameter and a tail of 230 nm. Microbiological characterization evidenced that phage B23 is stable at the temperatures from - 25 to 60 °C, and showed vigorous vitality at pH between 4.0 and 12.0. One-step growth experiment showed that it had a longer latent period and higher lysis efficiency. Furthermore, the complete genome of B23 was sequenced and analyzed, which consists of a 35132 bp DNA with a G + C content of 59.8% and 50 putative open reading frames. The genome was divided into five parts, consisting of DNA replication and regulation, phage packaging, phage structure, host lysis and hypothetical protein.


Asunto(s)
Genoma Viral , Marinobacter/virología , Siphoviridae/genética , Concentración de Iones de Hidrógeno , Filogenia , Siphoviridae/crecimiento & desarrollo , Siphoviridae/aislamiento & purificación , Siphoviridae/ultraestructura , Temperatura , Secuenciación Completa del Genoma
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