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1.
PLoS Pathog ; 20(9): e1012599, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39325829

RESUMEN

Emerging and recurrent infectious diseases caused by coronaviruses remain a significant public health concern. Here, we present a targeted approach to elicit antibodies capable of neutralizing SARS-CoV-2 variants and other SARS-related coronaviruses. By introducing amino acid mutations at mutation-prone sites, we engineered glycosylation modifications to the Receptor Binding Domain (RBD) of SARS-CoV-2, thereby exposing more conserved, yet less accessible epitopes. We developed both messenger RNA (mRNA) and recombination subunit vaccines using these engineered-RBDs (M1, M2) and the wild-type RBD as immunogens. The engineered-RBD vaccines elicited robust neutralizing responses against various SARS-CoV-2 variants as well as SARS-CoV and WIV1-CoV, and conferred protection in mice challenged with the XBB.1.16 strain. Furthermore, We highlighted that glycan masking is a decisive factor in antibody binding changes and RBD-conserved antibody response. Additionally, the glycan-engineered RBD mRNA vaccines stimulated stronger cell-mediated immune responses. Our glycan modification strategy significantly enhances broad-spectrum neutralizing efficacy and cellular immunity, providing valuable insights for the development of vaccines against a wide range of SARS-related coronaviruses.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Polisacáridos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , SARS-CoV-2/inmunología , Ratones , Polisacáridos/inmunología , Vacunas contra la COVID-19/inmunología , Humanos , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Neutralizantes/inmunología , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/virología , Anticuerpos Antivirales/inmunología , Ratones Endogámicos BALB C , Glicosilación , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología , Femenino , Desarrollo de Vacunas , Dominios Proteicos/inmunología
2.
Magn Reson Med ; 92(4): 1755-1767, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38860542

RESUMEN

PURPOSE: Tractography of the facial nerve based on diffusion MRI is instrumental before surgery for the resection of vestibular schwannoma, but no excellent methods usable for the suppression of motion and image noise have been proposed. The aim of this study was to effectively suppress noise and provide accurate facial nerve reconstruction by extend a fiber trajectory distribution function based on the fourth-order streamline differential equations. METHODS: Preoperative MRI from 33 patients with vestibular schwannoma who underwent surgical resection were utilized in this study. First, T1WI and T2WI were used to obtain mask images and regions of interest. Second, probabilistic tractography was employed to obtain the fibers representing the approximate facial nerve pathway, and these fibers were subsequently translated into orientation information for each voxel. Last, the voxel orientation information and the peaks of the fiber orientation distribution were combined to generate a fiber trajectory distribution function, which was used to parameterize the anatomical information. The parameters were determined by minimizing the cost between the trajectory of fibers and the estimated directions. RESULTS: Qualitative and visual analyses were used to compare facial nerve reconstruction with intraoperative recordings. Compared with other methods (SD_Stream, iFOD1, iFOD2, unscented Kalman filter, parallel transport tractography), the fiber-trajectory-distribution-based tractography provided the most accurate facial nerve reconstructions. CONCLUSION: The fiber-trajectory-distribution-based tractography can effectively suppress the effect of noise. It is a more valuable aid for surgeons before vestibular schwannoma resection, which may ultimately improve the postsurgical patient's outcome.


Asunto(s)
Imagen de Difusión Tensora , Nervio Facial , Neuroma Acústico , Humanos , Neuroma Acústico/diagnóstico por imagen , Neuroma Acústico/cirugía , Imagen de Difusión Tensora/métodos , Nervio Facial/diagnóstico por imagen , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Algoritmos , Procesamiento de Imagen Asistido por Computador/métodos , Cuidados Preoperatorios/métodos , Adulto Joven
3.
BMC Microbiol ; 24(1): 271, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39033096

RESUMEN

BACKGROUND: Selenium nanoparticles (SeNPs) are increasingly gaining attention due to its characteristics of low toxicity, high activity, and stability. Additionally, Bacillus licheniformis, as a probiotic, has achieved remarkable research outcomes in diverse fields such as medicine, feed processing, and pesticides, attracting widespread attention. Consequently, evaluating the activity of probiotics and SeNPs is paramount. The utilization of probiotics to synthesize SeNPs, achieving large-scale industrialization, is a current hotspot in the field of SeNPs synthesis and is currently the most promising synthetic method. To minimize production costs and maximize yield of SeNPs, this study selected agricultural by-products that are nutrient-rich, cost-effective, and readily available as culture medium components. This approach not only fulfills industrial production requirements but also mitigates the impact on downstream processes. RESULTS: The experimental findings revealed that SeNPs synthesized by B. licheniformis F1 exhibited a spherical morphology with diameters ranging from 110 to 170 nm and demonstrating high stability. Both the secondary metabolites of B. licheniformis F1 and the synthesized SeNPs possessed significant free radical scavenging ability. To provide a more robust foundation for acquiring large quantities of SeNPs via fermentation with B. licheniformis F1, key factors were identified through single-factor experiments and response surface methodology (RSM) include a 2% seed liquid inoculum, a temperature of 37 ℃, and agitation at 180 rpm. Additionally, critical factors during the optimization process were corn powder (11.18 g/L), soybean meal (10.34 g/L), and NaCl (10.68 g/L). Upon validating the optimized conditions and culture medium, B. licheniformis F1 can synthesize nearly 100.00% SeNPs from 5 mmol/L sodium selenite. Subsequently, pilot-scale verification in a 5 L fermentor using the optimized medium resulted in a shortened fermentation time, significantly reducing production costs. CONCLUSION: In this study, the efficient production of SeNPs by the probiotic B. licheniformis F1 was successfully achieved, leading to a significant reduction in fermentation costs. The exploration of the practical applications of this strain holds significant potential and provides valuable guidance for facilitating the industrial-scale implementation of microbial synthesis of SeNPs.


Asunto(s)
Bacillus licheniformis , Medios de Cultivo , Fermentación , Probióticos , Selenio , Bacillus licheniformis/metabolismo , Selenio/metabolismo , Medios de Cultivo/química , Probióticos/metabolismo , Nanopartículas/química , Nanopartículas del Metal/química
4.
Pharmacol Res ; 206: 107274, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38906205

RESUMEN

Mild traumatic brain injury (mTBI) is a known risk factor for neurodegenerative diseases, yet the precise pathophysiological mechanisms remain poorly understand, often obscured by group-level analysis in non-invasive neuroimaging studies. Individual-based method is critical to exploring heterogeneity in mTBI. We recruited 80 mTBI patients and 40 matched healthy controls, obtaining high-resolution structural MRI for constructing Individual Differential Structural Covariance Networks (IDSCN). Comparisons were conducted at both the individual and group levels. Connectome-based Predictive Modeling (CPM) was applied to predict cognitive performance based on whole-brain connectivity. During the acute stage of mTBI, patients exhibited significant heterogeneity in the count and direction of altered edges, obscured by group-level analysis. In the chronic stage, the number of altered edges decreased and became more consistent, aligning with clinical observations of acute cognitive impairment and gradual improvement. Subgroup analysis based on loss of consciousness/post-traumatic amnesia revealed distinct patterns of alterations. The temporal lobe, particularly regions related to the limbic system, significantly predicted cognitive function from acute to chronic stage. The use of IDSCN and CPM has provided valuable individual-level insights, reconciling discrepancies from previous studies. Additionally, the limbic system may be an appropriate target for future intervention efforts.


Asunto(s)
Conmoción Encefálica , Cognición , Sistema Límbico , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Adulto , Sistema Límbico/diagnóstico por imagen , Sistema Límbico/fisiopatología , Conmoción Encefálica/diagnóstico por imagen , Conmoción Encefálica/fisiopatología , Conmoción Encefálica/psicología , Conmoción Encefálica/complicaciones , Persona de Mediana Edad , Conectoma , Adulto Joven , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Estudios de Casos y Controles
5.
Molecules ; 29(11)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38893338

RESUMEN

Acting as a growth regulator, Indole-3-acetic acid (IAA) is an important phytohormone that can be produced by several Bacillus species. However, few studies have been published on the comprehensive evaluation of the strains for practical applications and the effects of selenium species on their IAA-producing ability. The present study showed the selenite reduction strain Bacillus altitudinis LH18, which is capable of producing selenium nanoparticles (SeNPs) at a high yield in a cost-effective manner. Bio-SeNPs were systematically characterized by using DLS, zeta potential, SEM, and FTIR. The results showed that these bio-SeNPs were small in particle size, homogeneously dispersed, and highly stable. Significantly, the IAA-producing ability of strain was differently affected under different selenium species. The addition of SeNPs and sodium selenite resulted in IAA contents of 221.7 µg/mL and 91.01 µg/mL, respectively, which were 3.23 and 1.33 times higher than that of the control. This study is the first to examine the influence of various selenium species on the IAA-producing capacity of Bacillus spp., providing a theoretical foundation for the enhancement of the IAA-production potential of microorganisms.


Asunto(s)
Bacillus , Ácidos Indolacéticos , Selenio , Ácidos Indolacéticos/metabolismo , Bacillus/metabolismo , Bacillus/efectos de los fármacos , Selenio/química , Selenio/farmacología , Selenio/metabolismo , Nanopartículas/química , Tamaño de la Partícula
6.
Angew Chem Int Ed Engl ; 63(33): e202407417, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-38818653

RESUMEN

Realizing durative dense, dendrite-free, and no by-product deposition configuration on Zn anodes is crucial to solving the short circuit and premature failure of batteries, which is simultaneously determined by the Zn interface chemistry, electro-reduction kinetics, mass transfer process, and their interaction. Herein, this work unmasks a domino effect of the ß-alanine cations (Ala+) within the hydrogel matrix, which effectively triggers the subsequent electrostatic shielding and beneficial knock-on effects via the specifical adsorption earliest event on the Zn anode surface. The electrostatic shielding effect regulates the crystallographic energetic preference of Zn deposits and retards fast electro-reduction kinetics, thereby steering stacked stockier block morphology and realizing crystallographic optimization. Meanwhile, the mass transfer rate of Zn2+ ions was accelerated via the SO4 2- anion immobilized caused by Ala+ in bulk electrolyte, finally bringing the balance between electroreduction kinetics and mass transfer process, which enables dendrite-free Zn deposition behavior. Concomitantly, the interfacial adsorbed Ala+ cations facilitate the electrochemical reduction of interfacial SO4 2- anions to form the inorganic-organic hybrid solid electrolyte interphase layer. The above domino effects immensely improve the utilization efficiency of Zn anodes and long-term stability, as demonstrated by the 12 times longer life of Zn||Zn cells (3650 h) and ultrahigh Coulombic efficiency (99.4 %).

7.
J Cell Physiol ; 238(10): 2228-2242, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37682901

RESUMEN

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in young women, but its pathogenesis remains unclear. The primary pathogenic factors contributing to its development include genetics, abnormal bone metabolism, and endocrine factors. Bone marrow stem cells (BMSCs) play a crucial role in the pathogenesis of AIS by regulating its occurrence and progression. Noncoding RNAs (ncRNAs) are also involved in the pathogenesis of AIS, and their role in regulating BMSCs in patients with AIS requires further evaluation. In this review, we discuss the relevant literature regarding the osteogenic, chondrogenic, and lipogenic differentiation of BMSCs. The corresponding mechanisms of ncRNA-mediated BMSC regulation in patients with AIS, recent advancements in AIS and ncRNA research, and the importance of ncRNA translation profiling and multiomics are highlighted.

8.
Small ; 19(21): e2300556, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36823337

RESUMEN

Atomically dispersed Zn moieties are efficient active sites for accelerating the electrode kinetics of carbons for sodium-ion hybrid capacitors (SIHCs), but the low utilization and symmetric configuration of Zn single-atom greatly hamper the Na ion storage capability. Herein, a molecular design strategy is employed to synthesize high-density Zn single atoms with asymmetric Zn-N3 S coordination embedded in nitrogen/sulfur codoped carbon (Zn-N3 S-NSC). The key to this strategy lies in the Zn power-catalyzed condensation of trithiocyanuric acid molecules to generate S-doped g-C3 N4 , which can in situ coordinate with Zn sources to form Zn-N3 S moieties during pyrolysis. By virtue of the highly exposed Zn-N3 S moieties, Zn-N3 S-NSC presents ultrahigh reactivity, efficient electron transfer, and decreased ion diffusion barriers for SIHCs, rendering an impressive energy density of 215 Wh kg-1 and a maximum power density of 15625 W kg-1 . Moreover, the pouch cell displays a high capacity of 279 mAh g-1 after 4000 cycles. This work provides a new avenue for the regulation of the coordination configuration of single metal atoms in carbons toward high-performance electrochemical energy technologies at the molecular level.

9.
Small ; 19(22): e2300162, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36866502

RESUMEN

Electrodes made of composites with heterogeneous structure hold great potential for boosting ionic and charge transfer and accelerating electrochemical reaction kinetics. Herein, hierarchical and porous double-walled NiTeSe-NiSe2 nanotubes are synthesized by a hydrothermal process assisted in situ selenization. Impressively, the nanotubes have abundant pores and multiple active sites, which shorten the ion diffusion length, decrease Na+ diffusion barriers, and increase the capacitance contribution ratio of the material at a high rate. Consequently, the anode shows a satisfactory initial capacity (582.5 mA h g-1 at 0.5 A g-1 ), a high-rate capability, and long cycling stability (1400 cycles, 398.6 mAh g-1 at 10 A g-1 , 90.5% capacity retention). Moreover, the sodiation process of NiTeSe-NiSe2 double-walled nanotubes and underlying mechanism of the enhanced performance are revealed by in situ and ex situ transmission electron microscopy and theoretical calculations.

10.
Appl Environ Microbiol ; 89(10): e0095623, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37815340

RESUMEN

Klebsiella pneumoniae is a ubiquitous human pathogen, and its clinical treatment faces two major challenges: multidrug resistance and the pathogenesis of hypervirulent K. pneumoniae. The discovery and study of conditionally essential (CE) genes that can function as potential antimicrobial targets has always been a research concern due to their restriction in the development of novel antibiotics. However, the lack of essential functional genomic data has hampered the study of the mechanisms of essential genes related to antimicrobial susceptibility. In this study, we developed a pooled CE genes mobile clustered regularly interspaced short palindromic repeat (CRISPR) interference screening method (Mobile-CRISPRi-seq) for K. pneumoniae to identify genes that play critical roles in antimicrobial fitness in vitro and host immunity in vivo. Targeting 870 predicted CE genes in K. pneumoniae, Mobile-CRISPRi-seq uncovered the depletion of tetrahydrofolate synthesis pathway genes folB and folP under trimethoprim pressure. Our screening also identified genes waaE and fldA related to polymyxin and ß-lactam susceptibility by applying a screening strategy based on Mobile-CRISPRi-seq and comparative genomics. Furthermore, using a mouse infection model and Mobile-CRISPRi-seq, multiple virulence genes were identified, and among these genes, pal, yciS, and ribB were demonstrated to contribute to the pathogenesis of K. pneumoniae. This study provides a simple, rapid, and effective platform for screening potential antimicrobial targets and virulence genes in K. pneumoniae, and this broadly applicable system can be expanded for high-throughput functional gene study in multiple pathogenic bacteria, especially in gram-negative bacteria. IMPORTANCE The discovery and investigation of conditionally essential (CE) genes that can function as potential antimicrobial targets has always been a research concern because of the restriction of antimicrobial targets in the development of novel antibiotics. In this study, we developed a pooled CE gene-wide mobile clustered regularly interspaced short palindromic repeat (CRISPR) interference sequencing (Mobile-CRISPRi-seq) strategy in Klebsiella pneumoniae to identify genes that play critical roles in the fitness of antimicrobials in vitro and host immunity in vivo. The data suggest a robust tool to screen for loss-of-function phenotypes in a pooled gene knockdown library in K. pneumoniae, and Mobile-CRISPRi-seq may be expanded to multiple bacteria for screening and identification of genes with crucial roles in the fitness of antimicrobials and hosts.


Asunto(s)
Genes Esenciales , Klebsiella pneumoniae , Humanos , Klebsiella pneumoniae/genética , Virulencia/genética , Técnicas de Silenciamiento del Gen , Bacterias/genética , Antibacterianos/farmacología
11.
J Med Virol ; 95(1): e28106, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36039848

RESUMEN

The discovery of broadly neutralizing monoclonal antibodies against influenza viruses has raised hope for the successful development of new antiviral drugs. However, due to the speed and variety of mutations in influenza viruses, single-component antibodies that recognize specific epitopes are susceptible to viral escape and have limited efficacy when administration is delayed. Hence, it is necessary to develop alternative strategies with better antiviral activity. Influenza B virus infection can cause severe illness in children and the elderly. Commonly used anti-influenza drugs have low clinical efficacy against influenza B virus. In this study, we investigated the antiviral efficacy of combinations of representative monoclonal antibodies targeting different antigenic epitopes against the influenza B virus. We found that combinations of antibodies recognizing the hemagglutinin (HA) head and stem regions showed a stronger neutralizing activity than single antibodies and other antibody combinations in vitro. In addition, we found that pair-wise combinations of antibodies recognizing the HA head region, HA stem region, and neuraminidase enzyme-activated region showed superior antiviral activity than single antibodies in both mouse and ferret in vivo protection assays. Notably, these antibody combinations still displayed good antiviral efficacy when treatment was delayed. Mechanistic studies further revealed that combining antibodies recognizing different epitope regions resulted in extremely strong antibody-dependent cell-mediated cytotoxicity, which may partly explain their superior antiviral effects. Together, the findings of this study provide new avenues for the development of better antiviral drugs and vaccines against influenza viruses.


Asunto(s)
Vacunas contra la Influenza , Gripe Humana , Infecciones por Orthomyxoviridae , Animales , Ratones , Humanos , Epítopos , Virus de la Influenza B , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Anticuerpos ampliamente neutralizantes , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Hurones , Hemaglutininas , Anticuerpos Monoclonales/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico
12.
NMR Biomed ; 36(10): e4991, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37392139

RESUMEN

We evaluated the fiber bundles in mild traumatic brain injury (mTBI) patients using differential and correlational tractography in a longitudinal analysis. Diffusion MRI data were acquired in 34 mTBI patients at 7 days (acute stage) and 3 months or longer (chronic stage) after mTBI. Trail Making Test A (TMT-A) and Digital Symbol Substitution Test changes were used to evaluate the cognitive performance. Longitudinal correlational tractography showed decreased anisotropy in the corpus callosum during the chronic mTBI stage. The changes in anisotropy in the corpus callosum were significantly correlated with the changes in TMT-A (false discovery rate [FDR] = 0.000094). Individual longitudinal differential tractography found that anisotropy decreased in the corpus callosum in 30 mTBI patients. Group cross-sectional differential tractography found that anisotropy increased (FDR = 0.02) in white matter in the acute mTBI patients, while no changes occurred in the chronic mTBI patients. Our study confirms the feasibility of using correlational and differential tractography as tract-based monitoring biomarkers to evaluate the disease progress of mTBI, and indicates that normalized quantitative anisotropy could be used as a biomarker to monitor the injury and/or repairs of white matter in individual mTBI patients.


Asunto(s)
Conmoción Encefálica , Sustancia Blanca , Humanos , Conmoción Encefálica/diagnóstico por imagen , Estudios Transversales , Imagen de Difusión Tensora , Imagen por Resonancia Magnética , Sustancia Blanca/diagnóstico por imagen , Biomarcadores , Encéfalo/diagnóstico por imagen
13.
Hum Brain Mapp ; 43(7): 2164-2180, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35092135

RESUMEN

The oculomotor nerve (OCN) is the main motor nerve innervating eye muscles and can be involved in multiple flammatory, compressive, or pathologies. The diffusion magnetic resonance imaging (dMRI) tractography is now widely used to describe the trajectory of the OCN. However, the complex cranial structure leads to difficulties in fiber orientation distribution (FOD) modeling, fiber tracking, and region of interest (ROI) selection. Currently, the identification of OCN relies on expert manual operation, resulting in challenges, such as the carries high clinical, time-consuming, and labor costs. Thus, we propose a method that can automatically identify OCN from dMRI tractography. First, we choose the multi-shell multi-tissue constraint spherical deconvolution (MSMT-CSD) FOD estimation model and deterministic tractography to describe the 3D trajectory of the OCN. Then, we rely on the well-established computational pipeline and anatomical expertise to create a data-driven OCN tractography atlas from 40 HCP data. We identify six clusters belonging to the OCN from the atlas, including the structures of three kinds of positional relationships (pass between, pass through, and go around) with the red nuclei and two kinds of positional relationships with medial longitudinal fasciculus. Finally, we apply the proposed OCN atlas to identify the OCN automatically from 40 new HCP subjects and two patients with brainstem cavernous malformation. In terms of spatial overlap and visualization, experiment results show that the automatically and manually identified OCN fibers are consistent. Our proposed OCN atlas provides an effective tool for identifying OCN by avoiding the traditional selection strategy of ROIs.


Asunto(s)
Imagen de Difusión Tensora , Nervio Oculomotor , Análisis por Conglomerados , Imagen de Difusión por Resonancia Magnética/métodos , Imagen de Difusión Tensora/métodos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Nervio Oculomotor/diagnóstico por imagen
14.
J Med Virol ; 94(9): 4533-4538, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35614018

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants could induce immune escape by mutations of the spike protein which are threatening to weaken vaccine efficacy. A booster vaccination is expected to increase the humoral immune response against SARS-CoV-2 variants in the population. We showed that immunization with two doses of wild type receptor-binding domain (RBD) protein, and booster vaccination with wild type or variant RBD protein all significantly increased binding and neutralizing antibody titers against wild type SARS-CoV-2 and its variants in mice. Only the booster immunization by Omicron (BA.1)RBD induced a strong antibody titer against the omicron virus strain and comparable antibody titers against all the other virus strains. These findings might shed the light on coronavirus disease 2019 booster immunogens.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Inmunidad Humoral , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Humanos , Inmunización Secundaria , Ratones , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Vacunación
15.
Clin Anat ; 35(3): 383-391, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35102603

RESUMEN

The aim of this study was to investigate the trajectory of the stria terminalis and develop a protocol for mapping the stria terminalis using multi-shell diffusion images based tractography. The stria terminalis was reconstructed by combining one region of interest at the amygdala with another region of interest at the bed nucleus of stria terminalis. In addition, one region of avoidance was placed on the fornix at the interventricular foramen and another was set at the anterior perforated substance. The fiber-tracking protocol was tested in a Human Connectome Project-842 template, 35 healthy subjects from Massachusetts General Hospital, and 20 healthy subjects from the Human Connectome Project using generalized q-sampling imaging based tractography. The stria terminalis was reconstructed in the Human Connectome Project-842 template, 35 Massachusetts General Hospital healthy subjects, and 20 Human Connectome Project healthy subjects with our protocol. The stria terminalis originated from the amygdala and traveled parallel to the fornix. Then, the stria terminalis followed a C-shaped trajectory around the inferior, posterior, and dorsal surfaces of the thalamus before projecting to the bed nucleus of stria terminalis between the thalamus and caudate nucleus. There were no significant differences in the quantitative anisotropy and fractional anisotropy values between the left and right stria terminalis. The stria terminalis was accurately visualized across subjects using multi-shell diffusion images through generalized q-sampling imaging based tractography. This method could be an important tool for the reconstruction and evaluation of the stria terminalis in various neurological disorders. One Sentence Summary The visualization of the stria terminalis through the multi-shell diffusion images using generalized q-sampling imaging based tractography.


Asunto(s)
Amígdala del Cerebelo , Tálamo , Humanos
16.
Clin Anat ; 35(3): 269-279, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34535922

RESUMEN

The aim of this study was to make a thorough investigation of the trajectory of the ansa lenticularis (AL) and its subcomponents using high-resolution fiber-tracking tractography. The subcomponents of the AL were reconstructed from one region of interest (ROI) in the area of the globus pallidus combined with another ROI in the red nucleus, substantia nigra, subthalamic nucleus, or thalamus. This fiber-tracking protocol was tested in an HCP-1065 template, 35 healthy subjects from Massachusetts General Hospital (MGH), and 20 healthy subjects from the human connectome project (HCP) using generalized q-sampling imaging (GQI)-based tractography. Quantitative anisotropy and fractional anisotropy were also computed for the AL subcomponents. The subcomponents of the AL could be reconstructed in the HCP-1065 template, 35 MGH healthy subjects, and 20 HCP healthy subjects. The AL descends from the globus pallidus and joins the ansa peduncularis for a short distance, subdividing later into fibers that continue separately to the red nucleus, substantia nigra, subthalamic nucleus, and thalamus. The study demonstrated the trajectory of the ansa lenticularis and its subcomponents using GQI-based tractography, improving our understanding of the anatomical connectivity between the globus pallidus and the thalamo-subthalamic region in the human brain. One Sentence Summary The investigation of the ansa lenticularis and its subcomponents using high-resolution diffusion images based tractography.


Asunto(s)
Imagen de Difusión Tensora , Sustancia Blanca , Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Humanos , Núcleo Rojo/diagnóstico por imagen , Tálamo
17.
Molecules ; 27(6)2022 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-35335379

RESUMEN

Our team discovered a moderate SphK1 inhibitor, SAMS10 (IC50 = 9.8 µM), which was screened by computer-assisted screening. In this study, we developed a series of novel diaryl derivatives with improved antiproliferative activities by modifying the structure of the lead compound SAMS10. A total of 50 new compounds were synthesized. Among these compounds, the most potent compound, named CHJ04022Rb, has significant anticancer activity in melanoma A375 cell line (IC50 = 2.95 µM). Further underlying mechanism studies indicated that CHJ04022R exhibited inhibition effect against PI3K/NF-κB signaling pathways, inhibited the migration of A375 cells, promoted apoptosis and exerted antiproliferative effect by inducing G2/M phase arrest in A375 cells. Furthermore, acute toxicity experiment indicated CHJ04022R exhibited good safety in vivo. Additionally, it showed a dose-dependent inhibitory effect on the growth of xenograft tumor in nude mice. Therefore, CHJ04022R may be a potential candidate for the treatment of melanoma.


Asunto(s)
Antineoplásicos , Animales , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular , Humanos , Ratones , Ratones Desnudos , Relación Estructura-Actividad
18.
Hum Brain Mapp ; 42(18): 6070-6086, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34597450

RESUMEN

The aim of this study is to investigate the trajectory of medial longitudinal fasciculus (MLF) and explore its anatomical relationship with the oculomotor nerve using tractography technique. The MLF and oculomotor nerve were reconstructed at the same time with preset three region of interests (ROIs): one set at the area of rostral midbrain, one placed on the MLF area at the upper pons, and one placed at the cisternal part of the oculomotor nerve. This mapping protocol was tested in an HCP-1065 template, 35 health subjects from Massachusetts General Hospital (MGH), 20 healthy adults and 6 brainstem cavernous malformation (BCM) patients with generalized q-sampling imaging (GQI)-based tractography. Finally, the 200 µm brainstem template from Center for In Vivo Microscopy, Duke University (Duke CIVM), was used to validate the trajectory of reconstructed MLF. The MLF and oculomotor nerve were reconstructed in the HCP-1065 template, 35 MGH health subjects, 20 healthy adults and 6 BCM patients. The MLF was in conjunction with the ipsilateral mesencephalic part of the oculomotor nerve. The displacement of MLF was identified in all BCM patients. Decreased QA, RDI and FA were found in the MLF of lesion side, indicating axonal loss and/or edema of displaced MLF. The reconstructed MLF in Duke CIVM brainstem 200 µm template corresponded well with histological anatomy. The MLF and oculomotor nerve were visualized accurately with our protocol using GQI-based fiber tracking. This GQI-based tractography is an important tool in the reconstruction and evaluation of MLF.


Asunto(s)
Tronco Encefálico/patología , Imagen de Difusión Tensora/métodos , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Nervio Oculomotor/anatomía & histología , Sustancia Blanca/anatomía & histología , Adulto , Tronco Encefálico/diagnóstico por imagen , Femenino , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/anatomía & histología , Vías Nerviosas/diagnóstico por imagen , Nervio Oculomotor/diagnóstico por imagen , Nervio Oculomotor/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Adulto Joven
19.
NMR Biomed ; 34(12): e4607, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34486766

RESUMEN

Small size and intricate anatomical environment are the main difficulties facing tractography of the facial-vestibulocochlear nerve complex (FVN), and lead to challenges in fiber orientation distribution (FOD) modeling, fiber tracking, region-of-interest selection, and fiber filtering. Experts need rich experience in anatomy and tractography, as well as substantial labor costs, to identify the FVN. Thus, we present a pipeline to identify the FVN automatically, in what we believe is the first study of the automated identification of the FVN. First, we created an FVN template. Forty high-resolution multishell data were used to perform data-driven fiber clustering based on the multishell multitissue constraint spherical deconvolution FOD model and deterministic tractography. We selected the brainstem and cerebellum (BS-CB) region as the seed region and removed the fibers that reach other brain regions. We then performed spectral fiber clustering twice. The first clustering was to create a BS-CB atlas and separate the fibers that pass through the cerebellopontine angle, and the other one was to extract the FVN. Second, we registered the subject-specific fibers in the space of the FVN template and assigned each fiber to the closest cluster to identify the FVN automatically by spectral embedding. We applied the proposed method to different acquirement sites, including two different healthy datasets and two tumor patient datasets. Experimental results showed that our automatic identification results have ideal colocalization with expert manual identification in terms of spatial overlap and visualization. Importantly, we successfully applied our method to tumor patient data. The FVNs identified by the proposed method were in agreement with intraoperative findings.


Asunto(s)
Imagen de Difusión Tensora/métodos , Nervio Facial/diagnóstico por imagen , Nervio Vestibulococlear/diagnóstico por imagen , Humanos , Procedimientos Neuroquirúrgicos
20.
Sleep Breath ; 25(1): 487-492, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32266661

RESUMEN

PURPOSE: To explore the effect of nighttime sleep duration and midday napping in early pregnancy on gestational diabetes mellitus (GDM) among Chinese women. METHODS: Information on midday napping and nighttime sleep duration was assessed by a questionnaire. Diagnostic information of GDM was derived from the routine oral glucose tolerance test (OGTT) during the second trimester of pregnancy. RESULTS: A total of 500 pregnant women, including 196 patients with GDM and 304 controls, were included in the present study. In the case group, 47% of women took a midday nap > 1 h/day, and the proportion was 22% in the control group. Compared with women who had a midday nap ≤ 1 h/day, women who had a nap > 1 h/day had a significantly increased risk of GDM (OR 3.00, 95% CI 1.87, 4.82, p < 0.001). Compared with women who had a nighttime sleep of 7 to 8.9 h/night, women who slept < 7 or ≥ 9 h/night all had a significantly increased risk of GDM. Stratified analyses showed that compared with the nighttime sleep duration of 7 to 8.9 h/day, the GDM risk of the < 7 h/night group increased among mothers who had a midday nap ≤ 1 h/day. The impact was stronger than among women who had a nap > 1 h/day (p = 0.006). CONCLUSIONS: Shorter or longer nighttime sleep duration and longer midday napping duration in early pregnancy were all related to GDM. Midday napping would reduce the risk of GDM among mothers with shorter nighttime sleep duration.


Asunto(s)
Diabetes Gestacional/etiología , Sueño , Adulto , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Embarazo , Factores de Riesgo
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