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1.
Nature ; 627(8005): 839-846, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38509363

RESUMEN

The bone marrow adjusts blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses are unknown owing to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent haematopoiesis, erythropoiesis and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of normal and stress haematopoiesis. In the steady state, across the skeleton, single stem cells and multipotent progenitors distribute through the marrow enriched near megakaryocytes. Lineage-committed progenitors are recruited to blood vessels, where they contribute to lineage-specific microanatomical structures composed of progenitors and immature cells, which function as the production sites for each major blood lineage. This overall anatomy is resilient to insults, as it was maintained after haemorrhage, systemic bacterial infection and granulocyte colony-stimulating factor (G-CSF) treatment, and during ageing. Production sites enable haematopoietic plasticity as they differentially and selectively modulate their numbers and output in response to insults. We found that stress responses are variable across the skeleton: the tibia and the sternum respond in opposite ways to G-CSF, and the skull does not increase erythropoiesis after haemorrhage. Our studies enable in situ analyses of haematopoiesis, define the anatomy of normal and stress responses, identify discrete microanatomical production sites that confer plasticity to haematopoiesis, and uncover unprecedented heterogeneity of stress responses across the skeleton.


Asunto(s)
Hematopoyesis , Células Madre Hematopoyéticas , Estrés Fisiológico , Animales , Femenino , Masculino , Ratones , Envejecimiento/fisiología , Infecciones Bacterianas/patología , Infecciones Bacterianas/fisiopatología , Vasos Sanguíneos/citología , Linaje de la Célula , Eritropoyesis , Factor Estimulante de Colonias de Granulocitos/metabolismo , Hematopoyesis/fisiología , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Hemorragia/patología , Hemorragia/fisiopatología , Linfopoyesis , Megacariocitos/citología , Células Madre Multipotentes/citología , Células Madre Multipotentes/metabolismo , Mielopoyesis , Cráneo/irrigación sanguínea , Cráneo/patología , Cráneo/fisiopatología , Esternón/irrigación sanguínea , Esternón/citología , Esternón/metabolismo , Estrés Fisiológico/fisiología , Tibia/irrigación sanguínea , Tibia/citología , Tibia/metabolismo
2.
Nature ; 623(7985): 106-114, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37880365

RESUMEN

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6-8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks' gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks' gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.


Asunto(s)
Encéfalo , Desarrollo Fetal , Feto , Preescolar , Femenino , Humanos , Embarazo , Encéfalo/anatomía & histología , Encéfalo/embriología , Encéfalo/crecimiento & desarrollo , Feto/embriología , Edad Gestacional , Sustancia Gris/anatomía & histología , Sustancia Gris/embriología , Sustancia Gris/crecimiento & desarrollo , Voluntarios Sanos , Internacionalidad , Imagen por Resonancia Magnética , Tamaño de los Órganos , Estudios Prospectivos , Organización Mundial de la Salud , Imagenología Tridimensional , Ultrasonografía
3.
Nature ; 590(7846): 457-462, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33568812

RESUMEN

In contrast to nearly all other tissues, the anatomy of cell differentiation in the bone marrow remains unknown. This is owing to a lack of strategies for examining myelopoiesis-the differentiation of myeloid progenitors into a large variety of innate immune cells-in situ in the bone marrow. Such strategies are required to understand differentiation and lineage-commitment decisions, and to define how spatial organizing cues inform tissue function. Here we develop approaches for imaging myelopoiesis in mice, and generate atlases showing the differentiation of granulocytes, monocytes and dendritic cells. The generation of granulocytes and dendritic cells-monocytes localizes to different blood-vessel structures known as sinusoids, and displays lineage-specific spatial and clonal architectures. Acute systemic infection with Listeria monocytogenes induces lineage-specific progenitor clusters to undergo increased self-renewal of progenitors, but the different lineages remain spatially separated. Monocyte-dendritic cell progenitors (MDPs) map with nonclassical monocytes and conventional dendritic cells; these localize to a subset of blood vessels expressing a major regulator of myelopoiesis, colony-stimulating factor 1 (CSF1, also known as M-CSF)1. Specific deletion of Csf1 in endothelium disrupts the architecture around MDPs and their localization to sinusoids. Subsequently, there are fewer MDPs and their ability to differentiate is reduced, leading to a loss of nonclassical monocytes and dendritic cells during both homeostasis and infection. These data indicate that local cues produced by distinct blood vessels are responsible for the spatial organization of definitive blood cell differentiation.


Asunto(s)
Rastreo Celular/métodos , Células Mieloides/citología , Mielopoyesis , Coloración y Etiquetado/métodos , Animales , Atlas como Asunto , Vasos Sanguíneos/citología , Vasos Sanguíneos/metabolismo , Linaje de la Célula , Autorrenovación de las Células , Células Dendríticas/citología , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Femenino , Granulocitos/citología , Listeria monocytogenes/patogenicidad , Listeriosis/microbiología , Factor Estimulante de Colonias de Macrófagos/deficiencia , Factor Estimulante de Colonias de Macrófagos/genética , Factor Estimulante de Colonias de Macrófagos/metabolismo , Masculino , Ratones , Monocitos/citología , Células Mieloides/metabolismo
4.
Genes Dev ; 32(23-24): 1537-1549, 2018 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-30463901

RESUMEN

Human globin gene production transcriptionally "switches" from fetal to adult synthesis shortly after birth and is controlled by macromolecular complexes that enhance or suppress transcription by cis elements scattered throughout the locus. The DRED (direct repeat erythroid-definitive) repressor is recruited to the ε-globin and γ-globin promoters by the orphan nuclear receptors TR2 (NR2C1) and TR4 (NR2C2) to engender their silencing in adult erythroid cells. Here we found that nuclear receptor corepressor-1 (NCoR1) is a critical component of DRED that acts as a scaffold to unite the DNA-binding and epigenetic enzyme components (e.g., DNA methyltransferase 1 [DNMT1] and lysine-specific demethylase 1 [LSD1]) that elicit DRED function. We also describe a potent new regulator of γ-globin repression: The deubiquitinase BRCA1-associated protein-1 (BAP1) is a component of the repressor complex whose activity maintains NCoR1 at sites in the ß-globin locus, and BAP1 inhibition in erythroid cells massively induces γ-globin synthesis. These data provide new mechanistic insights through the discovery of novel epigenetic enzymes that mediate γ-globin gene repression.


Asunto(s)
Regulación de la Expresión Génica/genética , Co-Represor 1 de Receptor Nuclear/genética , Co-Represor 1 de Receptor Nuclear/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina Tiolesterasa/metabolismo , gamma-Globinas/genética , Sitios de Unión , Línea Celular , Activación Enzimática/genética , Epigénesis Genética/genética , Células Eritroides/metabolismo , Silenciador del Gen , Células HEK293 , Humanos , Células K562 , Miembro 1 del Grupo C de la Subfamilia 2 de Receptores Nucleares/metabolismo , Dominios Proteicos , Receptores de Esteroides/metabolismo , Receptores de Hormona Tiroidea/metabolismo
5.
Nano Lett ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38591962

RESUMEN

Single-molecule electrical junctions possess a molecular core connected to source and drain electrodes via anchor groups, which feed and extract electricity from specific atoms within the core. As the distance between electrodes increases, the electrical conductance typically decreases, which is a feature shared by classical Ohmic conductors. Here we analyze the electrical conductance of cycloparaphenylene (CPP) macrocycles and demonstrate that they can exhibit a highly nonclassical increase in their electrical conductance as the distance between electrodes increases. We demonstrate that this is due to the topological nature of the de Broglie wave created by electrons injected into the macrocycle from the source. Although such topological states do not exist in isolated macrocycles, they are created when the molecule is in contact with the source. They are predicted to be a generic feature of conjugated macrocycles and open a new avenue to implementing highly nonclassical transport behavior in molecular junctions.

6.
Anal Chem ; 96(16): 6337-6346, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38613479

RESUMEN

The arsM gene is a critical biomarker for the potential risk of arsenic exposure in paddy soil. However, on-site screening of arsM is limited by the lack of high-throughput point-of-use (POU) methods. Here, a multiplex CRISPR/Cas12a microfluidic paper-based analytical device (µPAD) was constructed for the high-throughput POU analysis of arsM, with cascade amplification driven by coupling crRNA-enhanced Cas12a and horseradish peroxidase (HRP)-modified probes. First, seven crRNAs were designed to recognize arsM, and their LODs and background signal intensities were evaluated. Next, a step-by-step iterative approach was utilized to develop and optimize coupling systems, which improved the sensitivity 32 times and eliminated background signal interference. Then, ssDNA reporters modified with HRP were introduced to further lower the LOD to 16 fM, and the assay results were visible to the naked eye. A multiplex channel microfluidic paper-based chip was developed for the reaction integration and simultaneous detection of 32 samples and generated a recovery rate between 87.70 and 114.05%, simplifying the pretreatment procedures and achieving high-throughput POU analysis. Finally, arsM in Wanshan paddy soil was screened on site, and the arsM abundance ranged from 1.05 × 106 to 6.49 × 107 copies/g; this result was not affected by the environmental indicators detected in the study. Thus, a coupling crRNA-based cascade amplification method for analyzing arsM was constructed, and a microfluidic device was developed that contains many more channels than previous paper chips, greatly improving the analytical performance in paddy soil samples and providing a promising tool for the on-site screening of arsM at large scales.


Asunto(s)
Suelo , Suelo/química , Peroxidasa de Rábano Silvestre/metabolismo , Peroxidasa de Rábano Silvestre/química , Sistemas CRISPR-Cas , Oryza/química , Contaminantes del Suelo/análisis , Dispositivos Laboratorio en un Chip , Endodesoxirribonucleasas/metabolismo , Endodesoxirribonucleasas/química , Ensayos Analíticos de Alto Rendimiento/métodos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Proteínas Asociadas a CRISPR/metabolismo , Límite de Detección , Técnicas de Amplificación de Ácido Nucleico/métodos
7.
Anal Chem ; 96(8): 3679-3685, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38353671

RESUMEN

Recently, organic photoelectrochemical transistor (OPECT) bioanalysis has become a prominent technique for the high-performance detection of biomolecules. However, as a sensitive index of the OPECT, the dynamic regulation transconductance (gm) is still severely deficient. Herein, this work reports a new photosensitive metal-organic framework (MOF-on-MOF) heterostructure for the effective modulation of maximum gm and natural bienzyme interfacing toward choline detection. Specifically, the bidentate ligand MOF (b-MOF) was assembled onto the UiO-66 MOF (u-MOF) by a modular assembly method, which could facilitate the charge separation and generate enhanced photocurrents and offer a biophilic environment for the immobilization of choline oxidase (ChOx) and horseradish peroxidase (HRP) through hydrogen-bonded bridges. The transconductance of the OPECT could be flexibly altered by increased light intensity to maximal value at zero gate bias, and sensitive choline detection was achieved with a detection limit of 0.2 µM. This work reveals the potential of MOF-on-MOF heterostructures for futuristic optobioelectronics.


Asunto(s)
Técnicas Biosensibles , Estructuras Metalorgánicas , Estructuras Metalorgánicas/química , Peroxidasa de Rábano Silvestre/química , Colina , Técnicas Biosensibles/métodos
8.
Small ; : e2401315, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38747008

RESUMEN

Battery-type electrode materials with high capacity, wide potential windows, and good cyclic stability are crucial to breaking through energy storage limitations and achieving high energy density. Herein, a novel 2D-on-2D Al-doped NiCo layered double hydroxide (NiCoAlx LDH) nanosheet arrays with high-mass-loading are grown on a carbon cloth (CC) substrate via a two-step hydro/solvothermal deposition strategy, and the effect of Al doping is employed to modify the deposition behavior, hierarchical morphology, phase stability, and multi-metallic synergistic effect. The optimized NiCoAl0.1 LDH electrode exhibits capacities of 5.43, 6.52, and 7.25 C cm-2 (9.87, 10.88, and 11.15 F cm-2) under 0-0.55, 0-0.60, and 0-0.65 V potential windows, respectively, illustrating clearly the importance of the wide potential window. The differentiated deposition strategy reduces the leaching level of Al3+ cations in alkaline solutions, ensuring excellent cyclic performance (108% capacity retention after 40 000 cycles). The as-assembled NiCoAl0.1 LDH//activated carbon cloth (ACC) hybrid supercapacitor delivers 3.11 C cm-2 at 0-2.0 V, a large energy density of 0.84 mWh cm-2 at a power density of 10.00 mW cm-2, and excellent cyclic stability with ≈135% capacity retention after 150 000 cycles.

9.
Small ; : e2311491, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38682729

RESUMEN

Conductance quantization of 2D materials is significant for understanding the charge transport at the atomic scale, which provides a platform to manipulate the quantum states, showing promising applications for nanoelectronics and memristors. However, the conventional methods for investigating conductance quantization are only applicable to materials consisting of one element, such as metal and graphene. The experimental observation of conductance quantization in transition metal dichalcogenides (TMDCs) with complex compositions and structures remains a challenge. To address this issue, an approach is proposed to characterize the charge transport across a single atom in TMDCs by integrating in situ synthesized 1T'-WTe2 electrodes with scanning tunneling microscope break junction (STM-BJ) technique. The quantized conductance of 1T'-WTe2 is measured for the first time, and the quantum states can be modulated by stretching speed and solvent. Combined with theoretical calculations, the evolution of quantized and corresponding configurations during the break junction process is demonstrated. This work provides a facile and reliable avenue to characterize and modulate conductance quantization of 2D materials, intensively expanding the research scope of quantum effects in diverse materials.

10.
Chemistry ; : e202402095, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38943462

RESUMEN

In the cross-plane single-molecule junctions, the correlation between molecular aromaticity and conductance remained puzzling. Cross-plane break junction (XPBJ) provides new insight into understanding the role of aromaticity and conjugation to molecules on charge transport through the planar molecules. In this work, we investigated the modulation of cross-plane charge transport in pyrene derivatives by hydrogenation and substituents based on the XPBJ method that differs from those used in-plane transport. We measured the electrical conductance of the hydrogenated derivatives of the pyrenes and found that hydrogenation reduces conductance, and the fully hydrogenated molecule has the lowest conductance. Conductance of pyrene derivatives increased after substitution by both electron-donating and electron-withdrawing groups. By calculating, the trend in decreased conductance of hydrogenated pyrene was found to be consistent with the change in aromaticity. Electron-withdrawing substituents reduce the aromaticity of the molecule and narrow the HOMO-LUMO gap, while electron-donating groups increase the aromaticity but also narrow the gap. Our work reveals the potential of fine-tuning the structure of the pyrene molecule to control the cross-plane charge transport through the single-molecule junctions.

11.
J Org Chem ; 89(7): 4802-4817, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38477972

RESUMEN

A general approach for regioselective deacetylation at sugar 3-OH of peracetylated 6-deoxy-C-glucopyranosides mediated by BCl3 was developed. The approach could be extended to other sugar-derived 6-deoxy-C-glycopyranosides, such as those derived from mannose, galactose, and rhamnose, with deacetylation occurring at varied sugar hydroxyl groups, and further extended to 4-deoxy-C-glucopyranosides with deacetylation occurring at sugar 3-OH. The approach would enable access to synthetically challenging carbohydrate derivatives. A possible mechanism of the regioselectivity was proposed.

12.
Environ Sci Technol ; 58(21): 9082-9090, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38743497

RESUMEN

This prospective birth cohort study evaluated the association of exposure to PM2.5 (diameter ≤2.5 µm), PM1-2.5 (1-2.5 µm), and PM1 (≤1 µm) with maternal thyroid autoimmunity and function during early pregnancy. A total of 15,664 pregnant women were included at 6 to 13+6 gestation weeks in China from 2018 to 2020. Single-pollutant models using generalized linear models (GLMs) showed that each 10 µg/m3 increase in PM2.5 and PM1-2.5 was related with 6% (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.01, 1.12) and 15% (OR = 1.15, 95% CI: 1.08, 1.22) increases in the risk of thyroid autoimmunity, respectively. The odds of thyroid autoimmunity significantly increased with each interquartile range increase in PM2.5 and PM1-2.5 exposure (P for trend <0.001). PM1 exposure was not significantly associated with thyroid autoimmunity. GLM with natural cubic splines demonstrated that increases in PM2.5 and PM1-2.5 exposure were associated with lower maternal FT4 levels, while a negative association between PM1 and FT4 levels was found when exposure exceeded 32.13 µg/m3. Only PM2.5 exposure was positively associated with thyrotropin (TSH) levels. Our findings suggest that high PM exposure is associated with maternal thyroid disruption during the early pregnancy.


Asunto(s)
Autoinmunidad , Material Particulado , Glándula Tiroides , Humanos , Femenino , Embarazo , Adulto , China , Estudios Prospectivos , Contaminantes Atmosféricos , Exposición Materna
13.
Phys Chem Chem Phys ; 26(6): 4885-4897, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38258416

RESUMEN

The porous structure of composite nanofibers plays a key role in improving their electrochemical performance. However, the dynamic evolution of pore structures and their action during ion intercalation/extraction processes for negative electrodes are not clear. Herein, porous carbon composite nanofibers (Fe@Fe2O3/PCNFs) were prepared as negative electrode materials for potassium-ion batteries. Electrochemical test findings revealed that the composites had good electrochemical characteristics, and the porous structure endowed composite electrodes with pseudo-capacitive behaviors. After 1500 discharge/charge cycles at a current density of 1000 mA g-1, the specific capacity of the potassium-ion batteries was 144.8 mAh g-1. We innovatively used synchrotron small-angle X-ray scattering (SAXS) technique to systematically investigate the kinetic process of potassium formation in composites and showed that the kinetic process of potassium reaction in composites can be divided into four stages, and the pores with smaller average diameter distribution are more sensitive to changes in the reaction process. This work paves a new way to study the deposition kinetics of potassium in porous materials, which facilitates the design of porous structures and realizes the development of alkali metal ion-anode materials with high energies.

14.
BMC Pediatr ; 24(1): 203, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38519924

RESUMEN

Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH.


Asunto(s)
Histiocitosis de Células de Langerhans , Hipoalbuminemia , Niño , Humanos , Hipoalbuminemia/complicaciones , Hipoalbuminemia/patología , Histiocitosis de Células de Langerhans/complicaciones , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/patología , Tracto Gastrointestinal/patología , Biopsia , Diarrea/complicaciones
15.
Arch Gynecol Obstet ; 309(5): 1951-1958, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37306740

RESUMEN

PURPOSE: This study aimed to investigate the association between simple markers in fetal abdominal plane, intra-abdominal umbilical venous diameter (DIUV) and abdominal circumference (AC) discordance at 15-20 weeks' gestation, and adverse pregnancy outcomes in monochorionic diamniotic (MCDA) twins. METHODS: We performed a retrospective analysis of MCDA twins with two live fetuses examined at 15-20 weeks from Jun 2020 to Dec 2021 at Beijing Obstetrics and Gynecology Hospital. Measurement of fetal AC and DIUV was performed according to standard protocols. Twin pregnancies with major fetal structural anomalies, chromosomal abnormalities, miscarriage, and twin reversed arterial perfusion sequence were excluded. DIUV and AC discordance in MCDA twins with an adverse pregnancy outcome was compared with a normal pregnancy outcome. Furthermore, the performance of DIUV and AC discordance in predicting adverse pregnancy outcomes in MCDA twins was assessed. RESULTS: A total of 105 women with MCDA twin pregnancies were enrolled, contributing 179 visits. Adverse pregnancy outcomes occurred in 33.3% (35/105) of cases in our study. The intra-observer and inter-observer intraclass correlation coefficient (ICC) of both AC and DIUV were very good or excellent. There was no statistical difference in AC and DIUV discordance (%) between 15-16, 17-18, and 19-20 weeks (χ2 = 3.928, P = 0.140; χ2 = 2.840, P = 0.242). Both AC and DIUV discordance were greater in twins with adverse pregnancy outcomes than that in twins with normal pregnancy outcome at each pregnancy periods. Both AC discordance (OR 1.2, 95% CI 1.1-1.3) and DIUV discordance (OR 1.2, 95% CI 1.1-1.2) were associated with adverse pregnancy outcomes. The AUC for predicting adverse pregnancy outcomes by AC discordance was 0.75 (95% CI 0.68-0.83), with a sensitivity of 58.7% (95% CI 51.9-64.5) and a specificity of 86.2% (95% CI 81.7-88.4). The AUC for predicting adverse pregnancy outcomes by DIUV was 0.78 (95% CI 0.70-0.86), with sensitivity and specificity of 65.1% (95% CI 58.1-70.3) and 86.2% (95% CI 81.7-88.4), respectively. CONCLUSIONS: The AC discordance and DIUV discordance could predict adverse pregnancy outcomes in MCDA twins. When these simple markers occurred, intensive surveillance was recommended.


Asunto(s)
Resultado del Embarazo , Ultrasonografía Prenatal , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Primer Trimestre del Embarazo , Embarazo Gemelar , Músculos Abdominales , Gemelos Monocigóticos , Retardo del Crecimiento Fetal
16.
Arch Gynecol Obstet ; 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38852111

RESUMEN

BACKGROUND: Left-right laterality disorders are a heterogeneous group of disorders caused by an altered position or orientation of the thoracic and intra-abdominal organs and vasculature across the left-right axis. They mainly include situs inversus and heterotaxy. Those disorders are complicated by cardiovascular abnormalities significantly more frequently than situs solitus. METHODS: In this study, 16 patients with a fetal diagnosis of laterality disorder with congenital heart defects (CHD) were evaluated with a single nucleotide polymorphism array (SNP-arry) combined with whole-exome sequencing (WES). RESULTS: Although the diagnostic rate of copy number variations was 0 and the diagnostic rate of WES was 6.3% (1/16), the likely pathogenic gene DNAH11 and the candidate gene OFD1 were ultimately identified. In addition, novel compound heterozygous mutations in the DNAH11 gene and novel hemizygous variants in the OFD1 gene were found. Among the combined CHD, a single atrium/single ventricle had the highest incidence (50%, 8/16), followed by atrioventricular septal defects (37.5%, 6/16). Notably, two rare cases of common pulmonary vein atresia (CPVA) were also found on autopsy. CONCLUSION: This study identified the types of CHD with a high incidence in patients with laterality disorders. It is clear that WES is an effective tool for diagnosing laterality disorders and can play an important role in future research.

17.
Ann Diagn Pathol ; 73: 152357, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38941945

RESUMEN

Upper tract urothelial carcinoma (UTUC) is a relatively rare yet aggressive malignancy. While radical nephroureterectomy (RNU) remains the cornerstone treatment, UTUC has high local and metastatic relapse rates, leading to a dismal prognosis. To identify the clinicopathological factors associated with an increased risk of local and metastatic relapse in UTUC, we conducted a retrospective analysis of 133 consecutive UTUC patients who underwent RNU from 1998 to 2018. Patients lost to follow-up or with a history of bladder cancer were excluded from the study. The remaining 87 patients were categorized into two subgroups: those with tumor recurrence/relapse (40 cases) and those without recurrence/relapse (47 cases). Clinical and pathological characteristics were compared across the two groups. Multiple factors are associated with UTUC recurrence/relapse including larger tumor size, histology divergent differentiations/subtypes, high tumor grade, advanced pathologic T stage, positive margin, lymphovascular invasion (LVI), positive lymph node status, and preoperative hydronephrosis. Multivariate Cox regression analysis revealed that squamous differentiation predicted recurrence/relapse (p = 0.012), independent of tumor stage. Moreover, compared to the conventional histology type, UTUC with squamous differentiation had a significantly higher relapse rate (p = 0.0001) and poorer survival (p = 0.0039). This observation was further validated in invasive high-grade UTUC cases. Our findings suggest that many pathological factors contribute to UTUC recurrence/relapse, particularly, squamous differentiation may serve as an independent risk predictor for relapse and a potent prognosticator for adverse cancer-specific survival in UTUC patients. Recognizing and thoroughly assessing the pathological factors is essential for better oncologic management of UTUC.

18.
Nano Lett ; 23(13): 6027-6034, 2023 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-37387588

RESUMEN

Electrodes play an essential role in controlling electrode-molecule coupling. However, conventional metal electrodes require linkers to anchor the molecule. Van der Waals interaction offers a versatile strategy to connect the electrode and molecule without anchor groups. Except for graphene, the potential of other materials as electrodes to fabricate van der Waals molecular junctions remains unexplored. Herein, we utilize semimetallic transition metal dichalcogenides (TMDCs) 1T'-WTe2 as electrodes to fabricate WTe2/metalated tetraphenylporphyrin (M-TPP)/WTe2 junctions via van der Waals interaction. Compared with chemically bonded Au/M-TPP/Au junctions, the conductance of these M-TPP van der Waals molecular junctions is enhanced by ∼736%. More importantly, WTe2/M-TPP/WTe2 junctions exhibit the tunable conductance from 10-3.29 to 10-4.44 G0 (1.15 orders of magnitude) via single-atom control, recording the widest tunable range of conductance for M-TPP molecular junctions. Our work demonstrates the potential of two-dimensional TMDCs for constructing highly tunable and conductive molecular devices.

19.
J Am Chem Soc ; 145(3): 1617-1630, 2023 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-36625785

RESUMEN

Dipoles are widely involved in π-π interactions and are central to many chemical and biological functions, but their influence on the strength of π-π interactions remains unclear. Here, we report a study of π-π interaction between azulene-based, polar single molecules and between naphthalene-based, nonpolar single molecules. By performing scanning tunneling microscopy break junction measurements of single-molecule conductance, we show that the π-stacked dimers formed by the azulene-based, polar aromatic structures feature higher electrical conductivity and mechanical stability than those formed by the naphthalene-based, nonpolar molecules. Mechanical control of π-π interactions in both rotational and translational motion reveals a sensitive dependence of the stacking strength on relative alignment between the dipoles. The antiparallel alignment of the dipoles was found to be the optimal stacking configuration that underpins the observed enhancement of π-π stacking between azulene-based single molecules. Density functional theory calculations further explained the observed enhancement of stacking strength and the corresponding charge transport efficiency. Our experimental and theoretical results show that the antiparallel alignment of the dipole moments significantly enhances the electronic coupling and mechanical stability of π-π stacking. In addition, in the formation of single-molecule junctions, the azulene group was experimentally and theoretically proved to form a Au-π contact with electrodes with high charge transport efficiency. This paper provides evidence and interpretation of the role of dipoles in π-π interactions at the single-molecule level and offers new insights into potential applications in supramolecular devices.

20.
J Am Chem Soc ; 145(28): 15265-15274, 2023 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-37417934

RESUMEN

Since the early days of quantum mechanics, it has been known that electrons behave simultaneously as particles and waves, and now quantum electronic devices can harness this duality. When devices are shrunk to the molecular scale, it is unclear under what conditions does electron transmission remain phase-coherent, as molecules are usually treated as either scattering or redox centers, without considering the wave-particle duality of the charge carrier. Here, we demonstrate that electron transmission remains phase-coherent in molecular porphyrin nanoribbons connected to graphene electrodes. The devices act as graphene Fabry-Pérot interferometers and allow for direct probing of the transport mechanisms throughout several regimes. Through electrostatic gating, we observe electronic interference fringes in transmission that are strongly correlated to molecular conductance across multiple oxidation states. These results demonstrate a platform for the use of interferometric effects in single-molecule junctions, opening up new avenues for studying quantum coherence in molecular electronic and spintronic devices.

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