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1.
Cell ; 186(10): 2078-2091.e18, 2023 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-37172562

RESUMEN

Neural tube (NT) defects arise from abnormal neurulation and result in the most common birth defects worldwide. Yet, mechanisms of primate neurulation remain largely unknown due to prohibitions on human embryo research and limitations of available model systems. Here, we establish a three-dimensional (3D) prolonged in vitro culture (pIVC) system supporting cynomolgus monkey embryo development from 7 to 25 days post-fertilization. Through single-cell multi-omics analyses, we demonstrate that pIVC embryos form three germ layers, including primordial germ cells, and establish proper DNA methylation and chromatin accessibility through advanced gastrulation stages. In addition, pIVC embryo immunofluorescence confirms neural crest formation, NT closure, and neural progenitor regionalization. Finally, we demonstrate that the transcriptional profiles and morphogenetics of pIVC embryos resemble key features of similarly staged in vivo cynomolgus and human embryos. This work therefore describes a system to study non-human primate embryogenesis through advanced gastrulation and early neurulation.


Asunto(s)
Defectos del Tubo Neural , Neurulación , Técnicas de Cultivo de Tejidos , Animales , Humanos , Blastocisto , Embrión de Mamíferos , Desarrollo Embrionario , Macaca fascicularis , Defectos del Tubo Neural/genética , Defectos del Tubo Neural/patología , Técnicas de Cultivo de Tejidos/métodos
2.
Nature ; 633(8031): 960-967, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39169184

RESUMEN

Inorganic phosphate (Pi) is a fundamental macronutrient for all living organisms, the homeostasis of which is critical for numerous biological activities1-3. As the only known human Pi exporter to date, XPR1 has an indispensable role in cellular Pi homeostasis4,5. Dysfunction of XPR1 is associated with neurodegenerative disease6-8. However, the mechanisms underpinning XPR1-mediated Pi efflux and regulation by the intracellular inositol polyphosphate (InsPP) sensor SPX domain remain poorly understood. Here we present cryo-electron microscopy structures of human XPR1 in Pi-bound closed, open and InsP6-bound forms, revealing the structural basis for XPR1 gating and regulation by InsPPs. XPR1 consists of an N-terminal SPX domain, a dimer-formation core domain and a Pi transport domain. Within the transport domain, three basic clusters are responsible for Pi binding and transport, and a conserved W573 acts as a molecular switch for gating. In addition, the SPX domain binds to InsP6 and facilitates Pi efflux by liberating the C-terminal loop that limits Pi entry. This study provides a conceptual framework for the mechanistic understanding of Pi homeostasis by XPR1 homologues in fungi, plants and animals.


Asunto(s)
Transporte Biológico , Microscopía por Crioelectrón , Fosfatos , Ácido Fítico , Receptor de Retrovirus Xenotrópico y Politrópico , Humanos , Sitios de Unión , Homeostasis , Modelos Moleculares , Fosfatos/metabolismo , Fosfatos/química , Ácido Fítico/metabolismo , Ácido Fítico/química , Unión Proteica , Dominios Proteicos , Receptor de Retrovirus Xenotrópico y Politrópico/química , Receptor de Retrovirus Xenotrópico y Politrópico/metabolismo , Receptor de Retrovirus Xenotrópico y Politrópico/ultraestructura
3.
Nature ; 626(7998): 427-434, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38081299

RESUMEN

Vesicular monoamine transporter 2 (VMAT2) accumulates monoamines in presynaptic vesicles for storage and exocytotic release, and has a vital role in monoaminergic neurotransmission1-3. Dysfunction of monoaminergic systems causes many neurological and psychiatric disorders, including Parkinson's disease, hyperkinetic movement disorders and depression4-6. Suppressing VMAT2 with reserpine and tetrabenazine alleviates symptoms of hypertension and Huntington's disease7,8, respectively. Here we describe cryo-electron microscopy structures of human VMAT2 complexed with serotonin and three clinical drugs at 3.5-2.8 Å, demonstrating the structural basis for transport and inhibition. Reserpine and ketanserin occupy the substrate-binding pocket and lock VMAT2 in cytoplasm-facing and lumen-facing states, respectively, whereas tetrabenazine binds in a VMAT2-specific pocket and traps VMAT2 in an occluded state. The structures in three distinct states also reveal the structural basis of the VMAT2 transport cycle. Our study establishes a structural foundation for the mechanistic understanding of substrate recognition, transport, drug inhibition and pharmacology of VMAT2 while shedding light on the rational design of potential therapeutic agents.


Asunto(s)
Microscopía por Crioelectrón , Proteínas de Transporte Vesicular de Monoaminas , Humanos , Sitios de Unión , Citoplasma/efectos de los fármacos , Citoplasma/metabolismo , Ketanserina/química , Ketanserina/metabolismo , Ketanserina/farmacología , Reserpina/química , Reserpina/metabolismo , Reserpina/farmacología , Serotonina/química , Serotonina/metabolismo , Especificidad por Sustrato , Tetrabenazina/química , Tetrabenazina/metabolismo , Tetrabenazina/farmacología , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Proteínas de Transporte Vesicular de Monoaminas/química , Proteínas de Transporte Vesicular de Monoaminas/metabolismo , Proteínas de Transporte Vesicular de Monoaminas/ultraestructura
4.
Nature ; 610(7932): 575-581, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36224386

RESUMEN

RNA-guided systems, such as CRISPR-Cas, combine programmable substrate recognition with enzymatic function, a combination that has been used advantageously to develop powerful molecular technologies1,2. Structural studies of these systems have illuminated how the RNA and protein jointly recognize and cleave their substrates, guiding rational engineering for further technology development3. Recent work identified a new class of RNA-guided systems, termed OMEGA, which include IscB, the likely ancestor of Cas9, and the nickase IsrB, a homologue of IscB lacking the HNH nuclease domain4. IsrB consists of only around 350 amino acids, but its small size is counterbalanced by a relatively large RNA guide (roughly 300-nt ωRNA). Here, we report the cryogenic-electron microscopy structure of Desulfovirgula thermocuniculi IsrB (DtIsrB) in complex with its cognate ωRNA and a target DNA. We find the overall structure of the IsrB protein shares a common scaffold with Cas9. In contrast to Cas9, however, which uses a recognition (REC) lobe to facilitate target selection, IsrB relies on its ωRNA, part of which forms an intricate ternary structure positioned analogously to REC. Structural analyses of IsrB and its ωRNA as well as comparisons to other RNA-guided systems highlight the functional interplay between protein and RNA, advancing our understanding of the biology and evolution of these diverse systems.


Asunto(s)
ADN , Desoxirribonucleasa I , ARN Guía de Kinetoplastida , Sistemas CRISPR-Cas , Desoxirribonucleasa I/química , Desoxirribonucleasa I/metabolismo , Desoxirribonucleasa I/ultraestructura , ADN/química , ADN/metabolismo , ADN/ultraestructura , ARN Guía de Kinetoplastida/química , ARN Guía de Kinetoplastida/metabolismo , ARN Guía de Kinetoplastida/ultraestructura , Microscopía por Crioelectrón , Proteínas Asociadas a CRISPR/química
5.
Nat Methods ; 20(1): 123-130, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36522503

RESUMEN

Cryo-electron microscopy (cryo-EM) visualizes the atomic structure of macromolecules that are embedded in vitrified thin ice at their close-to-native state. However, the homogeneity of ice thickness, a key factor to ensure high image quality, is poorly controlled during specimen preparation and has become one of the main challenges for high-resolution cryo-EM. Here we found that the uniformity of thin ice relies on the surface flatness of the supporting film, and developed a method to use ultraflat graphene (UFG) as the support for cryo-EM specimen preparation to achieve better control of vitreous ice thickness. We show that the uniform thin ice on UFG improves the image quality of vitrified specimens. Using such a method we successfully determined the three-dimensional structures of hemoglobin (64 kDa), α-fetoprotein (67 kDa) with no symmetry, and streptavidin (52 kDa) at a resolution of 3.5 Å, 2.6 Å and 2.2 Å, respectively. Furthermore, our results demonstrate the potential of UFG for the fields of cryo-electron tomography and structure-based drug discovery.


Asunto(s)
Grafito , Microscopía por Crioelectrón/métodos , Grafito/química , Sustancias Macromoleculares , Tomografía con Microscopio Electrónico
6.
Brief Bioinform ; 24(6)2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37903413

RESUMEN

Accurate prediction of drug-target affinity (DTA) is of vital importance in early-stage drug discovery, facilitating the identification of drugs that can effectively interact with specific targets and regulate their activities. While wet experiments remain the most reliable method, they are time-consuming and resource-intensive, resulting in limited data availability that poses challenges for deep learning approaches. Existing methods have primarily focused on developing techniques based on the available DTA data, without adequately addressing the data scarcity issue. To overcome this challenge, we present the Semi-Supervised Multi-task training (SSM) framework for DTA prediction, which incorporates three simple yet highly effective strategies: (1) A multi-task training approach that combines DTA prediction with masked language modeling using paired drug-target data. (2) A semi-supervised training method that leverages large-scale unpaired molecules and proteins to enhance drug and target representations. This approach differs from previous methods that only employed molecules or proteins in pre-training. (3) The integration of a lightweight cross-attention module to improve the interaction between drugs and targets, further enhancing prediction accuracy. Through extensive experiments on benchmark datasets such as BindingDB, DAVIS and KIBA, we demonstrate the superior performance of our framework. Additionally, we conduct case studies on specific drug-target binding activities, virtual screening experiments, drug feature visualizations and real-world applications, all of which showcase the significant potential of our work. In conclusion, our proposed SSM-DTA framework addresses the data limitation challenge in DTA prediction and yields promising results, paving the way for more efficient and accurate drug discovery processes.


Asunto(s)
Benchmarking , Descubrimiento de Drogas , Sistemas de Liberación de Medicamentos
7.
Nature ; 571(7764): 275-278, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31181567

RESUMEN

Recently developed DNA base editing methods enable the direct generation of desired point mutations in genomic DNA without generating any double-strand breaks1-3, but the issue of off-target edits has limited the application of these methods. Although several previous studies have evaluated off-target mutations in genomic DNA4-8, it is now clear that the deaminases that are integral to commonly used DNA base editors often bind to RNA9-13. For example, the cytosine deaminase APOBEC1-which is used in cytosine base editors (CBEs)-targets both DNA and RNA12, and the adenine deaminase TadA-which is used in adenine base editors (ABEs)-induces site-specific inosine formation on RNA9,11. However, any potential RNA mutations caused by DNA base editors have not been evaluated. Adeno-associated viruses are the most common delivery system for gene therapies that involve DNA editing; these viruses can sustain long-term gene expression in vivo, so the extent of potential RNA mutations induced by DNA base editors is of great concern14-16. Here we quantitatively evaluated RNA single nucleotide variations (SNVs) that were induced by CBEs or ABEs. Both the cytosine base editor BE3 and the adenine base editor ABE7.10 generated tens of thousands of off-target RNA SNVs. Subsequently, by engineering deaminases, we found that three CBE variants and one ABE variant showed a reduction in off-target RNA SNVs to the baseline while maintaining efficient DNA on-target activity. This study reveals a previously overlooked aspect of off-target effects in DNA editing and also demonstrates that such effects can be eliminated by engineering deaminases.


Asunto(s)
ADN/genética , Edición Génica/métodos , Mutagénesis , Mutación , Nucleósido Desaminasas/genética , Ingeniería de Proteínas , ARN/genética , Adenina/metabolismo , Aminohidrolasas/genética , Aminohidrolasas/metabolismo , Citosina/metabolismo , Citosina Desaminasa/genética , Citosina Desaminasa/metabolismo , Células HEK293 , Humanos , Nucleósido Desaminasas/metabolismo , Especificidad por Sustrato , Transfección
8.
Proc Natl Acad Sci U S A ; 119(18): e2117559119, 2022 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-35471903

RESUMEN

The endoplasmic reticulum (ER) is a versatile organelle with diverse functions. Through superresolution microscopy, we show that the peripheral ER in the mammalian cell adopts two distinct forms of tubules. Whereas an ultrathin form, R1, is consistently covered by ER-membrane curvature-promoting proteins, for example, Rtn4 in the native cell, in the second form, R2, Rtn4 and analogs are arranged into two parallel lines at a conserved separation of ∼105 nm over long ranges. The two tubule forms together account for ∼90% of the total tubule length in the cell, with either one being dominant in different cell types. The R1­R2 dichotomy and the final tubule geometry are both coregulated by Rtn4 (and analogs) and the ER sheet­maintaining protein Climp63, which, respectively, define the edge curvature and lumen height of the R2 tubules to generate a ribbon-like structure of well-defined width. Accordingly, the R2 tubule width correlates positively with the Climp63 intraluminal size. The R1 and R2 tubules undergo active remodeling at the second/subsecond timescales as they differently accommodate proteins, with the former effectively excluding ER-luminal proteins and ER-membrane proteins with large intraluminal domains. We thus uncover a dynamic structural dichotomy for ER tubules with intriguing functional implications.


Asunto(s)
Citoesqueleto , Retículo Endoplásmico , Animales , Citoesqueleto/metabolismo , Retículo Endoplásmico/metabolismo , Mamíferos , Microscopía
9.
J Am Chem Soc ; 146(40): 27486-27498, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39198263

RESUMEN

The improvement of hydrogen evolution reaction kinetics can be largely accelerated by introducing a well-designed hydrogen spillover pathway into the catalysts. However, the driving force and mechanism of hydrogen migration on the surface of catalysts are poorly understood and are rarely explored in depth. Here, inspired by the specific ferroelectric property of HfO2, Mn-O-Ca sites in Mn4CaO5, and Fe-Fe sites in hydrogenases, we constructed a bioinspired HfO2 coupled with Ir catalysts (Ir/HfO2@C) with an alkaline hydrogen reverse spillover effect from HfO2 to interface and acid hydrogen spillover effect from Ir to interface. Benefiting from the bidirectional hydrogen spillover pathways controlled by pH, Ir/HfO2@C displays a narrow overpotential difference between acidic and alkaline electrolytes. Remarkably, Ir/HfO2@C shows a remarkable mass current density and turnover frequency value, far exceeding the benchmark Ir/C by 20.6 times. More importantly, this Ir/HfO2@C achieves extraordinarily low overpotentials of 146 and 39 mV at 10 mV cm-2 in seawater and alkaline seawater, respectively. The anion-exchange membrane water electrolyzer equipped with Ir/HfO2@C as a cathode exhibits excellent and stable H2-evolution performance on 2.22 V at 1.0 A cm-2. We expect that the bioinspired strategy will provide a new concept for designing catalytic materials for efficient and pH-universal electrochemical hydrogen production.

10.
Small ; 20(12): e2306991, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37939298

RESUMEN

The shuttle effect, which causes the loss of active sulfur, passivation of lithium anode, and leads to severe capacity attenuation, is currently the main bottleneck for lithium-sulfur batteries. Recent studies have disclosed that molybdenum compounds possess exceptional advantages as a polar substrate to immobilize and catalyze lithium polysulfide such as high conductivity and strong sulfiphilicity. However, these materials show incomplete contact with sulfur/polysulfides, which causes uneven redox conversion of sulfur and results in poor rate performance. Herein, a new type of 2D nano-channeled molybdenum compounds (2D-MoNx) via the 2D organic-polyoxometalate superstructure for accelerating interfacial polysulfide catalysis toward high-performance lithium-sulfur batteries is reported. The 2D-MoNx shows well-interlinked nano-channels, which increase the reactive interface and contact surface with polysulfides. Therefore, the battery equipped with 2D-MoNx displays a high discharge capacity of 912.7 mAh g-1 at 1 C and the highest capacity retention of 523.7 mAh g-1 after 300 cycles. Even at the rate of 2 C, the capacity retention can be maintained at 526.6 mAh g-1 after 300 cycles. This innovative nano-channel and interfacial design of 2D-MoNx provides new nanostructures to optimize the sulfur redox chemistry and eliminate the shuttle effect of polysulfides.

11.
Small ; 20(14): e2307405, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37988711

RESUMEN

The nitridation of noble metals-based catalysts to further enhance their hydrogen evolution reaction (HER) kinetics in neutral and alkaline conditions would be an effective strategy for developing high-performance wide pH HER catalysts. Herein, a facile molten urea method is employed to construct the nitrided Rh nanoclusters (RhxN) supported on N-doped carbon (RhxN-NC). The uniformly distributed RhxN clusters exhibited optimized water bonding and splitting effects, therefore resulting in excellent pH-universal HER performance. The optimized RhxN-NC catalyst only requires 8, 12, and 109 mV overpotentials to reach the current density of 10 mA cm-2 in 0.5 M H2SO4, 1.0 M KOH, and 1.0 M PBS electrolytes, respectively. The spectroscopic characterizations and theoretical calculation further confirm the vital role of Rh-N moieties in RhxN clusters in improving the transfer of electrons and facilitating the generation of H2. This work not only provides a suitable nitridation method for noble metal species in mild conditions but also makes a breakthrough in synthesizing noble metal nitrides-based electrocatalysts to achieve an exceptional wide-pH HER performance and other catalysis.

12.
Mol Carcinog ; 63(8): 1486-1499, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38780182

RESUMEN

Lactate dehydrogenase A (LDHA) is known to promote the growth and invasion of various types of tumors, affects tumor resistance, and is associated with tumor immune escape. But how LDHA reshapes the tumor microenvironment and promotes the progression of renal cell carcinoma (RCC) remains unclear. In this study, we found that LDHA was highly expressed in clear cell RCC (ccRCC), and this high expression was associated with macrophage infiltration, while macrophages were highly infiltrated in ccRCC, affecting patient prognosis via M2-type polarization. Our in vivo and in vitro experiments demonstrated that LDHA and M2-type macrophages could enhance the proliferation, invasion, and migration abilities of ccRCC cells. Mechanistically, high expression of LDHA in ccRCC cells upregulated the expression of EPHA2 in exosomes derived from renal cancer. Exosomal EPHA2 promoted M2-type polarization of macrophages by promoting activation of the PI3K/AKT/mTOR pathway in macrophages, thereby promoting the progression of ccRCC. All these findings suggest that EPHA2 may prove to be a potential therapeutic target for advanced RCC.


Asunto(s)
Carcinoma de Células Renales , Progresión de la Enfermedad , Exosomas , Neoplasias Renales , Macrófagos , Receptor EphA2 , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/genética , Receptor EphA2/metabolismo , Receptor EphA2/genética , Humanos , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Neoplasias Renales/genética , Exosomas/metabolismo , Animales , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Línea Celular Tumoral , Proliferación Celular , L-Lactato Deshidrogenasa/metabolismo , L-Lactato Deshidrogenasa/genética , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Masculino , Microambiente Tumoral , Pronóstico , Serina-Treonina Quinasas TOR/metabolismo , Femenino , Transducción de Señal , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt/metabolismo
13.
Bioconjug Chem ; 35(6): 826-842, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38722674

RESUMEN

In clinical practice, the treatment of colon cancer is faced with the dilemma of metastasis and recurrence, which is related to immunosuppression and hypoxia. Immune checkpoint blockade (ICB) is a negative regulatory pathway of immunity. Immune checkpoint blockade (ICB) is an important immunotherapy method. However, inadequate immunogenicity reduces the overall response rate of ICB. In this study, a tumor microenvironment-responsive nanomedicine (Cu-FACD@MnO2@FA) was prepared to increase host immune response and increase intracellular oxygen levels. Cu-FACD@MnO2@FA preferentially enriched at the tumor site, combined with the immune checkpoint inhibitor alpha PD-L1, induced sufficient immunogenicity to treat colon cancer. Immunofluorescence detection of tumor cells and tissues showed that the expression of hypoxa-inducing factor 1α was significantly down-regulated after treatment and the expression of immunoactivity-related proteins was significantly changed. In vivo treatment in a bilateral tumor mouse model showed complete ablation of the primary tumor and efficient inhibition of the distal tumor. In this study, for the first time, the oxygenation effects of MnO2-coated Cu-doped carbon dots and chemodynamic therapy and a strategy of combining with immuno-blocking therapy were used for treating colon cancer.


Asunto(s)
Carbono , Neoplasias del Colon , Cobre , Ácido Fólico , Compuestos de Manganeso , Óxidos , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Animales , Óxidos/química , Óxidos/farmacología , Cobre/química , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Ratones , Carbono/química , Humanos , Ácido Fólico/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Oxígeno/química , Puntos Cuánticos/química , Línea Celular Tumoral , Ratones Endogámicos BALB C , Microambiente Tumoral/efectos de los fármacos
14.
Chemistry ; 30(17): e202303594, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38278765

RESUMEN

Graphene aerogel (GA) has important application potential as piezoresistive sensors due to its low density, high conductivity, high porosity, and good mechanical properties. However, the fabrication of GA-based sensors with good mechanical properties and excellent sensing performance is still challenging. Herein, liquid- metal-modified GAs (GA/LM) are proposed for the development of an excellent GA-based sensor. GA/LM with three-dimensional interconnected layered structure exhibits excellent compressive stress of 41 KPa and fast response time (<20 ms). While generally flexible GA composites cannot be compressed beyond 80 % strain without plastic deformation, GA/LM demonstrates a high compressive strength of 60 kPa under a strain of 90 %. A real-time pressure sensor was fabricated based on GA/LM-2 to monitor swallowing, pulse beating, finger, wrist and knee bending, and even plantar pressure during walking. These excellent features enable potential applications in health detection.

15.
Psychol Med ; 54(10): 2688-2697, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38571298

RESUMEN

BACKGROUND: Extensive research has explored altered structural and functional networks in major depressive disorder (MDD). However, studies examining the relationships between structure and function yielded heterogeneous and inconclusive results. Recent work has suggested that the structure-function relationship is not uniform throughout the brain but varies across different levels of functional hierarchy. This study aims to investigate changes in structure-function couplings (SFC) and their relevance to antidepressant response in MDD from a functional hierarchical perspective. METHODS: We compared regional SFC between individuals with MDD (n = 258) and healthy controls (HC, n = 99) using resting-state functional magnetic resonance imaging and diffusion tensor imaging. We also compared antidepressant non-responders (n = 55) and responders (n = 68, defined by a reduction in depressive severity of >50%). To evaluate variations in altered and response-associated SFC across the functional hierarchy, we ranked significantly different regions by their principal gradient values and assessed patterns of increase or decrease along the gradient axis. The principal gradient value, calculated from 219 healthy individuals in the Human Connectome Project, represents a region's position along the principal gradient axis. RESULTS: Compared to HC, MDD patients exhibited increased SFC in unimodal regions (lower principal gradient) and decreased SFC in transmodal regions (higher principal gradient) (p < 0.001). Responders primarily had higher SFC in unimodal regions and lower SFC in attentional networks (median principal gradient) (p < 0.001). CONCLUSIONS: Our findings reveal opposing SFC alterations in low-level unimodal and high-level transmodal networks, underscoring spatial variability in MDD pathology. Moreover, hierarchy-specific antidepressant effects provide valuable insights into predicting treatment outcomes.


Asunto(s)
Antidepresivos , Conectoma , Trastorno Depresivo Mayor , Imagen de Difusión Tensora , Imagen por Resonancia Magnética , Humanos , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/diagnóstico por imagen , Masculino , Femenino , Adulto , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Conectoma/métodos , Persona de Mediana Edad , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Estudios de Casos y Controles , Adulto Joven
16.
Catheter Cardiovasc Interv ; 103(6): 897-908, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38654635

RESUMEN

BACKGROUND: Acute kidney injury (AKI) is a frequent and potentially life-threatening complication after percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction (STEMI). However, the relationship between obesity and the risk of AKI in this specific patient population has not been previously examined. METHODS: We queried the National Inpatient Sample (2016-2019) using ICD-10 codes to obtain a sample of adults with STEMI undergoing PCI. All patients were further subcategorized into obese and nonobese cohorts. The primary outcome was the incidence of AKI. Multivariate regression analysis was performed to assess the impact of obesity on AKI. The consistency of this correlation between subgroups was investigated using subgroup analysis and interaction testing. RESULTS: A total of 62,599 (weighted national estimate of 529,016) patients were identified, of which 9.80% (n = 6137) had AKI. Obesity comprised 19.78% (n = 1214) of the AKI cohort. Obese patients were on average younger, male, white, and had more comorbidities. Additionally, there was a significant positive association between obesity and AKI incidence (adjusted odds ratio [aOR]: 1.24, 95% confidence interval [CI]: 1.15-1.34), which was more pronounced in female patients (aOR: 1.56, 95% CI: 1.33-1.82, p < 0.001, p-interaction = 0.008). The AKI incidence in these patients increased steadily during the 4-year study period, and it was consistently higher in obese patients than in nonobese patients (p-trend < 0.001 for all). CONCLUSIONS: Obesity was independently associated with a greater risk of AKI among adults with STEMI undergoing PCI, particularly in female patients.


Asunto(s)
Lesión Renal Aguda , Bases de Datos Factuales , Obesidad , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Intervención Coronaria Percutánea/efectos adversos , Femenino , Masculino , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/epidemiología , Infarto del Miocardio con Elevación del ST/complicaciones , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Persona de Mediana Edad , Factores de Riesgo , Obesidad/epidemiología , Obesidad/complicaciones , Estados Unidos/epidemiología , Incidencia , Anciano , Medición de Riesgo , Resultado del Tratamiento , Factores de Tiempo , Estudios Retrospectivos
17.
Langmuir ; 40(37): 19619-19630, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39213539

RESUMEN

Sc2CO2 MXene has potential applications in energy storage and optoelectronics due to its superior structure and excellent properties. The electronic properties, quantum capacitance, and photocatalytic activity of Cr-doped Sc2CO2 under strain are studied by the density functional theory. Cr doping makes the system produce magnetism. The spin-down states of Sc2CO2-Cr under strain are direct semiconductors, while their spin-up states are indirect semiconductors. Sc2CO2-Cr under +5, -5, -3, and -2% strains in an aqueous system are suitable for cathode material. A large voltage drastically modulates the type of electrode materials. Sc2CO2-Cr under strains from 0 to +2% can perform the oxygen evolution reaction at an alkaline environment, while the Sc2CO2-Cr system under strain is a good for CO2 photocatalysis at pH 0 and 7.

18.
Lupus ; 33(10): 1034-1042, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39033374

RESUMEN

OBJECTIVE: Antiphospholipid syndrome (APS) is an autoimmune disease mainly affecting young individuals. Testing for antiphospholipid antibodies is recommended for young patients who are suspected to have APS. Yet, it is hard to differentiate APS from other acquired thrombophilia disorders in elderly-onset APS patients. This study aim to investigate the characteristics and prognosis of elderly-onset APS. METHODS: This is an observational cohort study. Thrombotic APS patients who underwent follow-ups between 2009 and 2022 were included. Elderly-onset APS patients (onset age ≥60 years) were compared to non-elderly-onset APS patients (onset age <60 years) and matched cases of elderly non-APS patients (age ≥60 years with thrombosis). RESULTS: A total of 161 APS patients were included in this study, 45 (28.0%) were elderly-onset APS. Stroke (35.6% vs. 18.1%, p = .018) was more common at disease onset in elderly-onset APS patients. Compared to non-elderly-onset patients, elderly-onset APS patients were associated with a higher number of cardiovascular risk factors. Elderly-onset APS patients showed significantly lower positive rate (51.1% vs. 71.6%, p = .014) and ratios [1.24 (1.01-1.38) vs. 1.37 (1.16-1.77), p = .004] of lupus anticoagulant. Elderly-onset APS patients had a significantly higher 10-years cumulative all-cause mortality (p < .001) and APS-related mortality than non-elderly-onset patients (p = .002) and elderly non-APS patients (p = .040). CONCLUSIONS: Elderly-onset APS patients have unique disease characteristics with higher 10-years cumulative all-cause mortality and APS-related mortality. Early recognition and control of comorbidities may reduce the recurrence of thrombosis and mortality in elderly-onset APS patients.


Asunto(s)
Edad de Inicio , Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Humanos , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/mortalidad , Femenino , Masculino , Anciano , Persona de Mediana Edad , Pronóstico , Anticuerpos Antifosfolípidos/sangre , Trombosis/epidemiología , Trombosis/etiología , Estudios de Cohortes , Adulto , Factores de Riesgo , Estudios Retrospectivos , Anciano de 80 o más Años , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología
19.
Eur J Neurol ; 31(2): e16147, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37975786

RESUMEN

BACKGROUND AND PURPOSE: The ventral pallidum (VP) regulates involuntary movements, but it is unclear whether the VP regulates the abnormal involuntary movements in Parkinson's disease (PD) patients who have levodopa-induced dyskinesia (LID). To further understand the role of the VP in PD patients with LID (PD-LID), we explored the structural and functional characteristics of the VP in such patients using multimodal magnetic resonance imaging (MRI). METHODS: Thirty-one PD-LID patients, 39 PD patients without LID (PD-nLID), and 28 healthy controls (HCs) underwent T1-weighted MRI, quantitative susceptibility mapping, multi-shell diffusion MRI, and resting-state functional MRI (rs-fMRI). Different measures characterizing the VP were obtained using a region-of-interest-based approach. RESULTS: The left VP in the PD-LID group showed significantly higher intracellular volume fraction (ICVF) and isotropic volume fraction (IsoVF) compared with the PD-nLID and HC groups. Rs-MRI revealed that, compared with the PD-nLID group, the PD-LID group in the medication 'off' state had higher functional connectivity (FC) between the left VP and the left anterior caudate, left middle frontal gyrus and left precentral gyrus, as well as between the right VP and the right posterior ventral putamen and right mediodorsal thalamus. In addition, the ICVF values of the left VP, the FC between the left VP and the left anterior caudate and left middle frontal gyrus were positively correlated with Unified Dyskinesia Rating Scale scores. CONCLUSION: Our multimodal imaging findings show that the microstructural changes of the VP (i.e., the higher ICVF and IsoVF) and the functional change in the ventral striatum-VP-mediodorsal thalamus-cortex network may be associated with pathophysiological mechanisms of PD-LID.


Asunto(s)
Prosencéfalo Basal , Discinesia Inducida por Medicamentos , Enfermedad de Parkinson , Humanos , Levodopa/efectos adversos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/tratamiento farmacológico , Prosencéfalo Basal/patología , Imagen por Resonancia Magnética/métodos , Discinesia Inducida por Medicamentos/diagnóstico por imagen
20.
Inorg Chem ; 63(38): 17372-17377, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39268867

RESUMEN

A zinc-organic hybrid (1) with multifunctional room temperature phosphorescence (RTP) was synthesized. 1 presents light/force-sensitive RTP properties due to the photochromic behavior from gray to light yellow and the transition from crystalline to amorphous state, respectively. Furthermore, inkless printing and information encryption models were successfully constructed to prove their widespread application prospect.

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