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1.
Cell ; 187(10): 2521-2535.e21, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38697107

RESUMEN

Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.


Asunto(s)
Inmunoterapia , Lípidos , ARN , Microambiente Tumoral , Animales , Perros , Femenino , Humanos , Ratones , Antígenos de Neoplasias/inmunología , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/inmunología , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Línea Celular Tumoral , Citocinas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Glioblastoma/terapia , Glioblastoma/inmunología , Glioma/terapia , Glioma/inmunología , Inmunoterapia/métodos , Ratones Endogámicos C57BL , Neoplasias/terapia , Neoplasias/inmunología , ARN/química , ARN/uso terapéutico , ARN Mensajero/metabolismo , ARN Mensajero/genética , Lípidos/química
2.
EMBO J ; 43(13): 2606-2635, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38806659

RESUMEN

Microtubule-based kinesin motor proteins are crucial for intracellular transport, but their hyperactivation can be detrimental for cellular functions. This study investigated the impact of a constitutively active ciliary kinesin mutant, OSM-3CA, on sensory cilia in C. elegans. Surprisingly, we found that OSM-3CA was absent from cilia but underwent disposal through membrane abscission at the tips of aberrant neurites. Neighboring glial cells engulf and eliminate the released OSM-3CA, a process that depends on the engulfment receptor CED-1. Through genetic suppressor screens, we identified intragenic mutations in the OSM-3CA motor domain and mutations inhibiting the ciliary kinase DYF-5, both of which restored normal cilia in OSM-3CA-expressing animals. We showed that conformational changes in OSM-3CA prevent its entry into cilia, and OSM-3CA disposal requires its hyperactivity. Finally, we provide evidence that neurons also dispose of hyperactive kinesin-1 resulting from a clinic variant associated with amyotrophic lateral sclerosis, suggesting a widespread mechanism for regulating hyperactive kinesins.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Cilios , Cinesinas , Neuroglía , Animales , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Cinesinas/metabolismo , Cinesinas/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Neuroglía/metabolismo , Cilios/metabolismo , Neuronas/metabolismo , Mutación , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/patología
3.
PLoS Biol ; 22(8): e3002615, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39159282

RESUMEN

Dynamic properties are essential for microtubule (MT) physiology. Current techniques for in vivo imaging of MTs present intrinsic limitations in elucidating the isotype-specific nuances of tubulins, which contribute to their versatile functions. Harnessing the power of the AlphaFold2 pipeline, we engineered a strategy for the minimally invasive fluorescence labeling of endogenous tubulin isotypes or those harboring missense mutations. We demonstrated that a specifically designed 16-amino acid linker, coupled with sfGFP11 from the split-sfGFP system and integration into the H1-S2 loop of tubulin, facilitated tubulin labeling without compromising MT dynamics, embryonic development, or ciliogenesis in Caenorhabditis elegans. Extending this technique to human cells and murine oocytes, we visualized MTs with the minimal background fluorescence and a pathogenic tubulin isoform with fidelity. The utility of our approach across biological contexts and species set an additional paradigm for studying tubulin dynamics and functional specificity, with implications for understanding tubulin-related diseases known as tubulinopathies.


Asunto(s)
Caenorhabditis elegans , Proteínas Fluorescentes Verdes , Microtúbulos , Tubulina (Proteína) , Tubulina (Proteína)/metabolismo , Tubulina (Proteína)/genética , Animales , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Humanos , Microtúbulos/metabolismo , Ratones , Proteínas Fluorescentes Verdes/metabolismo , Proteínas Fluorescentes Verdes/genética , Ingeniería de Proteínas/métodos , Oocitos/metabolismo
4.
Development ; 150(2)2023 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-36661357

RESUMEN

Olfactory sensory neurons (OSNs) form embryonically and mature perinatally, innervating glomeruli and extending dendrites with multiple cilia. This process and its timing are crucial for odor detection and perception and continues throughout life. In the olfactory epithelium (OE), differentiated OSNs proceed from an immature (iOSN) to a mature (mOSN) state through well-defined sequential morphological and molecular transitions, but the precise mechanisms controlling OSN maturation remain largely unknown. We have identified that a GTPase, ARL13B, has a transient and maturation state-dependent expression in OSNs marking the emergence of a primary cilium. Utilizing an iOSN-specific Arl13b-null murine model, we examined the role of ARL13B in the maturation of OSNs. The loss of Arl13b in iOSNs caused a profound dysregulation of the cellular homeostasis and development of the OE. Importantly, Arl13b null OSNs demonstrated a delay in the timing of their maturation. Finally, the loss of Arl13b resulted in severe deformation in the structure and innervation of glomeruli. Our findings demonstrate a previously unknown role of ARL13B in the maturation of OSNs and development of the OE.


Asunto(s)
Factores de Ribosilacion-ADP , GTP Fosfohidrolasas , Neuronas Receptoras Olfatorias , Animales , Ratones , Cilios , Neurogénesis , Mucosa Olfatoria , Factores de Ribosilacion-ADP/genética
5.
Mol Psychiatry ; 29(4): 914-928, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38212376

RESUMEN

We describe evidence for dissociable roles of the medial and lateral orbitofrontal cortex (OFC) in major depressive disorder (MDD) from structure, functional activation, functional connectivity, metabolism, and neurochemical systems. The reward-related medial orbitofrontal cortex has lower connectivity and less reward sensitivity in MDD associated with anhedonia symptoms; and the non-reward related lateral OFC has higher functional connectivity and more sensitivity to non-reward/aversive stimuli in MDD associated with negative bias symptoms. Importantly, we propose that conventional antidepressants act to normalize the hyperactive lateral (but not medial) OFC to reduce negative bias in MDD; while other treatments are needed to operate on the medial OFC to reduce anhedonia, with emerging evidence suggesting that ketamine may act in this way. The orbitofrontal cortex is the key cortical region in emotion and reward, and the current review presents much new evidence about the different ways that the medial and lateral OFC are involved in MDD.


Asunto(s)
Anhedonia , Trastorno Depresivo Mayor , Corteza Prefrontal , Humanos , Anhedonia/fisiología , Antidepresivos/uso terapéutico , Antidepresivos/farmacología , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/tratamiento farmacológico , Emociones/fisiología , Ketamina/uso terapéutico , Ketamina/farmacología , Corteza Prefrontal/metabolismo , Corteza Prefrontal/fisiopatología , Recompensa
6.
Chem Soc Rev ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39382539

RESUMEN

Reactions on electrocatalytic interfaces often involve multiple processes, including the diffusion, adsorption, and conversion of reaction species and the interaction between reactants and electrocatalysts. Generally, these processes are constantly changing rather than being in a steady state. Recently, dynamic evolution processes on electrocatalytic interfaces have attracted increasing attention owing to their significant roles in catalytic reaction kinetics. In this review, we aim to provide insights into the dynamic evolution processes in electrocatalysis to emphasize the importance of unsteady-state processes in electrocatalysis. Specifically, the dynamic structure evolution of electrocatalysts, methods for the characterization of the dynamic evolution and the strategies for the regulation of the dynamic evolution for improving electrocatalytic performance are summarized. Finally, the conclusion and outlook on the research on dynamic evolution processes in electrocatalysis are presented. It is hoped that this review will provide a deeper understanding of dynamic evolution in electrocatalysis, and studies of electrocatalytic reaction processes and kinetics on the unsteady-state microscopic spatial and temporal scales will be given more attention.

7.
Chem Soc Rev ; 53(21): 10620-10659, 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-39268976

RESUMEN

Electrocatalysts are the key components of electrochemical energy storage and conversion devices. High performance electrocatalysts can effectively reduce the energy barrier of the chemical reactions, thereby improving the conversion efficiency of energy devices. The electrocatalytic reaction mainly experiences adsorption and desorption of molecules (reactants, intermediates and products) on a catalyst surface, accompanied by charge transfer processes. Therefore, surface control of electrocatalysts plays a pivotal role in catalyst design and optimization. In recent years, many studies have revealed that the rational design and regulation of a defect structure can result in rearrangement of the atomic structure on the catalyst surface, thereby efficaciously promoting the electrocatalytic performance. However, the relationship between defects and catalytic properties still remains to be understood. In this review, the types of defects, synthesis methods and characterization techniques are comprehensively summarized, and then the intrinsic relationship between defects and electrocatalytic performance is discussed. Moreover, the application and development of defects are reviewed in detail. Finally, the challenges existing in defective electrocatalysts are summarized and prospected, and the future research direction is also suggested. We hope that this review will provide some principal guidance and reference for researchers engaged in defect and catalysis research, better help researchers understand the research status and development trends in the field of defects and catalysis, and expand the application of high-performance defective electrocatalysts to the field of electrocatalytic engineering.

8.
Nano Lett ; 24(42): 13285-13292, 2024 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-39439361

RESUMEN

Experimental realizations of bound states in the continuum (BICs) with strong robustness and advanced maneuverability in optical loss systems remain a long-standing challenge in nanophotonics. Here, we propose and fabricate a paradigm of diatomic metagratings incorporating the Su-Schrieffer-Heeger model into the design of plasmonic nanocavities to demonstrate optical resonators with a continuous "quasi-BICs (qBICs)-BICs-qBICs" transition. These resonators feature a topological band inversion, making high-quality (Q) resonances immune to the perturbation of incident angles and geometrical parameters. Furthermore, we strive to establish theoretical models to verify the topological nature of BICs-inspired resonances and introduce nonlinear optical probes to quantify strongly enhanced local fields at high-Q resonances. Our findings may provide a simple yet feasible design strategy for facilitating the dissipationless manipulation of surface/interface-enhanced light-matter interactions at the nanoscale, substantially broadening the functional scope of metaphotonics.

9.
Neuroimage ; 299: 120837, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39241898

RESUMEN

Sleep deprivation has been demonstrated to exert widespread and intricate impacts on the brain network. The human brain network is a modular network composed of interconnected nodes. This network consists of provincial hubs and connector hubs, with provincial hubs having diverse connectivities within their own modules, while connector hubs distribute their connectivities across different modules. The latter is crucial for integrating information from various modules and ensuring the normal functioning of the modular brain. However, there has been a lack of systematic investigation into the impact of sleep deprivation on brain connector hubs. In this study, we utilized functional connectivity from resting-state functional magnetic resonance imaging, as well as structural connectivity from diffusion-weighted imaging, to systematically explore the variation of connector hub properties in the cerebral cortex after one night of sleep deprivation. The normalized participation coefficients (PCnorm) were utilized to identify connector hubs. In both the functional and structural networks, connector hubs exhibited a significant increase in average PCnorm, indicating the diversity enhancement of the connector hub following sleep deprivation. This enhancement is associated with increased network cost, reduced modularity, and decreased small-worldness, but enhanced global efficiency. This may potentially signify a compensatory mechanism within the brain following sleep deprivation. The significantly affected connector hubs were primarily observed in both the Control Network and Salience Network. We believe that the observed results reflect the increasing demand on the brain to invest more effort at preventing performance deterioration after sleep loss, in exchange for increased communication efficiency, especially involving systems responsible for neural resource allocation and cognitive control. These results have been replicated in an independent dataset. In conclusion, this study has enhanced our understanding of the compensatory mechanism in the brain response to sleep deprivation. This compensation is characterized by an enhancement in the connector hubs responsible for inter-modular communication, especially those related to neural resource and cognitive control. As a result, this compensation comes with a higher network cost but leads to an improvement in global communication efficiency, akin to a more random-like network manner.


Asunto(s)
Conectoma , Imagen de Difusión por Resonancia Magnética , Imagen por Resonancia Magnética , Red Nerviosa , Privación de Sueño , Humanos , Privación de Sueño/fisiopatología , Privación de Sueño/diagnóstico por imagen , Masculino , Adulto , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Red Nerviosa/fisiología , Conectoma/métodos , Adulto Joven , Femenino , Encéfalo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatología , Corteza Cerebral/fisiología
10.
EMBO J ; 39(12): e103955, 2020 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-32338401

RESUMEN

Cytoskeletal-based molecular motors produce force perpendicular to their direction of movement. However, it remains unknown whether and why motor proteins generate sidesteps movement along their filamentous tracks in vivo. Using Hessian structured illumination microscopy, we located green fluorescent protein (GFP)-labeled intraflagellar transport (IFT) particles inside sensory cilia of live Caenorhabditis elegans with 3-6-nanometer accuracy and 3.4-ms resolution. We found that IFT particles took sidesteps along axoneme microtubules, demonstrating that IFT motors generate torque in a living animal. Kinesin-II and OSM-3-kinesin collaboratively drive anterograde IFT. We showed that the deletion of kinesin-II, a torque-generating motor protein, reduced sidesteps, whereas the increase of neck flexibility of OSM-3-kinesin upregulated sidesteps. Either increase or decrease of sidesteps of IFT kinesins allowed ciliogenesis to the regular length, but changed IFT speeds, disrupted axonemal ninefold symmetry, and inhibited sensory cilia-dependent animal behaviors. Thus, an optimum level of IFT kinesin sidestepping is associated with the structural and functional fidelity of cilia.


Asunto(s)
Animales Modificados Genéticamente/metabolismo , Axonema/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Cilios/metabolismo , Cinesinas/metabolismo , Animales , Animales Modificados Genéticamente/genética , Axonema/genética , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Cilios/genética , Cinesinas/genética
11.
Small ; 20(31): e2401506, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38431925

RESUMEN

Reaching rapid reaction kinetics of oxygen reduction (ORR) and oxygen evolution reactions (OER) is critical for realizing efficient rechargeable zinc-air batteries (ZABs). Herein, a novel CoNi-CoN3 composite site containing CoNi alloyed nanoparticles and CoN3 moieties is first constructed in N-doped carbon nanosheet matrix (CoNi-CoN3/C). Benefiting from the high electroactivity of CoNi-CoN3 composite sites and large surface area, CoNi-CoN3/C shows a superior half-wave potential (0.88 V versus RHE) for ORR and a small overpotential (360 mV) for OER at 10 mA cm-2. Theoretical calculations have demonstrated that the introduction of CoNi alloys has modulated the electronic distributions near the CoN3 moiety, inducing the d-band center of CoNi-CoN3 composite site to shift down, thus stabilizing the valence state of Co active sites and balancing the adsorption of OER/ORR intermediates. Accordingly, the reaction energy trends exhibit optimized overpotentials for OER/ORR, leading to superior battery performances. For aqueous and flexible quasi-solid-state rechargeable ZABs with CoNi-CoN3/C as catalyst, a large power density (250 mW cm-2) and high specific capacity (804 mAh g-1) are achieved. The in-depth understanding of the electroactivity enhancement mechanism of interactive metal nanoparticles and metal coordinated with nitrogen (MNx) moieties is crucial for designing novel high-performance metal/nitrogen-doped carbon (M─N─C) catalysts.

12.
Kidney Blood Press Res ; 49(1): 676-686, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39047687

RESUMEN

INTRODUCTION: There was limited research on the epidemiology of hyperphosphatemia in early-stage chronic kidney disease (CKD) patients. We aimed to explore the clinical characteristics and prognostic value of hyperphosphatemia in patients with CKD stages 1-2. METHODS: We enrolled adult patients with CKD stages 1-2 from 24 regional central hospitals across China. Hyperphosphatemia was defined as a serum phosphate level exceeding 1.45 mmol/L. The study outcomes included all-cause and cardiovascular (CV) mortality. Cox proportional hazard models were used to investigate the association of hyperphosphatemia with all-cause and CV mortality. RESULTS: Among 99,266 patients with CKD stages 1-2 across China, the prevalence of hyperphosphatemia was 8.3%. The prevalence of hyperphosphatemia was increased with the level of urinary protein and was higher in younger and female patients. Among 63,121 patients with survival information, during a median of 5.2 years follow-up period, there were 436 (8.0%) and 4,695 (8.1%) deaths in those with and without hyperphosphatemia, respectively. After adjusting for potential confounders, compared with patients without hyperphosphatemia, patients with hyperphosphatemia were associated with a higher risk of all-cause mortality (hazard ratio: 1.28, 95% CI: 1.16-1.41). Although nearly 60.3% of hyperphosphatemia could be relieved without phosphate-lowering drug therapy among patients with CKD stages 1-2, transient hyperphosphatemia was also associated with an increased risk of all-cause mortality (p = 0.048). CONCLUSIONS: Hyperphosphatemia was not rare in patients with CKD stages 1-2 and was associated with an increased risk of mortality. Clinicians should closely monitor serum phosphorus levels in patients with CKD, even in those with normal kidney function.


Asunto(s)
Hiperfosfatemia , Insuficiencia Renal Crónica , Humanos , Hiperfosfatemia/sangre , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/sangre , Femenino , Masculino , Persona de Mediana Edad , Anciano , China/epidemiología , Adulto , Pronóstico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Prevalencia
13.
BMC Geriatr ; 24(1): 237, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448801

RESUMEN

BACKGROUND: Quantitative computed tomography (QCT)-based lumbar bone mineral density (LBMD) has been used to diagnose osteoporosis. This study explored the value of lower thoracic BMD (TBMD) in diagnosing osteoporosis in older adults during CT lung cancer screening. METHODS: This study included 751 subjects who underwent QCT scans with both LBMD and TBMD. 141 of them was selected for a validation. Osteoporosis was diagnosed based on LBMD using the ACR criteria (gold standard). TBMD thresholds were obtained using receiver operating characteristic curve. TBMD was also translated into LBMD (TTBMD) and osteoporosis was defined based on TTBMD using ACR criteria. The performance of TBMD and TTBMD in identifying osteoporosis was determined by Kappa test. The associations between TBMD- and TTBMD-based osteoporosis and fracture were tested in 227 subjects with followed up status of spine fracture. RESULTS: The performance of TBMD in identifying osteoporosis was low (kappa = 0.66) if using the ACR criteria. Two thresholds of TBMD for identifying osteopenia (128 mg/cm3) and osteoporosis (91 mg/cm3) were obtained with areas under the curve of 0.97 and 0.99, respectively. The performance of the identification of osteoporosis/osteopenia using the two thresholds or TTBMD both had good agreement with the gold standard (kappa = 0.78, 0.86). Similar results were observed in validation population. Osteoporosis identified using the thresholds (adjusted hazard ratio (HR) = 18.72, 95% confidence interval (CI): 5.13-68.36) or TTBMD (adjusted HR = 10.28, 95% CI: 4.22-25.08) were also associated with fractures. CONCLUSION: Calculating the threshold of TBMD or normalizing TBMD to LBMD are both useful in identifying osteoporosis in older adults during CT lung cancer screening.


Asunto(s)
Enfermedades Óseas Metabólicas , Fracturas Óseas , Neoplasias Pulmonares , Osteoporosis , Humanos , Anciano , Detección Precoz del Cáncer , Densidad Ósea , Neoplasias Pulmonares/diagnóstico por imagen , Osteoporosis/diagnóstico por imagen , Osteoporosis/epidemiología , Vértebras Torácicas/diagnóstico por imagen , Tomografía Computarizada por Rayos X
14.
BMC Public Health ; 24(1): 2833, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39407171

RESUMEN

BACKGROUND: The post COVID-19 health condition of Chinese residents infected with Omicron is not clear after the change of epidemic prevention policies. This study aimed to clarify the epidemiology and associated factors about health status of rehabilitation patients. METHODS: A quick questionnaire study based on C19-YRSm was conducted in mainland China through internet from May 1, 2023, to May 7, 2023. Chinese native speakers infected with Omicron variant agreed to participate were included. Persisting symptom and living habits were simultaneously inquired. Logistic regression analysis was used to identify the associated factors. RESULTS: In this study 753 individuals were included. Of whom 57.90% were males, 89.38% did not seek medical service, 99.47% recovered within less than 120 days. Breathlessness (47.68%), cognitive impairment (44.89%), Anxiety/mood changes (33.20%), pain/discomfort (32.94%), fatigue or tiredness not improved by rest (32.27%) and post-exertional malaise (30.01%) were the top reported key symptoms. Less than 10% respondents reported functional limitations. The prevalence of fever was reported greater than that of other symptoms, with dry eyes at 14.87%, appetite change at 14.34%, and hair loss at 12.22%. Middle age (OR: 2.353, 95%CI: 1.171 ~ 4.729), underlying diseases (OR: 2.293, 95%CI: 1.216 ~ 4.324), severe key symptom (OR: 6.168, 95%CI: 1.376 ~ 27.642) and at least one other symptom (OR: 1.847, 95%CI: 1.225 ~ 2.718)during the recovery were the risk factors of poor overall health after infection (current overall health score <8; 74.10%), while daily exercise in recovery period (OR: 0.457, 95%CI: 0.229 ~ 0.913), a low-fat diet (OR: 0.600, 95%CI: 0.401 ~ 0.898) and the recovery time from 2 to 4 months (OR: 0.639, 95%CI: 0.445 ~ 0.918) were the protective factors. CONCLUSION: This is the first time to use the C19-YRSm scale to evaluate the health status in China. The study revealed prevalence of persistent symptoms within 120 days after Omicron onset.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , China/epidemiología , Masculino , Femenino , Estudios Transversales , Adulto , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto Joven , Anciano , Estado de Salud , Adolescente , Pandemias
15.
Echocardiography ; 41(8): e15897, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39045808

RESUMEN

Congenitally correct transposition of the great arteries (cc-TGA) is an extremely rare congenital cardiac malposition. It can be detected antenatally by echocardiography. This case report describes a 58-year-old female patient who presented with tachycardia. The combination of cc-TGA and isolated levocardia is incidentally diagnosed by transthoracic echocardiography and cardiac magnetic resonance imaging.


Asunto(s)
Ecocardiografía , Levocardia , Transposición de los Grandes Vasos , Humanos , Femenino , Transposición de los Grandes Vasos/diagnóstico por imagen , Persona de Mediana Edad , Ecocardiografía/métodos , Levocardia/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos
16.
Proc Natl Acad Sci U S A ; 118(37)2021 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-34507987

RESUMEN

The formation of the branched actin networks is essential for cell polarity, but it remains unclear how the debranching activity of actin filaments contributes to this process. Here, we showed that an evolutionarily conserved coronin family protein, the Caenorhabditis elegans POD-1, debranched the Arp2/3-nucleated actin filaments in vitro. By fluorescence live imaging analysis of the endogenous POD-1 protein, we found that POD-1 colocalized with Arp2/3 at the leading edge of the migrating C. elegans neuroblasts. Conditional mutations of POD-1 in neuroblasts caused aberrant actin assembly, disrupted cell polarity, and impaired cell migration. In C. elegans one-cell-stage embryos, POD-1 and Arp2/3, moved together during cell polarity establishment, and inhibition of POD-1 blocked Arp2/3 motility and affected the polarized cortical flow, leading to symmetric segregation of cell fate determinants. Together, these results indicate that F-actin debranching organizes actin network and cell polarity in migrating neuroblasts and asymmetrically dividing embryos.


Asunto(s)
Citoesqueleto de Actina/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Polaridad Celular/fisiología , Proteínas de Microfilamentos/metabolismo , Citoesqueleto de Actina/fisiología , Complejo 2-3 Proteico Relacionado con la Actina/metabolismo , Actinas/metabolismo , Animales , División Celular Asimétrica/fisiología , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/fisiología , Movimiento Celular/fisiología , Proteínas de Microfilamentos/fisiología , Células-Madre Neurales/metabolismo
17.
BMC Musculoskelet Disord ; 25(1): 479, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890706

RESUMEN

BACKGROUND: This work aimed to investigate the change in fingerprint depth and the recovery rule of fingerprint biological recognition function after repairing finger abdominal defects and rebuilding fingerprint with a free flap. METHOD: From April 2018 to March 2023, we collected a total of 43 cases of repairing finger pulp defects using the free flap of the fibular side of the great toe with the digital nerve. After surgery, irregular follow-up visits were conducted to observe fingerprint clarity, perform the ninhydrin test or detect visible sweating with the naked eye. We recorded fingerprint clarity, nail shape, two-point discrimination, cold perception, warm perception and fingerprint recognition using smartphones. The reconstruction process of the repaired finger was recorded to understand the changes in various observation indicators and their relationship with the depth of the fingerprint. The correlation between fingerprint depth and neural repair was determined, and the process of fingerprint biological recognition function repair was elucidated. RESULT: All flaps survived, and we observed various manifestations in different stages of nerve recovery. The reconstructed fingerprint had a clear fuzzy process, and the depth changes of the fingerprint were consistent with the changes in the biological recognition function curve. CONCLUSION: The free flap with the digital nerve is used to repair finger pulp defects. The reconstructed fingerprint has a biological recognition function, and the depth of the fingerprint is correlated with the process of nerve repair. The fingerprint morphology has a dynamic recovery process, and it can reach a stable state after 6-8 months.


Asunto(s)
Traumatismos de los Dedos , Colgajos Tisulares Libres , Traumatismos de los Tejidos Blandos , Humanos , Masculino , Femenino , Adulto , Colgajos Tisulares Libres/trasplante , Colgajos Tisulares Libres/inervación , Persona de Mediana Edad , Traumatismos de los Dedos/cirugía , Traumatismos de los Tejidos Blandos/cirugía , Adulto Joven , Recuperación de la Función , Procedimientos de Cirugía Plástica/métodos , Dedos del Pie/cirugía , Dedos del Pie/inervación , Dedos/inervación , Dedos/cirugía , Resultado del Tratamiento , Peroné/trasplante , Peroné/cirugía , Adolescente , Anciano
18.
J Electrocardiol ; 84: 27-31, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38479052

RESUMEN

BACKGROUND: In the field of mobile health, portable dynamic electrocardiogram (ECG) monitoring devices often have a limited number of lead electrodes due to considerations, such as portability and battery life. This situation leads to a contradiction between the demand for standard 12­lead ECG information and the limited number of leads collected by portable devices. METHODS: This study introduces a composite ECG vector reconstruction network architecture based on convolutional neural network (CNN) combined with recurrent neural network by using leads I, II, and V2. This network is designed to reconstruct three­lead ECG signals into 12­lead ECG signals. A 1D CNN abstracts and extracts features from the spatial domain of the ECG signals, and a bidirectional long short-term memory network analyzes the temporal trends in the signals. Then, the ECG signals are inputted into the model in a multilead, single-channel manner. RESULTS: Under inter-patient conditions, the mean reconstructed Root mean squared error (RMSE) for precordial leads V1, V3, V4, V5, and V6 were 28.7, 17.3, 24.2, 36.5, and 25.5 µV, respectively. The mean overall RMSE and reconstructed Correlation coefficient (CC) were 26.44 µV and 0.9562, respectively. CONCLUSION: This paper presents a solution and innovative approach for recovering 12­lead ECG information when only three­lead information is available. After supplementing with comprehensive leads, we can analyze the cardiac health status more comprehensively across 12 dimensions.


Asunto(s)
Aprendizaje Profundo , Electrocardiografía , Estudios de Factibilidad , Procesamiento de Señales Asistido por Computador , Humanos , Electrocardiografía/métodos , Reproducibilidad de los Resultados , Redes Neurales de la Computación
19.
J Headache Pain ; 25(1): 67, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38679721

RESUMEN

BACKGROUND: Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis. METHODS: We searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach. RESULTS: A total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23). CONCLUSION: Acupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence.


Asunto(s)
Terapia por Acupuntura , Antidepresivos Tricíclicos , Cefalea de Tipo Tensional , Humanos , Cefalea de Tipo Tensional/terapia , Cefalea de Tipo Tensional/prevención & control , Cefalea de Tipo Tensional/tratamiento farmacológico , Antidepresivos Tricíclicos/uso terapéutico , Terapia por Acupuntura/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto
20.
J Sports Sci Med ; 23(2): 465-474, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38841634

RESUMEN

This study aimed to identify the optimal surface for sprint interval training to maximize transfer effects on physical performance measures on the grass pitch. Using a randomized controlled trial design, 40 collegiate female soccer players were equally assigned to three experimental groups performing short sprint interval training (SSIT: 4 sets of 10 repetitions with 5 seconds all-out running, with a 50-second recovery period between each effort and a 3-minute rest interval between sets) on SAND, GRASS, LAND, and a control group. Before and after a 7-week training period, participants underwent a series of field-based tests to evaluate countermovement jump (CMJ), 20-m linear sprint, Illinois change of direction (CoD) speed, Yo-Yo IR1, 2.4 km time trial, and maximal kicking distance (MKD) performance. A two-way analysis of variance with repeated measures was conducted on the data, along with Bonferroni post hoc testing. After the intervention, the control group did not show any changes, while the SAND, GRASS and LAND training groups demonstrated improvements (p = 0.001) in their performance as follows: CMJ (effect size [ES] = 1.21, 0.97, 0.64), 20-m linear sprint (ES = -0.81, -0.55, -0.41), Illinois CoD (ES = -0.72, -0.79, -0.41), Yo-Yo IR1 (ES = 1.86, 1.19, 1.12), 2.4 km time trail (ES = -0.82, -0.62, -0.49), and MKD (ES = 0.60, 0.90, 0.72), respectively. Comparative analysis of SAND, GRASS, and LAND revealed that performing SSIT on SAND results in a significantly greater gain in CMJ than LAND (p = 0.041). Analyzing individual responses to training interventions indicated that the training surface had a favorable influence on CMJ (SAND vs. LAND, p = 0.009), but on other variables no statistically significant (p > 0.05) differences were observed. Considering these findings, it is advised that strength and conditioning coaches use the SAND surface as the initial choice for SSIT sessions regarding greater gains (i.e., ES) in performance. This recommendation aims to facilitate more favorable transfer in physical fitness adaptation on a soccer grass pitch. In case of unavailability of SAND surface, GRASS surface would be a suitable alternative to enhance the physical fitness of collegiate female soccer players.


Asunto(s)
Rendimiento Atlético , Aptitud Física , Poaceae , Carrera , Fútbol , Humanos , Fútbol/fisiología , Femenino , Rendimiento Atlético/fisiología , Aptitud Física/fisiología , Adulto Joven , Carrera/fisiología , Arena , Entrenamiento de Intervalos de Alta Intensidad/métodos , Prueba de Esfuerzo
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