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Potassium-ion batteries (PIBs) have attracted ever-increasing interest due to the abundant potassium resources and low cost, which are considered a sustainable energy storage technology. However, the graphite anodes employed in PIBs suffer from low capacity and sluggish reaction kinetics caused by the large radius of potassium ions. Herein, we report nitrogen-doped, defect-rich hollow carbon nanospheres with contact curved interfaces (CCIs) on carbon nanotubes (CNTs), namely CCI-CNS/CNT, to boost both electron transfer and potassium-ion adsorption. Density functional theory calculations validate that engineering CCIs significantly augments the electronic state near the Fermi level, thus promoting electron transfer. In addition, the CCIs exhibit a pronounced affinity for potassium ions, promoting their adsorption and subsequently benefiting potassium storage. As a result, the rationally designed CCI-CNS/CNT anode shows remarkable cyclic stability and rate capability. This work provides a strategy for enhancing the potassium storage performance of carbonaceous materials through CCI engineering, which can be further extended to other battery systems.
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Parvalbumin (PV) interneurons in the auditory cortex (AC) play a crucial role in shaping auditory processing, including receptive field formation, temporal precision enhancement, and gain regulation. PV interneurons are also the primary inhibitory neurons in the tail of the striatum (TS), which is one of the major descending brain regions in the auditory nervous system. However, the specific roles of TS-PV interneurons in auditory processing remain elusive. In this study, morphological and slice recording experiments in both male and female mice revealed that TS-PV interneurons, compared with AC-PV interneurons, were present in fewer numbers but exhibited longer projection distances, which enabled them to provide sufficient inhibitory inputs to spiny projection neurons (SPNs). Furthermore, TS-PV interneurons received dense auditory input from both the AC and medial geniculate body (MGB), particularly from the MGB, which rendered their auditory responses comparable to those of AC-PV interneurons. Optogenetic manipulation experiments demonstrated that TS-PV interneurons were capable of bidirectionally regulating the auditory responses of SPNs. Our findings suggest that PV interneurons can effectively modulate auditory processing in the TS and may play a critical role in auditory-related behaviors.
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Interneuronas , Parvalbúminas , Ratones , Masculino , Femenino , Animales , Parvalbúminas/metabolismo , Interneuronas/fisiología , Neuronas/fisiología , Cuerpo Estriado/fisiología , Percepción Auditiva/fisiologíaRESUMEN
Chemical compositions of crops are of great agronomical importance, as crops serve as resources for nutrition, energy, and medicines for human and livestock. For crop metabolomics research, the lack of crop reference metabolome and high-quality reference compound mass spectra, as well as utilities for metabolic profiling, has hindered the discovery and functional study of phytochemicals in crops. To meet these challenging needs, we have developed the Crop Metabolome database (abbreviated as CropMetabolome) that is dedicated to the construction of crop reference metabolome, repository, and dissemination of crop metabolomic data, and profiling and analytic tools for metabolomics research. CropMetabolome contains a metabolomics database for more than 50 crops (belonging to eight categories) that integrated self-generated raw mass spectral data and public-source datasets. The reference metabolome for 59 crop species was constructed, which have functions that parallel those of reference genome in genomic studies. CropMetabolome also contains 'Standard compound mass spectral library', 'Flavonoids library', 'Pesticide library', and a set of related analytical tools that enable metabolic profiling based on a reference metabolome (CropRefMetaBlast), annotation and identification of new metabolites (CompoundLibBlast), deducing the structure of novel flavonoid derivatives (FlavoDiscover), and detecting possible residual pesticides in crop samples (PesticiDiscover). In addition, CropMetabolome is a repository to share and disseminate metabolomics data and a platform to promote collaborations to develop reference metabolome for more crop species. CropMetabolome is a comprehensive platform that offers important functions in crop metabolomics research and contributes to improve crop breeding, nutrition, and safety. CropMetabolome is freely available at https://www.cropmetabolome.com/.
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Productos Agrícolas , Bases de Datos Factuales , Metaboloma , Metabolómica , Productos Agrícolas/metabolismo , Productos Agrícolas/genética , Metabolómica/métodos , Flavonoides/metabolismo , Espectrometría de MasasRESUMEN
Agent-based models have gained traction in exploring the intricate processes governing the spread of infectious diseases, particularly due to their proficiency in capturing nonlinear interaction dynamics. The fidelity of agent-based models in replicating real-world epidemic scenarios hinges on the accurate portrayal of both population-wide and individual-level interactions. In situations where comprehensive population data are lacking, synthetic populations serve as a vital input to agent-based models, approximating real-world demographic structures. While some current population synthesizers consider the structural relationships among agents from the same household, there remains room for refinement in this domain, which could potentially introduce biases in subsequent disease transmission simulations. In response, this study unveils a novel methodology for generating synthetic populations tailored for infectious disease transmission simulations. By integrating insights from microsample-derived household structures, we employ a heuristic combinatorial optimizer to recalibrate these structures, subsequently yielding synthetic populations that faithfully represent agent structural relationships. Implementing this technique, we successfully generated a spatially-explicit synthetic population encompassing over 17 million agents for Shenzhen, China. The findings affirm the method's efficacy in delineating the inherent statistical structural relationship patterns, aligning well with demographic benchmarks at both city and subzone tiers. Moreover, when assessed against a stochastic agent-based Susceptible-Exposed-Infectious-Recovered model, our results pinpointed that variations in population synthesizers can notably alter epidemic projections, influencing both the peak incidence rate and its onset.
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Enfermedades Transmisibles , Epidemias , Humanos , Enfermedades Transmisibles/epidemiología , Dinámicas no Lineales , China/epidemiologíaRESUMEN
Hippo-Yes-associated protein 1 (YAP1) plays an important role in gastric cancer (GC) progression; however, its regulatory network remains unclear. In this study, we identified Copine III (CPNE3) was identified as a novel direct target gene regulated by the YAP1/TEADs transcription factor complex. The downregulation of CPNE3 inhibited proliferation and invasion, and increased the chemosensitivity of GC cells, whereas the overexpression of CPNE3 had the opposite biological effects. Mechanistically, CPNE3 binds to the YAP1 protein in the cytoplasm, inhibiting YAP1 ubiquitination and degradation mediated by the E3 ubiquitination ligase ß-transducin repeat-containing protein (ß-TRCP). Thereby activating the transcription of YAP1 downstream target genes, which creates a positive feedback cycle to facilitate GC progression. Immunohistochemical analysis demonstrated significant upregulation of CPNE3 in GC tissues. Survival and Cox regression analyses indicated that high CPNE3 expression was an independent prognostic marker for GC. This study elucidated the pivotal involvement of an aberrantly activated CPNE3/YAP1 positive feedback loop in the malignant progression of GC, thereby uncovering novel prognostic factors and therapeutic targets in GC.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Transducción de Señal , Retroalimentación , Línea Celular Tumoral , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proliferación Celular , Regulación Neoplásica de la Expresión GénicaRESUMEN
Printed electronic technology serves as a key component in flexible electronics and wearable devices, yet achieving compatibility with both high resolution and high efficiency remains a significant challenge. Here, we propose a rapid fabrication method of high-resolution nanoparticle microelectronics via self-assembly and transfer printing. The tension gradient-electrostatic attraction composite-induced nanoparticle self-assembly strategy is constructed, which can significantly enhance the self-assembly efficiency, stability, and coverage by leveraging the meniscus Marangoni effect and the electric double-layer effect. The close-packed nanoparticle self-assembly layer can be rapidly formed on microstructure surfaces over a large area. Inspired by ink printing, a transfer printing strategy is further proposed to transform the self-assembly layer into conformal micropatterns. Large-area, high-resolution (2 µm), and ultrathin (1 µm) nanoparticle microelectronics can be stably fabricated, yielding a significant improvement over fluid printing methods. The unique deformability, recoverability, and scalability of nanoparticle microelectronics are revealed, providing promising opportunities for various academic and real applications.
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Intrauterine infection during pregnancy can enhance uterine contractions. A two-pore K+ channel TREK1 is crucial for maintaining uterine quiescence and reducing contractility, with its properties regulated by pH changes in cell microenvironment. Meanwhile, the sodium hydrogen exchanger 1 (NHE1) plays a pivotal role in modulating cellular pH homeostasis, and its activation increases smooth muscle tension. By establishing an infected mouse model of Escherichia coli (E. coli) and lipopolysaccharide (LPS), we used Western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence to detect changes of TREK1 and NHE1 expression in the myometrium, and isometric recording measured the uterus contraction. The NHE1 inhibitor cariporide was used to explore the effect of NHE1 on TREK1. Finally, cell contraction assay and siRNA transfection were performed to clarify the relationship between NHE1 and TREK1 in vitro. We found that the uterine contraction was notably enhanced in infected mice with E. coli and LPS administration. Meanwhile, TREK1 expression was reduced, whereas NHE1 expression was upregulated in infected mice. Cariporide alleviated the increased uterine contraction and promoted myometrium TREK1 expression in LPS-injected mice. Furthermore, suppression of NHE1 with siRNA transfection inhibited the contractility of uterine smooth muscle cells and activated the TREK1. Altogether, our findings indicate that infection increases the uterine contraction by downregulating myometrium TREK1 in mice, and the inhibition of TREK1 is attributed to the activation of NHE1.NEW & NOTEWORTHY Present work found that infection during pregnancy will increase myometrium contraction. Infection downregulated NHE1 and followed TREK1 expression and activation decrease in myometrium, resulting in increased myometrium contraction.
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Guanidinas , Lipopolisacáridos , Miometrio , Canales de Potasio de Dominio Poro en Tándem , Intercambiador 1 de Sodio-Hidrógeno , Sulfonas , Animales , Femenino , Ratones , Embarazo , Escherichia coli , Lipopolisacáridos/toxicidad , Miometrio/metabolismo , ARN Interferente Pequeño/metabolismo , Contracción Uterina/fisiología , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Intercambiador 1 de Sodio-Hidrógeno/metabolismoRESUMEN
Glutamine is a critical amino acid that serves as an energy source, building block, and signaling molecule for the heart tissue and the immune system. However, the role of glutamine metabolism in regulating cardiac remodeling following myocardial infarction (MI) is unknown. In this study, we show in adult male mice that glutamine metabolism is altered both in the remote (contractile) area and in infiltrating macrophages in the infarct area after permanent left anterior descending artery occlusion. We found that metabolites related to glutamine metabolism were differentially altered in macrophages at days 1, 3, and 7 after MI using untargeted metabolomics. Glutamine metabolism in live cells was increased after MI relative to no MI controls. Gene expression in the remote area of the heart indicated a loss of glutamine metabolism. Glutamine administration improved LV function at days 1, 3, and 7 after MI, which was associated with improved contractile and metabolic gene expression. Conversely, administration of BPTES, a pharmacological inhibitor of glutaminase-1, worsened LV function after MI. Neither glutamine nor BPTES administration impacted gene expression or bioenergetics of macrophages isolated from the infarct area. Our results indicate that glutamine metabolism plays a critical role in maintaining LV contractile function following MI, and that glutamine administration improves LV function. Glutamine metabolism may also play a role in regulating macrophage function, but macrophages are not responsive to exogenous pharmacological manipulation of glutamine metabolism.
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BACKGROUND: Convolutional neural network (CNN) can capture the structural features changes of brain aging based on MRI, thus predict brain age in healthy individuals accurately. However, most studies use single feature to predict brain age in healthy individuals, ignoring adding information from multiple sources and the changes in brain aging patterns after mild traumatic brain injury (mTBI) were still unclear. METHODS: Here, we leveraged the structural data from a large, heterogeneous dataset (N = 1464) to implement an interpretable 3D combined CNN model for brain-age prediction. In addition, we also built an atlas-based occlusion analysis scheme with a fine-grained human Brainnetome Atlas to reveal the age-sstratified contributed brain regions for brain-age prediction in healthy controls (HCs) and mTBI patients. The correlations between brain predicted age gaps (brain-PAG) following mTBI and individual's cognitive impairment, as well as the level of plasma neurofilament light were also examined. RESULTS: Our model utilized multiple 3D features derived from T1w data as inputs, and reduced the mean absolute error (MAE) of age prediction to 3.08 years and improved Pearson's r to 0.97 on 154 HCs. The strong generalizability of our model was also validated across different centers. Regions contributing the most significantly to brain age prediction were the caudate and thalamus for HCs and patients with mTBI, and the contributive regions were mostly located in the subcortical areas throughout the adult lifespan. The left hemisphere was confirmed to contribute more in brain age prediction throughout the adult lifespan. Our research showed that brain-PAG in mTBI patients was significantly higher than that in HCs in both acute and chronic phases. The increased brain-PAG in mTBI patients was also highly correlated with cognitive impairment and a higher level of plasma neurofilament light, a marker of neurodegeneration. The higher brain-PAG and its correlation with severe cognitive impairment showed a longitudinal and persistent nature in patients with follow-up examinations. CONCLUSION: We proposed an interpretable deep learning framework on a relatively large dataset to accurately predict brain age in both healthy individuals and mTBI patients. The interpretable analysis revealed that the caudate and thalamus became the most contributive role across the adult lifespan in both HCs and patients with mTBI. The left hemisphere contributed significantly to brain age prediction may enlighten us to be concerned about the lateralization of brain abnormality in neurological diseases in the future. The proposed interpretable deep learning framework might also provide hope for testing the performance of related drugs and treatments in the future.
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Envejecimiento , Conmoción Encefálica , Encéfalo , Imagen por Resonancia Magnética , Redes Neurales de la Computación , Humanos , Adulto , Masculino , Femenino , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Conmoción Encefálica/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Adulto Joven , Anciano , Disfunción Cognitiva/diagnóstico por imagen , Aprendizaje ProfundoRESUMEN
Diabetes (DM) and hypertension (HTN) are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. The combination of DM and HTN significantly accelerates development of renal injury; however, the underlying mechanisms of this synergy are still poorly understood. This study assessed whether mitochondria (MT) dysfunction is essential in developing renal injury in a rat model with combined DM and HTN. Type 1 DM was induced in Wistar rats by streptozotocin (STZ). HTN was induced six weeks later by inter-renal aorta constriction between the renal arteries, so that right kidneys were exposed to HTN while left kidneys were exposed to normotension. Kidneys exposed to DM or HTN alone had only mild glomerular injury and urinary albumin excretion (UAE). In contrast, kidneys exposed to DM plus 8 weeks HTN had significantly increased UAE and glomerular structural damage with reduced glomerular filtration rate. Marked increases in MT-derived reactive oxygen species (ROS) were also observed in right kidneys exposed to HTN+DM. We further tested whether treatment with MT-targeted antioxidant (MitoTEMPO) after the onset of HTN attenuates renal injury in rats with DM+HTN. Results show that kidneys in DM+AC+MitoTEMPO rats had lower UAE, less glomerular damage, and preserved MT function compared to untreated DM+AC rats. Our studies indicate that MT-derived ROS play a major role in promoting kidney dysfunction when DM is combined with HTN. Preserving MT function might be a potential therapeutic approach to halt the development of renal injury when DM coexists with HTN.
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Although obesity is recognized as a risk factor for cardiorenal and metabolic diseases, the impact of parental obesity on the susceptibility of their offspring to renal injury at adulthood is unknown. We examined the impact of parental obesity on offspring kidney function, morphology, and markers of kidney damage after acute kidney injury (AKI). Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN) or a high-fat (H) diet (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were fed N (HN) or H diet (HH) after weaning. All offspring groups were submitted to bilateral AKI by clamping the left and right renal pedicles for 30 min. Compared with male NH and NN offspring from lean parents, male HH and HN offspring from obese parents exhibited higher kidney injury markers such as urinary, renal osteopontin, plasma creatinine, urinary albumin excretion, and neutrophil gelatinase-associated lipocalin (NGAL) levels, and worse histological injury score at 22 wk of age. Only albumin excretion and NGAL were elevated in female HH offspring from obese parents compared with lean and obese offspring from lean parents. We also found an increased mortality rate and worse kidney injury scores after AKI in male offspring from obese parents, regardless of the diet consumed after weaning. Female offspring were protected from major kidney injury after AKI. These results indicate that parental obesity leads to increased kidney injury in their offspring after ischemia-reperfusion in a sex-dependent manner, even when their offspring remain lean.NEW & NOTEWORTHY Offspring from obese parents are more susceptible to kidney injury and worse outcomes following an acute ischemia-reperfusion insult. Male, but not female, offspring from obese parents exhibit increased blood pressure early in life. Female offspring are partially protected against major kidney injury induced by ischemia-reperfusion.
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Lesión Renal Aguda , Riñón , Ratones Endogámicos C57BL , Daño por Reperfusión , Animales , Masculino , Femenino , Daño por Reperfusión/patología , Daño por Reperfusión/metabolismo , Lesión Renal Aguda/etiología , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/fisiopatología , Lesión Renal Aguda/patología , Riñón/fisiopatología , Riñón/patología , Riñón/metabolismo , Factores Sexuales , Obesidad/complicaciones , Obesidad/fisiopatología , Dieta Alta en Grasa , Embarazo , Lipocalina 2/metabolismo , Obesidad Materna/metabolismo , Obesidad Materna/complicaciones , Obesidad Materna/fisiopatología , Efectos Tardíos de la Exposición Prenatal , Ratones , Factores de Riesgo , Modelos Animales de Enfermedad , Biomarcadores/sangreRESUMEN
While carotid intima-media thickness (cIMT) as a noninvasive surrogate measure of atherosclerosis is widely considered a risk factor for stroke, the intrinsic link underlying cIMT and stroke has not been fully understood. We aimed to evaluate the clinical value of cIMT in stroke through the investigation of phenotypic and genetic relationships between cIMT and stroke. We evaluated phenotypic associations using observational data from UK Biobank (N = 21,526). We then investigated genetic relationships leveraging genomic data conducted in predominantly European ancestry for cIMT (N = 45,185) and any stroke (AS, Ncase/Ncontrol=40,585/406,111). Observational analyses suggested an increased hazard of stroke per one standard deviation increase in cIMT (cIMTmax-AS: hazard ratio (HR) = 1.39, 95%CI = 1.09-1.79; cIMTmean-AS: HR = 1.39, 95%CI = 1.09-1.78; cIMTmin-AS: HR = 1.32, 95%CI = 1.04-1.68). A positive global genetic correlation was observed (cIMTmax-AS: [Formula: see text]=0.23, P=9.44 × 10-5; cIMTmean-AS: [Formula: see text]=0.21, P=3.00 × 10-4; cIMTmin-AS: [Formula: see text]=0.16, P=6.30 × 10-3). This was further substantiated by five shared independent loci and 15 shared expression-trait associations. Mendelian randomization analyses suggested no causal effect of cIMT on stroke (cIMTmax-AS: odds ratio (OR)=1.12, 95%CI=0.97-1.28; cIMTmean-AS: OR=1.09, 95%CI=0.93-1.26; cIMTmin-AS: OR=1.03, 95%CI = 0.90-1.17). A putative association was observed for genetically predicted stroke on cIMT (AS-cIMTmax: beta=0.07, 95%CI = 0.01-0.13; AS-cIMTmean: beta=0.08, 95%CI = 0.01-0.15; AS-cIMTmin: beta = 0.08, 95%CI = 0.01-0.16) in the reverse direction MR, which attenuated to non-significant in sensitivity analysis. Our work does not find evidence supporting causal associations between cIMT and stroke. The pronounced cIMT-stroke association is intrinsic, and mostly attributed to shared genetic components. The clinical value of cIMT as a surrogate marker for stroke risk in the general population is likely limited.
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OBJECTIVE: Assess the significance of enlarged lateral lymph nodes (LLN) for disease recurrence, metastasis, and organ preservation in patients with rectal cancer. BACKGROUND: Optimal treatment of rectal adenocarcinoma involving LLN is subject to debate. METHODS: A post hoc analysis of the OPRA trial, a multicenter study of patients with rectal cancer treated with total neoadjuvant therapy (TNT) followed by total mesorectal excision or watch-and-wait management. We analyzed the association of visible LLN (LLN+), LLN≥7 mm (short axis) on baseline MRI, and LLN≥4 mm on restaging MRI with recurrence, metastasis, and rectum preservation. RESULTS: At baseline, 57 out of 324 (18%) patients had LLN+. In 30 (53%) of 57 patients with LLN+ on baseline MRI, the LLN disappeared after TNT. Disease recurrence in LLN was rare (3.5% of patients with LLN+ and 0.4% of patients with LLN-). All patients with recurrence in LLN also had distant metastasis. The rate of organ preservation was significantly lower in patients with LLN≥4 mm on restaging MRI (P=0.013). We found no significant differences in rates of local recurrence or metastasis between patients with LLN+ vs. LLN- and in patients with LLN≥7 vs.<7 mm on baseline MRI. LLN dissection was performed in 3 patients; 2 of them died of distant metastasis. CONCLUSIONS: LLN involvement is not associated with disease recurrence or metastasis, but persistence of LLN≥4 mm after TNT is negatively associated with rectum preservation in patients with locally advanced rectal cancer treated with TNT. Dissection of lateral nodes likely benefits few patients.
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Naturalistic paradigms, such as watching movies during functional magnetic resonance imaging, are thought to prompt the emotional and cognitive processes typically elicited in real life situations. Therefore, naturalistic viewing (NV) holds great potential for studying individual differences. Previous studies have primarily focused on using shorter movie clips, geared toward eliciting specific and often isolated emotions, while the potential behind using full narratives depicted in commercial movies as a proxy for real-life experiences has barely been explored. Here, we offer preliminary evidence that a full narrative movie (FNM), that is, a movie covering a complete narrative arc, can capture complex socio-affective dynamics and their links to individual differences. Using the studyforrest dataset, we investigated inter- and intra-subject similarity in network functional connectivity (NFC) of 14 meta-analytically defined networks across a full narrative, audio-visual movie split into eight consecutive movie segments. We characterized the movie segments by valence and arousal portrayed within the sequences, before utilizing a linear mixed model to analyze which factors explain inter- and intra-subject similarity. Our results show that the model best explaining inter-subject similarity comprised network, movie segment, valence and a movie segment by valence interaction. Intra-subject similarity was influenced significantly by the same factors and an additional three-way interaction between movie segment, valence and arousal. Overall, inter- and intra-subject similarity in NFC were sensitive to the ongoing narrative and emotions in the movie. We conclude that FNMs offer complex content and dynamics that might be particularly valuable for studying individual differences. Further characterization of movie features, such as the overarching narratives, that enhance individual differences is needed for advancing the potential of NV research.
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Conectoma , Imagen por Resonancia Magnética , Películas Cinematográficas , Red Nerviosa , Humanos , Adulto , Conectoma/métodos , Red Nerviosa/fisiología , Red Nerviosa/diagnóstico por imagen , Emociones/fisiología , Individualidad , Femenino , Masculino , Narración , Adulto Joven , Nivel de Alerta/fisiologíaRESUMEN
BACKGROUND: Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1â s (FEV1) <80% predicted and FEV1/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated comorbidities. METHODS: We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected single nucleotide polymorphisms (SNPs) reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait linkage disequilibrium score regression to estimate genome-wide genetic correlation between PRISm and pulmonary and extrapulmonary traits. Phenome-wide association studies of top SNPs were performed. RESULTS: 22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (rg) between PRISm and spirometric COPD (rg=0.62, p<0.001) was observed, and genetic correlation with type 2 diabetes (rg=0.12, p=0.007). Phenome-wide association studies showed that 18 of 22 signals were associated with diabetic traits and seven with blood pressure traits. CONCLUSION: This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene MECOM), rs9431040 (HLX), rs62018863 (TMEM114) and rs185937162 (HLA-B), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity.
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Diabetes Mellitus Tipo 2 , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Estudio de Asociación del Genoma Completo , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/genética , Diabetes Mellitus Tipo 2/genética , Pulmón , Volumen Espiratorio Forzado/genética , Espirometría , Capacidad VitalRESUMEN
Understanding the growth mechanisms of nanomaterials is crucial for effectively controlling their morphology which may affect their properties. Here, the growth process of indium nanoplates is studied using in situ liquid cell transmission electron microscopy. Quantitative analysis shows that the growth of indium nanoplate is limited by surface reaction. Besides, the growth process has two stages, which is different from that of other metal nanoplates reported previously. At the first stage, indium particles transform gradually from face-centered cubic to body-centered tetragonal (bct) structure as the seeds grow. At the second stage, the seeds grow faster than at the first stage and form indium triangular nanoplates. Indium triangular nanoplates have a bct structure with {011}-twin, which is found to form through kinetic reactions. In addition, the shape evolution of truncated triangle nanoplate with multiple twin planes is studied. The growth rate of truncated edge changes with the varied number of re-entrant grooves. The present work provides valuable insights into the growth mechanism of metal nanoplates with low-symmetric structure and the role of twin planes in the shape evolution of plate-like metal nanomaterials.
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The advent of optical metrology applications has necessitated the development of compact, reliable, and cost-effective picosecond lasers operating around 900â nm, specifically catering to the requirements of precise ranging. In response to this demand, our work introduces an innovative solution-an all-fiber, all-polarization-maintaining (PM) figure-9 mode-locked laser operating at 915â nm. The proposed figure-9 Nd-doped fiber laser has a 69.2 m long cavity length, strategically designed and optimized to yield pulses with a combination of high pulse energy and low repetition rate. The laser can generate 915â nm laser pulses with a pulse energy of 4.65 nJ, a pulse duration of 15.2 ps under the repetition rate of 3.05â MHz. The 1064â nm amplified spontaneous emission (ASE) is deliberately filtered out, in order to prevent parasitic lasing and increase the spectral proportion of the 915â nm laser. The all-PM fiber configuration of this laser imparts exceptional mode-locking performance and environmental robustness, which is confirmed by long-term output power and spectral stability test. This compact and long-term reliable fiber laser could be a promising light source for applications like inter-satellite ranging.
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Endothelial permeability deterioration is involved in ventilator-induced lung injury (VILI). The integrality of vascular endothelial glycocalyx (EG) is closely associated with endothelial permeability. The hypothesis was that vascular EG shedding participates in VILI through promoting endothelial permeability. In the present study, male Sprague-Dawley (SD) rats were ventilated with high tidal volume (VT =40 ml/kg) or low tidal volume (VT =8 ml/kg) to investigate the effects of different tidal volume and ventilation durations on EG in vivo. We report disruption of EG during the period of high tidal volume ventilation characterized by increased glycocalyx structural components (such as syndecan-1, heparan sulfate, hyaluronan) in the plasma and decreased the expression of syndecan-1 in the lung tissues. Mechanistically, the disruption of EG was associated with increased proinflammatory cytokines and matrix metalloproteinase in the lung tissues. Collectively, these results demonstrate that the degradation of EG is involved in the occurrence and development of VILI in rats, and the inflammatory mechanism mediated by activation of the NF-κB signaling pathway may be partly responsible for the degradation of EG in VILI in rats. This study enhances our understanding of the pathophysiological processes underlying VILI, shedding light on potential therapeutic targets to mitigate VILI.
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Sindecano-1 , Lesión Pulmonar Inducida por Ventilación Mecánica , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Glicocálix/metabolismo , Lesión Pulmonar Inducida por Ventilación Mecánica/tratamiento farmacológico , Lesión Pulmonar Inducida por Ventilación Mecánica/metabolismo , Pulmón/metabolismoRESUMEN
OBJECTIVE: This study aims to examine the ability of deep learning (DL)-derived imaging features for the prediction of radiation pneumonitis (RP) in locally advanced non-small-cell lung cancer (LA-NSCLC) patients. MATERIALS AND METHODS: The study cohort consisted of 90 patients from the Fudan University Shanghai Cancer Center and 59 patients from the Affiliated Hospital of Jiangnan University. Occurrences of RP were used as the endpoint event. A total of 512 3D DL-derived features were extracted from two regions of interest (lung-PTV and PTV-GTV) delineated on the pre-radiotherapy planning CT. Feature selection was done using LASSO regression, and the classification models were built using the multilayered perceptron method. Performances of the developed models were evaluated by receiver operating characteristic curve analysis. In addition, the developed models were supplemented with clinical variables and dose-volume metrics of relevance to search for increased predictive value. RESULTS: The predictive model using DL features derived from lung-PTV outperformed the one based on features extracted from PTV-GTV, with AUCs of 0.921 and 0.892, respectively, in the internal test dataset. Furthermore, incorporating the dose-volume metric V30Gy into the predictive model using features from lung-PTV resulted in an improvement of AUCs from 0.835 to 0.881 for the training data and from 0.690 to 0.746 for the validation data, respectively (DeLong pâ¯< 0.05). CONCLUSION: Imaging features extracted from pre-radiotherapy planning CT using 3D DL networks could predict radiation pneumonitis and may be of clinical value for risk stratification and toxicity management in LA-NSCLC patients. CLINICAL RELEVANCE STATEMENT: Integrating DL-derived features with dose-volume metrics provides a promising noninvasive method to predict radiation pneumonitis in LA-NSCLC lung cancer radiotherapy, thus improving individualized treatment and patient outcomes.
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Psoriasis is a chronic systemic inflammatory cutaneous disease. Where the immune system plays an important role in its pathogenesis, with key inflammatory intercellular signalling peptides and proteins including IL-17 and IL-23. The psychoneurological system also figures prominently in development of psoriasis. There is a high prevalence of comorbidity between psoriasis and mental health disorders such as depression, anxiety and mania. Patients with psoriasis often suffer from pathological pain in the lesions, and their neurological accidents could improve the lesions in innervated areas. The immune system and the psychoneurological system interact closely in the pathogenesis of psoriasis. Patients with psoriasis exhibit abnormal levels of neuropeptides both in circulating and localized lesion, acting as immunomodulators involved in the inflammatory response. Moreover, receptors for inflammatory factors are expressed in both peripheral and central nervous systems (CNSs), suggesting that nervous system can receive and be influenced by signals from immune system. Key inflammatory intercellular signalling peptides and proteins in psoriasis, such as IL-17 and IL-23, can be involved in sensory signalling and may affect synaptic plasticity and the blood-brain barrier of CNS through the circulation. This review provides an overview of the multiple effects on the peripheral and CNS under conditions of systemic inflammation in psoriasis, providing a framework and inspiration for in-depth studies of neuroimmunomodulation in psoriasis.