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Pathological cardiac hypertrophy is a complex process that often leads to heart failure. Label-free proteomics has emerged as an important platform to reveal protein variations and to elucidate the mechanisms of cardiac hypertrophy. Endomyocardial biopsy is a minimally invasive technique for sampling cardiac tissue, but it yields only limited amounts of an ethically permissible specimen. After regular pathological examination, the remaining trace samples pose significant challenges for effective protein extraction and mass spectrometry analysis. Herein, we developed trace cardiac tissue proteomics based on the anchor-nanoparticles (TCPA) method. We identified an average of 6666 protein groups using â¼50 µg of myocardial interventricular septum samples by TCPA. We then applied TCPA to acquire proteomics from patients' cardiac samples both diagnosed as hypertrophic hearts and myocarditis controls and identified significant alterations in pathways such as regulation of actin cytoskeleton, oxidative phosphorylation, and cGMP-PKG signaling pathway. Moreover, we found multiple lipid metabolic pathways to be dysregulated in transthyretin cardiac amyloidosis compared to other types of cardiac hypertrophy. TCPA offers a new technique for studying pathological cardiac hypertrophy and can serve as a platform toolbox for proteomic research in other cardiac diseases.
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Miocardio , Nanopartículas , Proteómica , Proteómica/métodos , Humanos , Miocardio/metabolismo , Miocardio/patología , Miocardio/química , Nanopartículas/química , Cardiomegalia/metabolismo , Cardiomegalia/patología , Cardiomegalia/diagnóstico , Amiloidosis/metabolismo , Amiloidosis/patología , Neuropatías Amiloides FamiliaresRESUMEN
BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the most common neurological problems occurring in the perinatal period. However, there still is not a promising approach to reduce long-term neurodevelopmental outcomes of HIE. Recently, itaconate has been found to exhibit anti-oxidative and anti-inflammatory effects. However, the therapeutic efficacy of itaconate in HIE remains inconclusive. Therefore, this study attempts to explore the pathophysiological mechanisms of oxidative stress and inflammatory responses in HIE as well as the potential therapeutic role of a derivative of itaconate, 4-octyl itaconate (4OI). METHODS: We used 7-day-old mice to induce hypoxic-ischemic (HI) model by right common carotid artery ligation followed by 1 h of hypoxia. Behavioral experiments including the Y-maze and novel object recognition test were performed on HI mice at P60 to evaluate long-term neurodevelopmental outcomes. We employed an approach combining non-targeted metabolomics with transcriptomics to screen alterations in metabolic profiles and gene expression in the hippocampal tissue of the mice at 8 h after hypoxia. Immunofluorescence staining and RT-PCR were used to evaluate the pathological changes in brain tissue cells and the expression of mRNA and proteins. 4OI was intraperitoneally injected into HI model mice to assess its anti-inflammatory and antioxidant effects. BV2 and C8D1A cells were cultured in vitro to study the effect of 4OI on the expression and nuclear translocation of Nrf2. We also used Nrf2-siRNA to further validate 4OI-induced Nrf2 pathway in astrocytes. RESULTS: We found that in the acute phase of HI, there was an accumulation of pyruvate and lactate in the hippocampal tissue, accompanied by oxidative stress and pro-inflammatory, as well as increased expression of antioxidative stress and anti-inflammatory genes. Treatment of 4OI could inhibit activation and proliferation of microglial cells and astrocytes, reduce neuronal death and relieve cognitive dysfunction in HI mice. Furthermore, 4OI enhanced nuclear factor erythroid-2-related factor (Nfe2l2; Nrf2) expression and nuclear translocation in astrocytes, reduced pro-inflammatory cytokine production, and increased antioxidant enzyme expression. CONCLUSION: Our study demonstrates that 4OI has a potential therapeutic effect on neuronal damage and cognitive deficits in HIE, potentially through the modulation of inflammation and oxidative stress pathways by Nrf2 in astrocytes.
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Animales Recién Nacidos , Astrocitos , Hipoxia-Isquemia Encefálica , Factor 2 Relacionado con NF-E2 , Fármacos Neuroprotectores , Succinatos , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Hipoxia-Isquemia Encefálica/patología , Ratones , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Succinatos/farmacología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Modelos Animales de EnfermedadRESUMEN
Isoindigo, an electron-withdrawing building block for polymeric field-effect transistors, has long been considered to be non-fluorescent. Moreover, using electron-deficient heterocycle to replace the phenyl ring in the isoindigo core for better electron transport behaviour is synthetically challenging. Here we report the syntheses of a series of tetraazaisoindigos, including pyrazinoisoindigo (PyrII), pyrimidoisoindigo (PymII) and their hybrid (PyrPymII), and the investigation on their photophysical and electric properties. Proper flanking groups need to be chosen to stabilize these highly electron-deficient bislactams. Both PyrII and PymII derivatives show lower LUMO energy levels than that of naphthalene bisimide (NDI). Interestingly, PyrII is instinctively unstable and can be easily reduced, while both PymII derivatives are stable. More surprisingly, PymII derivatives are highly fluorescent and their photoluminescence quantum yields are around 40%, 133 times higher than that of reported isoindigo derivatives. UV-vis spectroscopic results and theoretical calculations show that strong intramolecular hydrogen-bond exists in PymII, which prohibits it from non-radiative decay and accounts for its fluorescent behaviour. PymII deriviatives are n-type semiconductors, while Ph-PyrII and the hybrid show balanced ambipolar charge transport behaviour, all among the best isoindigo derivatives. Our study not only discloses the structure-property relationship of tetraazaisoindigos, but also provides electron-deficient monomers for conjugated polymers.
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BACKGROUND: Smoking is a significant public health concern in China and a leading cause of lung cancer deaths among adults. This study aims to employ three methods to estimate smoking-attributable lung cancer mortality among Chinese adults from 2000 to 2020. METHODS: Population attributable fractions (PAFs) of lung cancer deaths caused by smoking were estimated using lagged smoking prevalence, Peto-Lopez, and dose-response relationship methods, separately. Smoking exposure was obtained from national tobacco surveys in China, and relative risks (RR) were derived from a meta-analysis of state-of-the-art studies among the Chinese population. Finally, we estimated the sex- and age-stratified smoking-attributable lung cancer deaths in Chinese population in 2000, 2005, 2010, 2015, and 2020. RESULTS: The PAFs estimated using 5- and 10-year lagged smoking prevalence method (45-47%) and Peto-Lopez method (46-47%) were similar, while PAFs calculated using the dose-response method were highest (47-58%). The PAFs were consistently higher in males than in females. Age-specific PAFs estimated by lagged smoking prevalence method (54-60%) and the Peto-Lopez method (57-61%) in males were similar and relatively stable, with slight decreases in older populations, while the dose-response relationship-based PAFs increased with age and fluctuated by year. By using the above methods, smoking-attributable lung cancer deaths were estimated to be 134,100, 134,600, 136,600, and 155,300 in 2000 increasing to 310,300, 301,100, 306,000, and 314,700 in 2020, respectively. CONCLUSION: The estimation from dose-response methods could better reflect the smoking effect, however, high-quality data and accurate estimation of parameters are necessary.
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Neoplasias Pulmonares , Adulto , Femenino , Humanos , Masculino , China/epidemiología , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Fumar/efectos adversos , Fumar/epidemiología , Fumar TabacoRESUMEN
OBJECTIVE: To investigate the effects of the school visual environment on depressive symptoms in children and adolescents based on cohort study in eastern China. The school visual environment-related indicators included in this study comprise personal factors (visual impairment) and school-related factors (classroom lighting, school green spaces and school air quality). METHOD: The follow-up cohort comprises 15,348 students from 283 primary and secondary schools in eastern China. This represents the one-year outcomes of a school-based myopia-mental health cohort study. Data collection includes basic demographics (age, gender, region, etc.), physical examination indicators, behavioral indicators, and school visual environment-related indicators. RESULT: After a one-year follow-up, we found that compared to the more severe vision impairment group (≤4.0), healthy vision group (≥5.0) had a positive effect against the occurrence of depressive symptoms during consecutive follow-ups, with an RR value of 0.61 (95% CI: 0.57-0.66). Higher values of blackboard illumination appear to be associated with greater positive effects, with an RR (Q75%â¼Q100% range) value of 0.87(95% CI: 0.81-0.93). School green spaces seem to exhibit relatively good positive effects when in the Q25%â¼Q75% range. The combination of physical activity (Weekly high-intensity exercise) with school air quality(PM2.5≤50%)showed a better positive effect, with an RR value of 0.51(95%CI:0.48-0.55). CONCLUSION: When addressing students' depressive symptoms, it is crucial to improve the visual environment both at the school level and in students' personal level. Paying appropriate attention to modifiable behaviors, like regular participation in high-intensity exercise sessions, can help alleviate students' depressive symptoms.
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Ciudades , Depresión , Instituciones Académicas , Estudiantes , Humanos , China/epidemiología , Masculino , Femenino , Depresión/epidemiología , Estudios Prospectivos , Adolescente , Niño , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , IluminaciónRESUMEN
Spacecraft pose estimation using computer vision has garnered increasing attention in research areas such as automation system theory, control theory, sensors and instruments, robot technology, and automation software. Confronted with the extreme environment of space, existing spacecraft pose estimation methods are predominantly multi-stage networks with complex operations. In this study, we propose an approach for spacecraft homography pose estimation with a single-stage deep convolutional neural network for the first time. We formulated a homomorphic geometric constraint equation for spacecraft with planar features. Additionally, we employed a single-stage 2D keypoint regression network to obtain homography 2D keypoint coordinates for spacecraft. After decomposition to obtain the rough spacecraft pose based on the homography matrix constructed according to the geometric constraint equation, a loss function based on pixel errors was employed to refine the spacecraft pose. We conducted extensive experiments using widely used spacecraft pose estimation datasets and compared our method with state-of-the-art techniques in the field to demonstrate its effectiveness.
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Attendance absences have a substantial impact on student's future physical and mental health as well as academic progress. Numerous personal, familial, and social issues are among the causes of student absences. Any kind of absence from school should be minimized. Extremely high rates of student absences may indicate the abrupt commencement of a serious school health crisis or public health crisis, such as the spread of tuberculosis or COVID-19, which provides school health professionals with an early warning. We take the extreme values in absence data as the object and attempt to apply the extreme value theory (EVT) to describe the distribution of extreme values. This study aims to predict extreme instances of student absences. School health professionals can take preventative measures to reduce future excessive absences, according to the predicted results. Five statistical distributions were applied to individually characterize the extreme values. Our findings suggest that EVT is a useful tool for predicting extreme student absences, thereby aiding preventative measures in public health.
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Absentismo , COVID-19 , Estudiantes , Humanos , China/epidemiología , Estudiantes/estadística & datos numéricos , COVID-19/epidemiología , COVID-19/prevención & control , Instituciones Académicas , Masculino , Femenino , Niño , AdolescenteRESUMEN
OBJECTIVES: This study aimed to investigate the diagnostic performance of computed tomography (CT) fractional flow reserve (CT-FFR) derived from standard images (STD) and images processed via first-generation (SnapShot Freeze, SSF1) and second-generation (SnapShot Freeze 2, SSF2) motion correction algorithms. METHODS: 151 patients who underwent coronary CT angiography (CCTA) and invasive coronary angiography (ICA)/FFR within 3 months were retrospectively included. CCTA images were reconstructed using an iterative reconstruction technique and then further processed through SSF1 and SSF2 algorithms. All images were divided into three groups: STD, SSF1, and SSF2. Obstructive stenosis was defined as a diameter stenosis of ≥ 50 % in the left main artery or ≥ 70 % in other epicardial vessels. Stenosis with an FFR of ≤ 0.8 or a diameter stenosis of ≥ 90 % (as revealed via ICA) was considered ischemic. In patients with multiple lesions, the lesion with lowest CT-FFR was used for patient-level analysis. RESULTS: The overall quality score in SSF2 group (median = 3.67) was markedly higher than that in STD (median = 3) and SSF1 (median = 3) groups (P < 0.001). The best correlation (r = 0.652, P < 0.001) and consistency (mean difference = 0.04) between the CT-FFR and FFR values were observed in the SSF2 group. At the per-lesion level, CT-FFRSSF2 outperformed CT-FFRSSF1 in diagnosing ischemic lesions (area under the curve = 0.887 vs. 0.795, P < 0.001). At the per-patient level, the SSF2 group also demonstrated the highest diagnostic performance. CONCLUSION: The SSF2 algorithm significantly improved CCTA image quality and enhanced its diagnostic performance for evaluating stenosis severity and CT-FFR calculations.
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Algoritmos , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Humanos , Reserva del Flujo Fraccional Miocárdico/fisiología , Femenino , Masculino , Angiografía por Tomografía Computarizada/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Angiografía Coronaria/métodos , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/fisiopatología , Anciano , Reproducibilidad de los Resultados , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Sensibilidad y Especificidad , Movimiento (Física)RESUMEN
BACKGROUND: Computed tomography (CT) fractional flow reserve (FFR)-derived functional SYNTAX score (FSSCT-FFR) is a valuable method for guiding treatment strategy in patients with multivessel coronary artery disease. Dynamic CT myocardial perfusion imaging (CT-MPI) demonstrates higher diagnostic accuracy than CT-FFR in identifying hemodynamically significant coronary artery disease. We aimed to evaluate the feasibility of CT-MPI-derived FSS (FSSCT-MPI) with reference to invasive FSS. METHODS: In this retrospective study, patients with multivessel coronary artery disease who underwent dynamic CT-MPI+ coronary CT angiography and invasive coronary angiography or FFR within 4 weeks were consecutively included. Invasive (FSSinvasive) and noninvasive FSS (FSSCT-MPI and FSSCT-FFR) were calculated by an online calculator, which assigned points to lesions with hemodynamic significance (defined as FFRinvasive ≤0.80, invasive coronary angiography diameter stenosis ≥90%, CT-FFR ≤0.80, and myocardial ischemia on CT-MPI). Weighted κ value and net reclassification index were calculated to determine the consistency and incremental discriminatory power of FSSCT-MPI. Receiver operating characteristic curve analysis was used for the comparison of FSSCT-MPI and FSSCT-FFR in detecting intermediate- to high-risk patients. RESULTS: A total of 119 patients (96 men; 64.6±10.6 years) with 305 obstructive lesions were included. The average FSSCT-MPI, FSSCT-FFR, and FSSinvasive were 15.58±13.03, 16.18±13.30, and 13.11±12.22, respectively. The agreement on risk classification based on the FSSCT-MPI tertiles was good (weighted κ, 0.808). With reference to FSSinvasive, FSSCT-MPI correctly reclassified 27 (22.7%) patients from the intermediate- to high SYNTAX score group to the low-score group (net reclassification index, 0.30; P<0.001). In patients with severe calcification, FSSCT-MPI had better diagnostic value than FSSCT-FFR in detecting intermediate- to high-risk patients when compared with FSSinvasive (area under the curve, 0.976 versus 0.884; P<0.001). CONCLUSIONS: Noninvasive FSS derived from CT-MPI is feasible and has strong concordance with FSSinvasive. It allows accurate categorization of FSS in patients with multivessel coronary artery disease, in particular with severe calcification.
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Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Imagen de Perfusión Miocárdica , Masculino , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Imagen de Perfusión Miocárdica/métodos , Estudios Retrospectivos , Estudios de Factibilidad , Tomografía Computarizada por Rayos X/métodos , Angiografía Coronaria/métodos , Angiografía por Tomografía Computarizada/métodos , Valor Predictivo de las PruebasRESUMEN
Protoporphyrinogen IX oxidase (PPO, E.C. 1.3.3.4) plays a pivotal role in chlorophyll biosynthesis in plants, making it a prime target for herbicide development. In this study, we conducted an investigation aimed at discovering PPO-inhibiting herbicides. Through this endeavor, we successfully identified a series of novel compounds based on the pyridazinone scaffold. Following structural optimization and biological assessment, compound 10ae, known as ethyl 3-((6-fluoro-5-(6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate, emerged as a standout performer. It exhibited robust activity against Nicotiana tabacum PPO (NtPPO) with an inhibition constant (Ki) value of 0.0338 µM. Concurrently, we employed molecular simulations to obtain further insight into the binding mechanism with NtPPO. Additionally, another compound, namely, ethyl 2-((6-fluoro-5-(5-methyl-6-oxo-4-(trifluoromethyl)pyridazin-1(6H)-yl)benzo[d]thiazol-2-yl)thio)propanoate (10bh), demonstrated broad-spectrum and highly effective herbicidal properties against all six tested weeds (Leaf mustard, Chickweed, Chenopodium serotinum, Alopecurus aequalis, Poa annua, and Polypogon fugax) at the dosage of 150 g a.i./ha through postemergence application in a greenhouse. This work identified a novel lead compound (10bh) that showed good activity in vitro and excellent herbicidal activity in vivo and had promising prospects as a new PPO-inhibiting herbicide lead.
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Diseño de Fármacos , Inhibidores Enzimáticos , Herbicidas , Nicotiana , Proteínas de Plantas , Protoporfirinógeno-Oxidasa , Piridazinas , Protoporfirinógeno-Oxidasa/antagonistas & inhibidores , Protoporfirinógeno-Oxidasa/metabolismo , Protoporfirinógeno-Oxidasa/química , Protoporfirinógeno-Oxidasa/genética , Piridazinas/química , Piridazinas/farmacología , Herbicidas/farmacología , Herbicidas/química , Herbicidas/síntesis química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Relación Estructura-Actividad , Nicotiana/metabolismo , Nicotiana/enzimología , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/antagonistas & inhibidores , Proteínas de Plantas/genética , Simulación del Acoplamiento Molecular , Estructura Molecular , Malezas/efectos de los fármacos , Malezas/enzimología , CinéticaRESUMEN
Brain structural changes in Parkinson's disease (PD) are progressive throughout the disease course. Changes in surface morphology with disease progression remain unclear. This study aimed to assess the volumetric and shape changes of the subcortical nuclei during disease progression and explore their association with clinical symptoms. Thirty-four patients and 32 healthy controls were enrolled. The global volume and shape of the subcortical nuclei were compared between patients and controls at baseline. The volume and shape changes of the subcortical nuclei were also explored between baseline and 2 years of follow-up. Association analysis was performed between the volume of subcortical structures and clinical symptoms. In patients with PD, there were significantly atrophied areas in the left pallidum and left putamen, while in healthy controls, the right putamen was dilated compared to baseline. The local morphology of the left pallidum was correlated with Mini Mental State Examination scores. The left putamen shape variation was negatively correlated with changes in Unified Parkinson's Disease Rating Scale PART III scores. Local morphological atrophy of the putamen and pallidum is an important pathophysiological change in the development of PD, and is associated with motor symptoms and cognitive status in patients with PD.
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Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/patología , Imagen por Resonancia Magnética , Encéfalo/patología , Putamen/patología , Progresión de la Enfermedad , Atrofia/patologíaRESUMEN
Introduction: Associations between parental anxiety and adolescent internet addiction have been documented in the literature; however, few studies have analyzed the role of the family environment in this relationship. This study aims to explore the relationship between parental anxiety and adolescent internet addiction while also investigating the indirect relationships involving multiple dimensions of the family environment and child emotional behavior issues. Methods: Surveys were conducted among 6,296 parent-child pairs. We administered SDQ, CIAS-R, and FES-CV to assess adolescents' issues and internet addiction, and evaluate family environment. Additionally, parents completed GAD-7 to assess parental anxiety levels.Results: Correlation analysis revealed that the family environment and adolescent emotional behavior issues played an indirect relationship in the link between parental anxiety and internet addiction. Discussion: The findings emphasize the importance of addressing parental anxiety and fostering a positive family environment as effective measures to alleviate adolescent emotional behavior problems and reduce the risk of internet addiction.
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OBJECTIVES: We undertook time-stratified analyses of the National Health and Nutrition Examination Survey in the US to assess time trends (1999-2020) in the associations of blood lead (BL) with blood pressure, mortality, the BL-associated population attributable fraction (PAF). METHODS: Vital status of participants, 20-79âyears old at enrolment, was ascertained via the National Death Index. Regressions, mediation analyses and PAF were multivariable adjusted and standardized to 2020 US Census data. RESULTS: In time-stratified analyses, BL decreased from 1.76âµg/dl in 1999-2004 to 0.93âµg/dl in 2017-2020, while the proportion of individuals with BLâ<â1âµg/dl increased from 19.2% to 63.0%. Total mortality was unrelated to BL (hazard ratio (HR) for a fourfold BL increment: 1.05 [95% confidence interval, CI: 0.93-1.17]). The HR for cardiovascular death was 1.44 (1.01-2.07) in the 1999-2000 cycle, but lost significance thereafter. BL was directly related to cardiovascular mortality, whereas the indirect BL pathway via BP was not significant. Low socioeconomic status (SES) was directly related to BL and cardiovascular mortality, but the indirect SES pathway via BL lost significance in 2007-2010. From 1999-2004 to 2017-2020, cardiovascular PAF decreased ( P â<â0.001) from 7.80% (0.17-14.4%) to 2.50% (0.05-4.68%) and number of lead-attributable cardiovascular deaths from 53 878 (1167-99 253) to 7539 (160-14 108). CONCLUSION: Due to implementation of strict environmental policies, lead exposure is no longer associated with total mortality, and the mildly increased cardiovascular mortality is not associated with blood lead via blood pressure in the United States.
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Plomo , Encuestas Nutricionales , Humanos , Persona de Mediana Edad , Plomo/sangre , Adulto , Estados Unidos/epidemiología , Femenino , Masculino , Anciano , Adulto Joven , Presión Sanguínea , Enfermedades Cardiovasculares/mortalidad , Estudios de CohortesRESUMEN
T cells recognize tumor antigens and initiate an anticancer immune response in the very early stages of tumor development, and the antigen specificity of T cells is determined by the T-cell receptor (TCR). Therefore, monitoring changes in the TCR repertoire in peripheral blood may offer a strategy to detect various cancers at a relatively early stage. Here, we developed the deep learning framework iCanTCR to identify patients with cancer based on the TCR repertoire. The iCanTCR framework uses TCRß sequences from an individual as an input and outputs the predicted cancer probability. The model was trained on over 2,000 publicly available TCR repertoires from 11 types of cancer and healthy controls. Analysis of several additional publicly available datasets validated the ability of iCanTCR to distinguish patients with cancer from noncancer individuals and demonstrated the capability of iCanTCR for the accurate classification of multiple cancers. Importantly, iCanTCR precisely identified individuals with early-stage cancer with an AUC of 86%. Altogether, this work provides a liquid biopsy approach to capture immune signals from peripheral blood for noninvasive cancer diagnosis. SIGNIFICANCE: Development of a deep learning-based method for multicancer detection using the TCR repertoire in the peripheral blood establishes the potential of evaluating circulating immune signals for noninvasive early cancer detection.
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Aprendizaje Profundo , Detección Precoz del Cáncer , Neoplasias , Receptores de Antígenos de Linfocitos T , Humanos , Neoplasias/inmunología , Neoplasias/sangre , Neoplasias/diagnóstico , Receptores de Antígenos de Linfocitos T/inmunología , Detección Precoz del Cáncer/métodos , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
The inference of cell-cell communication (CCC) is crucial for a better understanding of complex cellular dynamics and regulatory mechanisms in biological systems. However, accurately inferring spatial CCCs at single-cell resolution remains a significant challenge. To address this issue, we present a versatile method, called DeepTalk, to infer spatial CCC at single-cell resolution by integrating single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (ST) data. DeepTalk utilizes graph attention network (GAT) to integrate scRNA-seq and ST data, which enables accurate cell-type identification for single-cell ST data and deconvolution for spot-based ST data. Then, DeepTalk can capture the connections among cells at multiple levels using subgraph-based GAT, and further achieve spatially resolved CCC inference at single-cell resolution. DeepTalk achieves excellent performance in discovering meaningful spatial CCCs on multiple cross-platform datasets, which demonstrates its superior ability to dissect cellular behavior within intricate biological processes.
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Comunicación Celular , Análisis de la Célula Individual , Transcriptoma , Análisis de la Célula Individual/métodos , Humanos , Perfilación de la Expresión Génica/métodos , Análisis de Secuencia de ARN/métodos , Animales , Algoritmos , Biología Computacional/métodosRESUMEN
What is already known about this topic?: Mental health issues in Chinese children and adolescents have emerged as a substantial public health concern, causing distress and strain among families and society. What is added by this report?: This study examines the effects of gender and school grade on mental health symptoms and risky behaviors among Chinese children and adolescents, with a particular focus on the role of family and school environments. What are the implications for public health practice?: Caregivers and educators should enhance their awareness and skills in supporting the mental health of children. These findings offer critical insights for the early detection and intervention of mental health issues in Chinese children and adolescents.
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein continues to evolve antigenically, impacting antibody immunity. D1F6, an affinity-matured non-stereotypic VH1-2 antibody isolated from a patient infected with the SARS-CoV-2 ancestral strain, effectively neutralizes most Omicron variants tested, including XBB.1.5. We identify that D1F6 in the immunoglobulin G (IgG) form is able to overcome the effect of most Omicron mutations through its avidity-enhanced multivalent S-trimer binding. Cryo-electron microscopy (cryo-EM) and biochemical analyses show that three simultaneous epitope mutations are generally needed to substantially disrupt the multivalent S-trimer binding by D1F6 IgG. Antigenic mutations at spike positions 346, 444, and 445, which appeared in the latest variants, have little effect on D1F6 binding individually. However, these mutations are able to act synergistically with earlier Omicron mutations to impair neutralization by affecting the interaction between D1F6 IgG and the S-trimer. These results provide insight into the mechanism by which accumulated antigenic mutations facilitate evasion of affinity-matured antibodies.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Mutación , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , SARS-CoV-2/inmunología , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Humanos , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/inmunología , COVID-19/virología , COVID-19/inmunología , Epítopos/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , Microscopía por Crioelectrón , Unión ProteicaRESUMEN
Pulse pressure amplification (PPA) is the brachial-to-aortic pulse pressure ratio and decreases with age and cardiovascular risk factors. This individual-participant meta-analysis of population studies aimed to define an outcome-driven threshold for PPA. Incidence rates and standardized multivariable-adjusted hazard ratios (HRs) of cardiovascular and coronary endpoints associated with PPA, as assessed by the SphygmoCor software, were evaluated in the International Database of Central Arterial Properties for Risk Stratification (n = 5608). Model refinement was assessed by the integrated discrimination (IDI) and net reclassification (NRI) improvement. Age ranged from 30 to 96 years (median 53.6). Over 4.1 years (median), 255 and 109 participants experienced a cardiovascular or coronary endpoint. In a randomly defined discovery subset of 3945 individuals, the rounded risk-carrying PPA thresholds converged at 1.3. The HRs for cardiovascular and coronary endpoints contrasting PPA < 1.3 vs ≥1.3 were 1.54 (95% confidence interval [CI]: 1.00-2.36) and 2.45 (CI: 1.20-5.01), respectively. Models were well calibrated, findings were replicated in the remaining 1663 individuals analyzed as test dataset, and NRI was significant for both endpoints. The HRs associating cardiovascular and coronary endpoints per PPA threshold in individuals <60 vs ≥60 years were 3.86 vs 1.19 and 6.21 vs 1.77, respectively. The proportion of high-risk women (PPA < 1.3) was higher at younger age (<60 vs ≥60 years: 67.7% vs 61.5%; P < 0.001). In conclusion, over and beyond common risk factors, a brachial-to-central PP ratio of <1.3 is a forerunner of cardiovascular coronary complications and is an underestimated risk factor in women aged 30-60 years. Our study supports pulse wave analysis for risk stratification.
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What is already known about this topic?: China exhibits a significantly high prevalence of myopia compared to other countries globally. Children with vision impairment have been found to engage less in physical activities, achieve lower academic performance, and have increased vulnerability to depression. What is added by this report?: During a six-year observational study, a population-level correlation was identified between varying degrees of visual impairment and the presence of depressive symptoms among students. Specifically, individuals with a visual acuity below 4.0 had a significantly higher odds ratio of 1.90 (95% confidence interval: 1.53-2.37) compared to individuals with normal vision (visual acuity ≥5.0). What are the implications for public health practice?: This study highlights the importance of holistic health interventions that address both visual and psychological aspects. Understanding common mechanisms and influential factors can guide the development of more impactful public health strategies.