Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 507
Filtrar
1.
Cancer Discov ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39282709

RESUMEN

One of the most robust synthetic lethal interactions observed in multiple functional genomic screens has been dependency on PRMT5 in cancer cells with MTAP deletion. We report the discovery of the clinical stage MTA-cooperative PRMT5 inhibitor AMG 193, which preferentially binds PRMT5 in the presence of MTA and has potent biochemical and cellular activity in MTAP-deleted cells across multiple cancer lineages. In vitro, PRMT5 inhibition induces DNA damage, cell cycle arrest, and aberrant alternative mRNA splicing in MTAP-deleted cells. In human cell line and patient-derived xenograft models, AMG 193 induces robust antitumor activity and is well tolerated with no impact on normal hematopoietic cell lineages. AMG 193 synergizes with chemotherapies or the KRAS G12C inhibitor sotorasib in vitro, and combination treatment in vivo significantly inhibits tumor growth. AMG 193 is demonstrating promising clinical activity, including confirmed partial responses in patients with MTAP-deleted solid tumors from an ongoing phase 1/2 study.

2.
Sensors (Basel) ; 24(17)2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39275385

RESUMEN

Rotating machinery is widely used in modern industrial systems, and its health status can directly impact the operation of the entire system. Timely and accurate diagnosis of rotating machinery faults is crucial for ensuring production safety, reducing economic losses, and improving efficiency. Traditional deep learning methods can only extract features from the vertices of the input data, thereby overlooking the information contained in the relationships between vertices. This paper proposes a Legendre graph convolutional network (LGCN) integrated with a self-attention graph pooling method, which is applied to fault diagnosis of rotating machinery. The SA-LGCN model converts vibration signals from Euclidean space into graph signals in non-Euclidean space, employing a fast local spectral filter based on Legendre polynomials and a self-attention graph pooling method, significantly improving the model's stability and computational efficiency. By applying the proposed method to 10 different planetary gearbox fault tasks, we verify that it offers significant advantages in fault diagnosis accuracy and load adaptability under various working conditions.

3.
Anim Nutr ; 18: 296-308, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39281050

RESUMEN

Dietary fat content can reduce the methane production of dairy cows; however, the relevance fatty acid (FA) composition has towards this inhibitory effect is debatable. Furthermore, in-depth studies elucidating the effects of unsaturated fatty acids (UFA) on rumen function and the mechanism of reducing methane (CH4) production are lacking. This study exposed 10 Holstein cows with the same parity, similar milk yield to two total mixed rations: low unsaturated FA (LUFA) and high unsaturated FA (HUFA) with similar fat content. The LUFA group mainly added fat powder (C16:0 > 90%), and the HUFA group mainly replaced fat powder with extruded flaxseed. The experiment lasted 26 d, the last 5 d of which, gas exchange in respiratory chambers was conducted to measure gas emissions. We found that an increase in the UFA in diet did not affect milk production (P > 0.05) and could align the profile of milk FAs more closely with modern human nutritional requirements. Furthermore, we found that increasing the UFA content in the diet lead to a decrease in the abundance of Methanobrevibacter in the rumen (|linear discriminant analysis [LDA] score| > 2 and P < 0.05), which resulted in a decrease in the relative abundance of multiple enzymes (EC:1.2.7.12, EC:2.3.1.101, EC:3.5.4.27, EC:1.5.98.1, EC:1.5.98.2, EC:6.2.1.1, EC:2.1.1.86 and EC:2.8.4.1) during methanogenesis (P < 0.05). Compared with the LUFA group, the pathway of CH4 metabolism was inhibited in the HUFA group (|LDA| > 2 and P < 0.05), which ultimately decreased CH4 production (P < 0.05). Our results illustrated the mechanism involving decreased CH4 production when fed a UFA diet in dairy cows. We believe that our study provides new evidence to explore CH4 emission reduction measures for dairy cows.

4.
J Environ Manage ; 369: 122244, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39241600

RESUMEN

Wind power has become an essential direction for transforming energy structures in energy-intensive seawater desalination under the dual goals of carbon peaking and carbon neutrality. In this study, the energy footprint of the case project is analyzed by combining the hybrid life cycle analysis and environmentally extended input-output modeling, which is compared with the traditional thermal desalination processes from the whole life cycle perspective. The analysis revealed that the total energy consumption of the seawater desalination driven by wind power generation can be reduced by 79.77% compared with the traditional thermal drive mode under the same water production scale. Although the energy consumption in the construction phase accounts for 24.97% of the total, the energy consumption per unit of water production can be reduced by about 80% after adopting wind power technologies. The payback period is 7.2 years, that is, the energy consumption can be balanced after around 7 years during the operation phase. The results showed that the wind-driven seawater desalination system can significantly decrease the energy consumption of the project, which attempts to provide implications for the upgrading of energy-intensive seawater desalination in coastal areas towards low-carbon transition.


Asunto(s)
Agua de Mar , Viento , Agua de Mar/química , Purificación del Agua/métodos , Salinidad
5.
Nat Commun ; 15(1): 8041, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271676

RESUMEN

Large biobanks have dramatically advanced our understanding of genetic influences on human brain anatomy. However, most studies have combined rather than compared male and female participants. Here we screen for sex differences in the common genetic architecture of over 1000 neuroanatomical phenotypes in the UK Biobank and establish a general concordance between male and female participants in heritability estimates, genetic correlations, and variant-level effects. Notable exceptions include higher mean heritability in the female group for regional volume and surface area phenotypes; between-sex genetic correlations that are significantly below 1 in the insula and parietal cortex; and a common variant with stronger effect in male participants mapping to RBFOX1 - a gene linked to multiple neuropsychiatric disorders more common in men. This work suggests that common variant influences on human brain anatomy are largely consistent between males and females, with a few exceptions that will guide future research in growing datasets.


Asunto(s)
Encéfalo , Humanos , Masculino , Femenino , Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Factores de Empalme de ARN/genética , Fenotipo , Persona de Mediana Edad , Caracteres Sexuales , Reino Unido , Imagen por Resonancia Magnética , Bancos de Muestras Biológicas , Anciano , Polimorfismo de Nucleótido Simple , Factores Sexuales , Adulto , Estudio de Asociación del Genoma Completo
6.
Diabetol Metab Syndr ; 16(1): 215, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39223618

RESUMEN

BACKGROUND: Observational studies have found associations between sex hormones and metabolic syndrome(Mets), but the causal relationships remains unclear. This study utilizes univariable and multivariable Mendelian randomization (MR) to elucidate the associations between sex hormones (including sex hormone-binding globulin(SHBG), estradiol(E2), testosterone(T)) and Mets and its subtypes (including waist circumference(WC), fasting blood glucose(FBG), high blood pressure(HBP), high-density lipoprotein(HDL-C), triglycerides(TG)). METHODS: We utilized summary data from large-scale genome-wide association studies. Univariable Mendelian randomization (UMVMR) analysis was primarily conducted using the inverse variance weighted method (IVW), with secondary analyses employing the weighted median, MR-Egger regression, simple mode method, and weighted mode method. Subsequently, multivariable Mendelian randomization (MVMR) was employed to assess the causal relationships between SHBG, T, E2, and MetS and its components: WC, FPG, HBP, HDL-C, and TG. Sensitivity analyses were conducted to assess result reliability. RESULTS: Genetically predicted SHBG was significantly negatively associated with MetS (UMVMR: ß=-0.72; 95% CI = 0.41 to 0.57; P = 1.28e-17; MVMR: ß=-0.60; 95% CI=-0.83 to -0.38; P < 0.001). Positive causal relationships were observed between SHBG and WC(MVMR: ß = 0.10; 95% CI = 0.03 to 0.17; P = 0.01) and HDL-C (MVMR: ß = 0.41; 95% CI = 0.21 to 0.60; P < 0.001), while negative causal relationships were found between SHBG and HBP (MVMR: ß=-0.02; 95% CI=-0.04 to -0.00; P = 0.02), TG (MVMR: ß=-0.48; 95% CI=-0.70 to -0.26; P < 0.001). Genetically predicted E2 exhibited a negative association with TG (MVMR: ß=-1.49; 95% CI=-2.48 to -0.50; P = 0.003). Genetically predicted T was negatively associated with TG (MVMR: ß=-0.36; 95% CI=-0.71 to -0.00; P = 0.049) and WC (MVMR: ß=-0.13; 95% CI=-0.24 to -0.02; P = 0.02), with inconsistent sensitivity analyses. Additionally, No other causal associations were found. CONCLUSION: Our study indicates that SHBG is a protective factor for MetS, potentially delaying its onset and progression through improvements in HBP and TG. Furthermore, T and E2 may improve TG levels, with T also reducing WC levels. Importantly, our study provides new insights for the prevention and treatment of MetS.

7.
World J Pediatr Surg ; 7(3): e000884, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39183805

RESUMEN

Congenital diaphragmatic hernia (CDH) is a congenital malformation characterized by failure of diaphragm closure during embryonic development, leading to pulmonary hypoplasia and pulmonary hypertension, which contribute significantly to morbidity and mortality. The occurrence of CDH and pulmonary hypoplasia is theorized to result from both abnormalities in signaling pathways of smooth muscle cells in pleuroperitoneal folds and mechanical compression by abdominal organs within the chest cavity on the developing lungs. Although, the precise etiology of diaphragm maldevelopment in CDH is not fully understood, it is believed that interplay between genes and the environment contributes to its onset. Approximately 30% of patients with CDH possess chromosomal or single gene defects and these patients tend to have inferior outcomes compared with those without genetic associations. At present, approximately 150 gene variants have been linked to the occurrence of CDH. The variable expression of the CDH phenotype in the presence of a recognized genetic predisposition can be explained by an environmental effect on gene penetrance and expression. The retinoic acid pathway is thought to play an essential role in the interactions of genes and environment in CDH. However, apart from the gradually maturing retinol hypothesis, there is limited evidence implicating other environmental factors in CDH occurrence. This review aims to describe the pathogenesis of CDH by summarizing the genetic defects and potential environmental influences on CDH development.

8.
CNS Neurosci Ther ; 30(8): e14912, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39185787

RESUMEN

OBJECTIVE: To investigate the association between coronary heart disease (CHD) and the risk of perioperative ischemic stroke in patients undergoing noncardiac surgery. METHODS: This retrospective study evaluated the incidence of ischemic stroke within 30 days after a noncardiac surgery. A cohort of 221,541 patients who underwent noncardiac surgery between January 2008 and August 2019 was segregated according to whether they were diagnosed with CHD. Primary, sensitivity, and subgroup logistic regression analyses were conducted to confirm that CHD is an independent risk factor for perioperative ischemic stroke. Propensity score matching analysis was used to account for the potential residual confounding effect of covariates. RESULTS: Among the 221,541 included patients undergoing noncardiac surgery, 484 patients (0.22%) experienced perioperative ischemic stroke. The risk of perioperative ischemic stroke was higher in patients with CHD (0.7%) compared to patients without CHD (0.2%), and multivariate logistic regression analysis showed that CHD was associated with a significantly increased risk of perioperative ischemic stroke (odds ratio (OR), 3.7943; 95% confidence interval (CI) 2.865-4.934; p < 0.001). In a subset of patients selected by propensity score matching (PSM) in which all covariates between the two groups were well balanced, the association between CHD and increased risk of perioperative ischemic stroke remained significantly significant (OR 1.8150; 95% CI, 1.254-2.619; p = 0.001). In the subgroup analysis stratified by age, preoperative ß-blockers, and fibrinogen-to-albumin ratio (FAR), the association between CHD and perioperative ischemic stroke was stable (p for interaction >0.05). Subgroup analyses also showed that CHD was significantly increased the risk of perioperative ischemic stroke in the preoperative mean arterial pressure (MAP) ≥94.2 mmHg subgroups (p for interaction <0.001). CONCLUSION: CHD is significantly associated with an increased risk of perioperative ischemic stroke and is an independent risk factor for perioperative ischemic stroke after noncardiac surgery. Strict control of preoperative blood pressure may reduce the risk of perioperative ischemic stroke for patients with CHD undergoing noncardiac surgery.


Asunto(s)
Enfermedad Coronaria , Accidente Cerebrovascular Isquémico , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/etiología , Anciano , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Estudios de Cohortes , Adulto , Incidencia , Procedimientos Quirúrgicos Operativos/efectos adversos
9.
Bioresour Technol ; 408: 131193, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39094963

RESUMEN

Energy self-circulation systems, defined as energy systems incorporating the recycling utilization of waste biomass, have been proposed to reduce greenhouse gases emissions from livestock sector. In this study, a comprehensive review of the situation and challenges of biogas utilization in the livestock industry was provided. Moreover, two technological routes were proposed for a circular livestock system combined with Powerfuels production (CP-CLS), starting from biogas combustion for power generation and steam reforming to the sustainable development path of synthesizing, storing, and utilizing Powerfuels. The self-circulation capability and comprehensive benefits of the CP-CLS life cycle was discussed, along with future application scenarios and proposed standards for Powerfuels. To realize this potential, continuous research, development, and policy support are crucial. This study envisions the next generation of energy self-circulation systems, which expects to reduce the negative effect of livestock industry on climate change and promote sustainable development.


Asunto(s)
Ganado , Desarrollo Sostenible , Industria de Alimentos , Anaerobiosis , Crianza de Animales Domésticos
10.
BMC Public Health ; 24(1): 2219, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39148035

RESUMEN

BACKGROUND: Evidence on the prevalence of smoking in China remains insufficient, with most previous studies focusing on a single region. However, smoking prevalence exhibits significant inequalities across the entire country. This study aimed to evaluate the risk of tobacco prevalence across the country, taking into account spatial inequalities. METHODS: The data used in this study were collected in 23 provinces, 5 autonomous regions, and 4 municipalities directly under the central government in 2022. Large population survey data were used, and a Bayesian geostatistical model was employed to investigate smoking prevalence rates across multiple spatial domains. FINDINGS: Significant spatial variations were observed in smokers and exposure to secondhand smoke across China. Higher levels of smokers and secondhand smoke exposure were observed in western and northeastern regions. Additionally, the autonomous region of Tibet, Shanghai municipality, and Yunnan province had the highest prevalence of smokers, while Tibet, Qinghai province, and Yunnan province had the highest prevalence of exposure to secondhand smoke. CONCLUSION: We have developed a model-based, high-resolution nationwide assessment of smoking risks and employed rigorous Bayesian geostatistical models to help visualize smoking prevalence predictions. These prediction maps provide estimates of the geographical distribution of smoking, which will serve as strong evidence for the formulation and implementation of smoking cessation policies. HIGHLIGHTS: Our study investigated the prevalence of smokers and exposure to secondhand smoke in different spatial areas of China and explored various factors influencing the smoking prevalence. For the first time, our study applied Bayesian geostatistical modeling to generate a risk prediction map of smoking prevalence, which provides a more intuitive and clear understanding of the spatial disparities in smoking prevalence across different geographical regions, economic levels, and development status. We found significant spatial variations in smokers and secondhand smoke exposure in China, with higher rates in the western and northeastern regions.


Asunto(s)
Teorema de Bayes , Contaminación por Humo de Tabaco , Humanos , China/epidemiología , Estudios Transversales , Contaminación por Humo de Tabaco/estadística & datos numéricos , Prevalencia , Femenino , Masculino , Adulto , Persona de Mediana Edad , Fumar/epidemiología , Fumadores/estadística & datos numéricos , Medición de Riesgo , Análisis Espacial , Epidemias , Adulto Joven
11.
Nat Commun ; 15(1): 6886, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39128898

RESUMEN

The dehydration process is widely recognized as a significant phenomenon in nature. Hydrogels, which are important functional materials with high water content and crosslinked networks, encounter the issue of dehydration in their practical applications. Here, we report the distinctive anisotropic dehydration modality of dynamic hydrogels, which is fundamentally different from the more commonly observed isotropic dehydration of covalent hydrogels. Xerogels derived from dynamic hydrogel dehydration will fully cover a curved substrate surface and exhibit hollow structures with internal knots, in contrast to the bulk xerogels produced by covalent hydrogel dehydration. Depending on the competing cohesion of polymer chains and the adhesion at the hydrogel-substrate interface, the previously overlooked reorganization of polymer networks within dynamic hydrogels, triggered by dehydration-induced stress, has been discovered to regulate such macroscopic structural reconstruction for dynamic hydrogel dehydration. With the attached hydrogel-substrate interface, the surface microstructures of substrates can also be engraved onto xerogels with high resolution and on a large scale. This work will greatly enhance our understanding of the soft matter dehydration process and broaden the applications of dehydration technologies using water-containing materials.

12.
Age Ageing ; 53(9)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39216470

RESUMEN

BACKGROUND: Postoperative cognitive impairment are common neural complications in older surgical patients and exacerbate the burden of medical care on families and society. METHODS: A total of 140 older patients who were scheduled for elective orthopaedic surgery or pancreatic surgery with general anaesthesia were randomly assigned to Group S or Group I with a 1:1 allocation. Patients in Group S and Group I received intranasal administration of 400 µL of normal saline or 40 IU/400 µL of insulin, respectively, once daily from 5 minutes before anaesthesia induction until 3 days postoperatively. Perioperative cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Basic (MoCA-B) at 1 day before and 3 days after surgery and postoperative delirium (POD) incidence was assessed using the 3-minute Diagnostic Interview for CAM (3D-CAM) on postoperative days 1-3. Serum levels of interleukin-6 (IL-6), tumour necrosis factor α (TNF-α), S100-ß and C-reactive protein (CRP) were measured on the first day after surgery. RESULTS: Insulin treatment significantly increased postoperative MMSE and MoCA-B scores in group I than in group S (P < 0.001, P = 0.001, respectively), decreased the incidence of POD within the 3-day postoperative period in Group I than in Group S (10.9% vs 26.6%, P = 0.024), and inhibited postoperative IL-6 and S100-ß levels in Group I compared to Group S (P = 0.034, P = 0.044, respectively). CONCLUSIONS: Intranasal insulin administration is thus suggested as a potential therapy to improve postoperative cognition in older patients undergoing surgery. However, a more standardized multi-centre, large-sample study is needed to further validate these results.


Asunto(s)
Administración Intranasal , Cognición , Insulina , Complicaciones Cognitivas Postoperatorias , Humanos , Masculino , Femenino , Anciano , Método Doble Ciego , Insulina/administración & dosificación , Cognición/efectos de los fármacos , Complicaciones Cognitivas Postoperatorias/prevención & control , Complicaciones Cognitivas Postoperatorias/diagnóstico , Complicaciones Cognitivas Postoperatorias/etiología , Complicaciones Cognitivas Postoperatorias/epidemiología , Anciano de 80 o más Años , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Pruebas de Estado Mental y Demencia , Resultado del Tratamiento , Biomarcadores/sangre , Procedimientos Ortopédicos/efectos adversos , Factores de Tiempo
13.
Int J Biol Macromol ; 277(Pt 3): 134286, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39217036

RESUMEN

As the derivative of konjac glucomannan (KGM), carboxymethyl konjac glucomannan (CMK) has attracted increasing attention in the polysaccharide hydrogel fields with the aim of improving the performance related to drug delivery and release. In this study, we prepared a CMK-based hydrogel with dual characteristic crosslinks, and unlocked new applications of this type of hydrogel in soft sensor fields. CMK and poly (vinyl alcohol) were used as substrates, and physical crosslinks were constructed via the freeze-thawing treatments and covalent crosslinks were built via the boronic ester bonding. As-prepared hydrogel possessed significantly improved mechanical performance because the boronic ester bonding, on the one hand, well associated the two kinds of polymer chains, and on the other hand, played the role of 'sacrificial crosslinks'. Furthermore, the occurrence of dynamic boronic ester bonding gave the hydrogel strain- and temperature-sensitive ionic conductivity, and therefore, the hydrogels could be used to identify human motions and as-resulted environmental temperature alterations, and worked well in various scenarios. This work activates new application of CMK in the multimodal sensing field, and also proposes an intriguing way of building multiple crosslinks in the KGM derivative-based hydrogels.


Asunto(s)
Ácidos Borónicos , Hidrogeles , Mananos , Mananos/química , Hidrogeles/química , Ácidos Borónicos/química , Ésteres/química , Humanos , Alcohol Polivinílico/química , Temperatura , Reactivos de Enlaces Cruzados/química
14.
ACS Appl Mater Interfaces ; 16(35): 46538-46547, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39087831

RESUMEN

The development of wearable electronic devices for human health monitoring requires materials with high mechanical performance and sensitivity. In this study, we present a novel transparent tissue-like ionogel-based wearable sensor based on silver nanowire-reinforced ionogel nanocomposites, P(AAm-co-AA) ionogel-Ag NWs composite. The composite exhibits a high stretchability of 605% strain and a moderate fracture stress of about 377 kPa. The sensor also demonstrates a sensitive response to temperature changes and electrostatic adsorption. By encapsulating the nanocomposite in a polyurethane transparent film dressing, we address issues such as skin irritation and enable multidirectional stretching. Measuring resistive changes of the ionogel nanocomposite in response to corresponding strain changes enables its utility as a highly stretchable wearable sensor with excellent performance in sensitivity, stability, and repeatability. The fabricated pressure sensor array exhibits great proficiency in stress distribution, capacitance sensing, and discernment of fluctuations in both external electric fields and stress. Our findings suggest that this material holds promise for applications in wearable and flexible strain sensors, temperature sensors, pressure sensors, and actuators.


Asunto(s)
Nanocompuestos , Nanocables , Plata , Dispositivos Electrónicos Vestibles , Plata/química , Nanocompuestos/química , Nanocables/química , Humanos , Geles/química , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Poliuretanos/química
15.
J Affect Disord ; 362: 569-577, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39019228

RESUMEN

BACKGROUND: Childhood trauma is a risk factor for self-harm/suicidal behavior, but research on the potential association linking sleep quality and anxiety symptoms to childhood trauma and self-harm attempt is limited. The aim of this study was to describe the mediating role of sleep quality and anxiety symptoms between childhood trauma and self-harm attempt, and to provide a scientific basis for the prevention of self-harm behaviors. METHODS: This study ultimately included 11,063 study participants who participated in the baseline survey of this large prospective cohort study of the UK Biobank. We used structural equation modeling (SEM) to analyze the chain mediating role of sleep quality and anxiety symptoms in childhood trauma and self-harm attempt while controlling for covariates. RESULTS: A total of 19.58 % of study participants self-reported self-harm attempt. Sleep quality was negatively correlated with childhood trauma, anxiety symptoms, and self-harm attempt (p < 0.01). Childhood trauma, anxiety symptoms, and self-harm attempt were positively correlated (p < 0.01). In addition, after adjusting for confounders, anxiety symptoms were able to partially mediate the association between childhood trauma and self-harm attempt (effect value: 0.042, p < 0.01), and sleep quality and anxiety symptoms can chain mediate the association between childhood trauma and self-harm attempt (effect value:0.002, p < 0.01), with a total mediating effect of 65.67 % of the total effect. Subgroup analyses further showed that the mediating effects of sleep quality and anxiety symptoms on childhood trauma and self-harm attempt differed across age, gender, ethnicity, and smoking and drinking subgroups. CONCLUSIONS: This study found a complex relationship between childhood trauma, sleep quality, anxiety symptoms, and self-harm attempt, with sleep quality and anxiety symptoms mediating the relationship between childhood trauma and self-harm attempt. Multiple avenues of intervention, such as the provision of professional psychological interventions and timely monitoring, should be used to improve the sleep quality and mental health of individuals with traumatic childhood experiences and to prevent the occurrence of emotionally harmful behaviors such as self-harm/suicide.


Asunto(s)
Ansiedad , Conducta Autodestructiva , Calidad del Sueño , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Experiencias Adversas de la Infancia/estadística & datos numéricos , Ansiedad/epidemiología , Ansiedad/psicología , Estudios Prospectivos , Factores de Riesgo , Autoinforme , Conducta Autodestructiva/epidemiología , Conducta Autodestructiva/psicología , Intento de Suicidio/estadística & datos numéricos , Biobanco del Reino Unido , Reino Unido/epidemiología
16.
CNS Neurosci Ther ; 30(7): e14887, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39073013

RESUMEN

AIMS: Neuroinflammation is a recognized contributor to cognitive disorders like Alzheimer's disease, with ferroptosis emerging as a novel mechanism underlying cognitive dysfunction associated with neuroinflammation. Insulin, pivotal in the central nervous system, holds promise for cognitive function enhancement. This study aimed to establish a cognitive impairment model through intracerebroventricular injection of lipopolysaccharide (LPS) and explore the impact of intracerebroventricular insulin injection on cognitive function in mice. METHODS: We employed diverse experimental techniques, including animal behavior testing, molecular assays, targeted metabolomics, nuclear medicine, and electron microscopy, to assess neurodegenerative changes, brain insulin resistance (IR), glucose uptake and metabolism, and ferroptosis. The model of cognitive impairment was induced via intracerebroventricular injection of LPS, followed by intracerebroventricular administration of insulin to evaluate its effects. RESULTS: Insulin treatment effectively mitigated LPS-induced cognitive decline and safeguarded against neuronal degeneration. Furthermore, insulin alleviated LPS-induced insulin resistance, enhanced glucose uptake in the hippocampus, and promoted the Pentose Phosphate Pathway (PPP) and nicotinamide adenine dinucleotide phosphate (NADPH) production. Additionally, insulin activated the glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway, reducing lipid peroxidation, and mitochondrial damage characteristic of LPS-induced ferroptosis in the hippocampus. CONCLUSION: Our findings underscore the therapeutic potential of insulin in alleviating LPS-induced cognitive impairment and ferroptosis by modulating glucose metabolism. This study offers a promising avenue for future interventions targeting cognitive decline.


Asunto(s)
Disfunción Cognitiva , Ferroptosis , Glucosa , Hipocampo , Insulina , Lipopolisacáridos , Animales , Ferroptosis/efectos de los fármacos , Ferroptosis/fisiología , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/metabolismo , Lipopolisacáridos/toxicidad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Ratones , Masculino , Glucosa/metabolismo , Ratones Endogámicos C57BL , Resistencia a la Insulina/fisiología
17.
PLoS One ; 19(7): e0307525, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39052667

RESUMEN

Online measurement of disk part dimensions by the standard industrial camera features low cost, high efficiency and good universality, but the impact of projection distortion and end face chamfer on measurement is needed to overcome. Present work presents a measurement method to resolve above issues based on machine vision. To improve the measurement accuracy, lower end face of a disk part is determined as calibration plane and the upper end face is measurement plane. To reduce the impact of projection distortion and chamfer on measurement, the measurement points are reconstructed on the measurement plane by re-projection. Then, the inner and outer diameters of disk parts are measured by circle geometric fitting, and the thickness is calculated by the measurement plane position. The experimental results show that the method can online measure disk part dimensions just by a single image, and accuracy meets the requirements of universal grade disk parts.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Humanos , Calibración
18.
Nat Cell Biol ; 26(7): 1110-1123, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38997457

RESUMEN

Migrasomes are organelles that are generated by migrating cells. Here we report the key role of neutrophil-derived migrasomes in haemostasis. We found that a large number of neutrophil-derived migrasomes exist in the blood of mice and humans. Compared with neutrophil cell bodies and platelets, these migrasomes adsorb and enrich coagulation factors on the surface. Moreover, they are highly enriched with adhesion molecules, which enable them to preferentially accumulate at sites of injury, where they trigger platelet activation and clot formation. Depletion of neutrophils, or genetic reduction of the number of these migrasomes, significantly decreases platelet plug formation and impairs coagulation. These defects can be rescued by intravenous injection of purified neutrophil-derived migrasomes. Our study reveals neutrophil-derived migrasomes as a previously unrecognized essential component of the haemostasis system, which may shed light on the cause of various coagulation disorders and open therapeutic possibilities.


Asunto(s)
Coagulación Sanguínea , Plaquetas , Ratones Endogámicos C57BL , Neutrófilos , Neutrófilos/metabolismo , Animales , Humanos , Plaquetas/metabolismo , Ratones , Hemostasis , Movimiento Celular , Activación Plaquetaria , Masculino , Factores de Coagulación Sanguínea/metabolismo , Factores de Coagulación Sanguínea/genética
19.
Antioxidants (Basel) ; 13(7)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-39061833

RESUMEN

Gastrointestinal (GI) afflictions are prevalent among the feline population, wherein the intricacies of the gut microbiome exert a profound influence on their overall health. Alterations within this microbial consortium can precipitate a cascade of physiological changes, notably in immune function and antioxidant capacity. This research investigated the impact of Bifidobacterium lactis (B. lactis) and Lactobacillus plantarum (L. plantarum) on cats' GI health, exploring the effects of probiotic supplementation on the intestinal ecosystem using 16S rRNA gene sequencing. The findings demonstrated a significant improvement in gut barrier function by reducing plasma concentrations of D-lactate (D-LA) by 30.38% and diamine oxidase (DAO) by 22.68%, while increasing the population of beneficial bacteria such as Lactobacillus. There was a notable 25% increase in immunoglobulin A (IgA) levels, evidenced by increases of 19.13% in catalase (CAT), 23.94% in superoxide dismutase (SOD), and 21.81% in glutathione peroxidase (GSH-Px). Further analysis revealed positive correlations between Lactobacillus abundance and IgA, CAT, and total antioxidant capacity (T-AOC) levels. These correlations indicate that B. lactis and L. plantarum enhance feline immune and antioxidant functions by increasing the abundance of beneficial Lactobacillus in the GI tract. These findings provide a foundation for probiotic interventions aimed at enhancing health and disease resistance in feline populations.

20.
CNS Neurosci Ther ; 30(7): e14838, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38987899

RESUMEN

BACKGROUND: Body mass index (BMI) serves as a global metric for assessing obesity and overall health status. However, the impact of BMI, treated as a continuous variable, on the risk of perioperative stroke remains poorly understood. This retrospective cohort study aimed to elucidate the association between BMI and the risk of perioperative ischemic stroke in patients undergoing non-cardiovascular surgery. METHODS: A cohort of 223,415 patients undergoing noncardiac surgery at the First Medical Center of Chinese PLA General Hospital between January 1, 2008 and August 31, 2019 was screened. Preoperative high BMI, defined as BMI >22.64 kg/m2, was the primary exposure, and the outcome of interest was the new diagnosis of perioperative ischemic stroke within 30 days post-surgery. Robust controls for patient and intraoperative factors were implemented to minimize residual confounding. Logistic regression and propensity score matching were employed, and patients were stratified into subgroups for further investigation. RESULTS: The overall incidence of perioperative ischemic stroke was 0.23% (n = 525) in the cohort. After adjusting for patient-related variables (OR 1.283; 95% CI, 1.04-1.594; p < 0.05), surgery-related variables (OR 1.484; 95% CI, 1.2-1.849; p < 0.001), and all confounding variables (OR 1.279; 95% CI, 1.025-1.607; p < 0.05), patients with BMI >22.64 kg/m2 exhibited a significantly increased risk of perioperative ischemic stroke. This association persisted in the propensity score matched cohort (OR 1.577; 95% CI, 1.203-2.073; p < 0.01). Subgroup analyses indicated that preoperative BMI >22.64 kg/m2 correlated with an elevated risk of perioperative ischemic stroke in female patients, those with coronary heart disease, peripheral vascular diseases, and individuals undergoing neurosurgery. CONCLUSION: We first identified BMI >22.64 kg/m2 as a substantial and independent risk factor for perioperative ischemic stroke in Chinese noncardiac surgery patients. Normal BMI may not suffice as a universal preventive standard. Instead, a more stringent perioperative weight management approach is recommended, particularly for specific subgroups such as female patients, those with coronary heart disease and peripheral vascular disease, and individuals scheduled for neurosurgery.


Asunto(s)
Índice de Masa Corporal , Accidente Cerebrovascular Isquémico , Complicaciones Posoperatorias , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/epidemiología , Anciano , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios de Cohortes , Adulto , Obesidad/complicaciones , Obesidad/epidemiología , Procedimientos Quirúrgicos Operativos/efectos adversos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA