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1.
Heliyon ; 10(15): e35440, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39170139

RESUMEN

Diffusion-weighted imaging (DWI) is widely utilized for evaluating uterine diseases. However, the prevalent technique, single-shot echo planar imaging (ssEPI), is hindered by notable image distortion and low spatial resolution. Therefore, optimizing uterine DWI sequences is vital for improving image quality. To investigate the efficacy of multiplexed sensitivity encoding (MUSE) combined with reverse polarity gradient (RPG) in enhancing uterine DWI quality and assessing local invasion in endometrial and cervical cancer, we included 149 patients. Each patient underwent DWI of the uterus using ssEPI, MUSE, and RPG-MUSE techniques. We compared these three sequences regarding image quality, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), geometric distortion rate (GDR), ADC values, accuracy in determining the extent of cancer invasion, and the Area Under the Curve (AUC) for identifying endometrial cancer and benign endometrial lesions using ADC values. The results indicated that RPG-MUSE DWI had less artifacts than MUSE and ssEPI (P < 0.05). Lesions were more apparent in MUSE and RPG-MUSE sequences compared to ssEPI (P < 0.05), with RPG-MUSE providing clearer lesion edges (P < 0.05). Additionally, RPG-MUSE DWI demonstrated higher SNR and CNR than ssEPI and MUSE (P < 0.05), along with a lower GDR (P < 0.05). The ADC values did not show significant differences among the three sequences (P > 0.05). Furthermore, the AUC of the ROC for detecting endometrial cancer and benign endometrial lesions using ADC values showed no significant differences across the sequences (P = 0.7609, 0.7186, and 0.8706, respectively). When combining each DWI sequence with T2WI for FIGO staging, RPG-MUSE and MUSE exhibited better alignment with pathology findings compared to ssEPI (P < 0.05). Overall, RPG-MUSE DWI showed fewer artifacts, higher SNR and CNR, reduced geometric distortion, and clearer lesion visualization compared to ssEPI and MUSE, leading to a more precise assessment of endometrial and cervical cancer invasion extent.

2.
Clin Nutr ; 43(9): 2198-2210, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39163761

RESUMEN

Perioperative neurocognitive dysfunction (PND) occurs in elderly individuals undergoing anesthesia and surgery. To explore the potential molecular mechanisms, we performed right-sided cervical exploratory surgery under sevoflurane anesthesia in 18-month-old male Sprague-Dawley rats. Anxiety-depression-like behaviors and learning memory abilities were assessed using the Open Field Test (OFT) and Novel Object Recognition (NOR). Additionally, the hippocampus was collected one day after surgery for inflammatory factor detection, TUNEL staining, and metabolomics analysis. Mendelian randomization (MR) analyses were subsequently conducted to validate the causal relationships by using a series of GWAS datasets related to representative differential metabolites as exposures and cognitive impairment as endpoints. The results indicated that rats exposed to anesthesia and surgery exhibited poorer cognitive performance, significant elevations in hippocampal inflammatory factors such as IL-1ß and TNF-α, and extensive neuronal apoptosis. LC-MS/MS-based untargeted metabolomics identified 19 up-regulated and 32 down-regulated metabolites in the test group, with 6 differential metabolites involved in metabolic pathways enriched according to the KEGG database. ROC analysis revealed a correlation between α-linolenic acid (ALA) and linoleic acid (LA) and the development of PND. Further MR analysis confirmed that ALA was significantly associated with cognitive performance and the risk of depression, while LA was significantly associated with the risk of memory loss. Taken together, our results identified ALA and LA as potentially powerful biomarkers for PND.

3.
Int J Mol Sci ; 25(15)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39125922

RESUMEN

Oxidative stress has been identified as a major factor in the development and progression of pain and psychiatric disorders, but the underlying biomarkers and molecular signaling pathways remain unclear. This study aims to identify oxidative stress-related biomarkers and signaling pathways in pain-depression comorbidity. Integrated bioinformatics analyses were applied to identify key genes by comparing pain-depression comorbidity-related genes and oxidative stress-related genes. A total of 580 differentially expressed genes and 35 differentially expressed oxidative stress-related genes (DEOSGs) were identified. By using a weighted gene co-expression network analysis and a protein-protein interaction network, 43 key genes and 5 hub genes were screened out, respectively. DEOSGs were enriched in biological processes and signaling pathways related to oxidative stress and inflammation. The five hub genes, RNF24, MGAM, FOS, and TKT, were deemed potential diagnostic and prognostic markers for patients with pain-depression comorbidity. These genes may serve as valuable targets for further research and may aid in the development of early diagnosis, prevention strategies, and pharmacotherapy tools for this particular patient population.


Asunto(s)
Biomarcadores , Comorbilidad , Biología Computacional , Depresión , Redes Reguladoras de Genes , Estrés Oxidativo , Dolor , Mapas de Interacción de Proteínas , Estrés Oxidativo/genética , Humanos , Biología Computacional/métodos , Dolor/genética , Dolor/epidemiología , Mapas de Interacción de Proteínas/genética , Depresión/genética , Depresión/epidemiología , Perfilación de la Expresión Génica , Transducción de Señal/genética
4.
Age Ageing ; 53(7)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38984694

RESUMEN

OBJECTIVE: Whether physical activity could reduce the risk of atrial fibrillation (AF) remains unclear. This study was to investigate the relationship of leisure-time physical activity (LTPA) with AF incidence among Chinese older adults. METHODS: A total of 3253 participants aged ≥60 years from the Guangzhou Heart Study were successfully followed between March 2018 and September 2019. LTPA was assessed using a modified Global Physical Activity Questionnaire. AF was ascertained by 12-lead electrocardiograms, 24-hour single-lead Holter and clinical examination. The Cox proportional hazards model was used to the estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for confounders, and the population-attributable fraction (PAF) was estimated. RESULTS: A total of 76 (2.34%) new-onset cases of AF were identified during a median of 31.13 months of follow-up. After adjustment for confounders, subjects who had LTPA at least 10.0 metabolic equivalent (MET)-hours/week had a 55% lower risk of developing AF (HR: 0.45, 95%CI: 0.25-0.81), and at least 20 MET-hours/week reduced the risk by 45% (HR: 0.55, 95%CI: 0.34-0.92). At least 11% (PAF: 11%, 95%CI: 0%-20%) or 14% (PAF: 14%, 95%CI: 0%-26%) of AF cases could be avoided, respectively, if the subjects do LTPA at least 10 MET-hours/week or 20 MET-hours/week. A significant exposure-response trend was also observed between LTPA and AF risk (Plinear-trend = 0.002). For a specific LTPA, doing housework was associated with a 43% reduced risk, while engaging in ball games was associated with an increased risk. CONCLUSION: This prospective cohort study indicated that a higher LTPA volume was associated with a lower AF risk in Chinese older adults.


Asunto(s)
Fibrilación Atrial , Ejercicio Físico , Actividades Recreativas , Humanos , Fibrilación Atrial/epidemiología , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/prevención & control , Masculino , Femenino , Anciano , Estudios Prospectivos , Incidencia , Persona de Mediana Edad , China/epidemiología , Factores de Riesgo
5.
Discov Oncol ; 15(1): 271, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38976093

RESUMEN

BACKGROUND: Cellular senescence is essential to TME development, progression, and remodeling. Few studies have examined cellular senescence in HCC after TACE. Investigating the relationship between cellular senescence, post-TACE prognosis, the TME, and immune treatment responses is crucial. METHODS: We analyzed the GSE104580 dataset to identify DEGs. A cellular senescence-related signature was developed using LASSO Cox regression in the GSE14520 dataset and validated in the ICGC dataset. High- and low-risk subgroups were compared using GSVA and GSEA. Correlation studies were conducted to explore the relationship between the prognostic model, immune infiltration, immunotherapy response, and drug sensitivity. RESULTS: A cellular senescence-related signature comprising FOXM1, CDK1, CHEK1, and SERPINE1 was created and validated. High-risk patients showed significantly lower OS than low-risk patients. High-risk patients had carcinogenetic pathways activated, immunosuppressive cells infiltrated, and immunomodulatory genes overexpressed. They also showed higher sensitivity to EPZ004777_1237 and MK-2206_1053 and potential benefits from GSK-3 inhibitor IX, nortriptyline, lestaurtinib, and JNK-9L. CONCLUSIONS: This study constructed a cellular senescence-related signature that could be used to predict HCC patients' responses to and prognosis after TACE treatment, aiding in the development of personalized treatment plans.

6.
mSphere ; : e0043924, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012105

RESUMEN

Companion animals such as cats and dogs harbor diverse microbial communities that can potentially impact human health due to close and frequent contact. To better characterize their total infectomes and assess zoonotic risks, we characterized the overall infectomes of companion animals (cats and dogs) and evaluated their potential zoonotic risks. Meta-transcriptomic analyses were performed on 239 samples from cats and dogs collected across China, identifying 24 viral species, 270 bacterial genera, and two fungal genera. Differences in the overall microbiome and infectome composition were compared across different animal species (cats or dogs), sampling sites (rectal or oropharyngeal), and health status (healthy or diseased). Diversity analyses revealed that viral abundance was generally higher in diseased animals compared to healthy ones, while differences in microbial composition were mainly driven by sampling site, followed by animal species and health status. Disease association analyses validated the pathogenicity of known pathogens and suggested potential pathogenic roles of previously undescribed bacteria and newly discovered viruses. Cross-species transmission analyses identified seven pathogens shared between cats and dogs, such as alphacoronavirus 1, which was detected in both oropharyngeal and rectal swabs albeit with differential pathogenicity. Further analyses showed that some viruses, like alphacoronavirus 1, harbored multiple lineages exhibiting distinct pathogenicity, tissue, or host preferences. Ultimately, a systematic evolutionary screening identified 27 potential zoonotic pathogens in this sample set, with far more bacterial than viral species, implying potential health threats to humans. Overall, our meta-transcriptomic analysis reveals a landscape of actively transcribing microorganisms in major companion animals, highlighting key pathogens, those with the potential for cross-species transmission, and possible zoonotic threats. IMPORTANCE: This study provides a comprehensive characterization of the entire community of infectious microbes (viruses, bacteria, and fungi) in companion animals like cats and dogs, termed the "infectome." By analyzing hundreds of samples from across China, the researchers identified numerous known and novel pathogens, including 27 potential zoonotic agents that could pose health risks to both animals and humans. Notably, some of these zoonotic pathogens were detected even in apparently healthy pets, highlighting the importance of surveillance. The study also revealed key microbial factors associated with respiratory and gastrointestinal diseases in pets, as well as potential cross-species transmission events between cats and dogs. Overall, this work sheds light on the complex microbial landscapes of companion animals and their potential impacts on animal and human health, underscoring the need for monitoring and management of these infectious agents.

7.
Mar Pollut Bull ; 206: 116771, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39059221

RESUMEN

This study is the first work investigating the distribution of rare earth elements (REEs) in three different edible tissues of the swimming crab (Portunus trituberculatus) collected from seven cities of Shandong Province, China. The total concentrations of REEs ranged from 26.1 to 139 ng/g with an average of 63.0 ng/g. The ratio of light REEs to heavy REEs ranged from 9.78 to 16.6 ng/g with an average of 11.5 ng/g. There was no significant differences in REE levels between the edible tissues of male and female crabs. The content of REEs across different tissues followed a consistent pattern: gonads > body muscle > legs muscle, except for Eu. A significant correlation was observed between REEs in P. trituberculatus and marine sediments in the corresponding sea area, following the principle of "abundance law". A health risk assessment revealed a low health risk of REEs for local adults and children consuming Portunus trituberculatus.


Asunto(s)
Braquiuros , Metales de Tierras Raras , Animales , Metales de Tierras Raras/análisis , China , Medición de Riesgo , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Masculino , Femenino , Humanos , Alimentos Marinos/análisis
8.
Biomed Pharmacother ; 178: 117197, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39084077

RESUMEN

The steady increase in the prevalence of inflammatory bowel disease (IBD) is regarded as a worldwide health issue. Gut microorganisms could modulate host immune and metabolic status and are associated with health effects. Probiotics, Lactobacillus rhamnosus GG (LGG), are beneficial microorganisms that ameliorate disease and exert advantageous effects on intestinal homeostasis. However, the viability of probiotics will suffer from various risk factors in the digestive tract. In this view, we developed a probiotic coating with nanocomposite using tannic acid (TA) and casein phosphopeptide (CPP) through layer-by-layer technology to overcome the challenges after oral administration. LGG showed an improved survival rate in simulated gastrointestinal conditions after coated. The coating (LGG/TA-Mg2+/CPP) had potent reactive oxygen species (ROS) scavenging ability and improved the survival rate of colorectal epithelial cells after H2O2 stimulation. In DSS-induced colitis, administration of LGG/TA-Mg2+/CPP ameliorated intestinal inflammation and reduced the disruption of barrier function. Furthermore, LGG/TA-Mg2+/CPP increased the abundance and diversity of the gut microbiota. In the mouse model of DSS colitis, LGG/TA-Mg2+/CPP can better activate the EGFR/AKT signaling pathway, thereby protecting the epithelial barrier function of the colon epithelium. In conclusion, the probiotic coating with nanocomposite may become a delivery platform for probiotics applied to IBD.

9.
Cell Death Dis ; 15(7): 542, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39079960

RESUMEN

Breast cancer remains a significant global health challenge, and its mechanisms of progression and metastasis are still not fully understood. In this study, analysis of TCGA and GEO datasets revealed a significant increase in CCT2 expression in breast cancer tissues, which was associated with poor prognosis in breast cancer patients. Functional analysis revealed that CCT2 promoted breast cancer growth and metastasis through activation of the JAK2/STAT3 signaling pathway. Additionally, the E3 ubiquitin ligase Trim21 facilitated CCT2 ubiquitination and degradation, significantly reversing the protumor effects of CCT2. Most interestingly, we discovered that exosomal CCT2 derived from breast cancer cells suppressed the activation and proinflammatory cytokine secretion of CD4+ T cell. Mechanistically, exosomal CCT2 constrained Ca2+-NFAT1 signaling, thereby reducing CD40L expression on CD4+ T cell. These findings highlight CCT2 upregulation as a potential driver of breast cancer progression and immune evasion. Our study provides new insights into the molecular mechanisms underlying breast cancer progression, suggesting that CCT2 is a promising therapeutic target and prognostic predictor for breast cancer.


Asunto(s)
Neoplasias de la Mama , Linfocitos T CD4-Positivos , Progresión de la Enfermedad , Ribonucleoproteínas , Ubiquitinación , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/inmunología , Animales , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/genética , Ratones , Línea Celular Tumoral , Transducción de Señal , Activación de Linfocitos , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Proliferación Celular , Ratones Endogámicos BALB C , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Pronóstico
10.
Adv Sci (Weinh) ; : e2404628, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38981022

RESUMEN

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. TP53, which has a mutation rate of ≈70%-80% in TNBC patients, plays oncogenic roles when mutated. However, whether circRNAs can exert their effects on TNBC through regulating mutant TP53 has not been well evaluated. In this study, circCFL1, which is highly expressed in TNBC cells and tissues and has prognostic potential is identified. Functionally, circCFL1 promoted the proliferation, metastasis and stemness of TNBC cells. Mechanistically, circCFL1 acted as a scaffold to enhance the interaction between HDAC1 and c-Myc, further promoting the stability of c-Myc via deacetylation-mediated inhibition of K48-linked ubiquitylation. Stably expressed c-Myc further enhanced the expression of mutp53 in TNBC cells with TP53 mutations by directly binding to the promoter of TP53, which promoted the stemness of TNBC cells via activation of the p-AKT/WIP/YAP/TAZ pathway. Moreover, circCFL1 can facilitate the immune escape of TNBC cells by promoting the expression of PD-L1 and suppressing the antitumor immunity of CD8+ T cells. In conclusion, the results revealed that circCFL1 plays an oncogenic role by promoting the HDAC1/c-Myc/mutp53 axis, which can serve as a potential diagnostic biomarker and therapeutic target for TNBC patients with TP53 mutations.

11.
Sci Rep ; 14(1): 16250, 2024 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-39009645

RESUMEN

[11C]Carfentanil ([11C]CFN) is the only selective carbon-11 labeled radiotracer currently available for positron emission tomography (PET) imaging of mu opioid receptors (MORs). Though used extensively in clinical research, [11C]CFN has not been thoroughly characterized as a tool for preclinical PET imaging. As we were occasionally observing severe vital sign instability in rat [11C]CFN studies, we set out to investigate physiological effects of CFN mass and to explore its influence on MOR quantification. In anesthetized rats (n = 15), significant dose-dependent PCO2 increases and heart rate decreases were observed at a conventional tracer dose range (IV, > 100 ng/kg). Next, we conducted baseline and retest [11C]CFN PET scans over a wide range of molar activities. Baseline [11C]CFN PET studies (n = 27) found that nondisplaceable binding potential (BPND) in the thalamus was positively correlated to CFN injected mass, demonstrating increase of MOR availability at higher injected CFN mass. Consistently, when CFN injected mass was constrained < 40 ng/kg (~ 10% MOR occupancy in rats), baseline MOR availability was significantly decreased. For test-retest variability (TRTV), better reproducibility was achieved by controlling CFN injected mass to limit the difference between scans. Taken together, we report significant cardiorespiratory depression and a paradoxical influence on baseline MOR availability at conventional tracer doses in rats. Our findings might reflect changes in cerebral blood flow, changes in receptor affinity, or receptor internalization, and merits further mechanistic investigation. In conclusion, rat [11C]CFN PET requires stringent quality assurance of radiotracer synthesis and mass injected to avoid pharmacological effects and limit potential influences on MOR quantification and reproducibility.


Asunto(s)
Encéfalo , Radioisótopos de Carbono , Fentanilo , Tomografía de Emisión de Positrones , Receptores Opioides mu , Animales , Receptores Opioides mu/metabolismo , Fentanilo/análogos & derivados , Fentanilo/metabolismo , Fentanilo/farmacología , Ratas , Tomografía de Emisión de Positrones/métodos , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Masculino , Ratas Sprague-Dawley , Radiofármacos/farmacocinética
12.
Mol Cancer ; 23(1): 125, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38849860

RESUMEN

BACKGROUND: Breast cancer is the most common malignant tumor, and metastasis remains the major cause of poor prognosis. Glucose metabolic reprogramming is one of the prominent hallmarks in cancer, providing nutrients and energy to support dramatically elevated tumor growth and metastasis. Nevertheless, the potential mechanistic links between glycolysis and breast cancer progression have not been thoroughly elucidated. METHODS: RNA-seq analysis was used to identify glucose metabolism-related circRNAs. The expression of circSIPA1L3 in breast cancer tissues and serum was examined by qRT-PCR, and further assessed its diagnostic value. We also evaluated the prognostic potential of circSIPA1L3 by analyzing a cohort of 238 breast cancer patients. Gain- and loss-of-function experiments, transcriptomic analysis, and molecular biology experiments were conducted to explore the biological function and regulatory mechanism of circSIPA1L3. RESULTS: Using RNA-seq analysis, circSIPA1L3 was identified as the critical mediator responsible for metabolic adaption upon energy stress. Gain- and loss-of-function experiments revealed that circSIPA1L3 exerted a stimulative effect on breast cancer progression and glycolysis, which could also be transported by exosomes and facilitated malignant behaviors among breast cancer cells. Significantly, the elevated lactate secretion caused by circSIPA1L3-mediated glycolysis enhancement promoted the recruitment of tumor associated macrophage and their tumor-promoting roles. Mechanistically, EIF4A3 induced the cyclization and cytoplasmic export of circSIPA1L3, which inhibited ubiquitin-mediated IGF2BP3 degradation through enhancing the UPS7-IGF2BP3 interaction. Furthermore, circSIPA1L3 increased mRNA stability of the lactate export carrier SLC16A1 and the glucose intake enhancer RAB11A through either strengthening their interaction with IGF2BP3 or sponging miR-665, leading to enhanced glycolytic metabolism. Clinically, elevated circSIPA1L3 expression indicated unfavorable prognosis base on the cohort of 238 breast cancer patients. Moreover, circSIPA1L3 was highly expressed in the serum of breast cancer patients and exhibited high diagnostic value for breast cancer patients. CONCLUSIONS: Our study highlights the oncogenic role of circSIPA1L3 through mediating glucose metabolism, which might serve as a promising diagnostic and prognostic biomarker and potential therapeutic target for breast cancer.


Asunto(s)
Progresión de la Enfermedad , Exosomas , Regulación Neoplásica de la Expresión Génica , Glucosa , ARN Circular , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Exosomas/metabolismo , ARN Circular/genética , Glucosa/metabolismo , Ratones , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/genética , Animales , Pronóstico , Glucólisis , Línea Celular Tumoral , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Reprogramación Metabólica , Proteínas de la Membrana , Péptidos y Proteínas de Señalización Intracelular
13.
Sensors (Basel) ; 24(12)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38931732

RESUMEN

The recent advancements of mobile edge computing (MEC) technologies and unmanned aerial vehicles (UAVs) have provided resilient and flexible computation services for ground users beyond the coverage of terrestrial service. In this paper, we focus on a UAV-assisted MEC system in which the UAV equipped with MEC servers is used to assist user devices in computing their tasks. To minimize the weighted average energy consumption and delay in the UAV-assisted MEC system, a LQR-Lagrange-based DDPG (LLDDPG) algorithm, which jointly optimizes the user task offloading and the UAV trajectory design, is proposed. To be specific, the LLDDPG algorithm consists of three subproblems. The DDPG algorithm is used to address the issue of UAV desired trajectory planning, and subsequently, the LQR-based algorithm is employed to achieve the real-time tracking control of UAV desired trajectory. Finally, the Lagrange duality method is proposed to solve the optimization problem of computational resource allocation. Simulation results indicate that the proposed LLDDPG algorithm can effectively improve the system resource management and realize the real-time UAV trajectory design.

14.
PLoS One ; 19(6): e0302700, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38941343

RESUMEN

Causation and effectuation are two fundamental decision-making logics that managers use for crucial firm strategic decisions. However, existing research has yet to agree on the relationship between the two logics, supporting both the substitution and complementarity of causation and effectuation in influencing firm performance. This leaves us with a puzzle: How do causation and effectuation combine in balance to improve firm performance? To address the gap, we utilize a fuzzy set qualitative comparative analysis (fsQCA) with data collected from 344 small to medium-sized enterprises (SMEs) in China to uncover the dynamic relationships between the two logics. Our findings indicate that causation or effectuation alone is insufficient to achieve superior firm performance. By distinguishing between four dimensions of effectuation, we identify three types of configurations for high performance: (1) causation with promotion-focused effectuation principles; (2) causation with prevention-focused effectuation principles; (3) causation with hybrid-focused effectuation principles. More importantly, we find that the effectiveness of the configurations depends on the firm development stage. Our findings provide SMEs with practical insights into how to effectively choose their decision-making logic when faced with different firm growth challenges.


Asunto(s)
Toma de Decisiones , Humanos , China , Lógica Difusa
15.
Toxics ; 12(6)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38922113

RESUMEN

Physiologically based pharmacokinetic/toxicokinetic (PBPK/PBTK) models are designed to elucidate the mechanism of chemical compound action in organisms based on the physiological, biochemical, anatomical, and thermodynamic properties of organisms. After nearly a century of research and practice, good results have been achieved in the fields of medicine, environmental science, and ecology. However, there is currently a lack of a more systematic review of progress in the main research directions of PBPK models, especially a more comprehensive understanding of the application in aquatic environmental research. In this review, a total of 3974 articles related to PBPK models from 1996 to 24 March 2024 were collected. Then, the main research areas of the PBPK model were categorized based on the keyword co-occurrence maps and cluster maps obtained by CiteSpace. The results showed that research related to medicine is the main application area of PBPK. Four major research directions included in the medical field were "drug assessment", "cross-species prediction", "drug-drug interactions", and "pediatrics and pregnancy drug development", in which "drug assessment" accounted for 55% of the total publication volume. In addition, bibliometric analyses indicated a rapid growth trend in the application in the field of environmental research, especially in predicting the residual levels in organisms and revealing the relationship between internal and external exposure. Despite facing the limitation of insufficient species-specific parameters, the PBPK model is still an effective tool for improving the understanding of chemical-biological effectiveness and will provide a theoretical basis for accurately assessing potential risks to ecosystems and human health. The combination with the quantitative structure-activity relationship model, Bayesian method, and machine learning technology are potential solutions to the previous research gaps.

16.
Mol Neurobiol ; 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38829513

RESUMEN

Approximately one-third of postoperative patients are troubled by postoperative pain. Effective treatments are still lacking. The aim of this study is to investigate the role of brain-derived neurotrophic factor (BDNF)-VGF (non-acronymic) in dorsal root ganglia (DRG) in postoperative pain. Pain behaviors were assessed through measurements of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Transcriptome analysis was conducted to identify potential targets associated with postoperative pain. Western blotting, immunofluorescence, and ELISA were employed to further detect macrophage activation as well as the expression of BDNF, VGF, TNF-α, IL-1ß, and IL-6. Results showed that plantar incision induced both mechanical and thermal hyperalgesia. Transcriptome analysis suggested that plantar incision caused upregulation of BDNF and VGF. The expressions of BDNF and VGF were upregulated in isolectin B4-positive (IB4+) and calcitonin gene-related peptide-positive (CGRP+) neurons, rather than neurofilament 200-positive (NF200+) neurons. The activation of BDNF-VGF pathway upregulated expression of IL-6, TNF-α, and IL-1ß and promoted the activation of macrophages. In conclusion, BDNF-VGF pathway aggravates acute postoperative pain by promoting macrophage activation and pro-inflammatory cytokine production, which may provide a new target for the treatment of postoperative pain.

17.
Adv Sci (Weinh) ; 11(29): e2400451, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38828672

RESUMEN

Wound infections pose a major healthcare issue, affecting the well-being of millions of patients worldwide. Effective intervention and on-site detection are important in wound management. However, current approaches are hindered by time-consuming analysis and a lack of technology for real-time monitoring and prompt therapy delivery. In this study, a smart wound patch system (SWPS) designed for wireless closed-loop and in-situ wound management is presented. The SWPS integrates a microfluidic structure, an organic electrochemical transistor (OECT) based sensor, an electrical stimulation module, and a miniaturized flexible printed circuit board (FPCB). The OECT incorporates a bacteria-responsive DNA hydrogel-coated gate for continuous monitoring of bacterial virulence at wound sites. Real-time detection of OECT readings and on-demand delivery of electrical cues to accelerate wound healing is facilitated by a mobile phone application linked with an FPCB containing low-power electronics equipped with parallel sensing and stimulation circuitry. In this proof-of-concept study, the functionality of the SWPS is validated and its application both in vitro and in vivo is demonstrated. This proposed system expands the arsenal of tools available for effective wound management and enables personalized treatment.


Asunto(s)
Tecnología Inalámbrica , Cicatrización de Heridas , Tecnología Inalámbrica/instrumentación , Animales , Infección de Heridas/terapia , Diseño de Equipo/métodos , Ratones , Modelos Animales de Enfermedad , Humanos
18.
Ren Fail ; 46(1): 2338484, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38832469

RESUMEN

Critically ill COVID-19 patients may exhibit various clinical symptoms of renal dysfunction including severe Acute Kidney Injury (AKI). Currently, there is a lack of bibliometric analyses on COVID-19-related AKI. The aim of this study is to provide an overview of the current research status and hot topics regarding COVID-19 AKI. The literature was retrieved from the Web of Science Core Collection (WoSCC) database. Subsequently, we utilized Microsoft Excel, VOSviewer, Citespace, and Pajek software to revealed the current research status, emerging topics, and developmental trends pertaining to COVID-19 AKI. This study encompassed a total of 1507 studies on COVID-19 AKI. The United States, China, and Italy emerged as the leading three countries in terms of publication numbers, contributing 498 (33.05%), 229 (15.20%), and 140 (9.29%) studies, respectively. The three most active and influential institutions include Huazhong University of Science and Technology, Wuhan University and Harvard Medical School. Ronco C from Italy, holds the record for the highest number of publications, with a total of 15 papers authored. Cheng YC's work from China has garnered the highest number of citations, totaling 470 citations. The co-occurrence analysis of author keywords reveals that 'mortality', 'intensive care units', 'chronic kidney disease', 'nephrology', 'renal transplantation', 'acute respiratory distress syndrome', and 'risk factors' emerge as the primary areas of focus within the realm of COVID-19 AKI. In summary, this study analyzes the research trends in the field of COVID-19 AKI, providing a reference for further exploration and research on COVID-19 AKI mechanisms and treatment.


Asunto(s)
Lesión Renal Aguda , Bibliometría , COVID-19 , Pandemias , SARS-CoV-2 , Humanos , COVID-19/complicaciones , COVID-19/epidemiología , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/complicaciones , Neumonía Viral/epidemiología , Neumonía Viral/complicaciones , Italia/epidemiología , Betacoronavirus , China/epidemiología , Salud Global
19.
Molecules ; 29(12)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38930967

RESUMEN

The integration of two-dimensional Ti3C2Tx nanosheets and other materials offers broader application options in the antibacterial field. Ti3C2Tx-based composites demonstrate synergistic physical, chemical, and photodynamic antibacterial activity. In this review, we aim to explore the potential of Ti3C2Tx-based composites in the fabrication of an antibiotic-free antibacterial agent with a focus on their systematic classification, manufacturing technology, and application potential. We investigate various components of Ti3C2Tx-based composites, such as metals, metal oxides, metal sulfides, organic frameworks, photosensitizers, etc. We also summarize the fabrication techniques used for preparing Ti3C2Tx-based composites, including solution mixing, chemical synthesis, layer-by-layer self-assembly, electrostatic assembly, and three-dimensional (3D) printing. The most recent developments in antibacterial application are also thoroughly discussed, with special attention to the medical, water treatment, food preservation, flexible textile, and industrial sectors. Ultimately, the future directions and opportunities are delineated, underscoring the focus of further research, such as elucidating microscopic mechanisms, achieving a balance between biocompatibility and antibacterial efficiency, and investigating effective, eco-friendly synthesis techniques combined with intelligent technology. A survey of the literature provides a comprehensive overview of the state-of-the-art developments in Ti3C2Tx-based composites and their potential applications in various fields. This comprehensive review covers the variety, preparation methods, and applications of Ti3C2Tx-based composites, drawing upon a total of 171 English-language references. Notably, 155 of these references are from the past five years, indicating significant recent progress and interest in this research area.


Asunto(s)
Antibacterianos , Titanio , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Titanio/química , Titanio/farmacología , Humanos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología
20.
Anal Methods ; 16(24): 3839-3846, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38829181

RESUMEN

The level of sulfur dioxide (SO2) and viscosity in mitochondria play vital roles in various physiological and pathological processes. Abnormalities in mitochondrial SO2 and viscosity are closely associated with numerous biological diseases. It is of great significance to develop novel fluorescence probes for simultaneous detection of SO2 and viscosity within mitochondria. Herein, we have developed a water-soluble, mitochondrial-targeted and near-infrared fluorescent probe, CMBT, for the simultaneous detection of SO2 and viscosity. The probe CMBT incorporates benzothiazolium salt as a mitochondrial targeting moiety and 7-diethylaminocoumarin as a rotor for viscosity detection, respectively. Based on the prompt reaction between nucleophilic HSO3-/SO32- and the backbone of the benzothiazolium salt derivative, probe CMBT displayed high sensitivity and selectivity toward SO2 with a limit of detection as low as 0.17 µM. As viscosity increased, the twisted intramolecular charge transfer (TICT) process was restricted, resulting in fluorescence emission enhancement at 690 nm. Moreover, probe CMBT demonstrated exceptional mitochondrial targeting ability and was successfully employed to image variations of SO2 and viscosity in living cells and mice. The work highlights the great potential of the probe as a convenient tool for revealing the relationship between SO2 and viscosity in biological systems.


Asunto(s)
Colorantes Fluorescentes , Mitocondrias , Dióxido de Azufre , Dióxido de Azufre/análisis , Dióxido de Azufre/química , Colorantes Fluorescentes/química , Animales , Mitocondrias/química , Mitocondrias/metabolismo , Viscosidad , Ratones , Humanos , Imagen Óptica/métodos , Células HeLa , Límite de Detección
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