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1.
Sci China Life Sci ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38951429

RESUMO

Our knowledge on permafrost carbon (C) cycle is crucial for understanding its feedback to climate warming and developing nature-based solutions for mitigating climate change. To understand the characteristics of permafrost C cycle on the Tibetan Plateau, the largest alpine permafrost region around the world, we summarized recent advances including the stocks and fluxes of permafrost C and their responses to thawing, and depicted permafrost C dynamics within this century. We find that this alpine permafrost region stores approximately 14.1 Pg (1 Pg=1015 g) of soil organic C (SOC) in the top 3 m. Both substantial gaseous emissions and lateral C transport occur across this permafrost region. Moreover, the mobilization of frozen C is expedited by permafrost thaw, especially by the formation of thermokarst landscapes, which could release significant amounts of C into the atmosphere and surrounding water bodies. This alpine permafrost region nevertheless remains an important C sink, and its capacity to sequester C will continue to increase by 2100. For future perspectives, we would suggest developing long-term in situ observation networks of C stocks and fluxes with improved temporal and spatial coverage, and exploring the mechanisms underlying the response of ecosystem C cycle to permafrost thaw. In addition, it is essential to improve the projection of permafrost C dynamics through in-depth model-data fusion on the Tibetan Plateau.

2.
Comput Educ Open ; 6: None, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38947763

RESUMO

Automated writing evaluation (AWE) has shown promise in enhancing students' writing outcomes. However, further research is needed to understand how AWE is perceived by middle school students in the United States, as they have received less attention in this field. This study investigated U.S. middle school students' perceptions of the MI Write AWE system. Students reported their perceptions of MI Write's usefulness using Likert-scale items and an open-ended survey question. We used Latent Dirichlet Allocation (LDA) to identify latent topics in students' comments, followed by qualitative analysis to interpret the themes related to those topics. We then examined whether these themes differed among students who agreed or disagreed that MI Write was a useful learning tool. The LDA analysis revealed four latent topics: (1) students desire more in-depth feedback, (2) students desire an enhanced user experience, (3) students value MI Write as a learning tool but desire greater personalization, and (4) students desire increased fairness in automated scoring. The distribution of these topics varied based on students' ratings of MI Write's usefulness, with Topic 1 more prevalent among students who generally did not find MI Write useful and Topic 3 more prominent among those who found MI Write useful. Our findings contribute to the enhancement and implementation of AWE systems, guide future AWE technology development, and highlight the efficacy of LDA in uncovering latent topics and patterns within textual data to explore students' perspectives of AWE.

3.
Environ Geochem Health ; 46(8): 280, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963449

RESUMO

The chlor-alkali industry (CAI) is crucial for global chemical production; however, its operation has led to widespread heavy metal (HM) contamination at numerous sites, which has not been thoroughly investigated. This study analysed 122 soil and groundwater samples from a typical CAI site in Kaifeng, China. Our aim was to assess the ecological and health risks, identify the sources, and examine the migration characteristics of HMs at this site using Monte Carlo simulation, absolute principal component score-multiple linear regression (APCS-MLR), and the potential environmental risk index (Ei). Our findings revealed that the exceedance rates for Cd, Pb, Hg, and Ni were 71.96%, 45.79%, 49.59%, and 65.42%, respectively. Mercury (Hg) displayed the greatest coefficient of variation across all the soil layers, indicating a significant anthropogenic influence. Cd and Hg were identified as having high and extremely high potential environmental risk levels, respectively. The spatial distributions of the improved Nemerow index (INI), total ecological risk (Ri), and HM content varied considerably, with the most contaminated areas typically associated with the storage of raw and auxiliary materials. Surface aggregation and significant vertical transport were noted for HMs; As and Ni showed substantial accumulation in subsoil layers, severely contaminating the groundwater. Self-organizing maps categorized the samples into two different groups, showing strong positive correlations between Cd, Pb, and Hg. The APCS-MLR model suggested that industrial emissions were the main contributors, accounting for 60.3% of the total HM input. Elevated hazard quotient values for Hg posed significant noncarcinogenic risks, whereas acceptable levels of carcinogenic risk were observed for both adults (96.60%) and children (97.83%). This study significantly enhances historical CAI pollution data and offers valuable insights into ongoing environmental and health challenges.


Assuntos
Monitoramento Ambiental , Água Subterrânea , Metais Pesados , Poluentes do Solo , Poluentes Químicos da Água , Metais Pesados/análise , China , Água Subterrânea/química , Poluentes do Solo/análise , Medição de Risco , Poluentes Químicos da Água/análise , Humanos , Indústria Química
4.
PLoS One ; 19(7): e0306244, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38968269

RESUMO

Recurrent implantation failure (RIF) presents a significant clinical challenge due to the lack of established diagnostic and therapeutic guidelines. Emerging evidence underscores the crucial role of competitive endogenous RNA (ceRNA) regulatory networks in non-cancerous female reproductive disorders, yet the intricacies and operational characteristics of these networks in RIF are not fully understood. This study aims to demystify the ceRNA regulatory network and identify potential biomarkers for its diagnosis. We analyzed expression profiles of three RNA types (long noncoding RNAs [lncRNAs], microRNAs [miRNAs], and mRNAs) sourced from the GEO database, leading to the identification of the H19-hsa-miR-301a-3p-GAS1 ceRNA network. This network demonstrates significant diagnostic relevance for RIF. Notably, the H19/GAS1 axis within this ceRNA network, identified through correlation analysis, emerged as a promising diagnostic marker, as evidenced by operating receiver operator characteristic (ROC) curve analysis. Further investigation into the binding potential of miR-301a-3p with H19 and GAS1 revealed a close association of these genes with endometrial disorders and embryo loss, as per the Comparative Toxicogenomics Database. Additionally, our immune infiltration analysis revealed a lower proportion of T cells gamma delta (γδ) in RIF, along with distinct differences in the expression of immune cell type-specific markers between fertile patients and those with RIF. We also observed a correlation between aberrant expression of H19/GAS1 and these immune markers, suggesting that the H19/GAS1 axis might play a role in modifying the immune microenvironment, contributing to the pathogenesis of RIF. In conclusion, the ceRNA-based H19/GAS1 axis holds promise as a novel diagnostic biomarker for RIF, potentially enhancing our understanding of its underlying mechanisms and improving the success rates of implantation.


Assuntos
Biomarcadores , Implantação do Embrião , RNA Longo não Codificante , RNA Longo não Codificante/genética , Humanos , Feminino , Implantação do Embrião/genética , Biomarcadores/metabolismo , MicroRNAs/genética , Redes Reguladoras de Genes
5.
Int J Nanomedicine ; 19: 6643-6658, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979532

RESUMO

Purpose: Nanovesicles (NVs) derived from bone mesenchymal stem cells (BMSCs) as drug delivery systems are considered an effective therapeutic strategy for diabetes. However, its mechanism of action remains unclear. Here, we evaluated the efficacy and molecular mechanism of BMSC-derived NVs carrying the curcumin analog H8 (H8-BMSCs-NVs) on hepatic glucose and lipid metabolism in type 2 diabetes (T2D). Subjects and Methods: Mouse BMSCs were isolated by collagenase digestion and H8-BMSCs-NVs were prepared by microvesicle extrusion. The effects of H8-BMSCs-NVs on hepatic glucose and lipid metabolism were observed in a T2D mouse model and a HepG2 cell insulin resistance model. To evaluate changes in potential signaling pathways, the PI3K/AKT/AMPK signaling pathway and expression levels of G6P and PEPCK were assessed by Western blotting. Results: H8-BMSCs-NVs effectively improved lipid accumulation in liver tissues and restored liver dysfunction in T2D mice. Meanwhile, H8-BMSCs-NVs effectively inhibited intracellular lipid accumulation in the insulin resistance models of HepG2 cells. Mechanistic studies showed that H8-BMSCs-NVs activated the PI3K/AKT/AMPK signaling pathway and decreased the expression levels of G6P and PEPCK. Conclusion: These findings demonstrate that H8-BMSCs-NVs improved hepatic glucose and lipid metabolism in T2D mice by activating the PI3K/AKT/AMPK signaling pathway, which provides novel evidence suggesting the potential of H8-BMSCs-NVs in the clinically treatment of T2D patients.


Assuntos
Diabetes Mellitus Tipo 2 , Glucose , Metabolismo dos Lipídeos , Fígado , Células-Tronco Mesenquimais , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células Hep G2 , Glucose/metabolismo , Camundongos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Curcumina/farmacologia , Curcumina/química , Curcumina/administração & dosagem , Resistência à Insulina , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Diabetes Mellitus Experimental/metabolismo
6.
Adv Sci (Weinh) ; : e2404230, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984451

RESUMO

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and known for its challenging prognosis. Sonodynamic therapy (SDT) is an innovative therapeutic approach that shows promise in tumor elimination by activating sonosensitizers with low-intensity ultrasound. In this study, a novel sonosensitizer is synthesized using Cu-doped carbon dots (Cu-CDs) for the sonodynamic treatment of GBM. Doping with copper transforms the carbon dots into a p-n type semiconductor having a bandgap of 1.58 eV, a prolonged lifespan of 10.7 µs, and an improved electron- and hole-separation efficiency. The sonodynamic effect is efficiency enhanced. Western blot analysis reveals that the Cu-CDs induces a biological response leading to cell death, termed as cuproptosis. Specifically, Cu-CDs upregulate dihydrosulfanyl transacetylase expression, thereby establishing a synergistic therapeutic effect against tumor cell death when combined with SDT. Furthermore, Cu-CDs exhibit excellent permeability through the blood-brain barrier and potent anti-tumor activity. Importantly, the Cu-CDs effectively impede the growth of glioblastoma tumors and prolong the survival of mice bearing these tumors. This study provides support for the application of carbon-based nanomaterials as sonosensitizers in tumor therapy.

7.
Front Neurosci ; 18: 1411797, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988766

RESUMO

Neuroimaging-based prediction of neurocognitive measures is valuable for studying how the brain's structure relates to cognitive function. However, the accuracy of prediction using popular linear regression models is relatively low. We propose a novel deep regression method, namely TractoSCR, that allows full supervision for contrastive learning in regression tasks using diffusion MRI tractography. TractoSCR performs supervised contrastive learning by using the absolute difference between continuous regression labels (i.e., neurocognitive scores) to determine positive and negative pairs. We apply TractoSCR to analyze a large-scale dataset including multi-site harmonized diffusion MRI and neurocognitive data from 8,735 participants in the Adolescent Brain Cognitive Development (ABCD) Study. We extract white matter microstructural measures using a fine parcellation of white matter tractography into fiber clusters. Using these measures, we predict three scores related to domains of higher-order cognition (general cognitive ability, executive function, and learning/memory). To identify important fiber clusters for prediction of these neurocognitive scores, we propose a permutation feature importance method for high-dimensional data. We find that TractoSCR obtains significantly higher accuracy of neurocognitive score prediction compared to other state-of-the-art methods. We find that the most predictive fiber clusters are predominantly located within the superficial white matter and projection tracts, particularly the superficial frontal white matter and striato-frontal connections. Overall, our results demonstrate the utility of contrastive representation learning methods for regression, and in particular for improving neuroimaging-based prediction of higher-order cognitive abilities. Our code will be available at: https://github.com/SlicerDMRI/TractoSCR.

8.
J Health Econ ; 97: 102915, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-39002190

RESUMO

This paper examines the influence of housing wealth on fertility outcomes through a regression discontinuity design based on a 2006 Chinese housing-market policy. Our analysis reveals that the positive impact of this policy on housing wealth significantly enhances the likelihood of fertility by 7.3 %. Our result implies that a 1 % increase in housing wealth can raise the fertility rate by 0.18 %. Furthermore, we observe that children born subsequent to the positive housing wealth shock exhibit improved health, not only at birth but also over the long term. Lastly, we present suggestive evidence suggesting that both parental pre-birth time allocation and parental health may help explain the documented positive effects of housing wealth on fertility rates.

9.
Lasers Med Sci ; 39(1): 178, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990392

RESUMO

To evaluate the visual outcome and astigmatic correction following trifocal intraocular lens (IOL) implantation using the modified femtosecond laser-assisted arcuate keratotomy (FSAK) in Chinese cataract patients with low astigmatism. This retrospective study included consecutive cataract patients with regular corneal astigmatism ranging from 0.75 to 1.5 D who underwent FSAK combined with the trifocal IOL implantation between November 2020 and September 2022. Monocular uncorrected distance visual acuity, uncorrected intermediate visual acuity, uncorrected near visual acuity, and refractive data were collected at the 3-month follow-up. The pre- and post-operative high-order aberrations (HOAs) were recorded. The variation in astigmatism was analyzed using Alpins vector analysis. A total of 27 eyes from 23 patients were analyzed. The monocular uncorrected distance visual acuity (UDVA) (5 m) at the 3-month follow-up was 0.04 ± 0.09 logarithm of the minimum angle of resolution (logMAR), which was significantly improved compared with the preoperative value of 0.95 ± 0.51 logMAR (P <.001). The corneal astigmatism was significantly reduced from 1.24 ± 0.42 D to 0.49 ± 0.34 D (P <.001). The target-induced astigmatism (TIA) was 1.25 ± 0.43 D, the surgically induced astigmatism (SIA) was 1.16 ± 0.52 D, and the difference vector (DV) was 0.5 ± 0.34 D. The magnitude of error (ME) (difference between SIA and TIA) was -0.1 ± 0.41 D, and the correction index (CI) (ratio of SIA to TIA) was 0.93 ± 0.36. The angle of error was 3.92° ± 16.90°. Total HOA was reduced from 0.89 ± 1.11 to 0.41 ± 0.55 (P = 0.184), and the corneal HOA was lowered from 0.17 ± 0.18 to 0.10 ± 0.10 (P = 0.129). Implantation of trifocal IOL following the modified FSAK in Chinese cataract patients exhibited excellent visual efficacy and effectively reduced corneal astigmatism.


Assuntos
Astigmatismo , Catarata , Acuidade Visual , Humanos , Astigmatismo/cirurgia , Astigmatismo/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Catarata/complicações , Implante de Lente Intraocular/métodos , Lentes Intraoculares Multifocais , Adulto , China , Córnea/cirurgia , Córnea/fisiopatologia , Resultado do Tratamento , População do Leste Asiático
10.
Angew Chem Int Ed Engl ; : e202410118, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997791

RESUMO

Molecular phosphorescence in the second near-infrared window (NIR-II, 1000-1700 nm) holds promise for deep-tissue optical imaging with high contrast by overcoming background fluorescence interference. However, achieving bright and stable NIR-II molecular phosphorescence suitable for biological applications remains a formidable challenge. Herein, we report a new series of symmetric isocyanorhodium(I) complexes that could form oligomers and exhibit bright, long-lived (7-8 µs) phosphorescence in aqueous solution via metallophilic interaction. Ligand substituents with enhanced dispersion attraction and electron-donating properties were explored to extend excitation/emission wavelengths and enhanced stability. Further binding the oligomers with fetal bovine serum (FBS) resulted in NIR-II molecular phosphorescence with high quantum yields (up to 3.93%) and long-term stability in biological environments, enabling in vivo tracking of single-macrophage dynamics and high-contrast time-resolved imaging. These results pave the way for the development of highly-efficient NIR-II molecular phosphorescence for biomedical applications.

11.
Cell Mol Life Sci ; 81(1): 298, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992327

RESUMO

In spite of its essential role in culture media, the precise influence of lactate on early mouse embryonic development remains elusive. Previous studies have implicated lactate accumulation in medium affecting histone acetylation. Recent research has underscored lactate-derived histone lactylation as a novel epigenetic modification in diverse cellular processes and diseases. Our investigation demonstrated that the absence of sodium lactate in the medium resulted in a pronounced 2-cell arrest at the late G2 phase in embryos. RNA-seq analysis revealed that the absence of sodium lactate significantly impaired the maternal-to-zygotic transition (MZT), particularly in zygotic gene activation (ZGA). Investigations were conducted employing Cut&Tag assays targeting the well-studied histone acetylation and lactylation sites, H3K18la and H3K27ac, respectively. The findings revealed a noticeable reduction in H3K18la modification under lactate deficiency, and this alteration showed a significant correlation with changes in gene expression. In contrast, H3K27ac exhibited minimal correlation. These results suggest that lactate may preferentially influence early embryonic development through H3K18la rather than H3K27ac modifications.


Assuntos
Histonas , Ácido Láctico , Zigoto , Histonas/metabolismo , Histonas/genética , Animais , Acetilação , Zigoto/metabolismo , Camundongos , Ácido Láctico/metabolismo , Desenvolvimento Embrionário/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Epigênese Genética , Genoma , Processamento de Proteína Pós-Traducional
12.
Transl Neurodegener ; 13(1): 34, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39044270

RESUMO

BACKGROUND: Depressive symptoms often occur in patients with Alzheimer's disease (AD) and exacerbate the pathogenesis of AD. However, the neural circuit mechanisms underlying the AD-associated depression remain unclear. The serotonergic system plays crucial roles in both AD and depression. METHODS: We used a combination of in vivo trans-synaptic circuit-dissecting anatomical approaches, chemogenetic manipulations, optogenetic manipulations, pharmacological methods, behavioral testing, and electrophysiological recording to investigate dorsal raphe nucleus serotonergic circuit in AD-associated depression in AD mouse model. RESULTS: We found that the activity of dorsal raphe nucleus serotonin neurons (DRN5-HT) and their projections to the dorsal hippocampal CA1 (dCA1) terminals (DRN5-HT-dCA1CaMKII) both decreased in brains of early 5×FAD mice. Chemogenetic or optogenetic activation of the DRN5-HT-dCA1CaMKII neural circuit attenuated the depressive symptoms and cognitive impairments in 5×FAD mice through serotonin receptor 1B (5-HT1BR) and 4 (5-HT4R). Pharmacological activation of 5-HT1BR or 5-HT4R attenuated the depressive symptoms and cognitive impairments in 5×FAD mice by regulating the DRN5-HT-dCA1CaMKII neural circuit to improve synaptic plasticity. CONCLUSIONS: These findings provide a new mechanistic connection between depression and AD and provide potential pharmaceutical prevention targets for AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Depressão , Modelos Animais de Doenças , Núcleo Dorsal da Rafe , Camundongos Transgênicos , Neurônios Serotoninérgicos , Animais , Núcleo Dorsal da Rafe/metabolismo , Masculino , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/fisiopatologia , Camundongos , Neurônios Serotoninérgicos/metabolismo , Neurônios Serotoninérgicos/fisiologia , Depressão/metabolismo , Depressão/genética , Depressão/psicologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Hipocampo/metabolismo , Serotonina/metabolismo , Optogenética , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia
13.
Front Pharmacol ; 15: 1401961, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39045049

RESUMO

Diabetic cardiomyopathy (DCM) is a specific heart condition in diabetic patients, which is a major cause of heart failure and significantly affects quality of life. DCM is manifested as abnormal cardiac structure and function in the absence of ischaemic or hypertensive heart disease in individuals with diabetes. Although the development of DCM involves multiple pathological mechanisms, mitochondrial dysfunction is considered to play a crucial role. The regulatory mechanisms of mitochondrial dysfunction mainly include mitochondrial dynamics, oxidative stress, calcium handling, uncoupling, biogenesis, mitophagy, and insulin signaling. Targeting mitochondrial function in the treatment of DCM has attracted increasing attention. Studies have shown that plant secondary metabolites contribute to improving mitochondrial function and alleviating the development of DCM. This review outlines the role of mitochondrial dysfunction in the pathogenesis of DCM and discusses the regulatory mechanism for mitochondrial dysfunction. In addition, it also summarizes treatment strategies based on plant secondary metabolites. These strategies targeting the treatment of mitochondrial dysfunction may help prevent and treat DCM.

14.
JAAD Int ; 16: 206-213, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39040843

RESUMO

Background: A reliable instrument is needed to assess vitiligo severity and treatment response. Objective: To assess inter- and intrarater variability and accuracy of the Vitiligo Area Scoring Index among trained raters and to evaluate a proposed Vitiligo Area Scoring Index using equidistant 10% depigmentation increments (VASI 10%). Methods: In this prospective study, 12 raters evaluated images of 10 participants with vitiligo on 2 occasions using total body Vitiligo Area Scoring Index (T-VASI) and facial Vitiligo Area Scoring Index (F-VASI) scores after training. Inter- and intrarater reliabilities and accuracy vs digital scores were determined using intraclass correlation coefficients. VASI 10% scores were evaluated separately for interrater reliability and accuracy. Results: F-VASI interrater reliability improved from "moderate" to "good" between time points, while T-VASI was "good" at both time points. Intrarater reliability ranged from "good" to "excellent" for T-VASI and "poor" to "excellent" for F-VASI. Accuracy intraclass correlation coefficient was "good" to "excellent" for most raters. Interrater reliability using VASI 10% was "moderate" for both T-VASI and F-VASI. Limitations: Small participant population and number of raters; participants were not assessed in person; no repeated VASI 10% measures. Conclusion: Vitiligo Area Scoring Index generally provides good to excellent reliability for assessment of vitiligo by raters who receive standardized training.

15.
Technol Cancer Res Treat ; 23: 15330338241262483, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39043042

RESUMO

Spinal cord astrocytoma (SCA) is a rare subtype of astrocytoma, posing challenges in diagnosis and treatment. Low-grade SCA can achieve long-term survival solely through surgery, while high-grade has a disappointing prognosis even with comprehensive treatment. Diagnostic criteria and standard treatment of intracranial astrocytoma have shown obvious limitations in SCA. Research on the molecular mechanism in SCA is lagging far behind that on intracranial astrocytoma. In recent years, huge breakthroughs have been made in molecular pathology of astrocytoma, and novel techniques have emerged, including DNA methylation analysis and radiomics. These advances are now making it possible to provide a precise diagnosis and develop corresponding treatment strategies in SCA. Our aim is to review the current status of diagnosis and treatment of SCA, and summarize the latest research advancement, including tumor subtype, molecular characteristics, diagnostic technology, and potential therapy strategies, thus deepening our understanding of this uncommon tumor type and providing guidance for accurate diagnosis and treatment.


Assuntos
Astrocitoma , Neoplasias da Medula Espinal , Humanos , Astrocitoma/genética , Astrocitoma/terapia , Astrocitoma/diagnóstico , Astrocitoma/patologia , Neoplasias da Medula Espinal/terapia , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/patologia , Biomarcadores Tumorais/genética , Patologia Molecular , Metilação de DNA , Gerenciamento Clínico , Prognóstico , Gradação de Tumores
16.
Adv Sci (Weinh) ; : e2405299, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037903

RESUMO

During the process of muscle regeneration post-injury in adults, muscle stem cells (MuSCs) function is facilitated by neighboring cells within the pro-regenerative niche. However, the precise mechanism triggering the initiation of signaling in the pro-regenerative niche remains unknown. Using single-cell RNA sequencing, 14 different muscle cells are comprehensively mapped during the initial stage following injury. Among these, macrophages and fibro-adipogenic progenitor cells (FAPs) exhibit the most pronounced intercellular communication with other cells. In the FAP subclusters, the study identifies an activated FAP phenotype that secretes chemokines, such as CXCL1, CXCL5, CCL2, and CCL7, to recruit macrophages after injury. Il1rl1, encoding the protein of the interleukin-33 (IL-33) receptor, is identified as a highly expressed signature surface marker of the FAP phenotype. Following muscle injury, autocrine IL-33, an alarmin, has been observed to activate quiescent FAPs toward this inflammatory phenotype through the IL1RL1-MAPK/NF-κB signaling pathway. Il1rl1 deficiency results in decreased chemokine expression and recruitment of macrophages, accompanied by impaired muscle regeneration. These findings elucidate a novel mechanism involving the IL-33/IL1RL1 signaling pathway in promoting the activation of FAPs and facilitating muscle regeneration, which can aid the development of therapeutic strategies for muscle-related disorders and injuries.

17.
Chem Asian J ; : e202400716, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041455

RESUMO

Excessive sulfur dioxide (SO2) disturbs physiology of lysosomes causing diseases and threatening human health. A fluorescent probe has been regarded as one of the most attractive approaches, which is compatible with living cells and possesses high sensitivity. However, most of fluorescent probes' reaction sites are activated before they reach the destination. In this work, an acid-activatable fluorescent probe PT1 was synthesized, characterized, and used for SO2 detection. The introduction of oxazolines in PT1 enables the intelligent response of probe to release the activation stie for SO2 derivatives through Michael addition upon exposure to acid. In vitro studies showed a remarkable selectivity of PT1 to SO2 derivatives than other biothiols with a limit of detection as low as 62 nM. Precise spatiotemporal identification of lysosomal SO2 fluctuations has been successfully performed by PT1. Furthermore, PT1 can be applied for monitoring SO2 derivatives in traditional Chinese medicines.

18.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(4): 589-593, 2024 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-39041550

RESUMO

OBJECTIVE: To analyze the incidence and progression of overactive bladder (OAB) symptoms following radical prostatectomy for prostate cancer patients and to identify related risk factors. METHODS: A retrospective study was conducted on 263 local stage prostate cancer patients who underwent radical prostatectomy at Peking University Third Hospital from January 2013 to May 2017. Clinical baseline information, comprehensive imaging features, perioperative parameters, preoperative urinary control status, pathological diagnosis, and the incidence of OAB within one year postoperatively were collected and analyzed. In the imaging features, two parameters were defined: Bladder wall thickness (BWT) and bladder mucosal smoothness (BMS), which were used to predict the occurrence of OAB. Patients were evaluated based on their clinical baseline characteristics, including age, body mass index (BMI), comorbidities, and prostate-specific antigen (PSA) levels. The imaging characteristics were assessed using preoperative MRI, focusing on BWT and BMS. Perioperative parameters included operative time, blood loss, and length of hospital stay. The OAB symptoms were assessed using the overactive bladder symptom score (OABSS) and the international prostate symptom score (IPSS). These scores were correlated with the postoperative incidence of OAB. RESULTS: Among the 263 patients who underwent radical prostatectomy, 52 (19.8%) exhibited OAB within one year postoperatively. Of the 40 patients with preoperative OAB symptoms, 17 (42.5%) showed remission postoperatively, while 23 (57.5%) had persistent symptoms. Additionally, 29 patients developed new-onset OAB, accounting for 55.77% of all postoperative OAB cases. Univariate analysis indicated that BWT, BMS, OABSS, and IPSS score were all associated with the occurrence of postoperative OAB. Further multivariate analysis identified BMS as an independent risk factor for long-term OAB (P < 0.001). CONCLUSION: Long-term postoperative overactive bladder is a common complication following radical prostatectomy. The findings suggest that preoperative MRI measurements of bladder wall thickness and bladder mucosal smoothness during bladder filling phase can predict the risk of OAB occurrence postoperatively. Identifying these risk factors preoperatively can help in counseling patients about potential complications and in developing strategies to mitigate the risk of developing OAB after surgery. Early detection and management of these parameters might improve the quality of life for patients undergoing radical prostatectomy.


Assuntos
Prostatectomia , Neoplasias da Próstata , Bexiga Urinária Hiperativa , Humanos , Masculino , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/epidemiologia , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Próstata/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Incidência , Bexiga Urinária , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Idoso , Antígeno Prostático Específico/sangue
19.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(4): 617-623, 2024 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-39041555

RESUMO

OBJECTIVE: To summarize the clinical characteristics of patients with renal angiomyolipoma (RAML) combined with inferior vena cava (IVC) tumor thrombus, and to explore the feasibility of partial nephrectomy and thrombectomy in this series of patients. METHODS: The clinical data of patients diagnosed with RAML combined with IVC tumor thrombus in the Department of Urology of the Peking University Third Hospital from April 2014 to March 2023 were retrospectively analyzed, and demographic and perioperative data of RAML patients with IVC tumor thrombus were recorded and collected from Electronic Medical Record System, including age, gender, surgical methods, and follow-up time, etc. The clinical characteristics between classic angiomyolipoma (CAML) patients with IVC tumor thrombus and epithelioid angiomyolipoma (EAML) patients with IVC tumor thrombus were compared to determine the clinical characteristics of these patients. RESULTS: A total of 11 patients were included in this study, including 7 patients with CAML with IVC tumor thrombus and 4 patients with EAML with IVC tumor thrombus. There were 9 females (9/11, 81.8%) and 2 males (2/11, 18.2%), with an average age of (44.0±17.1) years. 9 patients (9/11, 81.8%) experienced clinical symptoms, including local symptoms including abdominal pain, hematuria, abdominal masses, and systemic symptoms including weight loss and fever; 2 patients (2/11, 18.2%) with RAML and IVC tumor thrombus did not show clinical symptoms, which were discovered by physical examination. Among the 11 patients, 10 underwent radical nephrectomy with thrombectomy, of whom, 3 underwent open surgery (3/10, 30.0%), 2 underwent laparoscopic surgery (2/10, 20.0%), and 5 underwent robot-assisted laparoscopic surgery (5/10, 50.0%). In addition, 1 patient underwent open partial nephrectomy and thrombectomy. The patients with EAML combined with IVC tumor thrombus had a higher proportion of systemic clinical symptoms (100% vs. 0%, P=0.003), more intraoperative bleeding [400 (240, 3 050) mL vs. 50 (50, 300) mL, P =0.036], and a higher proportion of tumor necrosis (75% vs. 0%, P=0.024) compared to the patients with CAML combined with IVC tumor thrombus. However, there was no statistically significant difference in operation time [(415.8±201.2) min vs. (226.0±87.3) min, P=0.053] between the two groups. CONCLUSION: Compared with the patients with CAML and IVC tumor thrombus, the patients with EAML and IVC tumor thrombus had a higher rate of systemic symptoms and tumor necrosis. In addition, in the selected patients with CAML with IVC tumor thrombus, partial nephrectomy and tumor thrombectomy could be performed to better preserve renal function.


Assuntos
Angiomiolipoma , Neoplasias Renais , Nefrectomia , Trombectomia , Veia Cava Inferior , Humanos , Angiomiolipoma/cirurgia , Angiomiolipoma/diagnóstico , Angiomiolipoma/patologia , Angiomiolipoma/complicações , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/diagnóstico , Feminino , Masculino , Veia Cava Inferior/cirurgia , Veia Cava Inferior/patologia , Estudos Retrospectivos , Nefrectomia/métodos , Trombectomia/métodos , Adulto , Pessoa de Meia-Idade , Trombose Venosa/cirurgia , Trombose Venosa/etiologia , Laparoscopia/métodos , Trombose/cirurgia , Trombose/diagnóstico
20.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(4): 624-630, 2024 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-39041556

RESUMO

OBJECTIVE: To analyze the clinicopathological features, prognostic value and surgical treatment experience in patients with adrenocortical carcinoma with venous tumor thrombus. METHODS: We collected relevant data of the patients with adrenocortical carcinoma who had undergone surgery in Peking University Third Hospital from 2018 to 2023. The patients were divided into venous tumor thrombus group and non-tumor thrombus group. The Wilcoxon rank sum test was used to compare the quantitative variables. The chi-squared test and Fisher's exact test were used to compare the categorical variables. The Kaplan-Meier method was used to estimate the survival rate. RESULTS: A total of 27 patients with adrenocortical carcinoma were included, of whom 11 cases (40.7%) had venous tumor thrombus. In the patients with venous tumor thrombus, 8 patients were female and 3 were male. The median age was 49 (36, 58) years. The median body mass index was 26.0 (24.1, 30.4) kg/m2. Seven patients presented with symptoms at their initial visit. Six patients had a history of hypertension. Elevated levels of cortisol were observed in 2 cases. Three tumors were found on the left side, while 8 were found on the right side. Median tumor diameter was 9.4 (6.5, 12.5) cm. On the left, there was a case of tumor thrombus limited to the central vein of the left adrenal gland without invasion into the left renal vein, and two cases of tumor thrombus growth extending into the inferior vena cava below the liver. One case of tumor thrombus on the right adrenal central vein did not invade the inferior vena cava. Four cases of tumor thrombus invaded the inferior vena cava below the liver and three cases extended to the posterior of the liver. Ten patients were in European Network for the Study of Adrenal Tumors (ENSAT) stage Ⅲ and one was in ENSAT stage Ⅳ. Open surgery was performed in 6 cases, laparoscopic surgery alone in 4 cases and robot-assisted laparoscopic surgery in 1 case. Two patients underwent ipsilateral kidney resection. Median operative time was 332 (261, 440) min. Median intraoperative bleeding was 900 (700, 2 200) mL. Median hospital stay was 9 (5, 10) days. Median survival time for the patients with tumor thrombus was 24.0 months and median time to recurrence was 7.0 months. The median survival and recurrence time of 16 patients without tumor thrombus were not reached. The patients with tumor thrombus had worse 3-year overall survival (OS) rate (40.9% vs. 71.4%; Log-rank, P=0.038) and 2-year recurrence-free survival (RFS) (9.1% vs.53.7%; Log-rank, P=0.015) rates compared with the patients with non-tumor thrombus. CONCLUSION: Patients with adrenocortical carcinoma with venous tumor thrombus have poor prognosis. Different adrenal tumor resections and venous tumor thrombus removal procedures based on different tumor thrombus locations are safe and effective in treating this disease.


Assuntos
Neoplasias do Córtex Suprarrenal , Adrenalectomia , Carcinoma Adrenocortical , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma Adrenocortical/cirurgia , Carcinoma Adrenocortical/complicações , Carcinoma Adrenocortical/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Neoplasias do Córtex Suprarrenal/complicações , Neoplasias do Córtex Suprarrenal/patologia , Adulto , Prognóstico , Adrenalectomia/métodos , Taxa de Sobrevida , Trombose Venosa/etiologia , Trombose Venosa/cirurgia , Veia Cava Inferior/patologia
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