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1.
Commun Biol ; 7(1): 1267, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39369076

RESUMEN

Cellular bioenergetics and mitochondrial dynamics are crucial for the secretion of insulin by pancreatic beta cells in response to elevated levels of blood glucose. To elucidate the interactions between energy production and mitochondrial fission/fusion dynamics, we combine live-cell mitochondria imaging with biophysical-based modeling and graph-based network analysis. The aim is to determine the mechanism that regulates mitochondrial morphology and balances metabolic demands in pancreatic beta cells. A minimalistic differential equation-based model for beta cells is constructed that includes glycolysis, oxidative phosphorylation, calcium dynamics, and fission/fusion dynamics, with ATP synthase flux and proton leak flux as main regulators of mitochondrial dynamics. The model shows that mitochondrial fission occurs in response to hyperglycemia, starvation, ATP synthase inhibition, uncoupling, and diabetic conditions, in which the rate of proton leakage exceeds the rate of mitochondrial ATP synthesis. Under these metabolic challenges, the propensities of tip-to-tip fusion events simulated from the microscopy images of the mitochondrial networks are lower than those in the control group and prevent the formation of mitochondrial networks. The study provides a quantitative framework that couples bioenergetic regulation with mitochondrial dynamics, offering insights into how mitochondria adapt to metabolic challenges.


Asunto(s)
Metabolismo Energético , Células Secretoras de Insulina , Mitocondrias , Dinámicas Mitocondriales , Células Secretoras de Insulina/metabolismo , Mitocondrias/metabolismo , Animales , Modelos Biológicos , Ratones , Adenosina Trifosfato/metabolismo , Humanos
3.
Endocrine ; 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39367996

RESUMEN

PURPOSE: Naltrexone-bupropion (Contrave®) has shown efficacy and safety in large randomised controlled trials, predominantly comprising Caucasians. Data are limited in Asian populations. We carried out a retrospective matched cohort study of Chinese patients with obesity to evaluate the efficacy and safety of naltrexone-bupropion in real-world clinical practice. METHODS: We performed a retrospective matched cohort study of Chinese patients with obesity managed in the Obesity Clinic of Queen Mary Hospital in Hong Kong between 1 January 2016 and 31 December 2020. Electronic health records of patients treated with naltrexone-bupropion were retrieved for body weight and height, obesity-related metabolic parameters, and adverse events over a 12-month period. Age- and sex-matched controls from the Obesity Clinic who were only on self-directed lifestyle management were identified for comparison of weight changes. General linear models were used to analyse the change in body weight over 12 months. RESULTS: Thirty-seven patients treated with naltrexone-bupropion were included (mean age 42.2 ± 8.4 years, 54.1% men, baseline body mass index 37.3 ± 4.6 kg/m2), and 37 age- and sex-matched controls were included. Among the 37 naltrexone-bupropion-treated patients, the mean weight loss was 9.2 ± 5.2% at 6 months and 9.7 ± 8.1% at 12 months, which were significantly more than in controls (p < 0.001). Improvements in the obesity-related parameters were observed in association with weight loss over 12 months. Ten patients (27.0%) discontinued naltrexone-bupropion due to side effects, mainly neurological and gastrointestinal manifestations, within the first 12 months. CONCLUSION: We demonstrated real-world efficacy and safety of naltrexone-bupropion among Chinese patients with obesity.

4.
Eur J Emerg Med ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39283737

RESUMEN

BACKGROUND AND IMPORTANCE: Out-of-hospital cardiac arrest (OHCA) poses major public health issues. Pre-arrest heart function is a prognostic factor, but the specific contribution of pre-arrest echocardiographic evaluation in predicting OHCA outcome remains limited. OBJECTIVE: The primary objective was to investigate the association between left ventricular ejection fraction (LVEF) measured in echocardiography prior to OHCA and survival to hospital discharge. DESIGN, SETTINGS, AND PARTICIPANTS: This multicenter retrospective cohort study analyzed data from the National Taiwan University Hospital and its affiliated hospitals. We included adult nontraumatic OHCA patients who were treated by the emergency medical services (EMS) and underwent echocardiography within 6 months prior to the OHCA event from January 2016 to December 2022. Data included demographics, preexisting diseases, resuscitation events, and echocardiographic reports. OUTCOMES MEASURE AND ANALYSIS: The primary outcome was the survival to hospital discharge after post-arrest care. Statistical analysis involved multivariable logistic regression to modify potential confounders, reported as adjusted odds ratio (aOR) and 95% confidence interval (CI), and evaluate the association between echocardiographic findings and survival to hospital discharge. MAIN RESULTS: This study analyzed 950 patients, with 33.6% surviving to discharge. A higher pre-arrest LVEF was independently associated with increased survival. Compared to patients with LVEF < 40%, those with LVEF between 40% and 60% had significantly higher odds of survival (aOR = 3.68, 95% CI = 2.14-6.35, P < 0.001), and those with LVEF > 60% had even greater odds of survival (aOR = 5.46, 95% CI = 3.09-9.66, P < 0.001). There was also an association between lower tricuspid regurgitation pressure gradient and survival (aOR = 0.98, 95% CI = 0.97-1.00, P = 0.015). Younger age, male gender, dyslipidemia, stroke, cancer, witnessed arrest, initial shockable rhythm, and shorter low-flow time are other significant predictors of survival. CONCLUSION: In adult, nontraumatic, EMS-treated OHCA patients, a higher LVEF 6 months prior to OHCA was associated with improved survival at hospital discharge.

5.
BMC Public Health ; 24(1): 2578, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334064

RESUMEN

BACKGROUND: Although the adverse impact of substandard informal housing has been widely documented, most studies concentrated on developing societies, thereby leaving informal housing in developed regions underexplored. This study examines Hong Kong, where limited dwelling size is a distinctive feature that characterises informal housing, to explore the impact of housing informality on mental health, with a particular focus on dwelling size. It centers on subdivided units (SDUs), which are tiny compartments partitioned from a large domestic quarter, to understand how housing informality and housing size affect the mental well-being of female caregivers, who typically bear the brunt of the housework. METHODS: In partnership with nongovernment organisations in three SDU-abundant districts, this mixed-methods study conducted a survey on 413 female caregivers aged 18-65 and qualitative research combining ethnographic observations and in-depth interviews on 36 families living in SDUs in Hong Kong between 2021 and 2023. The mental health outcomes and health-related quality of life (HRQoL) of the participants were assessed by using the Depression, Anxiety, and Stress Scale-21 and a EuroQol-5 Dimension-5 Level questionnaire. RESULTS: Depression, anxiety and stress were prevalent across the female caregivers living in SDUs (12.4%), as well as a significantly lower HRQoL compared with that of the general population (0.882 vs. 0.919). Findings showed that a total floor area smaller than 13.0 m2 was associated with increased likelihood of experiencing anxiety and depression and reduced HRQoL. Cramped living space adversely affected the caregivers' well-being through the 1) physical, 2) relational and 3) personal aspects of home experiences. Negative experiences at home can cause housework burnout, exacerbate family conflicts and lead to feelings of repression and low self-efficacy. CONCLUSIONS: This study contributes to the understanding of the consequences of housing informality in diverse geographical contexts and illuminates the effect of dwelling size by identifying the mechanisms through which housing size can affect the mental well-being of residents, which may vary depending on their family status. The findings yield important policy implications, including the need to establish a minimum space standard for subdivided residential dwellings and ensure equitable access to community spaces for deprived families.


Asunto(s)
Cuidadores , Vivienda , Salud Mental , Calidad de Vida , Humanos , Femenino , Hong Kong , Cuidadores/psicología , Cuidadores/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Adolescente , Vivienda/estadística & datos numéricos , Investigación Cualitativa , Estrés Psicológico , Depresión/epidemiología , Depresión/psicología , Encuestas y Cuestionarios , Ansiedad/epidemiología
6.
ACS Nano ; 18(33): 22034-22044, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39106126

RESUMEN

Ever since the ground-breaking isolation of graphene, numerous two-dimensional (2D) materials have emerged with 2D metal dihalides gaining significant attention due to their intriguing electrical and magnetic properties. In this study, we introduce an innovative approach via anhydrous solvent-induced recrystallization of bulk powders to obtain crystals of metal dihalides (MX2, with M = Cu, Ni, Co and X = Br, Cl, I), which can be exfoliated to 2D flakes. We demonstrate the effectiveness of our method using CuBr2 as an example, which forms large layered crystals. We investigate the structural properties of both the bulk and 2D CuBr2 using X-ray diffraction, along with Raman scattering and optical spectroscopy, revealing its quasi-1D chain structure, which translates to distinct emission and scattering characteristics. Furthermore, microultraviolet photoemission spectroscopy and electronic transport reveal the electronic properties of CuBr2 flakes, including their valence band structure. We extend our methodology to other metal halides and assess the stability of the metal halide flakes in controlled environments. We show that optical contrast can be used to characterize the flake thicknesses for these materials. Our findings demonstrate the versatility and potential applications of the proposed methodology for preparing and studying 2D metal halide flakes.

7.
Int J Cardiol ; 416: 132487, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39209033

RESUMEN

BACKGROUND: To examine whether left atrial (LA) strain was associated with adverse outcomes in asymptomatic chronic aortic regurgitation (AR). METHODS: Asymptomatic patients with ≥moderate-severe AR were retrospectively identified from 2008 through 2022 from a university hospital. Apical 4-chamber left ventricular longitudinal strain (A4C-LVLS), LA reservoir (LASr), conduit (LAScd), and contractile strain (LASct) were measured using fully-automated software. Primary endpoint was all-cause death (ACD); secondary endpoints were heart failure (HF) development or aortic valve surgery (AVS). RESULTS: Of 352 patients (59 ± 17 years; 19 % female), the mean LV ejection fraction (LVEF) was 60 ± 8 %. The median follow-up during medical surveillance was 4.7 (interquartile range: 1.8-9.0) years; during which 68 patients died. Multivariable analysis adjusted for covariates showed that larger maximal LA volume index (iLAVmax), lower LASr and LASct were independently associated with ACD (all P ≤ 0.047); A4C-LVLS and LAScd were not (P ≥ 0.15). Besides, iLAVmax, LASr, and LASct provided incremental prognostic value over A4C-LVLS in terms of ACD (all P ≤ 0.048). HF symptoms occurred in 126 patients at a median of 2 years. Multivariable determinants for HF development included larger minimal LAV index, lower LASr and LASct (all P ≤ 0.03). Adjusted spline curves showed LASr <38-40 % and LASct <20-24 % were associated with increased risks of ACD and HF development, respectively. Using abovementioned LASr and LASct cutoffs, adjusted Kaplan-Meier curves risk-stratified patients for ACD successfully (P ≤ 0.02). Lower LASr was also independently associated with AVS (Hazard ratio per 1 % increase: 0.98)(P = 0.02). CONCLUSIONS: In patients with asymptomatic AR, fully-automated LASr and LASct were robust markers for outcome determination; these markers may identify those who need timely surgical referral.


Asunto(s)
Insuficiencia de la Válvula Aórtica , Índice de Severidad de la Enfermedad , Humanos , Femenino , Masculino , Persona de Mediana Edad , Insuficiencia de la Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/diagnóstico , Insuficiencia de la Válvula Aórtica/fisiopatología , Estudios Retrospectivos , Pronóstico , Anciano , Enfermedad Crónica , Función del Atrio Izquierdo/fisiología , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Estudios de Seguimiento , Enfermedades Asintomáticas , Ecocardiografía/métodos , Adulto
8.
Langmuir ; 40(32): 16846-16854, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39094224

RESUMEN

Films of the discotic liquid crystalline hexabenzocoronene (HBC) derivative, HBC-1,3,5-Ph-C12, were prepared on the quartz substrate by the bar-coating method. Depending on the coating speed, regularly spaced stripes or continuous films were observed. In the former case, columns of the HBC derivatives align more along the stripes, which are perpendicular to the coating direction, whereas in the latter case, columns of the HBC derivatives in the film align more along the coating direction. These distinctive structures are confirmed via polarized optical microscopy (POM), polarized UV-vis spectroscopy, and grazing incidence small-angle X-ray scattering measurements.

9.
J Adolesc Health ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39152974

RESUMEN

PURPOSE: This study aims to organize an intergenerational program to provide unemployed young people with operational skills related to gerontechnology and the experience required to deliver digital outreach rehabilitation services to community-dwelling older people. METHODS: A quasi-experimental research design was adopted. The young participants received a 12-session training program on the management of common chronic diseases, communication with older people, the functions and use of interactive games, and techniques to teach and match interactive games with older people. The perception of elderly outcomes (i.e., knowledge and attitude toward elderly care, willingness to care for the elderly), personal outcomes (i.e., life satisfaction, self-efficacy), and desired vocational outcomes (i.e., hours worked in the nongovernmental organization's center, hours spent with older people) were evaluated preprogram and postprogram. RESULTS: Fifty-one young people joined the program. A statistically significant improvement was seen from preprogram to postprogram in their willingness to care for the elderly (p = .016) and life satisfaction (p = .005), as well as in the number of hours that they spent in the community center volunteering or engaged in social services for older people. DISCUSSION: The findings proved that the program could improve the willingness of young people to care for older people, as well as improve their own life satisfaction. Using gerontechnology can serve to bridge the intergenerational gap and bring benefits to both young adults and older people. It may provide policy makers with a way to address the manpower shortage in elderly care services and help frail older people to age in place.

10.
J Formos Med Assoc ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39198112

RESUMEN

In the rapidly evolving healthcare landscape, artificial intelligence (AI), particularly the large language models (LLMs), like OpenAI's Chat Generative Pretrained Transformer (ChatGPT), has shown transformative potential in emergency medicine and critical care. This review article highlights the advancement and applications of ChatGPT, from diagnostic assistance to clinical documentation and patient communication, demonstrating its ability to perform comparably to human professionals in medical examinations. ChatGPT could assist clinical decision-making and medication selection in critical care, showcasing its potential to optimize patient care management. However, integrating LLMs into healthcare raises legal, ethical, and privacy concerns, including data protection and the necessity for informed consent. Finally, we addressed the challenges related to the accuracy of LLMs, such as the risk of providing incorrect medical advice. These concerns underscore the importance of ongoing research and regulation to ensure their ethical and practical use in healthcare.

11.
Medicine (Baltimore) ; 103(28): e38884, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38996135

RESUMEN

RATIONALE: Brain metastasis is a major concern, and may occur in roughly 50% of patients during the clinical course of small cell lung cancer (SCLC). Because prophylactic cranial irradiation reduces the incidence of brain metastases and improves overall survival, prophylactic cranial irradiation is recommended for SCLC patients without distant metastases or an extensive stage and have responded well to systemic therapy. Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) is preferred to preserve hippocampal function while minimizing negative cognitive effects. PATIENT CONCERNS: Reducing the dose delivered to the hippocampus below the therapeutic brain dose may increase the risk of hippocampal progression; thus, HA-WBRT may be associated with a risk of perihippocampal recurrence. DIAGNOSIS: Three patients with SCLC received HA-WBRT and developed intracranial failure during clinical follow-up; 3 relapsed with intracranial failure in the perihippocampal region after 12, 13, and 7 months, respectively. INTERVENTION AND OUTCOMES: Compared to the therapeutic brain dose of cases and the underdose region around the HA region, we matched MRI scans of intracranial failure and previous planning scans of simulation and found a deviation of the underdosed region within the perihippocampal failure of approximately 55% to 63%. LESSONS: Perihippocampal failure is a rare clinical outcome in SCLC patients following HA-WBRT. Perihippocampal failure could be caused by an underdose of radiation or by the aggressiveness of the cancer itself. More research into this topic is encouraged.


Asunto(s)
Neoplasias Encefálicas , Irradiación Craneana , Hipocampo , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Hipocampo/efectos de la radiación , Irradiación Craneana/efectos adversos , Irradiación Craneana/métodos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundario , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana Edad , Anciano , Femenino , Imagen por Resonancia Magnética
12.
ACS Appl Mater Interfaces ; 16(24): 31473-31479, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38850243

RESUMEN

Scalable micro graphene Hall sensors (µGHSs) hold tremendous potential for highly sensitive and label-free biomagnetic sensing in physiological solutions. To enhance the performance of these devices, it is crucial to optimize frequency-dependent flicker noise to reduce the limit of detection (LOD), but it remains a great challenge due to the large contact resistance at the graphene-metal contact. Here we present a surface modification strategy employing persistent carbene on gold electrodes to reduce the contact resistivity by a factor of 25, greatly diminishing µGHS flicker noise by a factor of 1000 to 3.13 × 10-14 V2/Hz while simultaneously lowering the magnetic LOD SB1/2 to 1440 nT/Hz1/2 at 1 kHz under a 100 µA bias current. To the best of our knowledge, this represents the lowest SB1/2 reported for scalable µGHSs fabricated through wafer-scale photolithography. The reduction in contact noise is attributed to the π-π stacking interaction between the graphene and the benzene rings of persistent carbene, as well as the decrease in the work function of gold as confirmed by Kelvin Probe Force Microscopy. By incorporating a microcoil into the µGHS, we have demonstrated the real-time detection of superparamagnetic nanoparticles (SNPs), achieving a remarkable LOD of ∼528 µg/L. This advancement holds great potential for the label-free detection of magnetic biomarkers, e.g., ferritin, for the early diagnosis of diseases associated with iron overload, such as hereditary hemochromatosis (HHC).

13.
Front Endocrinol (Lausanne) ; 15: 1368944, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756997

RESUMEN

Background: The 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role of transcription factors (TF) in the diagnosis of PitNET. Here, we investigated the clinical utility of the 2022 WHO classification, as compared to that of 2017, in a cohort of patients with non-functioning PitNET (NF-PitNET). Methods: A total of 113 NF-PitNET patients who underwent resection between 2010 and 2021, and had follow-up at Queen Mary Hospital, Hong Kong, were recruited. Surgical specimens were re-stained for the three TF: steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (Pit-1). The associations of different NF-PitNET subtypes with tumour-related outcomes were evaluated by logistic and Cox regression analyses. Results: Based on the 2022 WHO classification, the majority of NF-PitNET was SF-1-lineage tumours (58.4%), followed by TPIT-lineage tumours (18.6%), tumours with no distinct lineage (16.8%) and Pit-1-lineage tumours (6.2%). Despite fewer entities than the 2017 classification, significant differences in disease-free survival were present amongst these four subtypes (Log-rank test p=0.003), specifically between SF-1-lineage PitNET and PitNET without distinct lineage (Log-rank test p<0.001). In multivariable Cox regression analysis, the subtype of PitNET without distinct lineage (HR 3.02, 95% CI 1.28-7.16, p=0.012), together with tumour volume (HR 1.04, 95% CI 1.01-1.07, p=0.017), were independent predictors of a composite of residual or recurrent disease. Conclusion: The 2022 WHO classification of PitNET is a clinically useful TF and lineage-based system for subtyping NF-PitNET with different tumour behaviour and prognosis.


Asunto(s)
Tumores Neuroendocrinos , Neoplasias Hipofisarias , Organización Mundial de la Salud , Humanos , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/clasificación , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/metabolismo , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/clasificación , Tumores Neuroendocrinos/metabolismo , Adulto , Anciano , Pronóstico , Adulto Joven , Estudios de Seguimiento , Proteínas de Dominio T Box/metabolismo
14.
Circ J ; 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38811198

RESUMEN

BACKGROUND: There are no sex-specific guidelines for chronic aortic regurgitation (AR). This retrospective study examined sex-specific differences and propose treatment criteria from an Asian AR cohort.Methods and Results: Consecutive 1,305 patients with moderate-severe AR or greater at 3 tertiary centers in Taiwan and Japan (2008-2022) were identified. Study endpoints were aortic valve surgery (AVS), all-cause death (ACD), and cardiovascular death (CVD). The median follow up was 3.9 years (interquartile range 1.3-7.1 years). Compared with men (n=968), women (n=337) were older, had more advanced symptoms, more comorbidities, larger indexed aorta size (iAortamax) and indexed left ventricular (LV) end-systolic dimension (LVESDi; P<0.001 for all). Symptomatic status was poorly correlated with the degree of LV remodeling in women (P≥0.18). Women received fewer AVS (P≤0.001) and men had better overall 10-year survival (P<0.01). Ten-year post-AVS survival (P=0.9) and the progression of LV remodeling were similar between sexes (P≥0.16). Multivariable determinants of ACD and CVD were age, advanced symptoms, iAortamax, LV ejection fraction (LVEF), LVESDi, LV end-systolic volume index (LVESVi), and Taiwanese ethnicity (all P<0.05), but not female sex (P≥0.05). AVS was associated with better survival (P<0.01). Adjusted LVEF, LVESDi, LVESVi, and iAortamaxcut-off values for ACD were 53%, 24.8 mm/m2, 44 mL/m2, and 25.5 mm/m2, respectively, in women and 52%, 23.4 mm/m2, 52 mL/m2, and 23.2 mm/m2, respectively, in men. CONCLUSIONS: Early detection and intervention using sex-specific cut-off values may improve survival in women with AR.

15.
Data Brief ; 54: 110428, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38764458

RESUMEN

This dataset investigates the complex interactions between perceived organizational support (POS) and Employee's intention to stay (ITS) in Vietnam's electronics industry, emphasizing the subtleties of job satisfaction (JS) and work-life balance (WLB) against a backdrop of socialist economic principles. The analysis is underpinned by a structured questionnaire distributed among employees across various corporations, including prominent entities like Samsung, Foxconn, and Luxshare, in Vietnam's northern industrial zones. A total of 604 legitimate responses were amassed via a convenience sampling strategy. After meticulous collation and organization, the dataset was subjected to Partial Least Squares Structural Equation Modeling (PLS-SEM) to elucidate the symbiotic relationships among POS, JS, WLB, and ITS. The outcomes obtained from this dataset show the relationship between POS, JS and WLB had a positive and significant impact on ITS. This dataset can offer valuable insights to countries with similar characteristics to Vietnam.

16.
Angiogenesis ; 27(3): 545-560, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38733496

RESUMEN

Regenerative capabilities of the endothelium rely on vessel-resident progenitors termed endothelial colony forming cells (ECFCs). This study aimed to investigate if these progenitors are impacted by conditions (i.e., obesity or atherosclerosis) characterized by increased serum levels of oxidized low-density lipoprotein (oxLDL), a known inducer of Endothelial-to-Mesenchymal Transition (EndMT). Our investigation focused on understanding the effects of EndMT on the self-renewal capabilities of progenitors and the associated molecular alterations. In the presence of oxLDL, ECFCs displayed classical features of EndMT, through reduced endothelial gene and protein expression, function as well as increased mesenchymal genes, contractility, and motility. Additionally, ECFCs displayed a dramatic loss in self-renewal capacity in the presence of oxLDL. RNA-sequencing analysis of ECFCs exposed to oxLDL validated gene expression changes suggesting EndMT and identified SOX9 as one of the highly differentially expressed genes. ATAC sequencing analysis identified SOX9 binding sites associated with regions of dynamic chromosome accessibility resulting from oxLDL exposure, further pointing to its importance. EndMT phenotype and gene expression changes induced by oxLDL in vitro or high fat diet (HFD) in vivo were reversed by the silencing of SOX9 in ECFCs or the endothelial-specific conditional knockout of Sox9 in murine models. Overall, our findings support that EndMT affects vessel-resident endothelial progenitor's self-renewal. SOX9 activation is an early transcriptional event that drives the mesenchymal transition of endothelial progenitor cells. The identification of the molecular network driving EndMT in vessel-resident endothelial progenitors presents a new avenue in understanding and preventing a range of condition where this process is involved.


Asunto(s)
Lipoproteínas LDL , Factor de Transcripción SOX9 , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacología , Animales , Factor de Transcripción SOX9/metabolismo , Factor de Transcripción SOX9/genética , Ratones , Humanos , Aterosclerosis/metabolismo , Aterosclerosis/patología , Aterosclerosis/genética , Transición Epitelial-Mesenquimal , Ratones Endogámicos C57BL , Masculino , Células Progenitoras Endoteliales/metabolismo , Células Progenitoras Endoteliales/citología , Autorrenovación de las Células , Células Endoteliales/metabolismo
17.
J Neurooncol ; 169(2): 369-378, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38814405

RESUMEN

PURPOSE: This study aimed to examine the effect of postoperative radiotherapy on survival outcomes in patients with malignant meningiomas. METHODS: We identified patients with malignant meningioma diagnosed between 2007 and 2018 using the Taiwan Cancer Registry and followed them up using the death registry. Survival was compared between patients with and without adjuvant radiotherapy. The potential confounding factors evaluated in this study included age, sex, comorbidities, and the Charlson Comorbidity Index (CCI). RESULTS: The analysis included 204 patients; 94 (46%) received adjuvant radiotherapy. The two groups had similar sex distributions (p = 0.53), mean age (p = 0.33), histologic subtype (p = 0.13), and CCI (p = 0.62). The prognosis of malignant meningioma was poor, with a median overall survival (OS) of 2.4 years. The median OS was 3.0 years (interquartile range (IQR) [1.4-6.1], and 2.0 years (IQR [0.5-3.9]) in the radiotherapy and non-radiotherapy groups, respectively (p = 0.001). However, Kaplan-Meier curves with the log-rank test showed no significant difference in OS between the two groups (p = 0.999). Controlling for age group, sex, histologic subtype, treatment, comorbidities, and CCI, adjuvant radiotherapy did not impart a survival benefit (hazard ratio [HR] = 0.87; 95% confidence interval [CI]: 0.6‒1.26); however, only factor of higher comorbidity score (HR = 2.03, 95%CI: 1.04‒3.94) was associated with unfavorable survival. CONCLUSION: This population-based retrospective analysis suggests that the role of radiotherapy remains unclear and underscores the need for randomized clinical trials to assess the usefulness of adjuvant radiotherapy in malignant meningioma.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/radioterapia , Meningioma/mortalidad , Meningioma/patología , Meningioma/cirugía , Masculino , Femenino , Radioterapia Adyuvante , Persona de Mediana Edad , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/cirugía , Anciano , Taiwán/epidemiología , Tasa de Supervivencia , Bases de Datos Factuales , Adulto , Pronóstico , Estudios Retrospectivos , Sistema de Registros/estadística & datos numéricos , Estudios de Seguimiento
18.
ACS Appl Mater Interfaces ; 16(22): 29016-29028, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38783839

RESUMEN

Graphene has received much scientific attention as an electrode material for lithium-ion batteries because of its extraordinary physical and electrical properties. However, the lack of structural control and restacking issues have hindered its application as carbon-based anode materials for next generation lithium-ion batteries. To improve its performance, several modification approaches such as edge-functionalization and electron-donating/withdrawing substitution have been considered as promising strategies. In addition, group 7A elements have been recognized as critical elements due to their electronegativity and electron-withdrawing character, which are able to further improve the electronic and structural properties of materials. Herein, we elucidated the chemistry of nanographenes with edge-substituted group 7A elements as lithium-ion battery anodes. The halogenated nanographenes were synthesized via bottom-up organic synthesis to ensure the structural control. Our study reveals that the presence of halogens on the edge of nanographenes not only tunes the structural and electronic properties but also impacts the material stability, reactivity, and Li+ storage capability. Further systematic spectroscopic studies indicate that the charge polarization caused by halogen atoms could regulate the Li+ transport, charge transfer energy, and charge storage behavior in nanographenes. Overall, this study provides a new molecular design for nanographene anodes aiming for next-generation lithium-ion batteries.

19.
In Vivo ; 38(3): 1512-1518, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38688598

RESUMEN

BACKGROUND/AIM: Progressive fibrosing interstitial lung disease (PF-ILD) refers to a group of chronic lung conditions commonly associated with immunoglobulin G4-related disorders. It is characterized by progressive scarring (fibrosis) within the pulmonary interstitium, resulting in respiratory failure and early mortality. Some patients do not respond to standard therapeutic interventions. Numerous studies have confirmed the anti-inflammatory and antioxidant properties of molecular hydrogen in various disease models. CASE REPORT: In this report, we present a case study of an 85-year-old female diagnosed with suspected IgG4-related PF-ILD complicated by hospital-acquired pneumonia. On the fourth day of hydrogen-assisted therapy, a noticeable improvement in lung infiltrations was observed in chest X-rays as the patient gradually progressed towards weaning off mechanical ventilation. To assess treatment responses, we compared immune phenotypes before and after hydrogen treatment. A marked increase was observed in resting regulatory T cell levels after treatment, accompanied by a notable decrease in Fas+ helper T cell and cytotoxic T cell subtypes. CONCLUSION: This case study highlights the effectiveness of hydrogen-assisted therapy in managing PF-ILD complicated by pneumonia, warranting further research in the future.


Asunto(s)
Hidrógeno , Inmunoglobulina G , Enfermedades Pulmonares Intersticiales , Linfocitos T Reguladores , Humanos , Femenino , Anciano de 80 o más Años , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/patología , Linfocitos T Reguladores/inmunología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Receptor fas/metabolismo , Resultado del Tratamiento
20.
Analyst ; 149(10): 3017-3025, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38606503

RESUMEN

Tumor necrosis factor-alpha (TNF-α) serves as a crucial biomarker in various diseases, necessitating sensitive detection methodologies. This study introduces an innovative approach utilizing an aptamer-functionalized surface plasmon resonance (SPR) substrate together with an ultrasensitive measure, the Goos-Hänchen (GH) shift, to achieve sensitive detection of TNF-α. The developed GH-aptasensing platform has shown a commendable figure-of-merit of 1.5 × 104 µm per RIU, showcasing a maximum detectable lateral position shift of 184.7 ± 1.2 µm, as characterized by the glycerol measurement. Employing aptamers as the recognition unit, the system exhibits remarkable biomolecule detection capabilities, including the experimentally obtained detection limit of 1 aM for the model protein bovine serum albumin (BSA), spanning wide dynamic ranges. Furthermore, the system successfully detects TNF-α, a small cytokine, with an experimental detection limit of 1 fM, comparable to conventional SPR immunoassays. This achievement represents one of the lowest experimentally derived detection limits for cytokines in aptamer-based SPR sensing. Additionally, the application of the GH shift marks a ground breaking advancement in aptamer-based biosensing, holding significant promise for pushing detection limits further, especially for small cytokine targets.


Asunto(s)
Aptámeros de Nucleótidos , Resonancia por Plasmón de Superficie , Factor de Necrosis Tumoral alfa , Animales , Bovinos , Humanos , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Oro/química , Límite de Detección , Albúmina Sérica Bovina/química , Resonancia por Plasmón de Superficie/métodos , Factor de Necrosis Tumoral alfa/análisis
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