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1.
ACS Appl Mater Interfaces ; 16(19): 24943-24950, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38693823

RESUMEN

Designing high-performance polarization-sensitive photodetectors is essential for photonic device applications. Anisotropic one-dimensional (1D) van der Waals (vdW) materials have provided a promising platform to that end. Despite significant advances in 1D vdW photonic devices, their performance is still far from delivering practical potential. Herein, we propose the design of high-performance polarization-sensitive photodetectors using unique 1D vdW materials. By leveraging the chemical vapor transport technique, we successfully fabricate high-quality 1D vdW Nb2Pd1-xSe5 (x = 0.29) nanowires. The 1D vdW Nb2Pd1-xSe5 photodetector exhibits a high mobility of ∼56 cm2/(V s) and superior photoresponse performance, including a high responsivity of 1A/W and an ultrafast response time of ∼8 µs under 638 nm illumination. Moreover, the 1D vdW Nb2Pd1-xSe5 photodetector demonstrates excellent polarization-sensitive photoresponse with a degree of linear polarization (DOLP) up to 0.85 and can be modulated by adjusting the gate voltage, laser power density, and wavelength. Those exceptional performance are believed to be relevant to the symmetry-reduction induced by the partial occupation of Pd sites. This study offers feasible approaches to enhance the anisotropy of 1D vdW materials and the modulation of their polarization-sensitive photoresponse, which may provide deep insights into the physical origin of anisotropic properties of 1D vdW materials.

2.
Mikrochim Acta ; 191(6): 300, 2024 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-38709399

RESUMEN

Glycated hemoglobin (HbA1c), originating from the non-enzymatic glycosylation of ßVal1 residues in hemoglobin (Hb), is an essential biomarker indicating average blood glucose levels over a period of 2 to 3 months without external environmental disturbances, thereby serving as the gold standard in the management of diabetes instead of blood glucose testing. The emergence of HbA1c biosensors presents affordable, readily available options for glycemic monitoring, offering significant benefits to small-scale laboratories and clinics. Utilizing nanomaterials coupled with high-specificity probes as integral components for recognition, labeling, and signal transduction, these sensors demonstrate exceptional sensitivity and selectivity in HbA1c detection. This review mainly focuses on the emerging probes and strategies integral to HbA1c sensor development. We discussed the advantages and limitations of various probes in sensor construction as well as recent advances in diverse sensing strategies for HbA1c measurement and their potential clinical applications, highlighting the critical gaps in current technologies and future needs in this evolving field.


Asunto(s)
Técnicas Biosensibles , Hemoglobina Glucada , Hemoglobina Glucada/análisis , Técnicas Biosensibles/métodos , Humanos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/sangre , Glucemia/análisis
3.
Br J Pharmacol ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38698737

RESUMEN

BACKGROUND AND PURPOSE: Activation of the renin-angiotensin system, as a hallmark of hypertension and chronic kidney diseases (CKD) is the key pathophysiological factor contributing to the progression of tubulointerstitial fibrosis. LIM and senescent cell antigen-like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)-induced hypertension and tubulointerstitial fibrosis was investigated. EXPERIMENTAL APPROACH: C57BL/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia-inducible factor-1α (HIF-1α) renal tubular-specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II-induced renal interstitial fibrosis. In vitro, HIF-1α or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II. KEY RESULTS: Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II-induced hypertension model. Tubular-specific knockdown of LIMS1 ameliorated Ang II-induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF-1α in tubular cells and that tubular HIF-1α knockout ameliorates LIMS1-mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II-induced tubulointerstitial fibrosis by interacting with vimentin. CONCLUSION AND IMPLICATIONS: We conclude that HIF-1α transcriptionally regulated LIMS1 plays a central role in Ang II-induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II-induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD.

4.
Sci Total Environ ; 934: 173213, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38750739

RESUMEN

Uncrewed Aerial Spray Systems (UASS), commonly called drones, have become an important application technique for plant protection products in Asia and worldwide. As such, environmental variables and spray system parameters influencing spray drift deserve detailed investigations. This study presents the data analysis of 114 UASS drift trials conducted between December 2021 and December 2022 in China. Study design was based on the ISO 22866:2005 protocol for spray drift trials and considered different UASS platforms, nozzles, and release heights, and specifically continuously measured weather conditions. The relative importance of the environmental variables and spray system parameters was evaluated by a random forest (RF) feature importance analysis, a Sobol sensitivity analysis and partial dependence plots. This approach was preferred to linear ranking techniques such as ANOVA (analysis of variance) due to the non-linearity of the system. In addition, partial dependence plots are proposed to visualize the relationship between specific input parameters within the system. Drift deposition curves calculated from the 114 trials show good agreement with previous UASS trials reported in the literature. As reported in previous studies, spray drift following UASS applications is lower than for manned aerial vehicles, greater than for ground spray applications, and similar to drift observed from orchard air blast applications. In addition, 9 trials were conducted on corn fields in order to evaluate the potential effect of crop cover on spray drift. Spray drift was observed to be reduced over the cropped soil, suggesting that plant cover might possibly reduce spray drift. These findings could help supporting drift mitigation policies, stewardship advice and product labelling around the world.

5.
Clin Transl Oncol ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38602642

RESUMEN

PURPOSE: This study aims to determine the clinical features and outcomes of PD-1 inhibitor therapy as the initial treatment in patients aged 65 years or older with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: The retrospective study conducted a comprehensive analysis of elder patients diagnosed with locally advanced or metastatic ESCC who underwent combined immunochemotherapy in the first affiliated hospital of Nanchang University from January 2019 to January 2023. The main efficacy measures were the objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR) and overall survival (OS). The evaluation of safety was based on the assessment of adverse events (AEs). RESULTS: A total of 88 patients were enrolled in the study. All patients received PD-1 inhibitors combined with chemotherapy including taxane and platinum as the first-line treatment. The median PFS was 6.2 months (95% CI: 5.1-7.3), and the median OS was 15.3 months (95% CI: 12.9-17.7). The ORR and DCR were 42.0% and 72.7%, correspondingly. 68 (77.3%) patients experienced treatment-related adverse events (TRAEs) of various degrees, with neutrophil count decreased (21, 23.9%) being the most frequent. TRAEs of grade 3 or 4 occurred in 13 (14.8%) patients. CONCLUSION: The study demonstrated that individuals older than 65 years with locally advanced or metastatic ESCC have a survival benefit from the first-line treatment of PD-1 inhibitors combined therapy, with a manageable safety profile.

6.
Clin Chem Lab Med ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38687473

RESUMEN

OBJECTIVES: Accurate measurements of renin and aldosterone levels play an important role in primary aldosteronism screening, which is of great importance in the management and categorization of hypertension. The objective of this study is to investigate the current status of plasma renin and aldosterone measurements in China, which is achieved by analyzing the results of 526 clinical laboratories nationwide for three pooled fresh plasma samples derived from more than 2,000 patients. METHODS: Renin and aldosterone in three pooled plasma samples were measured four times in 526 laboratories employing various measurement systems. The inter- and intra-laboratory %CV were calculated and compared. To determine the source of the substantial inter-laboratory %CV, laboratories were categorized according to the measurement systems they are using, and both the inter- and intra-measurement-system %CV were calculated and compared. RESULTS: Regarding renin, the majority of laboratories use four primary commercial immunoassays. However, for aldosterone, in addition to commercial immunoassays, laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS) methods are also used by laboratories. The median values of intra-laboratory %CVs, intra-measurement-system %CVs, inter-laboratory %CVs, and inter-measurement systems %CVs varied between 1.6 and 2.6 %, 4.6 and 14.9 %, 8.3 and 25.7 %, and 10.0 and 34.4 % for renin, respectively. For aldosterone, these values ranged from 1.4 to 2.2 %, 2.5-14.7 %, 9.9-31.0 %, and 10.0-35.5 %, respectively. CONCLUSIONS: The precision within laboratories and measurement systems for plasma renin and aldosterone measurements is satisfactory. However, the comparability between laboratories using different measurement systems remains lacking, indicating the long way to achieve standardization and harmonization for these two analytes.

7.
Int J Biol Sci ; 20(5): 1669-1687, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38481813

RESUMEN

Direct tubular injury caused by several medications, especially chemotherapeutic drugs, is a common cause of AKI. Inhibition or loss of cyclin-dependent kinase 12 (CDK12) triggers a transcriptional elongation defect that results in deficiencies in DNA damage repair, producing genomic instability in a variety of cancers. Notably, 10-25% of individuals developed AKI after treatment with a CDK12 inhibitor, and the potential mechanism is not well understood. Here, we found that CDK12 was downregulated in the renal tubular epithelial cells in both patients with AKI and murine AKI models. Moreover, tubular cell-specific knockdown of CDK12 in mice enhanced cisplatin-induced AKI through promotion of genome instability, apoptosis, and proliferative inhibition, whereas CDK12 overexpression protected against AKI. Using the single molecule real-time (SMRT) platform on the kidneys of CDK12RTEC+/- mice, we found that CDK12 knockdown targeted Fgf1 and Cast through transcriptional elongation defects, thereby enhancing genome instability and apoptosis. Overall, these data demonstrated that CDK12 knockdown could potentiate the development of AKI by altering the transcriptional elongation defect of the Fgf1 and Cast genes, and more attention should be given to patients treated with CDK12 inhibitors to prevent AKI.


Asunto(s)
Lesión Renal Aguda , Factor 1 de Crecimiento de Fibroblastos , Humanos , Ratones , Animales , Factor 1 de Crecimiento de Fibroblastos/genética , Quinasas Ciclina-Dependientes/genética , Riñón , Lesión Renal Aguda/inducido químicamente , Inestabilidad Genómica
8.
J Cardiothorac Surg ; 19(1): 155, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38532497

RESUMEN

BACKGROUND: To demonstrate the effectiveness and feasibility of robotic portal resection (RPR) for mediastinal tumour using a prospectively collected database. METHODS: Data from 73 consecutive patients with mediastinal tumours who underwent RPRs were prospectively collected from August 2018 to April 2023. All patients underwent chest and abdominal enhanced computed tomography (CT) and preoperative multidisciplinary team (MDT) discussion. The patients were stratified into two groups based on tumour size: Group A (tumour size < 4 cm) and Group B (tumour size ≥ 4 cm). General clinical characteristics, surgical procedures, and short outcomes were promptly recorded. RESULTS: All of the cases were scheduled for RPRs. One patient (1/73, 1.4%) was switched to a small utility incision approach because of extensive pleural adhesion. Two patients (2.8%) converted to sternotomy, however, no perioperative deaths occurred. Most of the tumours were located in the anterior mediastinum (51/73, 69.9%). Thymoma (27/73, 37.0%) and thymic cyst (16/73, 21.9%) were the most common diagnoses. The median diameter of tumours was 3.2 cm (IQR, 2.4-4.5 cm). The median total operative time was 61.0 min (IQR, 50.0-90.0 min). The median intraoperative blood loss was 20 mL (IQR, 5.0-30.0 ml), and only one patient (1.4%) experienced an intraoperative complication. The median length of hospital stay was 3 days (IQR, 2-4 days). Compared with Group A, the median total operative time and console time of Group B were significantly longer (P = 0.006 and P = 0.003, respectively). The volume of drainage on the first postoperative day was greater in group B than in group A (P = 0.013). CONCLUSION: RPR is a safe and effective technique for mediastinal tumour treatment, which can expand the application of minimally invasive surgery for the removal of complicated mediastinal tumours.


Asunto(s)
Neoplasias del Mediastino , Procedimientos Quirúrgicos Robotizados , Robótica , Timoma , Neoplasias del Timo , Humanos , Neoplasias del Mediastino/cirugía , Robótica/métodos , Neoplasias del Timo/cirugía , Timoma/cirugía , Resultado del Tratamiento , Estudios Retrospectivos
9.
J Am Heart Assoc ; 13(6): e031732, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38497484

RESUMEN

BACKGROUND: The relevance of iron status biomarkers for coronary artery disease (CAD), heart failure (HF), ischemic stroke (IS), and type 2 diabetes (T2D) is uncertain. We compared the observational and Mendelian randomization (MR) analyses of iron status biomarkers and hemoglobin with these diseases. METHODS AND RESULTS: Observational analyses of hemoglobin were compared with genetically predicted hemoglobin with cardiovascular diseases and diabetes in the UK Biobank. Iron biomarkers included transferrin saturation, serum iron, ferritin, and total iron binding capacity. MR analyses assessed associations with CAD (CARDIOGRAMplusC4D [Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus The Coronary Artery Disease Genetics], n=181 522 cases), HF (HERMES [Heart Failure Molecular Epidemiology for Therapeutic Targets), n=115 150 cases), IS (GIGASTROKE, n=62 100 cases), and T2D (DIAMANTE [Diabetes Meta-Analysis of Trans-Ethnic Association Studies], n=80 154 cases) genome-wide consortia. Observational analyses demonstrated J-shaped associations of hemoglobin with CAD, HF, IS, and T2D. In contrast, MR analyses demonstrated linear positive associations of higher genetically predicted hemoglobin levels with 8% higher risk per 1 SD higher hemoglobin for CAD, 10% to 13% for diabetes, but not with IS or HF in UK Biobank. Bidirectional MR analyses confirmed the causal relevance of iron biomarkers for hemoglobin. Further MR analyses in global consortia demonstrated modest protective effects of iron biomarkers for CAD (7%-14% lower risk for 1 SD higher levels of iron biomarkers), adverse effects for T2D, but no associations with IS or HF. CONCLUSIONS: Higher levels of iron biomarkers were protective for CAD, had adverse effects on T2D, but had no effects on IS or HF. Randomized trials are now required to assess effects of iron supplements on risk of CAD in high-risk older people.


Asunto(s)
Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Adulto , Humanos , Anciano , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/genética , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Hierro , Factores de Riesgo , Análisis de la Aleatorización Mendeliana , Estudio de Asociación del Genoma Completo/métodos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genética , Biomarcadores , Hemoglobinas , Polimorfismo de Nucleótido Simple
10.
RSC Adv ; 14(8): 4975-4989, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38332790

RESUMEN

In this study, Sb2S3/In2S3/TiO2 (SIT) heterojunction photocatalysts were prepared by a simple two-step hydrothermal method and applied to the photocatalytic degradation of levofloxacin (LEV). After 160 min of reaction under visible light, the SIT heterojunction photocatalyst degraded 10 mg L-1 LEV at a rate of 86.7%. The degradation of LEV follows pseudo-first-order kinetics with a rate constant 1.16 × 10-2 min-1, which is 1.42, 1.22 and 1.05 times higher than that of TiO2, SI and IT, respectively. Meanwhile, the SIT photocatalysts also showed high photocatalytic activity for other antibiotics. The enhanced photocatalytic activity of the ternary heterostructures was attributed to the full-spectrum response and the synergistic effect of the dual Z-type heterojunctions, which improved the visible light absorption and facilitated the charge separation. In addition, ˙OH and ˙O2- play a dominant role in the photodegradation process. This work contributes to the design of novel photocatalytic materials with dual Z-type heterojunctions and efficient photocatalysts for the degradation of antibiotics.

11.
Phys Chem Chem Phys ; 26(10): 8148-8157, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38380536

RESUMEN

Probing the interaction between molecules and protocells is crucial for understanding the passive transport of functional molecules in and out of artificial and real cells. Second-harmonic generation (SHG) has been proven to be a powerful method for analyzing the adsorption and cross-membrane transport of molecules on lipid bilayers. In this study, we used SHG and two-photon fluorescence (TPF) imaging to study the interaction of charged dye molecules (D289) with a lipid vesicle. Unexpectedly, it was observed that the transport of D289 at a relatively high concentration is not as efficient as that at a lower dye concentration. Periodic shrinking of the model protocell and discharging of D289 out from the vesicle were revealed by combined analyses of SHG and TPF images. The response of the vesicle to a surfactant was also analyzed with D289 as a probe. This work demonstrates that the combined SHG and TPF imaging method is a unique approach that can provide detailed information on the interaction of molecules and lipids (both morphology and molecular kinetics). Determining these subtle interfacial kinetics in molecules is important for understanding the mechanism of many biophysical processes occurring on lipids.

12.
J Colloid Interface Sci ; 660: 334-344, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38244500

RESUMEN

Due to the challenges involved in achieving high metal load, uniform metal dispersion and nanosized metal particles simultaneously, it is difficult to develop a simple protocol for the rapid and efficient synthesis of Pt-based composites for electrocatalytic ethanol oxidation reaction (EOR). In this study, a facile ultrafast thermal shock strategy via Joule heating was applied to fabricate a series of PtCoCu ternary nanoalloys decorated carbon nanotube composites (TS-PtCoCu/CNTs), without the need for a reducing agent or surfactant. The TS-PtCoCu/CNTs with optimal Pt content (∼15 %) exhibited excellent EOR activity, with mass and specific activity of 3.58 A mgPt-1 and 5.79 mA cm-2, respectively, which are 3.8 and 13.5 times higher than those of Pt/C. Compared with the control prepared through the traditional furnace annealing, the catalyst also showed excellent activity and stability. DFT calculations revealed that the TS-PtCoCu/CNTs possesses a downshifted d-band center, weakened CO adsorption and higher OH affinity compared with monometallic Pt, all of which lead to the preferred C1 pathway for EOR. This study demonstrates an ultrafast construction of a highly efficient Pt-Co-Cu ternary catalyst for EOR. Additionally, it provides insights into the reaction mechanism based on structural characterization, electrochemical characterization, and theoretical calculations.

13.
Artículo en Inglés | MEDLINE | ID: mdl-38294753

RESUMEN

Background: Lumbar disc herniation (LDH) is a prevalent condition in spinal surgery, and Traditional Chinese Medicine (TCM) acupuncture has gained clinical attention as a potential treatment for LDH in recent years. Objective: This study aimed to assess the therapeutic efficacy of acupuncture combined with acupoint massage in LDH patients. Methods: We enrolled a total of 135 LDH patients treated at our hospital from May 2021 to February 2023. Among them, 63 patients received acupuncture treatment (control group), while the remaining 72 received acupuncture combined with acupoint massage (observation group). We compared treatment efficacy and the time it took for lumbar stiffness, lower back and leg pain, bending and flexing difficulties, and other symptoms to disappear between the two groups. The Visual Analogue Scale (VAS) and Japanese Orthopedic Association Scoring System (JOA) were used to evaluate patients' pain levels and lumbar vertebral function before and after treatment. Additionally, we assessed patients using the Generic Quality of Life Inventory-74 (GQOL-74) and recorded their treatment satisfaction. Results: The observation group exhibited a slightly higher total effective rate compared to the control group, with a shorter time for the resolution of lumbar stiffness, lower back pain, leg pain, and other symptoms (P < .05). Furthermore, the observation group had lower VAS scores and higher JOA scores (P < .05). They also achieved higher GQOL-74 scores and reported greater treatment satisfaction (P < .05). Conclusions: Acupuncture combined with acupoint massage effectively alleviated clinical symptoms and pain in LDH patients, demonstrating significant clinical utility.

14.
BMC Pregnancy Childbirth ; 24(1): 77, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38263003

RESUMEN

OBJECTIVE: To improve the understanding of the clinical features and imaging characteristics of pregnant women with and without in-vitro fertilisation-embryo transfer combined with pulmonary tuberculosis (TB). METHODS: A retrospective analysis was conducted involving 50 patients with pregnancy who had pulmonary TB and were admitted to the Third People's Hospital of Kunming (China) between 1 January 2017 and 31 December 2021. These patients were divided into an in-vitro fertilisation and embryo transfer (IVF-ET) conception group and a natural conception group according to the conception method. The clinical and imaging data were then collected and compared. RESULTS: The mean age of the IVF-ET group (n = 13, 31.85 ± 5.84 years) was higher than in the natural conception group (n = 37, 27.05 ± 5.5 years). The proportions of fever, haematogenous TB and extrapulmonary TB in the IVF-ET group (92.31%, 84.62% and 76.92%, respectively) were higher than those in the natural conception group (40.54%,16.22%,27.03%,respectively). The percentage of patients with pregnancy who had intracranial TB (76.9%) in the IVF-ET group was higher than in the natural conception group (10.8%). The percentage of pregnancy terminations in the IVF-ET conception group (84.62%) was higher than in the natural conception group (48.65%). All the above results had statistically significant differences (p < 0.05). CONCLUSION: Overall, IVF-ET conception combined with extensive pulmonary TB lesions lead to heavy systemic toxic symptoms, severe disease and poor pregnancy outcomes. Therefore, screening for TB prior to performing IVF-ET is recommended.


Asunto(s)
Tuberculosis Pulmonar , Tuberculosis , Femenino , Humanos , Embarazo , Transferencia de Embrión , Fertilización , Estudios Retrospectivos , Estudios de Casos y Controles
15.
Gen Psychiatr ; 37(1): e101209, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38292861

RESUMEN

Background: Cardiovascular risk burden is associated with dementia risk and neurodegeneration-related brain structure, while the role of genetics and incident cardiovascular disease (CVD) remains unclear. Aims: To examine the association of overall cardiovascular risk burden with the risk of major dementia subtypes and volumes of related brain regions in a large sample, and to explore the role of genetics and CVD onset. Methods: A prospective study among 354 654 participants free of CVD and dementia (2006-2010, mean age 56.4 years) was conducted within the UK Biobank, with brain magnetic resonance imaging (MRI) measurement available for 15 104 participants since 2014. CVD risk burden was evaluated by the Framingham General Cardiovascular Risk Score (FGCRS). Dementia diagnosis was ascertained from inpatient and death register data. Results: Over a median 12.0-year follow-up, 3998 all-cause dementia cases were identified. Higher FGCRS was associated with increased all-cause dementia risk after adjusting for demographic, major lifestyle, clinical factors and the polygenic risk score (PRS) of Alzheimer's disease. Comparing the high versus low tertile of FGCRS, the odds ratios (ORs) and 95% confidence intervals (CIs) were 1.26 (1.12 to 1.41) for all-cause dementia, 1.67 (1.33 to 2.09) for Alzheimer's disease and 1.53 (1.07 to 2.16) for vascular dementia (all ptrend<0.05). Incident stroke and coronary heart disease accounted for 14% (95% CI: 9% to 21%) of the association between FGCRS and all-cause dementia. Interactions were not detected for FGCRS and PRS on the risk of any dementia subtype. We observed an 83% (95% CI: 47% to 128%) higher all-cause dementia risk comparing the high-high versus low-low FGCRS-PRS category. For brain volumes, higher FGCRS was associated with greater log-transformed white matter hyperintensities, smaller cortical volume and smaller grey matter volume. Conclusions: Our findings suggest that the positive association of cardiovascular risk burden with dementia risk also applies to major dementia subtypes. The association of cardiovascular risk burden with all-cause dementia is largely independent of CVD onset and genetic predisposition to dementia.

16.
Eur J Prev Cardiol ; 31(1): 13-20, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-37697428

RESUMEN

AIMS: Denture use may potentially increase the risk of cardiometabolic diseases (CMDs), but the casual relevance and strength of the associations are currently unknown. METHODS AND RESULTS: A total of 495 938 participants from the UK Biobank were included in the observational analyses. Linkage disequilibrium score (LDSC) regression and Mendelian randomization analyses were employed to estimate genetic correlation and the associations between the genetic liability for denture use with coronary artery disease, myocardial infarction, heart failure (HF), any stroke (AS), ischaemic stroke, haemorrhagic stroke, type 2 diabetes (T2D), and related clinical risk factors. In observational analysis, denture use was associated with 14-25% higher risks of various CMDs. The LDSC analysis found that denture use showed a positive genetic correlation with CMDs (rg 0.21-0.38). Genetic liability for denture use was associated with an elevated risk of HF [odds ratio: 1.49 (1.20-1.83)] and T2D [1.11 (1.01-1.24)]. By integrating genetic summary data of denture use with the sum of decayed, missing, and filled tooth surfaces (DMFS), a clinical measure of dental caries obtained from an independent source, genetically determined denture use/DMFS was also associated with an elevated risk of AS [1.21 (1.04-1.40)]. Furthermore, genetically predicted denture use/DMFS was significantly associated with established cardiometabolic risk factors, including HDL cholesterol, triglycerides, waist circumference, waist-to-hip ratio, and height. CONCLUSION: Our study supported potential causal associations between the genetic liability for denture use and risks for HF, AS, T2D, and related clinical risk factors. These findings may inform prevention and intervention strategies targeting dental diseases and CMDs.


This study examined the association of denture use with cardiometabolic diseases (CMDs) and related clinical risk factors through Mendelian randomization analyses using data from UK Biobank and published consortia. Genetic liability for denture use was associated with an 11­49% higher risk of heart failure, stroke, and type 2 diabetes.The potential causal relationship between denture use and CMDs was further strengthened by the associations of denture use with HDL cholesterol, triglycerides, waist circumference, waist-to-hip ratio, and height, which are among the major risk factors of CMDs.


Asunto(s)
Isquemia Encefálica , Caries Dental , Diabetes Mellitus Tipo 2 , Accidente Cerebrovascular , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Análisis de la Aleatorización Mendeliana , Caries Dental/complicaciones , Índice de Masa Corporal , Factores de Riesgo , Dentaduras/efectos adversos , Polimorfismo de Nucleótido Simple
17.
ACS Appl Mater Interfaces ; 16(1): 401-410, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38145926

RESUMEN

Protein glycosylation is ubiquitous and crucial for regulating biological processes in organisms. Given the heterogeneity and low abundance of glycoproteins, efficient and specific enrichment procedures are required for the mass spectrometry analysis of glycopeptides. Hydrophilic interaction liquid chromatography (HILIC) has emerged as an effective strategy for glycopeptide enrichment. However, the relatively weak hydrophilic affinity restricts the achievement of a satisfactory enrichment performance. Here, we presented a rational design of an amide and multihydroxyl complementary tailored metal-organic framework, denoted as U6N/Pv@Glc, which exhibited ultrahydrophilicity and enhanced glycan affinity. Our results demonstrated a significant increase in glycopeptide coverage after enrichment, accompanied by extremely low detection limits (0.05 fmol µL-1) and high selectivity (IgG/BSA, 1:4000) as evaluated using trypsin-digested standard glycoproteins. A total of 379 glycopeptides and 247 intact glycopeptides (containing a total of 1577 site-specific N-glycans) were identified and characterized within human serum samples from individuals with type 2 diabetes in-depth. Additionally, we extended the application of this material to capture undigested glycoproteins, demonstrating potential compatibility with top-down MS analysis. These results highlight the promising potential of this novel material for comprehensive glycoproteomic analysis of every potential aspect.


Asunto(s)
Diabetes Mellitus Tipo 2 , Estructuras Metalorgánicas , Humanos , Estructuras Metalorgánicas/química , Amidas , Glicoproteínas , Polisacáridos , Glicopéptidos/química , Interacciones Hidrofóbicas e Hidrofílicas
18.
Cancer Treat Res ; 190: 143-179, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38113001

RESUMEN

RNA epigenetics, or epitranscriptome, is a growing group of RNA modifications historically classified into two categories: RNA editing and RNA modification. RNA editing is usually understood as post-transcriptional RNA processing (except capping, splicing and polyadenylation) that changes the RNA nucleotide sequence encoded by the genome. This processing can be achieved through the insertion or deletion of nucleotides or deamination of nucleobases, generating either standard nucleotides such as uridine (U) or the rare nucleotide inosine (I). Adenosine-to-inosine (A-to-I) RNA editing is the most prevalent type of RNA modification in mammals and is catalyzed by adenosine deaminase acting on the RNA (ADAR) family of enzymes that recognize double-stranded RNAs (dsRNAs). Inosine mimics guanosine (G) in base pairing with cytidine (C), thereby A-to-I RNA editing alters dsRNA secondary structure. Inosine is also recognized as guanosine by the splicing and translation machineries, resulting in mRNA alternative splicing and protein recoding. Therefore, A-to-I RNA editing is an important mechanism that causes and regulates "RNA mutations" in both normal physiology and diseases including cancer. In this chapter, we reviewed current paradigms and developments in the field of A-to-I RNA editing in the context of cancer.


Asunto(s)
Neoplasias , ARN , Animales , Humanos , ARN/genética , ARN/metabolismo , Edición de ARN , Neoplasias/genética , Nucleótidos/metabolismo , Inosina/genética , Inosina/metabolismo , Adenosina/genética , Adenosina/metabolismo , Guanosina/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
19.
Infect Drug Resist ; 16: 6871-6879, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37908784

RESUMEN

Objective: This study aimed to examine the radiographic manifestations of seminal vesicle tuberculosis (SVT) on magnetic resonance imaging to gain a deeper understanding of this disease. Methods: The clinical symptoms, general conditions, relevant laboratory tests and radiological data of 13 patients diagnosed with SVT were collected through bacteriological examination. A descriptive analysis was used to explore the composition ratio and rate values of the collected data. Results: All 13 cases (100.0%) showed isointense signals on T1WI and hypointense signals on T2WI in the affected seminal vesicles, with the disappearance of the multi-chambered high signal on T2WI in normal seminal vesicles. Eight cases (61.5%) showed diffusion restriction on DWI of the affected seminal vesicle and significant enhancement on the contrast scan, whereas five cases (38.5%) showed unrestricted diffusion and mild enhancement on the contrast scan. Patients with significant enhancements exhibited higher counts and neutrophil percentages than patients with mild enhancements, with statistically significant differences (Z = 2.196, P = 0.030; Z = 2.781, P = 0.003, respectively). The counts and percentage of lymphocytes, CD3+T cells and CD4+T cells were significantly lower in patients with significant enhancements than in those with mild enhancements, with statistically significant differences (Z = -2.196, P = 0.030; Z = -2.928, P = 0.002; Z = -2.928, P = 0.002; Z = -2.928, P = 0.002, respectively). Patients with significant enhancements were more likely to have active pulmonary tuberculosis than those with mild enhancements, with a statistically significant difference (P = 0.035). Conclusion: Magnetic resonance imaging reveals distinct radiographic features of SVT, and variations in imaging presentations can indicate a patient's immune status.

20.
Obes Surg ; 33(12): 3988-3998, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37910328

RESUMEN

PURPOSE: Remission of type 2 diabetes (T2D) can be achieved by many, but not all, people following bariatric/metabolic surgery. The mechanisms underlying T2D remission remain incompletely understood. This observational study aimed to identify novel weight-loss independent clinical, metabolic and genetic factors that associate with T2D remission using comprehensive phenotyping. MATERIALS AND METHODS: Ten patients without T2D remission (non-remitters) were matched to 10 patients with T2D remission (remitters) for age, sex, type of surgery, body weight, BMI, post-operative weight loss, duration from surgery and duration of T2D. Detailed body composition assessed using magnetic resonance imaging, gut hormones, serum metabolomics, insulin sensitivity, and genetic risk scores for T2D and anthropometric traits were assessed. RESULTS: Remitters had significantly greater ß-cell function and circulating acyl ghrelin levels, but lower visceral adipose tissue (VAT): subcutaneous adipose tissue (SAT) ratio than non-remitters. Branched-chain amino acids (BCAAs) and VLDL particle size were the most discriminant metabolites between groups. A significant positive correlation between, VAT area, VAT:SAT ratio and circulating levels of BCAAs was observed, whereas a significant negative correlation between BCAAs and ß-cell function was revealed. CONCLUSION: We highlight a potentially novel relationship between VAT and BCAAs, which may play a role in glucoregulatory control. Improvement in ß-cell function, and the role ghrelin plays in its recovery, is likely another key factor influencing T2D remission post-surgery. These findings suggest that adjunctive approaches that target VAT loss and restoration of BCAA metabolism might achieve higher rates of long-term T2D remission post-surgery.


Asunto(s)
Cirugía Bariátrica , Diabetes Mellitus Tipo 2 , Obesidad Mórbida , Humanos , Ghrelina , Obesidad Mórbida/cirugía , Resultado del Tratamiento , Pérdida de Peso , Biomarcadores
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