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1.
Int J Med Sci ; 21(9): 1604-1611, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006846

RESUMEN

Purpose: To investigate morphological and hemodynamic characteristics of the ophthalmic artery (OA) in patients with white matter hyperintensity (WMH), and the association of the presence and severity of WMH with OA characteristics. Methods: This cross-sectional study included 44 eyes of 25 patients with WMH and 38 eyes of 19 controls. The Fazekas scale was adopted as criteria for evaluating the severity of white matter hyperintensities. The morphological characteristics of the OA were measured on the basis of three-dimensional reconstruction. The hemodynamic parameters of the OA were calculated using computational fluid dynamics simulations. Results: Compared with the control group, the diameter (16.0±0.27 mm vs. 1.71±0.18 mm, P=0.029), median blood flow velocity (0.12 m/s vs. 0.22 m/s, P<0.001), mass flow ratio (2.16% vs. 3.94%, P=0.012) and wall shear stress (2.65 Pa vs. 9.31 Pa, P<0.001) of the OA in patients with WMH were significantly decreased. After adjusting for confounding factors, the diameter, blood flow velocity, wall shear stress, and mass flow ratio of the OA were significantly associated with the presence of WMH. Male sex and high low-density protein level were associated with moderate-to-severe total WMH, and smoking was associated with the moderate-to-severe periventricular WMH. Conclusions: The diameter, blood flow velocity, mass flow ratio, and wall shear stress of the OA were independently associated with the presence of WMH. Atherosclerosis might be involved in the common mechanism of the occurrence of WMH and the OA changes.


Asunto(s)
Hemodinámica , Arteria Oftálmica , Sustancia Blanca , Humanos , Masculino , Femenino , Arteria Oftálmica/diagnóstico por imagen , Arteria Oftálmica/fisiopatología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/fisiopatología , Sustancia Blanca/irrigación sanguínea , Sustancia Blanca/patología , Estudios Transversales , Hemodinámica/fisiología , Persona de Mediana Edad , Anciano , Velocidad del Flujo Sanguíneo , Imagen por Resonancia Magnética , Adulto
2.
ACS Biomater Sci Eng ; 10(6): 4046-4058, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38722544

RESUMEN

Cadmium poses a severe health risk, impacting various bodily systems. Monitoring human exposure is vital. Urine and blood cadmium serve as critical biomarkers. However, current urine and blood cadmium detection methods are expensive and complex. Being cost-effective, user-friendly, and efficient, visual biosensing offers a promising complement to existing techniques. Therefore, we constructed a cadmium whole-cell biosensor using CadR10 and deoxyviolacein pigment in this study. We assessed the sensor for time-dose response, specific response to cadmium, sensitivity response to cadmium, and stability response to cadmium. The results showed that (1) the sensor had a preferred signal-to-noise ratio when the incubation time was 4 h; (2) the sensor showed excellent specificity for cadmium compared to the group 12 metals and lead; (3) the sensor was responsive to cadmium down to 1.53 nM under experimental conditions and had good linearity over a wide range from 1.53 nM to 100 µM with good linearity (R2 = 0.979); and (4) the sensor had good stability. Based on the excellent results of the performance tests, we developed a cost-effective, high-throughput method for detecting urinary and blood cadmium. Specifically, this was realized by adding the blood or urine samples into the culture system in a particular proportion. Then, the whole-cell biosensor was subjected to culture, n-butanol extraction, and microplate reading. The results showed that (1) at 20% urine addition ratio, the sensor had an excellent curvilinear relationship (R2 = 0.986) in the range of 3.05 nM to 100 µM, and the detection limit could reach 3.05 nM. (2) At a 10% blood addition ratio, the sensor had an excellent nonlinear relationship (R2 = 0.978) in the range of 0.097-50 µM, and the detection limit reached 0.195 µM. Overall, we developed a sensitive and wide-range method based on a whole-cell biosensor for the detection of cadmium in blood and urine, which has the advantages of being cost-effective, ease of operation, fast response, and low dependence on instrumentation and has the potential to be applied in the monitoring of cadmium exposure in humans as a complementary to the mainstream detection techniques.


Asunto(s)
Técnicas Biosensibles , Cadmio , Humanos , Cadmio/orina , Cadmio/sangre , Cadmio/análisis , Técnicas Biosensibles/métodos , Límite de Detección
3.
Nat Commun ; 15(1): 3961, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38729932

RESUMEN

Mechanically interlocked molecules (MIMs) including famous catenanes show switchable physical properties and attract continuous research interest due to their potential application in molecular devices. The advantages of using spin crossover (SCO) materials here are enormous, allowing for control through diverse stimuli and highly specific functions, and enabling the transfer of the internal dynamics of MIMs from solution to solid state, leading to macroscopic applications. Herein, we report the efficient self-assembly of catenated metal-organic frameworks (termed catena-MOFs) induced by stacking interactions, through the combination of rationally selected flexible and conjugated naphthalene diimide-based bis-pyridyl ligand (BPND), [MI(CN)2]- (M = Ag or Au) and Fe2+ in a one-step strategy. The obtained bimetallic Hofmann-type SCO-MOFs [FeII(BPND){Ag(CN)2}2]·3CHCl3 (1Ag) and [FeII(BPND{Au(CN)2}2]·2CHCl3·2H2O (1Au) possess a unique three-dimensional (3D) catena-MOF constructed from the polycatenation of two-dimensional (2D) layers with hxl topology. Both complexes undergo thermal- and light-induced SCO. Significantly, abnormal increases in the maximum emission intensity and dielectric constant can be detected simultaneously with the switching of spin states. This research opens up SCO-actuated bistable MIMs that afford dual functionality of coupled fluorescence emission and dielectricity.

4.
Sci Data ; 11(1): 463, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714688

RESUMEN

Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.


Asunto(s)
Encéfalo , Desarrollo Infantil , Niño , Preescolar , Humanos , Encéfalo/crecimiento & desarrollo , Encéfalo/diagnóstico por imagen , China , Cognición , Bases de Datos Factuales , Neuroimagen
5.
World J Gastrointest Oncol ; 16(3): 577-582, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38577447

RESUMEN

We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor (ICI) and the occurrence of immune-related adverse events (irAEs). The predictive potential of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in determining ICI effectiveness has been extensively investigated, while limited research has been conducted on predicting irAEs. Furthermore, the combined model incorporating NLR and PLR, either with each other or in conjunction with additional markers such as carcinoembryonic antigen, exhibits superior predictive capabilities compared to individual markers alone. NLR and PLR are promising markers for clinical applications. Forthcoming models ought to incorporate established efficacious models and newly identified ones, thereby constituting a multifactor composite model. Furthermore, efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.

6.
Cancer Med ; 13(7): e7161, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38613173

RESUMEN

BACKGROUND: Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. METHODS: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). RESULTS: In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762-0.823), 0.904 (0.835-0.973), 0.759 (0.731-0.787), 0.221 (0.186-0.256), 0.974 (0.967-0.982), 0.353 (0.306-0.399), and 0.834 (0.696-0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753-0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. CONCLUSIONS: This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions.


Asunto(s)
Adenocarcinoma de Células Claras , Neoplasias Ováricas , Femenino , Humanos , Teorema de Bayes , Algoritmos , Carcinoma Epitelial de Ovario , Aprendizaje Automático
7.
Acta Neuropathol Commun ; 12(1): 38, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38444036

RESUMEN

Accurate differential diagnosis among various dementias is crucial for effective treatment of Alzheimer's disease (AD). The study began with searching for novel blood-based neuronal extracellular vesicles (EVs) that are more enriched in the brain regions vulnerable to AD development and progression. With extensive proteomic profiling, GABRD and GPR162 were identified as novel brain regionally enriched plasma EVs markers. The performance of GABRD and GPR162, along with the AD molecule pTau217, was tested using the self-developed and optimized nanoflow cytometry-based technology, which not only detected the positive ratio of EVs but also concurrently presented the corresponding particle size of the EVs, in discovery (n = 310) and validation (n = 213) cohorts. Plasma GABRD+- or GPR162+-carrying pTau217-EVs were significantly reduced in AD compared with healthy control (HC). Additionally, the size distribution of GABRD+- and GPR162+-carrying pTau217-EVs were significantly different between AD and non-AD dementia (NAD). An integrative model, combining age, the number and corresponding size of the distribution of GABRD+- or GPR162+-carrying pTau217-EVs, accurately and sensitively discriminated AD from HC [discovery cohort, area under the curve (AUC) = 0.96; validation cohort, AUC = 0.93] and effectively differentiated AD from NAD (discovery cohort, AUC = 0.91; validation cohort, AUC = 0.90). This study showed that brain regionally enriched neuronal EVs carrying pTau217 in plasma may serve as a robust diagnostic and differential diagnostic tool in both clinical practice and trials for AD.


Asunto(s)
Enfermedad de Alzheimer , Vesículas Extracelulares , Humanos , Enfermedad de Alzheimer/diagnóstico , Diagnóstico Diferencial , NAD , Proteómica
8.
Clin Transl Med ; 14(3): e1605, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38445456

RESUMEN

BACKGROUND: Bone or brain metastases may develop in 20-40% of individuals with late-stage non-small-cell lung cancer (NSCLC), resulting in a median overall survival of only 4-6 months. However, the primary lung cancer tissue's distinctions between bone, brain and intrapulmonary metastases of NSCLC at the single-cell level have not been underexplored. METHODS: We conducted a comprehensive analysis of 14 tissue biopsy samples obtained from treatment-naïve advanced NSCLC patients with bone (n = 4), brain (n = 6) or intrapulmonary (n = 4) metastasis using single-cell sequencing originating from the lungs. Following quality control and the removal of doublets, a total of 80 084 cells were successfully captured. RESULTS: The most significant inter-group differences were observed in the fraction and function of fibroblasts. We identified three distinct cancer-associated fibroblast (CAF) subpopulations: myofibroblastic CAF (myCAF), inflammatory CAF (iCAF) and antigen-presenting CAF (apCAF). Notably, apCAF was prevalent in NSCLC with bone metastasis, while iCAF dominated in NSCLC with brain metastasis. Intercellular signalling network analysis revealed that apCAF may play a role in bone metastasis by activating signalling pathways associated with cancer stemness, such as SPP1-CD44 and SPP1-PTGER4. Conversely, iCAF was found to promote brain metastasis by activating invasion and metastasis-related molecules, such as MET hepatocyte growth factor. Furthermore, the interaction between CAFs and tumour cells influenced T-cell exhaustion and signalling pathways within the tumour microenvironment. CONCLUSIONS: This study unveils the direct interplay between tumour cells and CAFs in NSCLC with bone or brain metastasis and identifies potential therapeutic targets for inhibiting metastasis by disrupting these critical cell-cell interactions.


Asunto(s)
Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Encéfalo , Fibroblastos , Microambiente Tumoral
9.
Front Med (Lausanne) ; 11: 1367900, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38500953

RESUMEN

Purpose: We aimed to explore the effects of percutaneous coronary intervention (PCI) on the ophthalmic artery (OA) hemodynamics in patients with acute coronary syndrome (ACS). Methods: A total of 73 participants (Group0: healthy controls, Group1: Patients with ACS underwent PCI < 3 months, Group2: Patients with ACS underwent PCI ≥ 3 months) were enrolled. Computed tomographic angiography images were used to construct three-dimensional models of participants' OAs. Numerical simulations based on computational fluid dynamics were used to acquire hemodynamic parameters. Results: The angle between the OA and internal carotid artery in Group2 was significantly larger compared with Group0 and Group1 (P = 0.003 and P = 0.044). Hemodynamic simulation showed a significantly slower OA blood velocity in Group1 than in the control (P < 0.001) and Group2 (P = 0.033). Lower wall shear stress was found in Group1 than that in control (P = 0.040). Patients after PCI had a higher wall pressure than healthy controls (P = 0.012 and P = 0.004). Mass flow ratios were decreased in Group1 and Group2 (P = 0.021 and P = 0.002). The hemodynamic parameters of OA were correlated with several clinical indicators. Conclusions: The OA blood flow velocity of patients with ACS after PCI initially slowed down, which increased the risk of plaque formation, and then showed an increasing trend. There was a correlation between OA hemodynamic parameters and clinical indexes related to cardiac stress. Ischemia-reperfusion injury and changes in blood flow status after PCI may affect OA morphology and hemodynamics, leading to ocular lesions. Trial registration: ChiCTR2100050428.

10.
Int Immunopharmacol ; 127: 111411, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38113689

RESUMEN

Proinflammatory cytokines are crucial contributors to neuroinflammation in the development of chronic pain. Here, we identified il16, which encodes interleukin-16 (IL-16), as a differentially expressed gene in spinal dorsal horn of a complete Freund's Adjuvant (CFA) inflammatory pain model in mice by RNA sequencing. We further investigated whether and how IL-16 regulates pain transmission in the spinal cord and contributes to the development of inflammatory pain hypersensitivity. RNA sequencing and bioinformatics analysis revealed elevated IL-16 transcript levels in the spinal dorsal horn after CFA injection. This increase was further confirmed by qPCR, immunofluorescence, and western blotting. Knockdown of IL-16 by intrathecal injection of IL-16 siRNA not only attenuated CFA-induced mechanical and thermal pain hypersensitivity, but also inhibited enhanced c-fos expression and glial activation in the spinal dorsal horn in male mice injected with CFA. Moreover, exogenous IL-16 induced nociceptive responses and increased c-fos expression and glial activation in spinal dorsal horn. This effect was largely impaired when CD4, the binding receptor for IL-16, was inhibited. In addition, CD4 expression was upregulated in the spinal dorsal horn after CFA injection and CD4 was present in microglia and in contact with astrocytes and activated spinal neurons. Taken together, these results suggest that enhanced IL-16-CD4 signaling triggers pain and activates microglia and astrocytes in the spinal dorsal horn, thus contributing to inflammatory pain. IL-16 may serve as a promising target for the treatment of inflammatory pain.


Asunto(s)
Hiperalgesia , Interleucina-16 , Ratones , Masculino , Animales , Interleucina-16/genética , Interleucina-16/metabolismo , Interleucina-16/farmacología , Hiperalgesia/metabolismo , Dolor/inducido químicamente , Asta Dorsal de la Médula Espinal/metabolismo , Médula Espinal , Neuronas , Adyuvante de Freund , Inflamación/metabolismo
11.
J Med Syst ; 47(1): 112, 2023 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-37924486

RESUMEN

In conjunction with pandemics, medical image data are growing exponentially. In some countries, hospitals collect biometric data from patients, such as fingerprints, iris, or faces. This data can be used for things like identity verification and security management. However, this medical data can be easily compromised by hackers. In order to prevent illegal tampering with medical images and invasion of privacy, a new texture fusion medical image encryption (TFMIE) algorithm derived from biometric images is proposed, which can encrypt the image using biometric information for storage or transmission. First, the medical image is decomposed into n-bit-planes by bit-plane decomposition. Secondly, a fusion image is generated by a biometric image with a circular local binary pattern and pixel-weighted average method. The fused image is further decomposed into n bit-planes through bit-plane decomposition and performs XOR operation with the original medical image in reverse order. Following the execution of the XOR operation, a new scrambling and diffusion algorithm based on a one-dimensional fractional trigonometric function (1DFTF) chaotic map is employed to form the cipher image. The experimental results show that compared with the existing methods, the average information entropy value of TFMIE is 7.99, and the average values of NPCR and UACI reach 0.9958 and 0.3346, respectively, which have strong key sensitivity, good robustness, and anti-attack ability. The method is lossless and has high transmission efficiency, which can meet the needs of medical big data encryption.


Asunto(s)
Algoritmos , Biometría , Humanos , Entropía , Hospitales , Iris
12.
World J Stem Cells ; 15(9): 931-946, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37900938

RESUMEN

BACKGROUND: Umbilical cord (UC) mesenchymal stem cell (MSC) transplantation is a potential therapeutic intervention for atherosclerotic vascular disease. Integrin beta 3 (ITGB3) promotes cell migration in several cell types. However, whether ITGB-modified MSCs can migrate to plaque sites in vivo and play an anti-atherosclerotic role remains unclear. AIM: To investigate whether ITGB3-overexpressing MSCs (MSCsITGB3) would exhibit improved homing efficacy in atherosclerosis. METHODS: UC MSCs were isolated and expanded. Lentiviral vectors encoding ITGB3 or green fluorescent protein (GFP) as control were transfected into MSCs. Sixty male apolipoprotein E-/- mice were acquired from Beijing Vital River Lab Animal Technology Co., Ltd and fed with a high-fat diet (HFD) for 12 wk to induce the formation of atherosclerotic lesions. These HFD-fed mice were randomly separated into three clusters. GFP-labeled MSCs (MSCsGFP) or MSCsITGB3 were transplanted into the mice intravenously via the tail vein. Immunofluorescence staining, Oil red O staining, histological analyses, western blotting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction were used for the analyses. RESULTS: ITGB3 modified MSCs successfully differentiated into the "osteocyte" and "adipocyte" phenotypes and were characterized by positive expression (> 91.3%) of CD29, CD73, and CD105 and negative expression (< 1.35%) of CD34 and Human Leukocyte Antigen-DR. In a transwell assay, MSCsITGB3 showed significantly faster migration than MSCsGFP. ITGB3 overexpression had no effects on MSC viability, differentiation, and secretion. Immunofluorescence staining revealed that ITGB3 overexpression substantially enhanced the homing of MSCs to plaque sites. Oil red O staining and histological analyses further confirmed the therapeutic effects of MSCsITGB3, significantly reducing the plaque area. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction revealed that MSCITGB3 transplantation considerably decreased the inflammatory response in pathological tissues by improving the dynamic equilibrium of pro- and anti-inflammatory cytokines. CONCLUSION: These results showed that ITGB3 overexpression enhanced the MSC homing ability, providing a potential approach for MSC delivery to plaque sites, thereby optimizing their therapeutic effects.

13.
Invest Ophthalmol Vis Sci ; 64(12): 20, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37695602

RESUMEN

Purpose: To investigate the morphological characteristics of the ophthalmic artery (OA) and retinal vessels in ocular ischemic syndrome (OIS) and to compare their ability to identify OIS. Methods: This cross-sectional observational study included 21 patients with unilateral OIS and 17 controls matched for age, sex, degree of internal carotid artery (ICA) stenosis, and cerebral collateral patency. This study used a three-dimensional reconstruction based on computed tomographic angiography to measure the morphological characteristics of the OA and the ICA. Quantitative measurements of retinal vessel diameter were performed using the Integrative Vessel Analysis software. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of the OA diameter and the central retinal artery equivalent (CRAE) to identify OIS. Results: The diameter of the OA (odds ratio = 0.001; P = 0.001) and the CRAE (odds ratio = 0.951; P = 0.028) were significantly associated with the presence of OIS after adjusting for age, sex, and the degree of the ICA stenosis. The areas under the curve for the OA diameter and the CRAE were, respectively, 0.871 (P < 0.001) and 0.744 (P = 0.017) according to the ROC curves analysis. Conclusions: The OA diameter measurement identified OIS better than CRAE measurement. The OA may reflect the changes in ocular blood supply in patients with OIS earlier than retinal vessels. The OA of eyes with OIS may undergo arterial wall remodeling, leading to a decrease in OA diameter and further reduction in blood flow.


Asunto(s)
Estenosis Carotídea , Oftalmopatías , Humanos , Arteria Oftálmica/diagnóstico por imagen , Constricción Patológica , Estudios Transversales , Vasos Retinianos/diagnóstico por imagen
14.
Am J Clin Nutr ; 118(3): 614-626, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37661106

RESUMEN

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are new drugs for the treatment of obesity. OBJECTIVE: To assess the weight-loss effects of GLP-1RAs in the treatment of patients with overweight or obesity without diabetes. METHODS: This is a systematic review with meta-analysis and trial sequential analysis. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from their inception to January 1, 2022. Eligible trials report on outcomes including body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), or total body fat (TBF). Mean differences (MDs) and standardized mean differences (SMDs) were summarized using random-effects models. RESULTS: Forty-one trials involving 15,135 participants were included. Compared with controls, GLP-1RAs significantly reduced BW (MD -5.319 kg, 95% CI: -6.465, -4.174), BMI (MD -2.373 kg/m2, 95% CI: -2.821, -1.924), WC (MD -4.302 cm, CI:-5.185 to -3.419), WHR (MD -0.011, CI -0.015 to -0.007), but not TBF (MD -0.320%, CI -1.420 to -0.780). Trial sequential analysis (TSA) supported conclusive evidence of the effects of GLP-1RAs on BW, BMI, and WC for weight loss. GLP-1RAs had nonlinear dose-response relationships with weight loss. Extensive sensitivity analyses demonstrated the robustness of the results, though the GRADE certainty of the evidence ranged from high to very low. High to moderate GRADE certainty of evidence suggested semaglutide as the most effective GLP-1RA agent, with the best efficacy and low to moderate risk of adverse effects. CONCLUSIONS: The present study provides conclusive evidence for the effect of GLP-1RAs on weight loss in a nonlinear dose-response manner in patients with obesity or overweight without diabetes. In terms of changes in BW, BMI, and WC, there is firm evidence for the overall weight-loss effects of GLP-1RAs. Of the GLP-1RAs, semaglutide might be the most effective agent.


Asunto(s)
Receptor del Péptido 1 Similar al Glucagón , Sobrepeso , Humanos , Sobrepeso/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Obesidad/tratamiento farmacológico , Peso Corporal , Pérdida de Peso
15.
Am J Pathol ; 193(12): 2133-2143, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37544503

RESUMEN

Although approximately 70% of bladder cancers are noninvasive and have high recurrence rates, early-stage disease is understudied. The lack of models to validate the contribution of molecular drivers of bladder tumorigenesis is a significant issue. Although mutations in PIK3CA are frequent in human bladder cancer, an in vivo model for understanding their contribution to bladder tumorigenesis is unavailable. Therefore, a Upk2-Cre/Pik3caH1047R mouse model expressing one or two R26-Pik3caH1047R alleles in a urothelium-specific manner was generated. Pik3caH1047R functionality was confirmed by quantifying Akt phosphorylation, and mice were characterized by assessing urothelial thickness, nuclear atypia, and expression of luminal and basal markers at 6 and 12 months of age. While at 6 months, Pik3caH1047R mice developed increased urothelial thickness and nuclear atypia, progressive disease was not observed at 12 months. Immunohistochemistry showed urothelium maintained luminal differentiation characterized by high forkhead box A1 (Foxa1) and peroxisome proliferator-activated receptor γ expression. Surprisingly, Pik3caH1047R mice subjected to low-dose carcinogen exposure [N-butyl-N-(4-hydroxybutyl)nitrosamine] exhibited no significant differences after exposure relative to mice without exposure. Furthermore, single-sample gene set enrichment analysis of invasive human tumors showed those with mutant PIK3CA did not exhibit significantly increased phosphatidylinositol 3-kinase/AKT pathway activity compared with wild-type PIK3CA tumors. Overall, these data suggest that Pik3caH1047R can elicit early tumorigenic changes in the urothelium, but progression to invasion may require additional genetic alterations.


Asunto(s)
Proteínas Proto-Oncogénicas c-akt , Neoplasias de la Vejiga Urinaria , Animales , Humanos , Ratones , Carcinogénesis/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Mutación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Urotelio/metabolismo
16.
Sci Data ; 10(1): 545, 2023 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-37604823

RESUMEN

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.


Asunto(s)
Pueblo Asiatico , Encéfalo , Humanos , Encéfalo/diagnóstico por imagen , China , Data Warehousing , Bases de Datos Factuales , Neurociencias
17.
Cancers (Basel) ; 15(12)2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37370698

RESUMEN

Background: SHR-5 has been used as an "adaptogen" for enhancing physical and mental performance and for fighting stress in the healthy population. The purpose of this study is to determine the chemopreventive efficacy of SHR-5 for superficial bladder cancer and to investigate the underlying mechanisms of action. Methods: UPII-mutant Ha-ras bladder-cancer-transgenic mice, that developed low-grade and noninvasive papillary transitional urothelial cell carcinoma, were fed with 1.25 and 6.25 mg/mL SHR-5 in drinking water for 6 months. The survival of the mice, obstructive uropathy, tumor burden and morphology, and proliferation were evaluated by pathological, molecular, metabolic, and statistical analyses. Results: Approximately 95% or more of the male UPII-mutant Ha-ras mice that drank SHR-5 daily survived over 6 months of age, while only 33.3% of those mice that drank normal water survived over 6 months of age (p < 0.0001); SHR-5 drinking exposure also reduced tumor-bearing bladder weight and urinary tract obstruction and inhibited mTOR signaling in neoplastic tissues. Global metabolic analysis revealed that SHR-5 resulted in increased phenolic metabolites and decreased CoA, a critical metabolic cofactor for lipid metabolism. Conclusions: Our findings highlight the potential of SHR-5 as an anti-aging agent for bladder cancer prevention through reshaping tumor metabolism via the inhibition of the mTOR signaling. Global metabolomics profiling provides a unique and efficient tool for studying the mechanisms of complex herb extracts' action.

18.
J Environ Manage ; 339: 117823, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37129967

RESUMEN

Riparian buffers benefit both natural and man-made ecosystems by preventing soil erosion, retaining soil nutrients, and filtering pollutants. Nevertheless, the relationship between vertical methane fluxes, soil carbon, and methane microbial communities in riparian buffers remains unclear. This study examined vertical methane fluxes, soil carbon, and methane microbial communities in three different soil depths (0-5 cm, 5-10 cm, and 10-15 cm) within a riparian buffer of a Sponge City Park for one year. Structural equation model (SEM) results demonstrated that vertical methane fluxes varied with soil depths (λ = -0.37) and were primarily regulated by methanogenic community structure (λ = 0.78). Notably, mathematical regression results proposed that mcrA/pmoA ratio (R2 = 0.8) and methanogenic alpha diversity/methanotrophic alpha diversity ratio (R2 = 0.8) could serve as valid predictors of vertical variation in methane fluxes in the riparian buffer of urban river. These findings suggest that vertical variation of methane fluxes in riparian buffer soils is mainly influenced by carbon inputs and methane microbial abundance and community diversity. The study's results quantitatively the relationship between methane fluxes in riparian buffer soils and abiotic and biotic factors in the vertical direction, therefore contributing to the further development of mathematical models of soil methane emissions.


Asunto(s)
Euryarchaeota , Microbiota , Humanos , Suelo/química , Metano , Carbono , Microbiología del Suelo
19.
Huan Jing Ke Xue ; 44(5): 2974-2982, 2023 May 08.
Artículo en Chino | MEDLINE | ID: mdl-37177969

RESUMEN

Assessing regional carbon emissions and their relationship with socio-economic conditions is very important for developing strategies for carbon emission reduction. This study explored the impact of the proportion of non-fossil energy, the land development degree, the urbanization rate of permanent residents, the proportion of secondary industry, per capita GDP, and per capita construction land area on per capita CO2 emissions in 339 prefecture-level and above cities in China (excluding some cities in Xinjiang, Hong Kong, Macao, and Taiwan). A Bayesian belief network modeling carbon emissions was constructed to identify the global effects of various factors on per capita CO2 emissions, and multiscale geographically weighted regression was used to analyze their local effects. The results showed that first, per capita CO2 emissions of cities in China increased from the south to the north and decreased from the eastern coast to the inland region. Second, globally, the sensitivity of per capita CO2 emissions to various factors from high to low was in the order of per capita construction land area>per capita GDP>urbanization rate of permanent residents>land development degree>proportion of secondary industry>proportion of non-fossil energy. Third, locally, the direction of the spatial relationship between each factor and per capita CO2 emissions was consistent with the global relationship, and there was spatial heterogeneity in the strength of the relationship. Finally, clean energy, decarbonization technologies, saving and intensive use of land, and green living were effective ways to achieve the dual-carbon goal.

20.
Inorg Chem ; 62(15): 6047-6054, 2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37017204

RESUMEN

This study used the tert-butylcalix[6]arene (TBC[6]) as the ligand and successfully synthesized six TBC[6]-stabilized titanium-oxo clusters (TOCs) by the one-step solvothermal reaction. These six compounds were [Ti4O2(TBC[6])2] (Ti4), {Ti2(TBC[6])(EtO)2(SaH2)2} (Ti2-SA, H2Sa = squaric acid), {Ti2(TBC[6])2(EtO)2(Oa)} (Ti2-OA, H2Oa = oxalic acid), [H2Ti4(TBC[6])(BA)2(EtO)10] (Ti4-BA, HBA = benzoic acid), [Ti6O2(TBC[6])(BA)4(OiPr)10] (Ti6-BA), and [Ti8(TBC[6])2(Sal)4(EtO)16] (Ti8-Sal, H2Sal = salicylic acid). These clusters contain one or two TBC[6] ligands, with the biconical or monoconical configuration, greatly increasing the variety of TOCs it could support. The introduction of auxiliary carboxylic ligands can further stimulate the growth of structures, with the cluster core gradually increased from {Ti-TBC[6]-Ti} to {Ti2-TBC[6]-Ti2}, to {Ti3-TBC[6]-Ti3}, and finally to {Ti3-TBC[6]-Ti2-TBC[6]-Ti3} with 3.1 nm length. Structural regulation may affect their solution stability, absorption spectra, and photocurrent response. The study of catalytic activities shows that these clusters can be used as recyclable heterogeneous photocatalysts for the oxidation of sulfide to sulfoxide. The catalytic efficiency of the TBC[6]-Tix system is closely related to the cluster structure, and the exposure of the Ti site on the catalyst surface can significantly enhance the catalytic activity of the clusters.

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